Väitöstiivistelmät

Nyligen publicerat

  • Hormio, Säde (Helsingin yliopisto, 2017)
    The topic of my thesis is individual and collective responsibility for collectively caused systemic harms, with climate change as the case study. Can an individual be responsible for these harms, and if so, how? Furthermore, what does it mean to say that a collective is responsible? A related question, and the second main theme, is how ignorance and knowledge affect our responsibility. My aim is to show that despite the various complexities involved, an individual can have responsibility to address climate change. I argue that climate change is not a problem just for states and international bodies, but also for individuals. There are three possible sources of moral responsibility for individuals in relation to climate change harms: direct responsibility (individuals qua individuals), shared responsibility as members (individuals qua members of collective agents), and shared responsibility as constituents (individuals qua constituents of unorganised collectives). Accounts that deny individual responsibility fail to either take our interdependent reality seriously or fail to understand marginal participation (or in the case direct responsibility, fail to appreciate the nature of the climate change phenomenon). Individuals can be complicit in climate change harms, either as members of collective agents (e.g. as citizens of states or employees of a corporation) or as constituents of unorganised collectives (e.g. as consumers or polluters). Although I focus on individual complicity, I do not deny the obligations of collective agents. However, nation-states, governments, and international bodies are not the only relevant collective agents in climate ethics: other collective agents, such as corporations, matter also and can have obligations concerning making sure that their activities are as carbon-neutral as possible. In addition, those corporations that have engaged in lobbying against climate regulation through creating and disseminating misleading information have acquired themselves additional obligations to mitigate climate change and compensate for the harm they have caused. Even so, the ethical claims can only be understood by individual members of these collective agents because only they can feel the pull of moral claims. I suggest that we could distinguish between what one must possess in order to be capable of making moral claims (i.e. moral agency conditions), and what it means to have the ability to exhibit such claims through one’s conduct. Individual direct responsibility is to not to increase the probable risk of serious harm to other people, at least as long as we can do so at a less than significant cost to ourselves. It is limited to relatively wealthy individuals. Offsetting is not a reliable way to meet this duty; we need to look at the emissions from our lifestyle choices (within the available infrastructure). Shared responsibility qua members of collective agents is the key individual responsibility, and it presses especially on those occupying key positions within key collective agents. Saying that, our shared responsibility qua constituents of unorganised collectives has the potential to be decisive in whether some action is taken or not, either through a set of actions that can signal certain acceptance or support, or as a form of political support from the grass roots.
  • Tseng, Kuan-Yin (UNIVERSITY OF HELSINKI, 2017)
    Stroke is one of the leading causes of death and a major cause of disabilities in adults. More than half of stroke victims suffer some type of disability, ranging from different levels of minor weak- ness in a limb to a complete loss of mobility. Currently, treatment of stroke requires a stringent re- habilitation programs. Nevertheless, two thirds of all patients will still have some type of difficulty with regular daily activities. Recent experimental findings raise the possibility that functional improvement after stroke may be achieved through neuronal replacement by endogenous neural stem cells (NSCs) residing in the adult brain. Therefore, additional understanding of the properties of NSCs will help to identify their optimal potential in cell-based therapy. Neurotrophic factors are a family of proteins that are important in neuronal development and function, and have been studied as possible drugs for ischemic brain injury. In addition to Brain-Derived Neurotrophic Factor (BDNF) and Glial cell line-Derived Neurotrophic Factor (GDNF), Mescenphalic Astrocyte-Derived Neurotrophic Factor (MANF) and Cerebral Dopamine Neurotrophic Factor (CDNF), that form a distinct family of evolutionary conserved proteins with neuroprotective effects, have potential in the treatment of stroke. While MANF has been shown to protect cortical neurons from death in a rodent model of ischemic brain injury, the effects of post-stroke MANF ad- ministration on cellular processes during the recovery phase are poorly understood. To shed light on the possible regenerative potential of MANF for the injured brain, we need to first investigate the roles of endogenous MANF in neural stem cells (NSC) in a normal or pathological condition. We developed and optimized a work platform for studying the regulation and effect of MANF on biological properties of NSCs and cortical development. Our findings reveal an important role of MANF in neurite outgrowth and neuronal migration in the developing cortex. In addition, we demonstrated that endogenous MANF has the potential to protect NSCs against oxygen and glucose-deprivation conditions. Next, using neurosphere and subventricular zone (SVZ) explant cultures, we further studied the effect of MANF administration on cell differentiation and migration. We presented the data that exogenously added MANF can induce neural/glial differentiation and promote cell migration out of SVZ explants. Also, utilizing the advantage of NSCs as a target for MANF, we discovered that exogenous MANF can induce the phosphorylation of STAT3 in NSCs. Finally, we used the rat model of ischemic stroke to compare the effects of MANF and GDNF in neurogenesis after stroke. While injection of GDNF into lateral ventricle has a strong mitogenic effect to increase neurogenesis in SVZ, it does not induce migration of neuroblasts towards the ischemic area. In contrast, MANF facilitates the migration of neuroblasts towards the lesioned cortex. Regarding long-term infusions in the peri-infarct zone, both GDNF and MANF recruited the neuroblasts in the infarct area. However, only MANF accelerated functional recovery after stroke. In summary, this work has extended the knowledge of MANF’s capacity for neuronal differentiation as well as migration, and the regenerative capacity for its therapeutic use in further studies.
