Abstracts of doctoral theses

Recent Submissions

  • Figueiredo, Patrícia (2020)
    Lignin is part of the lignocellulosic biomass and represents the second most abundant biopolymer after cellulose. However, only about 2% of the annually isolated lignin is used for low-value applications, mainly due to its complex structure. The fabrication of lignin nanoparticles offers a structural and morphological control of the lignin polymer, which enables lignin to be used for high-value products in biomedical applications like drug delivery and tissue engineering. Therefore, the main aim of this thesis was to exploit the potential of the under-investigated lignin-based nanoparticles as vehicles to deliver different therapeutic compounds for improved cancer therapy. Although multiple treatment options are available to treat cancer diseases, they still represent illnesses with very high incidence and mortality worldwide. Nanotechnology has opened doors to improve the limitations of current therapeutic modalities, such as chemotherapy or administration of immunomodulatory agents, by improving the solubility, stability and circulating half-life of the therapeutics, and by minimizing the systemic side effects. Firstly, different lignin-based nanoparticles were prepared and characterized, and their cytocompatibility investigated towards several cell lines. The ability of lignin nanoparticles to load different chemotherapeutic compounds was assessed, and drug release profiles were evaluated in two different buffers (pH 5.5 and 7.4). Secondly, after a carboxylation reaction of the original lignin polymer, the carboxylated lignin nanoparticles were surface modified with a polymer/peptide, as a proof-of-concept of the nanoparticles’ functionalization. The release profile of a poorly-water soluble cytotoxic compound (benzazulene) from the lignin nanoparticles was evaluated, and the in vitro antiproliferative effect investigated against several cell lines. Next, lignin polymers with different degrees of carboxylation were prepared in order to investigate the long-term stability of the resulting lignin nanoparticles at physiological conditions. After finding the optimal conditions in terms of stability, the lignin nanoparticles were further functionalized with a cell-penetrating peptide, and the cellular interactions of the resulting nanosystem were evaluated and compared with internalizing arginine-glycine-aspartic acid peptide-functionalized lignin nanoparticles, using two- and three-dimensional cell culture models. Finally, the lignin nanoparticles were loaded with resiquimod, an agonist of the toll-like receptors 7 and 8 that can induce the re-education of M2 to M1-like macrophages, and further functionalized with a peptide that targets the mannose receptor expressed by the M2 macrophages. Afterwards, the homing ability of these nanoparticles was investigated in vivo, using an orthotopic 4T1 triple-negative breast cancer model. The therapeutic effect of these nanosystems was studied in combination with a chemotherapeutic compound (vinblastine), and the immunological profile of the cells isolated from the tumors was compared. Overall, this thesis provides new insights on the use of lignin polymer as a novel starting material to develop lignin-based nanocarriers, in particular for cancer therapeutics.
  • 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.
  • Bärlund, Katariina (Helsingin yliopisto, 2019)
    Katariina Bärlund: Homicides, attempted homicides and violence by mothers of under one-year-olds’ as portrayed in forensic psychiatric examinations. A narrative study. Filicides (child killing by parents) have decreased remarkably in Finland during the past decades. Despite the decrease in numbers, Finnish children still end up as victims of filicides and violent abuse by parents. The present research investigated forensic psychiatric examinations of mothers who targeted their children with filicide, attempted filicide or violence during the child’s first year of life. The research approached this phenomenon by asking what kind of narratives the events in the examinations gave rise to. The theoretical foundations of the research focused on motherhood, evil, violence, and homicides. Motherhood was seen as part of a cultural understanding of motherhood and evil was considered as a human dimension. The mission of the research was to investigate filicides, attempted filicides and violent acts of mothers towards their children from the point of view of social science, to form a picture of the events that includes the circumstances, and to illuminate the events narratively. The research approached the uncovered areas of social work research: filicide by mothers and the thematic of evil. The research material included forensic psychiatric examinations and the sample narratives written on the basis of these cases. Reading these narratives, it must be noted that they do not concern individual cases but are a mixture of different cases within the material and include only rough descriptions as interpreted by the researcher. The research was based on documents and thus does not reach the authentic viewpoint of mothers or their inner social circle. The research produced two sample narratives, the story of a mother who killed her newborn baby (neonaticide) and the story of a mother who killed her under one year old baby (infanticide). Comparing these narratives produced a clear result as the narratives differed from each other. The first narrative was named as “Concealed Story “ and the second as “Fractured Story”. The present research reinforced the view of filicide and violence towards children as complex event where the parents’ differing degrees of inability in responding to life’s challenges can be seen. The research produced a need to research the subject further, especially from the viewpoints of loneliness and multiprofessional co-operation. Keywords: motherhood, homicides, violence, evil, evilness, narrative research
