E-thesis

Recent Submissions

  • Kilpinen, Lotta (Helsingin yliopisto, 2017)
    Human mesenchymal stromal cells (hMSCs) are currently used in many advanced cellular therapies. The clinical use of hMSCs requires extensive cell expansion, but the consequences of expansion, especially at the molecular level, are not fully understood. The therapeutic effect of hMSCs is mediated paracrine interactions with immune cells modulating both innate and adaptive immune response. Membrane glycerophospholipids (GPLs) provide precursors for signaling lipids, which modulate cellular functions, including immunological effects. In this thesis, I investigated the effect of the donor’s age and cell doublings on the GPLs, gene expression and microRNA (miRNA) profiles of human bone marrow MSCs (hBM-MSCs). In order to gain more insight into the functional mechanisms of hMSCs, I investigated the extracellular vesicle secretion from human umbilical cord blood derived MSCs, and evaluated their immunosuppressive capacity in vitro as well as their possible immunomodulative and protective effect in kidney ischemia-reperfusion injury in vivo. In this study, I was able to demonstrate that the hBM-MSCs, harvested from 5 young adults and 5 old donors, showed clear compositional changes in their GPL profiles during expansion. Most strikingly, the molar ratio of arachidonic acid (20:4n-6) containing species of phosphatidylcholine and phosphatidylethanolamine accumulated, while the species containing monounsaturated fatty acids decreased during passaging. The lipid changes correlated with the decreased immunosuppressive capacity of hBM-MSCs suggesting a connection between lipid signaling and immunomodulatory functions. Although there were clear alterations in gene expression levels and lipid profiles, the miRNA expression levels were more stable. The expression levels of 37 miRNAs were changed in the old donors group and 36 miRNAs were changed in the young donors group. Of these, only 12 were differentially expressed in both young and old donor BM-MSCs and their predicted target mRNAs, the expression of which was changed, were mainly linked to cell proliferation and senescence. This thesis provides a detailed analysis of molecular changes during MSC expansion. The combination of in vitro and in vivo models accompanied with a detailed analysis of molecular characteristics is essential to understand the complexity of the MSC paracrine mechanisms and functionality.
  • Ronkainen, Riitta (Helsingin yliopisto, 2017)
    Speech and language therapy for children with cochlear implants focuses on promoting the children's spoken language skills. In this dissertation, the professional practices of one speech and language therapist in promoting language learning are examined using a conversation analysis methodology. The research data consist of video recordings from speech and language therapy sessions, totalling approximately 36 hours. The total duration of analysed sequences is 3 hours, 52 minutes. The participants in the study are seven children with profound congenital hearing impairment who have received a cochlear implant and their speech and language therapist. The general aim of the dissertation is to increase knowledge of speech and language therapists' professional practices in supporting spoken language learning of children with cochlear implants. The therapist's practices are examined in both play and task interactions at three different stages of the therapy. First, the dissertation examines the ways in which the therapist enhances the children's listening and imitation skills in the early stages of therapy and cochlear implant use (Study I). Second, it analyses the therapist's professional practices of involving the parents in multiparty therapy interaction (Study II). Third, it demonstrates how the therapist promotes lexical learning in children with cochlear implants in the later stages of therapy (Study III). The dissertation offers new insights into the institutional nature of interaction in the speech and language therapy for children with cochlear implants. It demonstrates the therapist's professional practices and pinpoints techniques and strategies used in the intervention. Primarily, the children are provided with a repetitive and prosodically emphasised spoken language model to enhance their listening skills and spoken language learning. In addition multimodal elements such as gestures, signs and body movements are systematically used. The dissertation shows how the therapist supports the children's participation and fosters their competence, which is seen in the form of enhanced collaboration. Furthermore, the dissertation provides information about the ways in which the therapist involves parents in the therapy. The findings reported here contribute to research on speech and language therapy interaction, as well as more broadly to the study of institutional interaction. The findings expand and specify the professional stock of interactional knowledge about speech and language therapy. The dissertation provides detailed and concrete descriptions of therapeutic practices and suggests practical guidelines for supporting the spoken language learning of children with cochlear implants. These may be useful for clinicians and students working both with children with cochlear implants and children who have other communication disabilities.