  • Jokinen, Viljami (Viljami Jokinen, 2017)
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  • Gurkov, Aleksandr (Unigrafia, 2017)
    The dissertation is focused on the analysis of Russian regulations on arbitral awards deciding over relationships that are subject to competition law rules. This thesis investigates whether such relationships are arbitrable in Russia; in case these disputes can be resolved in arbitration, are there any additional requirements for arbitrators in such cases to secure state competition law policies; and finally, how can a public authority verify that antitrust policies were upheld in an arbitral award? To answer these questions, the research uses a doctrinal methodology, analyzing norms of Russian law. To support the study and make the answers more concrete, judicial practices of Russian courts are analyzed. The structure of this dissertation reflects the study’s set goals. After an introduction to the research, Chapter 2 provides a brief overview of some of the aspects of the Russian legal system that are relevant for the further study. Chapter 3 addresses arbitrability of disputes in question in Russia. Chapters 4, 5, and 6 deal with different aspects of public policy concept application in arbitration in Russia in the targeted group of cases. In particular, Chapter 4 focuses on the general characteristics of the public policy concept of arbitration in Russia, while Chapter 5 tackles more specifically a correlation between a prospective violation of competition law rules and public policy infringement in Russia. Finally, Chapter 6 addresses the extent of court review of arbitral awards and the possibility of such review in awards that could potentially violate Russian antitrust law provisions. Correspondingly, the study provides the following conclusions: 1) disputes involving competition law regulations are arbitrable in Russia, except for those disputes originating from public procurement contracts; 2) violation of Russian competition law can be considered as a violation of Russian public policy, if such violation evidently breaches the prohibition to engage in economic activity aimed at monopolisation and unfair competition; 3) Russian law does not allow substantive review of arbitral awards, even in cases where public policy could be at stake; at the same time, courts do not always follow this rule and sometimes take a closer look at the relations between parties and re-evaluate findings of arbitrators on matters of law.
