Väitöskirjat

Recent Submissions

  • Töyräänvuori, Joanna (Helsingin yliopisto, 2016)
    This dissertation examines the political use of the ancient North West Semitic myth of divine combat between the Storm-God and the Sea. The myth originated with the rise of the Sargonic Empire and was disseminated across ancient Near Eastern polities during the Amorite Kingdom period. Vestiges of the myth have also been retained in the Hebrew Bible. The aim of the study was to demonstrate how the myth was used in ancient North West Semitic societies to resolve the crisis of monarchy through appeal to numinous legitimacy, and how reading a selection of Biblical texts in the framework of the tradition confirms the use of the myth in the same context in the emergent Palestinian kingdoms of the Iron Age. As methods, the study employs form- and tradition-criticism, as well as the comparative/contrastive analysis of Ugaritic epic poetry, Akkadian diplomatic correspondence and royal inscriptions, and Hebrew poetry. A new method of textual triangulation has also been devised in an attempt to use the hypothetical convergence of traditions to approximate what of the mythology would have been known in ancient Palestine, from which few textual sources remain. Most of what is known of Israelite kingship and the monarchic institution is largely based on later and ideologically slanted material. This makes the comparison of Biblical texts to their antecedents necessary. The structure of the dissertation is three-pronged, beginning with the texts from ancient Mari, comparing them with witnesses from Ugarit, and finally contrasting them with the traditions of the broader Near East. The references to the myth in the Hebrew Bible are discussed in connection with the relevant witnesses from these traditions. The different examples of the tradition witness to the continuation, longevity, malleability, and the capacity of the myth to transform to suit changing historical realities. The investigation concludes that a myth of symbolic combat between the Storm-God and the Sea was likely used as a foundational myth by the mostly polytheistic Pre-Exilic kingship in Palestine. In contrast to previous research, the study demonstrates three distinct sources for the Biblical traditions in addition to living local iterations of the myth. In addition to vestiges retained in the Hebrew Bible, based on the analogy of preceding, concurrent, and continuing traditions in the shared cultural sphere, the accumulation of mythic traditions suggests that it was used in the Palestinian kingdoms to resolve the crisis of monarchy and to legitimize sovereign political rule. After the end of the Jerusalem monarchy, the myth was democratized and reforged to legitimize the existence of the people.
  • Kopra, Jaakko (Helsingin yliopisto, 2016)
    Midbrain dopamine neurons exert a powerful influence on behavior and their dysfunction is associated with many neurological and neuropsychiatric diseases, including Parkinson s disease (PD). Dopamine neurons are large, complex and sensitive cells. Hence, their survival and correct function requires coordinated action of various transcription and regulatory factors both during development and aging. Potentially, one such factor is glial cell line-derived neurotrophic factor (GDNF). Ectopically applied GDNF is best known for its potent ability to protect and restore damaged dopaminergic neurons both in vitro and in vivo. GDNF-based therapies have been tested in clinical trials with PD patients with variable success. However, the function of endogenous GDNF in brain dopamine system development, aging and disease is poorly understood. Improvement in GDNF-based therapies requires better understanding of the physiological functions of GDNF in the brain. The current knowledge of endogenous GDNF function remains obscure, mainly due to the lack of proper animal models. The present study investigated the regulatory role of endogenous GDNF in the development, maintenance and function of midbrain dopamine neurons utilizing novel mouse models: GDNF conditional knock-out (cKO) mice and GDNF hypermorphic (GDNFh) mice over-expressing GDNF from the endogenous locus. GDNF cKO mice enable GDNF deletion solely from the central nervous system during embryonic development or later in adulthood, preserving its vital role in kidney development. Midbrain dopamine systems of these new mouse strains were studied with immunohistochemical, neurochemical, pharmacological, behavioral and molecular biology methods. We found more substantia nigra dopaminergic cells and elevated striatal dopamine levels in immature and adult GDNFh mice. In cKO mice, dopamine levels and cell numbers were unaltered, even upon aging, and regardless of the timing of GDNF deletion. Both mouse strains exhibited enhanced dopamine uptake, while responses to amphetamine were augmented in GDNFh mice and reduced in cKO mice. GDNFh mice also released more dopamine and GDNF elevation protected them in a lactacystin-based model of PD. Overall, dopamine neurons were more sensitive to moderate elevation than complete absence of endogenous GDNF, which suggests that they can adaptively compensate for GDNF loss. This highlights the limitation of broadly utilized gene deletion approaches in analyzing gene function. Our results indicate a clear role for endogenous GDNF in midbrain dopamine neuron development and function, but also demonstrate that GDNF is not required for their maintenance during aging. Furthermore, the ability of endogenous GDNF to protect animals in a PD model without the side effects associated with ectopic GDNF application suggests that elevation in endogenous GDNF levels may be an important future route for PD therapy.