  • Kemppainen, Teemu (Helsingin yliopisto, 2017)
    Insecure and restless neighbourhood conditions lower the quality of life, imply health risks and may accelerate segregation through selective migration. This study examined subjective insecurity and perceptions of social disorder—including public drunkenness, vandalism, threatening behaviour and the like—in different residential contexts. The focus was on Finnish post-WWII housing estates built in the 1960s and 1970s. Compared to other kinds of neighbourhoods, these areas often suffer from a negative reputation related to poverty, insecurity and disorder. However, the residents’ views are often at odds with the negative public image. There is a lack of reliable evidence on where estates stand in comparison to other kinds of neighbourhoods. Furthermore, the full diversity of estates has typically not been addressed in prior studies. Empirically, the study relied on three sets of survey data that were combined with contextual register data. The covered area varies from Helsinki to the entire country while the contextual units range from statistical grids to city districts. The key findings were the following: 1) The level of perceived social disorder was only slightly higher in the estates built in the 1960s and 1970s than in other multi-storey neighbourhoods. This small difference was due to socio-economic disadvantage. As expected, the low-rise neighbourhoods were considerably more peaceful than the multi-storey ones. 2) Rental-dominated tenure structure exposed the estate residents to higher levels of perceived disorder because rental estates are typically more disadvantaged. Social integration of the estate community played no role in terms of disorder. In contrast, the level of normative regulation partly explained why disadvantage is related to disorder. 3) At the district level, disadvantage, disorder (from police registers), residing in proximity to a metro or train station and living in a social housing flat exposed residents to subjective insecurity. Victimisation partly mediated the association between disadvantage and insecurity. The study shed light on the diversity of estates. From the point of view of social life, estates markedly differ from each other. Tenure structure has a decisive influence on the socio-economic structure, which implies differences in normative regulation and social order. This is an important finding in terms of tenure-mix policies. Compared to rental-dominated neighbourhoods, a more mixed tenure structure implies a less disadvantaged and more regulated local community, which paves way for a more peaceful local social life.
  • Koivisto, Jaana-Maija (Helsingin yliopisto, 2017)
    The aim of this study was to obtain knowledge about learning clinical reasoning through game-based simulation. This knowledge could be used in developing and embedding new learning methods for clinical reasoning in nursing education. Research has shown that nursing students lack knowledge and skills in detecting and managing changes in patients’ clinical conditions. This is often due to insufficient clinical reasoning, and thus, educational organisations need to more effectively enable the development of clinical reasoning during education. Digitalisation in higher education is increasing, and the use of virtual simulations and, recently, serious games to support professional learning and competence development is growing. The purpose of this research was to generate design principles for simulation games and to design and develop a simulation game for learning clinical reasoning. Furthermore, the purpose was to investigate nursing students learning through gaming. A design-based research methodology was used: iterative cycles of analysis, design, development, testing and refinement were conducted via collaboration among researchers, nurse educators, students, programmers, 3D artist and interface designers in a real-world setting. Mixed research methods were used. The results indicated that games used to provide significant learning experiences for nursing students need to share some of the characteristics of leisure games, especially visual authenticity, immersion, interactivity and feedback systems. In terms of the clinical reasoning process, students improved in their ability to take action and collect information. The findings showed that usability, application of nursing knowledge and exploration are the aspects of a simulation game that have the greatest impact on learning clinical reasoning. It was also revealed that authentic patient-related experiences, feedback and reflection have an indirect effect on learning clinical reasoning. This study provided opportunities to advance our knowledge of nursing students’ learning processes and experiences of learning clinical reasoning through game-based simulation. Its results add to the growing body of literature on game development in the field of nursing education by providing design principles for educational simulation games. The present study confirms previous findings and contributes additional evidence that suggests that game-based simulations are a valuable learning method for healthcare education. However, in order for serious games to add value to healthcare education, the essence of the profession needs to be built into the game, and here the contribution of healthcare professionals is priceless.