  • Katajisto, Milla (Unigrafia, 2017)
    Chronic obstructive pulmonary disease (COPD), mainly caused by inhaling tobacco smoke, is very common an the main symptom is slowly proceeding dyspnoea, which often reduces a patient’s physical activity. Physical inactivity in COPD relates to poor prognosis and lower quality of life. Pulmonary rehabilitation (PR), based on exercising, has been proven to be an effective intervention among COPD patients. One of the aims of this study was to evaluate physical activity among Finnish COPD patients, to better understand the reasons behind activity or inactivity and their interest in exercise-based PR, in order to improve their care in the future. The patient cohort of the Chronic Airway Disease (CAD) study made it possible to study physical activity in relation to quality of life and severity of disease, among other characteristics. A questionnaire asking about exercise habits, daily activities and patient history regarding sports and rehabilitation was sent to all COPD study patients in spring 2010. The main result was that dyspnoea was more severe among the inactive patients, even when adjusted to the forced expiratory capacity in one second (FEV1). Dyspnoea was also the main subjective obstacle to exercising. The study patients had given their consent to allow the study of their registries for medication purchases. The reimbursement registry of the National social insurance office made it possible to track the study patients' COPD drug medication in the same year that their physical activity status was evaluated. Episodes of severe exacerbation and pneumonia were also of interest, in relation to medication and physical activity. The result of this investigation was that the maintenance medication did not differ significantly among active and inactive patients; however, inactive patients suffered more from severe exacerbations and needed more rescue medication, antibiotics and oral steroids. Only half of the patients reached the daily defined dose (DDD), a dose considered relevant in care. During 2010 to 2013, PR was started with special funding available for workers of the Helsinki and Uusimaa (HUS) district, to development of new type of care for patients. Patients with COPD from Helsinki university hospital, who had severe disease, were included and the majority of them had a history of hospital admissions. The primary aim of the third study of this thesis, was to evaluate the short-term and long-term results and also to evaluate the cost effectiveness. The patients performed well in the PR programme, their test results improved as expected, and the hospitalisation days during the year after PR were less than half of the number of hospitalisation days during the year before.The secondary aim was to gather information, which so far had been lacking, about the occurrence of serious exacerbations in the Helsinki; in this district. Data for every hospital admission with the COPD ICD-code year 2014 were collected from eMr and the patient’s COPD diagnosis and the cause of hospital stay was evaluated. The data showed that there were 437 patients with severe exacerbations; 3 out of 4 of whom were treated in city hospitals and none of them was offered PR. The rate of readmissions due to exacerbations was 50% and total mortality during the year was 41%.Understanding of the importance of physical activity or exercise-based PR in treatment for COPD is not sufficient in health care. Access to PR should be made possible for all patients in need, inparticular for patients with severe COPD exacerbations.
  • Hasygar, Kiran (Painosalama Oy, 2017)
    The ability to dynamically adapt to fluctuating nutrient availability determines the survival of living organisms. While the capacity to grow rapidly and build energy stores on a nutritious diet can provide a selective advantage, being able to endure nutrient scarcity is also key to survival. Insulin/Insulin-like Signaling (IIS) is a conserved anabolic pathway which drives growth and energy storage during nutrient abundance. However, the IIS needs to be suppressed during starvation to readjust growth and energy homeostasis. The molecular factors which regulate the IIS to determine the optimal balance between anabolism and catabolism, aiding the survival of animals in a wide range of nutrient conditions remain poorly characterized. Using Drosophila melanogaster as a model organism, we aimed to identify novel nutrient responsive signaling pathways that coordinate animal growth and metabolic homeostasis. Conservation of the IIS pathway, availability of extensive genetic toolkit, and little genetic redundancy make Drosophila an attractive model to study growth and energy metabolism. Insulin secretion is dynamically regulated by nutrition in flies, and multiple nutrient sensing pathways converge on the Insulin Producing Cells (IPCs) to modulate Insulin secretion according to the nutrient status. Hence, we aimed to perform a tissue specific RNAi screen in the IPCs to identify novel regulators of the IIS in vivo. In this thesis, we discover a novel role for a ribosome surveillance pathway in starvation response. We show that suppression of ribosome biogenesis in the IPCs leads to activation of a ribosome surveillance response, resulting in inhibition of Insulin secretion and animal growth. Also, we identify tumor suppressor p53 and an atypical MAP kinase ERK7 as essential components of this pathway. We demonstrate that ERK7 is expressed in the IPCs upon starvation, and its expression is sufficient and essential to inhibit Insulin secretion and growth. Moreover, inhibition of p53 or ERK7 in the IPCs results in a blunted starvation response, highlighting the importance of this cell intrinsic pathway. Further, we establish that another component of the secretory pathway, the Exocyst complex is essential for Insulin secretion in flies. In addition to its function in the IPCs, we show that ERK7 expression is elevated upon starvation in fat body, the fly counterpart of liver and adipose tissue, to regulate growth and metabolism. While ERK7 in the fat body limits animal growth through inhibiting the expression of an insulinotropic peptide, Stunted, it inhibits de novo lipogenesis and triacylglycerol (TAG) storage by suppressing the expression of a transcription factor, Sugarbabe. Also, we have generated ERK7 mutant flies, which display accelerated growth rate and store more TAG on a nutrient rich diet, consistent with ERK7 being an inhibitor of growth and lipid synthesis. However, ERK7 mutants fail to limit their growth, and sufficiently mobilize lipid stores during nutrient scarcity, and consequently survive poorly upon starvation. Further, we show that ERK7 regulates a majority of the starvation-induced gene expression on a genome wide scale, thus establishing ERK7 as a major determinant of systemic starvation response. Thus, we demonstrate that ERK7 is a starvation induced molecular factor regulating growth and metabolic homeostasis. Through inhibiting anabolic processes such as the Insulin signaling and lipid synthesis, and activating catabolic processes such as lipid breakdown, ERK7 facilitates survival of animals upon starvation.