  • Kylväjä, Riikka (Helsingin yliopisto, 2016)
    For understanding the interaction between bacteria and the host, it is essential to identify and characterize bacterial adhesive proteins, adhesins, and other bacterial molecules that interact or interfere with the host. Adhesins mediate the initial colonization steps of bacteria. The colonization may lead to infection or commensalism. When the molecular mechanisms are known, new treatments to prevent the infections can more easily be designed. For assessment of the functions of bacterial proteins in vitro, the proteins are usually purified from the cells or displayed on the surface of a heterologous host. Various surface display techniques, such as phage or fimbria-assisted display, have been developed for the analysis of polypeptides complicated to overproduce by conventional expression methods. Secretion of recombinant proteins to the culture medium of E. coli is an appealing approach since the purifying step is simple. However, reports on high-level extracellular protein secretion in bacteria are scarce. In the first part of this study, a random chromosomal library of Staphylococcus aureus was created in the secretion-competent E. coli strain MKS12. S. aureus expresses several adhesins, some of which are well characterized. Here, we wanted to identify possible new adhesins or proteins with novel functions. All the extracellularly secreted staphylococcal polypeptides of this study were tested for binding to some well-known receptors of S. aureus such as fibronectin, fibrinogen, collagens, and plasminogen. We found three putative moonlighting proteins i.e. proteins with functions additional to their conventional functions: a universal stress protein and an ATPase subunit of phosphoribosylaminoimidazole carboxylase, which both bound to fibronectin and fibrinogen, and the penicillin binding protein 3 capable of binding and activating plasminogen. Adhesins have been studied at the molecular level in many human pathogenic bacteria, such as S. aureus, but the knowledge on the surface molecules mediating adhesion of commensals, such as Lactobacillus, has not drawn as much attention. The second part of this study dealt with the interaction of Lactobacillus crispatus ST1 with the epithelium of the chicken crop and the human vagina. We investigated the molecular mechanisms underlying the interaction of L. crispatus ST1 with the epithelium and identified a novel high-molecular-mass adhesin that was named as lactobacillus epithelium adhesin (LEA). LEA was shown to bind efficiently to the stratified squamous epithelium of the crop and to the similar type of epithelium in the human vagina. In this thesis work we have applied a novel secretion method for heterologous protein expression and characterized novel adhesive proteins of two Gram-positive bacterial species.
  • Laitinen, Anita (Helsingin yliopisto, 2016)
    Mesenchymal stem/stromal cells (MSCs) are multipotent cells that can be found in various tissues. These cells have the capacity to differentiate into bone, adipose, and cartilage. They also have the capacity to suppress immune reactions and the capacity to support angiogenesis. The utilization of these cells in cell based therapies has therefore been intensively studied. There are several clinical studies on going to demonstrate the therapeutic potential of these cells. The utilization of MSCs has been studied in for example graft-versus-host-disease (a severe complication after hematopoietic stem cell transplantation), stroke, myocardial infarction, and cartilage lesions. The frequency of MSCs is variable in different tissues. The number of these cells in tissues is so low that these cells need to be cultured outside of the body, in vitro, to obtain adequate numbers of MSCs for cell therapy purposes. It has been demonstrated that different in vitro culture conditions have effects on the properties of MSCs. Traditionally cells are cultured in growth medium containing fetal bovine serum (FBS). There is a great interest to find alternative supplements to replace FBS for clinical grade production of MSCs to avoid the patients to become predisposed to xenogenic infectious agents or antigens. Platelet-derived supplements might be one potential alternative for FBS. An efficient method to culture MSCs from cord blood was established in this thesis. Additionally a method to produce clinical-grade bone marrow MSCs in platelet-derived supplement containing culture medium was established. Different culture conditions were demonstrated to have an effect on proliferative and immunosuppressive capacity of MSCs as well as on their capacity to support angiogenesis. In this thesis it is also indicated that MSCs can suppress immunoreactions producing an immunosuppressive molecule, adenosine, via a cell surface enzyme, CD73. The knowledge of the impact of culture conditions on the properties of cells as well as understanding the functional mechanisms of the cells is a prerequisite to produce safe and efficacious cell therapy products.