  • Valenzuela, Daniel (Helsingin yliopisto, 2017)
    This thesis is motivated by two important processes in bioinformatics, namely variation calling and haplotyping. The contributions range from basic algorithms for sequence analysis, to the implementation of pipelines to deal with real data. Variation calling characterizes an individual's genome by identifying how it differs from a reference genome. It uses reads -- small DNA fragments -- extracted from a biological sample, and aligns them to the reference to identify the genetic variants present in the donor's genome. A related procedure is haplotype phasing. Sexual organisms have their genome organized in two sets of chromosomes, with equivalent functions. Each set is inherited from the mother and the father respectively, and its elements are called haplotypes. The haplotype phasing problem is, once genetic variants are discovered, to attribute them to either of the haplotypes. The first problem we consider is to efficiently index large collections of genomes. The Lempel-Ziv compression algorithms is a useful tool for this. We focus on two of its exponents, namely the RLZ and LZ77 algorithms. We analyze the first, and propose some modifications to both, to finally develop a scalable index for large and repetitive collections. Then, using that index, we propose a novel pipeline for variation calling to replace the single reference by thousands of them. We test our variation calling pipeline on a mutation-rich subsequence of a Finnish population genome. Our approach consistently outperforms the single-reference approach to variation calling. The second part of this thesis revolves around the haplotype phasing problem. First, we propose a generalization of sequence alignment for diploid genomes. Next we extend this model to offer a solution for the haplotype phasing problem in the family-trio setting (that is, when we know the variants present in an individual and in her parents). Finally, in the context of an existing read-based approach to haplotyping, we go back to basic algorithms, where we model the problem of pruning a set of reads aligned to a reference as an interval scheduling problem. We propose a exact solution that runs in subquadratic time and a 2-approximation algorithm that runs in linearithmic time.
  • 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.
  • Laaksonen, Salla-Maaria (Helsingin yliopisto, 2017)
    This doctoral thesis investigates how the reputations of organizations are narrated in the hybrid media system, characterized by different media logics and technological principles, and the affective attunement of storytelling stakeholders. The research problem is two-fold: first, to study how the new communication landscape affects the formation of organizational reputation, and second, to investigate the cognitive and emotional influences of reputation in the hybrid media system. The dissertation sees organizational reputation as a communicative phenomenon, which exists both as individual beliefs and socially constructed narratives that are born and circulated in the hybrid media system. Hybrid stands for a combination of older and newer media forms, which are intertwined in complex and dynamic assemblages, formed by individuals, affects, social contexts, organizations, and technological platforms, who all mutually influence the process of storytelling. The dissertation is a compilation of five articles. It employs a parallel mixed methods approach by using four different data sets: interviews with communication professionals in organizations; social media discussions; Wikipedia data; and psychophysiological measurements. With a multimethodological approach the study builds a bridge between the different schools of reputation studies: reputations are constructed as narratives that also have measurable effects on the people who consume them. In light of the results, a hybrid reputation narrative is polyphonic, emotional, and is formed in a context characterized by relative power structures between human and non-human actors. It is a form of narrative, in which the story elements can be stored in databases, searched, and hyperlinked by various, interacting actors, who through their use of the technical platforms generate the reputation narrative from fragmentary story pieces by merging opinions and facts. This dissertation highlights two aspects: the interplay between the social and the technological, and the importance of affect. First, the technological affordances and the social practices together form the settings in which the narrating takes place in the hybrid media system. Second, affect emerges as an inherent property of reputation, as an important characteristic of the reputation narratives, and as a feature to evaluate different platforms.