  • Pipatti, Otto (2017)
    This study offers an overall interpretation of the sociologist and anthropologist Edward Westermarck’s (1862–1939) moral and social theory. It focuses on the key elements of Westermarck’s theory of moral emotions as presented in The Origin and Development of the Moral Ideas (1906-08) and summarized in Ethical Relativity (1932), and examines the importance of his work for understanding and explaining a wide range of social and moral phenomena that may be observed in all social environments. The study has two main aims. First, it lays out the key features of Westermarck’s theory of moral judgement, the nature of retributive emotions in which moral judgements are based, and the various psychological and social elements influencing them. At the same time, it shows that Westermarck’s account of morality is an ambitious and wide-ranging analysis of the fundamentals of human social behaviour and social reality. By combining the moral-psychological and sociological aspects of Westermarck’s work, the study reconstructs his understanding of emotions, and the different forms of emotional contagion in particular, as the fundamental elements of human sociality. What emerges is that at the heart of Westermarck’s theory-building is his neglected account of sympathy, proving to be crucial to his understanding of morality and human social life. The second aim of this study is to examine Westermarck’s thought in the context of his main sources of inspiration, enabling a better understanding of his work. In this regard, it highlights the importance of Darwinian evolutionism to the different aspects of Westermarck’s project, especially to his approach to the human mind. In addition, the study demonstrates how Westermarck’s theory of moral emotions developed out of, and in response to, David Hume’s and Adam Smith’s moral philosophy, combining their views on human nature, moral sentiments, and sympathy with Darwinian evolutionary thinking. The first part of this work focuses on the central elements in Westermarck’s moral and social theory, especially with respect to the nature of moral emotions, the role of sympathy and society, reciprocity, the emergence and maintenance of moral norms, and moral responsibility. The remaining part of the study expands upon and deepens these discussions by looking at Westermarck’s theory of moral emotions in relation to the sentimentalist tradition in British moral philosophy, whose importance Westermarck himself emphasised as the background for his thinking. Today, his legacy serves as an example of sociological theory-building that is not organized around the dualisms of nature/culture and animal/human which penetrate much of the social sciences. The study demonstrates Westermarck’s sociological relevance and broadens the view of Westermarck as the forerunner of modern evolutionary approaches to morality.
  • Mäihäniemi, Beata (University of Helsinki, 2017)
    The role of information intermediaries has grown significantly in recent years, due to an increased importance of information as an industry input. It seems that posting any information, independently of using a dominant online platform, may be detrimental to one’s business. Such companies can be considered as unavoidable trading partners, which may enable them to manipulate information and possibly exclude or damage effective competition. These intermediaries may block access to, or bias, the quality of information. The main reason why competition law would be interested in regulating the access to information is that where information is controlled by one network-based dominant undertaking — significant competition problems may occur. Firstly, access to the market may be prevented due to indirect network effects, such as consumers preferring a particular network because of its good reputation or everybody else using it and due to the fact that some networks may give preference to its own complementary services. Secondly, companies that control information may also affect the quality of information provided and this may, in turn, affect consumer welfare. Finally, in some cases, where information is created by means of complicated and costly research, but where it is unprotected by an intellectual property right, the danger of free riding may arise. Therefore, competition law should be extremely careful in granting access to information that constitutes a basis for some business models (e.g. trade secrets), even where such information belongs to a dominant company. One of the findings of this study is that special responsibility should not be extended outside competition law to include general fairness considerations in order to allow access to information. Special responsibility should still, as it has been perceived by conventional competition analysis, only be imposed where the company in question is dominant and where it behaves anticompetitively. On the contrary, business justifications could be increasingly used by the dominant company to show that the dominant undertaking competed on merits and did not resort to anticompetitive practices. Abuse of dominance that occurs in digital markets does not always fit into criteria that were crafted for physical inputs, however this does not denote that the conventional way of conducting an analysis of an abuse of dominance should undergo a total makeover. The Commission should not therefore aim at long-term changes; instead, it should acknowledge how characteristics of digital markets affect analysis of competition law. Law on abuse, as applied to situations where access to information is refused or granted on discriminatory terms, should accommodate rapid technological change; preserve incentives to invest and innovate; focus on consumer harm in the analysis of abuse of dominance and grant a larger role to objective (business) justifications provided by dominant companies. The above-mentioned theoretical findings are applied to a case study on one of the most recognised online platforms that is Google Search investigations in the EU which have recently proceeded to the Commission’s decision, however one that is not yet publically available. The initial outcome of the investigations has been as follows: Google has been fined €2.42 billion for abusing its dominant position as a search engine by granting illegal advantage to another of its products - own comparison shopping service. The thesis analyses two of the practices Google has been initially involved in namely, search bias and restrictions on portability of online search advertising campaigns. These are analysed in detail as to whether they are in fact anticompetitive and can be addressed with a valid theory of harm. The thesis in question confirms the Commission’s findings on Google’s dominance, however it offers alternative arguments for the appropriate theory of harm as to the abusive practice of search bias.