  • Kumar, Anmol (Helsingin yliopisto, 2014)
    Neurotrophic factors such as brain¬-derived neurotrophic factor (BDNF) and glial cell line¬¬¬-derived neurotrophic factor (GDNF) are a family of proteins which play an important role inside and outside central nervous system. While precise regulation of BDNF and GDNF levels in time and space in an organism is crucial in determining the biological outcome, mechanisms involved in controlling their levels are not fully understood. Messenger RNAs (mRNAs) play a critical role in gene expression by conveying genetic information from DNA to protein synthesis. 3ʹ untranslated region (3ʹUTR) is a part of mRNA sequence which regulates gene expression by binding to microRNAs (miRs), RNA-binding proteins (RBPs) and other trans-acting factors. In this thesis, we investigated the 3ʹUTR mediated regulation of BDNF and GDNF. We demonstrate the presence of regulatory elements in the 3ʹUTR of BDNF and GDNF and, show that BDNF is regulated by four different miRs, namely miR-1, miR-10b, miR-155 and miR-191 and, RBP tristetraprolin (TTP) in different cell lines. Further, we show that GDNF is regulated by multiple miRs in cell lines and identify binding sites for miR-146a and miR-96 in the GDNF 3ʹUTR. Finally, we demonstrate that replacement of GDNF 3ʹUTR in mice with a 3ʹUTR with reduced responsiveness to negative regulators including miRs leads to elevated level of endogenous GDNF mRNA and protein in various organs with profound biological effects including in the brain dopamine system function in mice. We conclude that 3ʹUTR mediated regulation of BDNF and GDNF is biologically important and propose that 3ʹUTR replacement is an informative way to study gene function in vivo.
  • Salonen, Kirsi (Helsingin yliopisto, 2016)
    The incidence of type 1 diabetes has been increasing over recent decades. The reason for the increase, and the initial trigger for the autoimmune process remain unknown. Children with significantly increased risk for type 1 diabetes can be recognized from the general population based on their HLA-genotype and a panel of autoantigen-specific antibody assays. Recently a novel autoantibody specificity was discovered, the ZnT8 autoantibodies (ZnT8A). The advanced glycation end products (AGEs) are produced via glycation reactions between reducing sugars and proteins. AGEs and their interaction with the receptor for AGEs (RAGE), have been implicated to play a role in the pathogenesis and complications of diabetes. The soluble form of RAGE (sRAGE) is counteracting the effects of proinflammatory, membrane-bound RAGE. A decrease in sRAGE has been observed in various studies on acute inflammation. Polymorphisms of the gene encoding RAGE, AGER, are associated with the risk and the complications of diabetes according to previous studies. This thesis set out to define the characteristics of ZnT8A and RAGE in clinical and pre-clinical type 1 diabetes. Among the newly diagnosed children with type 1 diabetes, 63% tested positive for ZnT8A. ZnT8A were associated with age and metabolic state at diagnosis as well as to HLA genotype. ZnT8A-assay did not improve the detection rate of beta-cell autoimmunity. Concentrations of sRAGE correlated positively with age in children with newly diagnosed type 1 diabetes, but not in controls. Diabetic ketoacidosis at diagnosis and the high-risk HLA-genotype were related to lower sRAGE. Two polymorphic variants of the AGER gene, associated with increased risk for type 1 diabetes, correlated with reduced sRAGE. Prediabetic children had higher sRAGE than autoantibody-negative controls. A reduction in sRAGE coincides with the appearance of autoantibodies in children progressing to overt type 1 diabetes, but not in healthy controls, or in children seroconverting to autoantibody positivity later in childhood. After the seroconversion, the sRAGE concentrations remained stable. The RAGE/AGE ratio was higher in the cases than in the controls. To conclude, sRAGE, which has been considered cytoprotective in previous studies, is positively associated with older age at disease onset, protection from metabolic decompensation at diagnosis and AGER genotypes with a lower risk for type 1 diabetes. Children, who seroconvert to humoral islet cell autoimmunity early in childhood, experience a drop in sRAGE coinciding with the appearance of the first autoantibodies. They have higher sRAGE and sRAGE/AGE-ratio than the controls before seroconversion. These observed associations might be a result of an intrinsic protective mechanism, which fails at seroconversion.