  • Wasastjerna, Maria (Unigrafia, 2019)
    This doctoral thesis examines the role of privacy in competition law in the age of digitalization and big data. It explores the growing significance of data protection and looks at the interlinkage between privacy and competition policy, thereby testing conventional boundaries and expanding horizons. With the transition to the data-driven economy, our society has grown to rely on products and services that are free of charge to consumers, but because they have no monetary price, there is hesitation whether, and how, action should follow. The thesis questions whether competition policy is too fixated on the idea that the only real harm to consumers consists of rising prices. Consumers pay for online services with time and data. When many products and services seem free in today’s online markets, with user data as the invisible cost, looking only at price effects in competition analysis is misleading. The thesis asserts that an overly price-centered approach to competition policy risks overlooking welfare harms that relate to significant non-price dimensions, such as privacy and consumer choice. The research objectives and questions explored in the thesis can be summarized by way of sub-questions, namely what is the role (if any) of personal data and privacy in competition law? Should competition policy protect privacy among its objectives, and if so - how? The findings point to current shortcomings in competition law and propose a rethinking of competition policy for the data economy. This includes a proposal to expand horizons beyond a static price-centric approach, incorporating a privacy dimension to competition law and exploring a conjoined policy approach. Here, competition law is examined not only from a strictly legal perspective, but in a wider context, including elements that are societal, political, economic, historical and cultural. The thesis emphasizes that over time, many different values have been advocated in the name of competition law and depending on the interests that are being promoted, different objectives are put forward as a driver for law enforcement. This is all the more true today when observing the public discussion and politics around competition in digital markets and companies’ use of data as market power, think only of the Cambridge-Analytica scandal and Facebook’s handling of personal information. The topic of the thesis is timely and highly relevant. By providing a comprehensive insight into competition policy in the digital economy, and especially the role of personal data in this context, the thesis offers important contributions and policy considerations to the current debate. Readers are provided with an overview of the contemporary interplay between competition, data and privacy in the digital economy, including implications for business practice, reflections on the way forward and suggestions for future research.
  • Matilainen, Sanna (2019)
    Leigh syndrome is a progressive mitochondrial encephalopathy manifesting in early childhood, with characteristic symmetric lesions of the brainstem and basal ganglia, and a spectrum of clinical findings. Often multi-organ manifestation is known to occur. The genetic background of Leigh syndrome is exceptionally wide, with over 75 known disease genes affecting mitochondrial function, in both the mitochondrial and nuclear genomes. The molecular characteristics of this clinically and genetically heterogenetic disease, however, remain largely unknown. In this study genetic diagnoses were found for patients with Leigh syndrome and the underlying molecular pathomechamisms were studied. The disease found in two families was caused by a novel Scandinavian founder mutation in SUCLA2, causing deficiency of succinyl-CoA ligase (SCL) of the TCA cycle, a central metabolic pathway. The substrate for the reaction catalyzed by SCL is succinyl-CoA, also serving as the substrate for succinylation, a recently characterized post-translational modification with yet unknown biological significance. These results show SCL deficiency to lead to increased protein succinylation via accumulation of succinyl-CoA in cell lines of patients. Metabolic disturbances caused by the succinylation of hundreds of target lysine residues, found on a wide range of metabolic proteins in nearly all cell compartments, propose succinylation as a mechanism for the simultaneous control of several metabolic pathways. Also, defects of the mitochondrial polynucleotide phosphorylase (PNPase) caused by PNPT1 mutations were established among the causative mechanisms of Leigh syndrome with next-generation sequencing in one patient with a progressive Leigh encephalomyopathy. Defective mitochondrial RNA metabolism due to loss of RNA degradation activity of PNPase is shown as a novel mechanism for mitochondrial disease. The paths to molecular diagnoses for the patients in this study portray the recent advancements of molecular and genetic diagnostics, which have developed dramatically with the era of next-generation sequencing methods. Genetic diagnoses were provided for patients with Leigh syndrome of unknown molecular etiology, crucial for the well-being of the families and treatment of the patients. Simultaneously, patient-derived cell lines and tissues with a disarrangement of mitochondrial metabolism were utilized to increase our understanding of the related metabolic pathways and mitochondrial metabolism.