  • Kontro, Mika (Helsingin yliopisto, 2017)
    Direct translation of cancer-specific genomic information into effective personalized therapies for acute leukemias has proven to be difficult. The aim of this study was to utilize novel tools for detailed characterization of genomic, transcriptomic, and functional aberrations in acute leukemia to gain understanding of disease pathology and guide individualized therapies. The main methods used were ex vivo drug sensitivity and resistance testing (DSRT), exome and transcriptome (RNA) sequencing, all of which were facilitated by extensive biobanking. In study I, we developed DSRT platform performed on primary leukemic cells ex vivo for identification of effective patient-specific drugs. Exome and RNA sequencing of serial samples were used for molecular characterization and to understand mechanisms of acquired resistance. Although AML samples exhibited unique DSRT profiles, responses could be clustered in five distinctive groups. Individualized treatment of refractory patients with DSRT-guided therapy resulted in meaningful clinical responses in 3/7 patients. In study II, we studied molecular drivers for relapsed T-cell acute lymphoblastic leukemia (T-ALL) and found novel STAT5B mutations. Functional studies demonstrated these mutations to enhance the transcriptional activity and to induce constitutive phosphorylation of STAT5B. The mutated blasts showed elevated BCL-XL expression and sensitivity to the pan-BCL-2 inhibitor navitoclax. Targeted sequencing revealed activating STAT5B mutations in 6/68 patients. In study III, we first evaluated ex vivo BCL-2 inhibitor sensitivity of AML cells, then we systematically assessed whether these responses correlated to specific mutations or gene expression signatures. BCL-2 inhibitor sensitivity associated with mutations in IDH1/IDH2 and WT1, as well as with aberrations in chromatin modifiers. Importantly, overexpression of a specific set of HOX genes predicted highly selective responses to BCL-2 inhibition. In study IV, we developed a national hematological biobank to allow researchers to access high-quality samples with accompanying clinical data. The samples from three collection time-points—diagnosis, potential remission, and relapse—are available. For this study, we evaluated the quality of stored samples and demonstrated that extracted DNA and RNA remain usable for demanding down-stream experiments.