  • Zhao, Pei (Helsingin yliopisto, 2017)
    This doctoral study aims principally to reflect and investigate Finnish and Chinese education with information and communication technologies (ICTs) especially at the fields of arts and culture. Finland has a reputation as one of the top education and research systems in the world and is also highly recognized in arts, design and ICT use in education. China has been reforming the education system especially in the areas of ICT, media and arts, as the educational informatization process has been an important part of education reforms during last ten years. Digital culture and online resources link individuals with similar interests and make possible modes of learning and communicating that differ from conventional schooling. The increasing use of digital technologies in everyday life has generated the need for renewing perspectives and approaches in the development of education and pedagogical methods and models in both countries. This study has some resemblance to comparative studies, but the viewpoint is more a matter of reflecting than comparing. A theoretical literature review has been done for each paper. Document analyses and interviews are the main data collection methods in this dissertation. The empirical case study method has been used as well to investigate the teachers’ digital literacy in both one Finnish kindergarten and one Chinese kindergarten. Documentary analysis is the main methodology in the reflection and analysis of government policy and strategy. In this dissertation, I reported and analysed the Finnish and Chinese ICT education policies and strategies, and designed a study to compare Finnish and Chinese kindergarten teachers’ digital literacy in teaching. I also studied Chinese arts teachers’ digital literacy and the usage of ICT in secondary schools. Beside those aspects, I have also investigated Google Art Project and Finna as cultural online resources and pondered the pedagogical functions of arts and cultural-heritage education within online art galleries and museums. Both countries promote informatization and digitalization processes in education. The informatization of Chinese education focuses on the progress towards an information society, and the effective use of ICTs. However, in Finland, digitalization emphasizes transformation to a new media ecology, which covers digital business, digital culture and media. Goverment’s ICT policies and strategies are important factors in teachers using digital technology and media in education. But simply incorporating more technology into teaching and learning does not go far enough in ensuring that children and young people are equipped to deal with the future and social change. In this study, the differences between arts teachers’ digital literacy in Finland and China were reflected, and mainly considered with one factor, which affects it – the respective governments’ policy and strategies. It is important to realize that these two aspects, state policies and strategies and teachers’ digital literacy, are not independent but interrelated. The focus and accent of government’s strategies have a notable effect on education reform. This study suggests some recommendations for policy makers for future education reform from the point of view of informatization and digitalization.
  • Kaipainen, Kirsi Maria (2017)
    Tämän pro gradu -tutkielman aihe on nuorten nuuskaaminen yhteiskunnallisen hallinnan viitekehyksessä. Tutkielmassa tarkastellaan koulu- ja opiskeluterveydenhuollon ammattilaisten käsityksiä nuuska-ilmiön rakentumisesta sekä nuuskaavista nuorista. Sosiologista tutkimusta nuuskaavien nuorten yhteiskunnallisesta hallinnasta perustelee Michel Foucault’n ajatuksiin nojaava käsitys biovallan ja -politiikan leimaamasta modernista ajasta, jolle on ominaista yhteiskunnallisen hallinnan keinojen kohdistaminen yhä enemmän terveyden ja sairauden kysymyksiin ja biopoliittisiin tavoitteisiin, kuten yksilön hyvän terveyden vaalimiseen. Sosiaalitieteellistä tutkimusta aiheesta perustelee myös kasvanut huoli nuorten nuuskan käytön lisääntymisestä viime vuosina. Nuorten nuuskaamisen hallinnan tutkimuksessa on kyse myös nuorten terveyden edistämisestä ja siitä, millaisen yhteiskunnallisen hallinnan kohteiksi ja toimijoiksi nuuskaavat nuoret määrittyvät. Tutkielman aineistona on Terveyden ja hyvinvoinnin laitoksen (THL) keräämä haastatteluaineisto, joka sisältää 12 koulu- ja opiskeluterveyden ammattilaisen yksilöhaastattelua. Aineisto on litteroituna tekstinä 447-sivuinen. Haastateltavat ovat terveydenhoitajia, suuhygienistejä ja hammaslääkäri, ja heidät on valittu kouluterveyskyselyn perusteella niistä kouluista ja oppilaitoksista, joissa nuuskaamista esiintyy. Tutkimusalueet ovat Uusimaa, Pohjanmaa ja Lappi. Tämä pro gradu -tutkielma on oma itsenäinen kokonaisuutensa, jossa