  • Svanbäck, Sami (Helsingin yliopisto, 2016)
    Key physicochemical properties determining the developability of a drug include solubility, dissolution rate, lipophilicity and pKa. Not only do these properties affect synthesis and solid form optimization, choice of administration route, processability and formulation strategies; they also greatly influence, directly or indirectly, the absorption, distribution, metabolism, excretion, toxicity and efficacy of drugs. However, miniaturized methods that would enable small-scale determination of these fundamental properties in an accurate and rapid way, are lacking. Image-based microscopy could provide an opportune method for non-specific, rapid and miniaturized applications. First, the applicability of image-based microscopy and single-particle analysis in drug dissolution rate measurement was evaluated. This was done by comparing image analysis data with traditional UV spectrophotometric data of individual dissolving drug pellets. It was found that dissolution rates obtained by image analysis and UV spectrophotometry were practically identical. Next, a single-particle trap flow-through device was developed, wherein it is possible to continuously monitor individual drug particles under constant flow conditions. Based on the promising results of image-based dissolution rate analysis, the possibility of acquiring the intrinsic dissolution rate from individual freely rotating particles, trapped inside the flow through device, was evaluated. It was found that image analysis can be used for rapid real-time determination of intrinsic dissolution rates from continuously changing effective surface areas of dissolving individual micro-particles. The method was then further extended to determine the equilibrium solubility of drugs. Based on the diffusion layer dissolution rate model, solubility is the rate limiting factor of dissolution and can therefore be determined. While solubility is generally determined from bulk solutions after long incubation times, it was shown that the equilibrium solubility can be rapidly determined from individual pure-substance particles by means of the diffusion layer theory and image analysis. Finally, the single-particle method was further miniaturized and a second device developed, in order to allow imaging of individual powder crystals. It was shown that dissolution rate and solubility can be acquired from individual nanogram crystals. The single-particle method was further extended to acquire pKa, logP and logD of the studied substances, using aqueous buffers, simulated physiological solutions and organic solvents. Using this method and device, it is possible to acquire a complete pH-solubility profile for an unknown material of unknown composition, with individual measurements of less than 30 seconds. In summary, these results strongly suggest that image-based analysis of materials could be applied in high-throughput experimentation (HTE) applications. The possibility of acquiring solubility, dissolution rate, lipophilicity and pKa using a single analytical method, could significantly simplify and speed up accurate data acquisition. This in turn, could lead to faster and more informed decision-making and, ultimately, better and more affordable drugs.
  • Juntunen, Pirkko (Helsingin yliopisto, 2016)
    This thesis introduces and explores a new aural based approach for play-together education of first- and second-grade string instrument students in music school. The research problems are to create a music technology based teaching method and to study violin and play-together learning in the context of music technological applications. The theoretical background is based on new learning environments, blended learning and flipped classroom in music education. In this recent method, Playback Orchestra, the students practice their part with the support of an audio of the full score, in most cases the playback of a notation program. Hearing the audio supports learning the harmony, rhythm, and dynamic changes. The learning situation is a kind of a virtual play-together rehearsal: it is essential that playing continues without stopping at mistakes, which are corrected afterwards. The method is a learning by doing approach and the flow-like practicing strategy develops flexibility, which is essential in play-together situations. The Playback Orchestra method was tested with first (N=10) and second (N=4) grade string instrument students of a music school with a quasi-experimental study design. The test group (playback group) practiced a score with the support of an audio and the control group (no playback group) without it. The aim was to find out if there were differences between study groups in learning. The first research question was: which playing skills possibly benefit from the audio background, the performance as a whole, understanding the atmosphere, style and general structure of the music, right and left hand technique, reading the score, or play-together skills. The second research question was concerned with learning improvisation: does the audio background support starting the improvisation decisively, continuing it intensively and logically, finding and maintaining the flow and atmosphere, finding own ideas and showing independence and joy of playing, using relaxed movements and creating a general structure in the improvisation. Two professional violin teachers evaluated the play performances from video before and after a practice period and the quantitative analysis was made with SPSS 22 using general linear model and linear mixed model, which can be applied for small study groups. The results showed that when the piece of music to be learned was a main melody of a chamber music composition, the playback group had learned faster than the other group essential features connected with understanding the musical content: the style and atmosphere and the general structure of the music. The playback group had learned