  • Möller, Tia (Suomalainen Lakimiesyhdistys, 2017)
    The Europeanization of private international law is a well-recognized fact. The European Union (EU) has adopted a number of legal instruments in the field of private international law (PIL) in order to create a European area of justice, the objective defined by the EU Treaties. In addition to the Treaty provisions and the EU legislature there is also a third element influencing the Europeanization of PIL: multiannual programmes for the Area of Freedom, Security and Justice. These multiannual programmes have been adopted successively since 1998 (Vienna Action Plan 1998, Tampere Conclusions 1999, Hague Programme 2004, Stockholm Programme 2009, Strategic Guidelines 2014), and they have been adopted by the European Council, and thus by the Member States together with the Commission, and since the Lisbon Treaty, with the president of the European Council. This study analyses the impact of the multiannual programmes in the EU legislative process in the field of PIL and thus, their impact for the Europeanization of PIL. This is discussed from the various angles: the programmes’ relationship to the relevant EU Treaty provisions, concrete guidelines in the programmes for PIL (thus defining the vision of EU PIL) and the programmes’ influence on the EU legislative process. The latter aspect is analysed by examining all the EU PIL legislative acts adopted thus far. Moreover, possible future changes to the content and adoption procedure of multiannual programmes and their impact on future Europeanization of PIL are discussed. The study proposes that the vision of a European area of justice created by the multiannual programmes has played a central role not only in defining the direction of the Europeanization of PIL but also in its actual Europeanization, i.e. in the adoption of EU PIL instruments. In particular, in the area of family law, which varies widely between different legal traditions and legal cultures, the vision of a European area of justice has fostered a common understanding of the legislative work required, thereby furthering the Europeanization of PIL. The multiannual programmes have determined, prior to the formal EU legislative procedure, the PIL issues to be addressed by various legislative acts and also defined the general principles on which PIL cooperation should be based in the EU. The vision has brought real value to the EU Treaty provisions. However, the impact has been limited due to the general nature of the programmes and their limited possibilities in influencing the law on its different aspects. The study is based on the paradigms of legal dogmatics, i.e. legal positivism and the theory of the sources of law. The study uses methods from law and politics and legal history. The impacts of the programmes for the Europeanization of PIL are reflected on different aspects of law: legal order, judicial practices, the legal system and legal culture.
  • Tuori, Klaus (2017)
    The thesis assesses the constitutional implications of the Eurosystem’s changing role and measures during the crisis. It is a supranational central banking system that does not have the state’s economic and political will-formation as its counterpart and control, but rather the constitutional framework in which it was supposed to work, called the European economic constitution. The common macroeconomic policy was elevated to a constitutional level in the Maastricht Treaty and the underlying economic, political and even constitutional assumptions and constraints were agreed upon. The Eurosystem can be assessed as an economic policy actor. How it achieves its objectives and how it performs its tasks. As an independent EU expert institution it also needs to be assessed on the grounds of how it respects and advances the values it is supposed to protect and serve, which is a constitutional perspective. The main question is twofold: How should the legal mandate of the Eurosystem and the ECB be defined and how should the Eurosystem’s measures during the crisis be constitutionally assessed? In the first part, the thesis discovers the economic and institutional framework of the EMU, by reconstructing this economic framework as the European economic constitution. The new elements introduced in the Maastricht Treaty formed a new macroeconomic layer to it, named the European macroeconomic constitution. The EMU and the European macroeconomic constitution are based on three different foundations. The philosophical foundation was economic constitutional thinking largely based on the German ordoliberal approach to the economy. The economic foundation was built on the evolution in central banking and economics that culminated in some form of consensus towards the end of the 1980s. The institutional foundation was the economic, political and legal development in the EU that pave the way towards macroeconomic integration in the form of a common currency. These three different but interlinked foundations happened to share a common ground towards the end of the 1980s and early 1990s that made an agreement on the main elements of the Maastricht Treaty possible. The first part concludes with the forming of the key constitutional principles of the European macroeconomic constitution. The second part of the book places the principles to the test of reality, by analysing the common central banking system through the lens of the constitutional principles, including assessments of many unconventional and contested decisions and measures by the Eurosystem during the crisis. The final conclusions ask some simple questions that raise issues of the constitutional implications of the economic and constitutional crisis and particularly the Eurosystem’s responses to and during the crisis.
  • Caiazza, Ida (Helsingin yliopisto, 2017)
    Love Epistolography of the XVI and XVII Centuries. The Evolution of a Literary Genre This thesis examines the Libri di lettere amorose (love letter collections) printed in Italy in the sixteenth and seventeenth centuries by authors and collectors who sought to offer a literary product to the public. The “Love letter books” (as they are usually known) have generally been considered as a sub-category within the “Letter books” genre, inaugurated by Aretino's Primo libro in 1538, which merged in into the “Secretary” genre in the early decades of the seventeenth century. However, this is an inadequate way of classifying the love letter collections. Unlike the Lettere familiari (letters between friends or relatives) and Lettere di negozi (official letters), the love letter collections are characterised by a communicative intent which implies a relationship between sender and recipient entirely different to that of friendly or official correspondence. Moreover, they reference the tradition of erotic literature and reveal themselves to be open to the development of narrative impulses. The aim of this study is to provide an accurate classification of these works, which should be defined as an autonomous development of the sixteenth-century discourse on love. Together they form part of a broader pattern made up of the diverse guises assumed by the European epistolary love novel. The works that make up this corpus (identified according to specific literary criteria outlined within this study) are described in an attempt to identify their specificity. Their relationship with literary tradition is examined, and the possible presence of narrative tendencies identified. This study seeks to trace the evolution of the genre and map out the corpus according to chronological-typological “categories”. In doing so, it provides an exhaustive and up-to-date inventory of the love letter collections. The picture that emerges is of a varied whole, united by a clearly identifiable common core. The unique characteristic of the works is their very structure, consisting of letters exchanged between lovers, which renders the reader a participant in their love affair as it unfolds, like a diary in several voices. Finally, despite their stylistic variety, certain topoi found in previous and subsequent love epistolary works are almost always present in these collections, highlighting the deeply-rooted literary awareness at play in the exchange of letters between lovers.