haastattelupuhetta analysoidaan diskurssianalyyttisesti. Diskurssianalyysin avulla tutkitaan terveydenhuollon ammattilaisten käsityksiä nuuska-ilmiön rakentumisesta ja tarkastellaan ilmiön hallinnan ulottuvuuksia ja mahdollisuuksia. Haastattelupuheesta analysoidaan nuuskaavien nuorten saamia subjektipositioita puheessa esiin tulleiden nuuskaamiselle altistavien tekijöiden ja nuuskaamisen syiden teemoittelun perusteella. Näin hahmotetaan sitä, millaisia toimijuuden mahdollisuuksia nuori puheessa saa. Teoreettinen viitekehys on Foucault’n tuotannosta ammentava hallinnan analytiikan perinne, ja tutkielmassa tarkastellaan nuorten nuuskaamista hallinnananalyyttisten käsitteiden, terveyskansalaisuuden tuottamisen ja biovallan ulottuvuuksien näkökulmasta. Nuorten nuuskaaminen määrittyy tulkinnan mukaan monitahoiseksi ilmiöksi, jonka ympärillä käydään paljon neuvottelua ja josta ei vallitse täyttä yhteistä ymmärrystä ammattilaisten puheessa. Terveydenhuollon ammattilaiset ovat ammattinsa puolesta velvoitettuja tekemään nuuskaamista ennaltaehkäisevää työtä nuorten parissa, mutta työhön tuovat omat haasteensa muun muassa ilmiön neuvottelunalaisuus ja monen eri toimijan erilaiset käsitykset nuuskaamisen haitallisuudesta. Nuorten nuuskaamisen yhteiskunnallinen hallinta ei ole samalla tavalla yksiselitteistä kuin esimerkiksi poltettavien savukkeiden käytön hallinta, sillä nuuskaamisen kulttuuriset paikat ja ilmiön määrittyminen ovat moniselitteisempiä. Tämän tutkielman tulkinnan mukaan terveydenhuollon ammattilaisten haastattelupuheessa tulee esiin nuorta kannustava ja tukeva hallinnan tapa nuuskaamisen säätelyssä. Nuuskaavan nuoren omaa ajattelua halutaan herättää ja auttaa nuorta itseään tekemään päätöksiä nuuskaamisen vähentämisestä tai lopettamisesta. Nuuskaava nuori määrittyy kuitenkin passiiviseksi ja herkäksi erilaisille vaikutteille, kuten ryhmäpaineelle ja mallioppimiselle. Tämä herättää kysymyksen, millaisiksi hallinnan kohteiksi nuoret määrittyvät terveyden edistämisessä, kun kyseessä ovat nuorten haitalliset terveyteen liittyvät valinnat.
  • Laakso, Senja (Helsingin yliopisto, 2017)
    This dissertation examines local experimentation from a practice theoretical perspective. By doing this, the dissertation bridges the gap between two fields of research: one relating to the governance of experiments and the other to the dynamics of practices. In this way the dissertation contributes to the timely issue of steering consumption in a more sustainable direction by utilising experiments and interventions at multiple societal levels – an issue attracting wide interest within both research and policy communities. The dissertation focuses on the role of participants in accommodating novel technologies and services into their everyday lives, and the role of social interplay between individuals and their collectives in supporting or opposing the change and diffusion of practices. These factors – how everyday practices are linked together, how change in one practice affects other surrounding practices, and how individuals adjust and evaluate their performances with respect to social norms, expectations, standards and rules – are fundamental to both stability and change in practices. The dissertation comprises of five articles that illustrate, firstly, what can be expected from a local experiment and what the role of each experiment is and, secondly, what can be learnt from an everyday practice perspective on experiments and how the experiments are accommodated into the system of everyday practices. The study draws on a meta-study on 25 papers on climate governance experiments and on three empirical case studies on local experiments in Jyväskylä, Finland. This dissertation asserts that a practice approach and a participant perspective can provide new opportunities for experimental governance by illustrating the complexities of everyday practices and how to acknowledge them in experimentation. Although sustainability transitions require changes in practices as entities, a focus on the performances of practices is crucial for any intervention, as it sheds light on individual learning and experiences. The findings highlight the interdependencies and path dependencies of practices, as well as the collective perceptions of normality steering understandings of acceptable or unacceptable actions. The results also demonstrate that the participants are active contributors in experimentation, adjusting the new configurations of elements and practices in the prevailing system and reflecting on their performances in relation to others. Addressing the dynamics between individual performers of practice and their communities in (re)producing practices, and then targeting the interventions at the collective underpinnings preventing (or accelerating) change might be the key to stabilising emerging, sustainable practices.