  • Scherleitner, Moritz (2019)
    In many different circumstances, hybrid financial instruments (HFIs) can be an appealing source of finance. At the same time, however, such instruments may also be used in tax planning. Its differential treatment in the affected jurisdictions can give rise to double non-taxation of a payment. Exploiting this allows for significant reductions in the corporate tax liability. In the aftermath of the recent financial crisis, such “tax arbitrage” has increasingly entered debate within the G20, OECD, EU and UN. As a result various concepts of how to engage with the problem were developed. Besides these, some states already rely on provisions that can be of relevance in this context. Starting from these developments, the objective of the monograph is to help those in charge of solving the problem to make a more educated decision. As such, it addresses tax policymakers around the world. For the sake of reaching its goals, the thesis applies a socio-legal method. This should acknowledge that tax policymakers design rules in a context that is broader than existing tax law. They have to consider the traditional principles of tax policy, including tax competition constraints, as well as legal dogmatic restrictions – and does this thesis. Against this background, the dissertation is structured in the following way: In chapter 1, the reader is introduced into the topic and the design of the research. In chapter 2, HFIs are shed light on from the perspective of tax law, corporate finance and economics. The goal is to understand their role in reality. In chapter 3, the guiding principles for company taxation are reviewed. Contemporary tax research relies on the triumvirate: (i) equity, (ii) efficiency and (iii) administrability. So does this thesis. The literature on these issues is considered in sufficient depth, but with a strong focus on the research objectives. Chapter 4 builds the bridge between the above preparatory part and the core research. This happens by working out the non-legal concerns attached to tax arbitrage with HFIs. They include three from an inter-taxpayer equity perspective, three from an inter-nation equity perspective and two from an efficiency perspective. This is the problem definition. Chapters 5¬8 investigate how four approaches address these concerns. These are the “OECD approach”, the “low tax approach”, the “UN approach” and the “recharacterisation approach”. The focus will be on tax arbitrage transactions with HFIs that rely on a qualification conflict and substitute transactions with financial instruments that reach the same, or a similar, result. The research on these approaches also takes into account their administrability and legal dogmatic considerations. In doing so, the collateral damage caused by the rules is assessed as well. Also this happens from a multi-disciplinary perspective. In chapter 9, the author presents his own thoughts on what developed and developing countries may want to consider in dealing with the problem of tax arbitrage with HFIs. The author is aware of tax arbitrage with HFIs only being a part of the challenges tax policymakers have to deal with. In an attempt to consider this, the discussion is put into a broader context. As a direct consequence thereof, the thesis also lacks a clear solution. Rather, it aims to provide information that should improve tax policymakers´ ability to address the issue. It is left up to them to trade-off equity, efficiency and administrability considerations, paying attention to what is possible de lege lata.
  • Räsänen, Markus (Helsingin yliopisto, 2019)
    Cardiovascular diseases are the leading cause of mortality worldwide, and they have become the most important and most significant cause of non-communicable diseases. In the Western world, they also rank first when listed by disability-adjusted life years (DALY). In particular, ischemic heart disease is still a major burden to the society, causing up to one third of the deaths of persons over 35 years. My aim in this thesis was to investigate the translational potential of vascular endothelial growth factor B (VEGF-B) and the downstream Bone marrow kinase X (Bmx) tyrosine kinase in the treatment of pathological cardiac conditions, such as myocardial ischemia, pathological cardiac hypertrophy and cardiotoxicity. Vascular endothelial growth factors (VEGFs) are major regulators of blood and lymphatic vessel development and growth. Based on earlier studies, VEGF-B appeared as a potential angiogenic growth factor because of its relative specificity to the heart and adipose tissue. Furthermore, I was interested in analyzing the Bmx tyrosine kinase, which has been shown to receive signals from VEGF receptors, and to be required for the development of cardiac hypertrophy. In the first study of my thesis, we showed that the expression of a VEGF-B transgene (TG) in the cardiomyocytes leads to an expansion of the coronary arterial tree. The VEGF-B transgenic hearts were also protected against myocardial ischemia. This opened further possibilities to study VEGF-B and its signaling in different pathological conditions in the heart. In the second publication of the thesis, we showed that angiotensin II (Ang II)-induced cardiac hypertrophy was significantly reduced in mice, which were either deleted for the Bmx gene or in which the tyrosine kinase activity of Bmx was inactivated. This suggests that a selective Bmx tyrosine kinase inhibitor could be used in the treatment of pathological cardiac hypertrophy. Cardiotoxicity and congestive heart failure are growing problems in cardio-oncology, due to decreased cancer mortality and associated increased long-term use of cytotoxic drugs. Doxorubicin (DOX) is an anthracycline antibiotic, which is associated with cardiotoxicity that may further develop into congestive heart failure. In the third paper of my thesis we showed that, in mice, VEGF-B gene therapy can be used to protect the endothelium and to inhibit cardiac atrophy and capillary rarefaction induced by DOX. In the fourth study of this thesis, we found that VEGF-B gene therapy can induce endocardium to venous endothelial cell (EC) transition, opening the possibility of a new pathway for coronary reperfusion. The sinus venosus and the endocardium are the major sources of the coronary vessels that support the expanding myocardium in the developing heart. The adult heart can no longer generate new blood vessels from the endocardium, because the endocardium-to-coronary vessel transition is inhibited after the neonatal stage. Importantly, in this study the subendocardial EC proliferation was obtained also in adult mice by VEGF-B gene delivery to the cardiomyocytes. Furthermore, we were able to induce the endocardial to EC transdifferentiation by VEGF-B gene delivery after myocardial infarction (MI). Thus, re-activation of the adult endocardium by growth factors could be a new therapeutic strategy for cardiac neovascularization after MI. Overall, these findings open translational therapeutic possibilities for the treatment of coronary artery disease, cardiac hypertrophy and anthracycline-induced cardiotoxicity.
  • Koskinen, Suvi (Picaset Oy, 2019)
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