  • Kangaskoski, Matti (Unigrafia, 2017)
    This study concentrates on reading digital poetry. Reading entails the act of reading, strategies of analysis, and the means of understanding. Specifically, this study constructs a model of reading and interpreting poetry in digital form by close analysis of three complex case studies. Broadly, this study concerns the aesthetic means and meanings of poetry in the contemporary moment, where new and old media are in visible negotiation with each other. In digital poetry artistic expression, digital media, technology and cultural practices clash and combine to produce new poetic forms. With new forms of poetry come new challenges to reading, analysis, and interpretation. Digital poetry presents new material, literary, technical, and rhetorical strategies and techniques that offer novel possibilities – and restrictions – for reading. Thus, my broad question is: How do we read digital poetry? This broad question is broken down to a subset of research questions. These deal with the material medium, readerly action, and the processes of the poem, which are all to be seen as constituent of its effects and meanings. In answering these questions, I construct a new model for reading digital poetry. The model is distilled from my close readings of the case studies. The readings are literary, cultural, media-historical and media-specific. The background methodology for the investigation comes from the notion of close reading (sensu Culler 2010; Simanowski 2011; Pressman 2014). My reading model consists of three main elements: interface, interaction, and interpretation. I further divide the interface into elements of data (e.g. text, music, images), processes (e.g. temporal control, text generation), and medium (as material and conceptual). Interaction consists of logic, performance, and effect, which designate the mode of engagement with the work, the joint performance of the poem and the reader, and the effects these produce. Interpretation includes the articulation of effects and meanings. Whereas the effects are created in interaction with the work, articulating them is seen as part of interpretation. Interpretation includes the articulation of the meanings and connections the poem invites. In other words, the poem’s interface guides the concrete act of reading, interaction guides the reader’s mode of engagement with the interface, and interpretation guides the means of understanding what is read. The case studies renegotiate the interrelated and overlapping arenas of print and digital poetry, old and new media, and traditional and digital literary criticism. The first includes Cia Rinne’s zaroum (2001), archives zaroum (2008; with Christian Yde Frostholm) and notes for soloists (2009). The second is Young-Hae Chang Heavy Industries’ Dakota (2002). And the third is Stephanie Strickland’s “V-project”, which includes two print books (V:WaveSon.nets /Losing L’Una 2002; V: WaveTercets /Losing L’Una 2014) two web applications (V:Vniverse Shockwave application 2002 with Cynthia Lawson-Jaramillo; Errand Upon Which We Came 2001; with M. D. Coverley), and an iPad application (Vniverse 2014; with Ian Hatcher). The emphasis in the case studies is on examining strategies of reading and interpretation as well as producing new readings and interpretations of the poetry in question. I investigate the interdependence of traditional print-based and emerging digital strategies of reading poetry, and combine print-based scholarly approaches with digital-based scholarship.