  • Kuha, Jukka (Helsingin yliopisto, 2017)
    ABSTRACT Jukka Kuha: Suomen musiikkioppilaitoshistoriaa – toiminta ulkomaisten esikuvien pohjalta vuoteen 1969. University of Helsinki, Faculty of Arts, Department of Musicology The topic of this doctoral study, as mentioned in the title, is the history of educational institutes of music in Finland during the years 1882–1969. In addition, a common thread throughout the study examines knowledge about European music life, especially about music education from the very early centuries up to the year 1880, and knowledge about the common music life in our country, mainly that previous to the founding of permanent educational institutes of music. The goal of this study is to review the intellectual background and identify the reasons which have enabled the establishment of institutional art schools of music (schools for sacred music, schools for orchestra musicians, schools of music, colleges of music and conservatories). Among the included initiatives are those concerning the establishment of institutes that have not been previously examined, because these initiatives can reveal common attitudes of the community concerning music education. The primary idea is to introduce the creation of educational institutes of music as a phenomenon and to describe their course of development. The aim is not to write the history of every institute but to clarify the organization of the educational institutes of schools of music. Only a few of these have been described from their beginning over some years or decades. The focuses of this study are to outline the importance of the mentioned schools of music, to describe their growth during the time of the study, to name the directors and teachers of the first institutes founded, to list the subjects and total amount of the students in each institutes, to describe political initiatives toward the law of state aid and the confirmed law, to give an account of the opinions concerning the law, and to identify two types of curriculums (developed over the long term and developed in only a few years) of educational institutions of music compared with the curriculum of Sibelius Academy in the year 1969. In fact, this study does not concern Sibelius Academy (nowadays part of an art university), but its activities under the leadership of its first director Martin Wegelius (1882–1906) have been examined because of the extensive amount of inaccurate and wrong information written in the history books on this academy. In addition, the preparations of law concerning state aid for Sibelius Academy have been clarified because these were carried out at the same time as similar initiatives for other educational institutions of music. My interest in this subject arose during my career. As I had dealings with the educational institutes of music throughout this time, I became interested in obtaining information about previous activities in these institutions in Finland, but I only found time for this research after retirement. Keywords: institutionaalinen, musiikkioppilaitos, lukkari- ja urkurikoulu, musiikkikoulu, musiikkiopisto, konservatorio, orkesterikoulu, valtionavustus
  • Neuvonen, Anu (Helsingin yliopisto, 2017)
    Finland’s unusual history and resulting genetic structure have a number of consequences for the practical applications of genetic testing in Finland today, including forensic analysis. The objective of this study was to characterize coding and noncoding genetic variation in the Finnish gene pool using forensic markers, in order to improve the efficiency of forensic testing in Finland while simultaneously broadening our understanding of its history. Finland is characterized by a clear genetic delineation between Eastern and Western regions of the country, the origins of which have heretofore remained undetermined. Here, patterns of distribution observed in markers of prehistoric association suggest this delineation represents the vestiges of an ancient border between Mesolithic hunter-gatherer and Neolithic farmer populations, undetectable in other regions of Europe. This study provides further insight into the development of the current population structure and clarifies the resolution of uniparental marker variation in contemporary Finland, with implications for forensic applications such as ancestry- informative testing. Along with the aforementioned population stratification, Finland’s unusual history has also left its mark on the population in the form of reduced diversity, visible especially in the Y-chromosome. In order to improve the efficiency of Finnish Y-profiling, novel multiplex panels of highly polymorphic Y-microsatellite markers were developed and evaluated. The new 7- and 24-locus Y-STR panels demonstrate improved suitability for practical forensic applications, with enhanced discrimination power and a reduction in regional subdivision compared to commercial sets. In order to assess the applicability of a novel commercial panel of insertion-deletion markers in Finnish forensic profiling, the Investigator DIPplex kit was evaluated in the Finnish population. Earlier studies of the applicability of insertion/deletion polymorphisms as a tool of forensics had indicated that they were likely to be beneficial for casework analysis both in individual identification as well as the testing of familial relationships. The results suggest that while these markers were well suited for individualization purposes, they were inefficient for paternity testing in the Finnish population. These two studies highlight the need for careful population-specific validation of commercial marker sets widely in use in forensics. Historical population bottlenecks can result in the enrichment of mutations, including those with clinical effects. The assessment of metabolic gene ABCB1 polymorphisms in Finns found increased frequency of these mutations in comparison to other populations, suggesting that Finns may demonstrate an increased susceptibility to drug intoxication. A further investigation performed on post-mortem samples revealed a positive correlation between mutation frequency and level of blood digoxin, confirming previous results of the adverse effect of ABCB1 mutations on metabolic processes. These findings will aid forensic medicine by providing valuable additional evidence for molecular autopsies. A thorough understanding of underlying patterns of genetic variation and the history that created them is vital in recognizing the factors affecting practical forensic analysis today. In these studies, the deep genetic delineation between Eastern and Western regions of Finland was observed in a variety of forensic loci, and shown for the first time to extend also to mitochondrial markers, giving further evidence of its ancient history. The results of this thesis thus reveal new information about the history and demographics of the Finnish population while offering globally applicable improvements to forensic typing. The end result is more straightforward analysis and improved reliability for a spectrum of forensic applications ranging from individualization to cause of death determinations.
  • 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.
  • Bastman, Eeva-Liisa (Helsingin yliopisto, 2017)
    This dissertation examines Finnish Pietist hymn poetry from the 18th and 19th centuries. The study focuses on the hymn as a lyric genre and investigates the poetics of Pietist hymns; that is, the formal and thematic features and the ways of creating meaning that are characteristic for the hymn as a genre and for Pietist hymns in particular. The research material consists of two hymn collections: a handwritten hymnbook compiled in the 1780s in the town of Orimattila in southern Finland and a printed hymnbook, Halullisten Sieluin Hengelliset Laulut from 1790 (“Spiritual Songs for Devout Souls”), together with its extended editions published in the 19th century. The introductory chapter of the dissertation places the hymns in their historical and religious context. It is followed by the analysis part, which consists of two chapters. The first deals with questions of metre, and the second discusses forms of speech and address in hymn poetry. The chapter on hymn metrics focuses on stanza structures, metres, and rhyming. In addition to detailed textual analyses of individual hymns, it provides an overview of the poetic structures used in hymn poetry and discusses the changes in hymn metrics that took place in the 18th and 19th centuries. The analysis casts new light on the rhyming of the hymns. Here, rhyming is understood as one form of phonetic repetition together with assonance and alliteration, and emphasis is placed on the poetic functions of these phonetic devices. The second analysis chapter examines poetry as speech and lyric address. In particular, ritualistic and performative elements, which seek to involve and engage the reader or the listener, turn out to be central features of hymn poetics. These elements include, in addition to rhythm and sound, forms of speech and address, rhetorical devices that activate senses and emotion, as well as imagery used to illustrate the speaker’s innermost thoughts and feelings. The study shows that the poetics of Pietist hymns has three central features: rhetoric, oral-literary forms of expression and the recycling and reshaping of a traditional repertoire, formed in the interaction between the hymn and its neighbouring genres, such as biblical texts and devotional literature. These features have a common function: to create a sense of community and belonging in singers and listeners and to depict inner change in an engaging way.