  • Immanen, Mikko (Unigrafia, 2017)
    As prominent figures in continental philosophy, both Martin Heidegger and the Frankfurt School critical theorists Theodor W. Adorno, Max Horkheimer, and Herbert Marcuse have all been studied extensively. However, there has been little interest in a comparative approach toward these giants of twentieth-century European thought. This is understandable considering that during their lifetimes the relationship between Heidegger and the neo-Marxist Frankfurt School thinkers was mostly hostile or ignorant. Heidegger never commented on the critical theorists in his published works, and after World War II the German Jewish critical theorists attacked Heidegger’s refusal to apologize for his Nazi politics as symptomatic of the wider German incapacity to come to terms with the past. While this antagonistic image reigns widely today, recent years have seen attempts to disclose unexpected parallels in Heidegger’s and Frankfurt School’s post-war concerns about “oblivion of being” and “dialectic of enlightenment” and in their emphasis on aesthetic experience as an antidote to the one-dimensionality of the modern technological mindset. Although inspired by these philosophical openings, this thesis focuses on the overlooked Weimar period, and, using the methods of intellectual history, shows that during their philosophically formative years in 1927–1933 – also the period between the publication of Heidegger’s magnum opus, "Being and Time," and his Nazi turn – Adorno, Horkheimer, and Marcuse saw Heidegger’s promise of philosophical concreteness as a serious, if flawed, effort to make philosophy relevant to life again. Rather than claiming that Heidegger influenced the critical theorists in a positive way, as Marx and Freud for instance did, the thesis argues that the critical theorists saw Heidegger’s existentialism as the most provocative challenge and competitor to their nascent materialist diagnoses of the discontents and prospects of European modernity. Demonstrating Heidegger’s surprising presence in the works of the twentieth century’s most important leftist social theorists, the thesis not only offers a groundbreaking historical reconstruction of the Frankfurt School’s unacknowledged early confrontation with their later arch-enemy, but also contributes to our understanding of Heidegger’s major impact on twentieth-century philosophy, an impact hitherto reconstructed by studies on his influence on key French, American, and Jewish thinkers.
  • Haikala, Heidi (2017)
    MYC is a transcription factor and a proto-oncogene, which is overexpressed in almost 50% of all breast cancers. Cell cycle promoting oncogenic MYC supports the altered energetic needs of continuously proliferating cancer cells, since there is an immense requirement for nucleic acids, proteins, and lipids to support the cell division. MYC supports the metabolic switch by enhancing the main nutrient (glucose and glutamine) uptake, increasing glycolysis and glutamine utilization, as well as by instructing the normally ATP generating citric acid cycle to serve biosynthetic growth promoting reactions. In this study we found that the metabolic changes induced by MYC lead to decreased production of ATP and the consequent activation of a key cellular energy sensor protein AMP-activated kinase (AMPK). AMPK is a metabolic guardian, which instructs cells to perform catabolic reactions to restore the ATP levels. However, persistent AMPK activity directs MYC-transformed cells towards apoptotic cell death. We found that MYC-activated AMPK phosphorylated the tumor suppressor protein p53, which accumulated on the mitochondrial surface. In the mitochondria, p53 primed the cell death promoting protein BAK for apoptotic cell death induction, thus connecting MYC-driven metabolic transformation to apoptotic sensitivity. In addition, we discovered a novel synthetic lethal and potentially druggable interaction between MYC activation and inhibition of a small GTPase RhoA. We found that RhoA assists MYC to upregulate glutamine metabolism, which highlights the relevance of metabolism as a sweet spot for targeting oncogenic MYC. Furthermore, we found that supraphysiological, highly expressed MYC is globally repressing the transcriptional targets of serum response factor (SRF), a RhoA downstream target, thus exposing new pathways needed for cancer cell survival. In addition, the same study contributed to a finding that supraphysiological MYC represses a set of genes related to luminal identity of breast epithelial cells, which possibly affects the cell differentiation and apoptotic sensitivity in vivo. The described mechanisms suggest a possible answer to the old paradox why cancerous MYC expression levels, but not physiological MYC, sensitize cells to apoptosis. Finally we studied how the altered metabolism-derived sensitivity to apoptosis could be exploited as a potential therapeutic strategy to kill MYC expressing cancer cells. In a rationalized drug combination screen, we found that the pharmacological superactivation of AMPK is able to potentiate the anticancer activity of apoptosis targeting therapies, which usually do not show great efficacy in solid tumors as single agents. The described combination proved substantial efficacy against highly MYC expressing breast cancer models in vitro, in vivo and in ex vivo. Thus, we describe the first pharmacological MYC apoptosis activation strategy that could be easily translated to the benefit of breast cancer patients, and currently clinical trials to test the combination are under consideration. In addition to the described scientific findings, the ex vivo and in vivo preclinical research models of breast cancers developed during this study are likely to serve breast cancer research community by providing more predictive and more translationally relevant platforms for studies of breast cancer biology and drug discovery.