musical communication and leading a group by playing better than the no playback group. This finding was significant in large numbers. Concerning the instrument specific technique, audio background seemed not to have clear beneficial effects. However, the students learned to use singing bow style when practicing with the support of a CD track from film music better than without it, the difference was significant in large numbers. When the score to be learned was in baroque style, expressing terrace dynamics , an essential feature of the genre, benefited from the audio background in significant numbers. The improvisation study was a by-product when testing the learning of a musical tale with many sections in different keys, playing styles and atmospheres. The improvisation task was to describe storm by playing. The results showed that musical story telling in improvisation passage benefited from practicing the musical tale with the playback support. Because the study groups were small, the results cannot be widely generalised. However, the aural based approach seems to create a good basis for learning deep understanding of musical content. Further, because learning is fast, using the Playback Orchestra method makes possible for instrument teachers to create well-working play-together culture with large repertoires. The pedagogy of music institutions at its best includes both traditional and new learning environments, such as blended learning. New technological applications can benefit playing and play-together skills and lead to richer musical expression and joy of playing. More research and open-mindedness is needed in order to the new ways of thinking, using and developing new tools could be included in the curricula of music institutions. In this way using the traditional methods together with new approaches the appreciated Finnish music education system can develop and offer even better quality of education. ________________________________________ Keywords: string instrument education, orchestra teaching in music schools, technology-based music education, new music learning envi-ronments, blended learning
  • Vesa, Juho (Helsingin yliopisto, 2016)
    In the Finnish consensus democracy, public discussion has traditionally played a small role in policymaking. Consensus and compromises have been built within small circles of policymakers behind closed doors, and the strong position of civil servants, president and interest organizations has limited public discussion. Institutional and cultural changes have, however, created new pressures for policymakers to act in media publicity. The norm of openness has been strengthened in society (i.e. policymaking is expected to be more transparent than before); politics has been mediatized (i.e. the significance of media in politics seems to have increased); the role of committees has been reduced in policy preparation; and parliamentarism has been strengthened. This thesis examines how openly Finnish policymakers (i.e. politicians, civil servants and interest organizations) act towards public discussion. It studies how policymakers participate in discussions taking place in media publicity, what kind of rules on public communication policymaking institutions include and how institutions have reacted to the strengthening of the norm of openness. The study also asks how strongly policymaking is mediatized i.e. what is the significance of media publicity in policymaking and to what extent does the news media affect policymaking. The article-based thesis is based on two case studies and a survey of members of parliament (MPs). The case studies focus on a social security reform committee (2007 2009) and a government s programme to increase productivity in state administration (2002 2011). Case study data consists of interviews with policymakers and journalists, media articles, government information material and policy documents. MPs were surveyed on the news media s agenda-setting power (i.e. the media s influence on political institution agendas). The results show that the tradition of looking for a consensus constrains the openness of public discussion in Finland. Policymakers prefer not to talk about policy negotiations in detail in public because publicity can freeze negotiations. The way that members of the multi-party government manage the news can weaken accountability by reducing citizens possibilities to evaluate politicians behaviour. Policymakers manage publicity through common publicity rules. For instance, ministers are not usually expected to make public statements during tripartite policy preparation. Citizens and the media, however, presume openness. Thus, policymakers cannot withdraw completely from publicity. They have created public information practices that simultaneously meet the expectations of openness and secure working peace for policy preparation. For instance, policymakers can publish information regarding policy preparation actively but on such a general level that it does not lead to public discussion. Civil servants, who act in a neutral way regarding publicity, often have a central role in informing the public, which can narrow publicity and transparency. Moreover, the majority of MPs think that the news media s behaviour affects public discussions much more than policy processes and decisions made by the government and parliament. Results indicate that the core of policymaking is often still rather isolated from publicity. Media publicity affects symbolic politics (i.e. politicians competition for voters) more than actual decisions. Policymaking institutions have developed means to protect policy processes against media publicity and the demands for openness. Results support conclusions of earlier research, suggesting that mediatization is rather shallow: it has changed symbolic politics and public information activities more than policymaking.
  • Kontro, Inkeri (Helsingin yliopisto, 2016)
    Elastic X-ray scattering is a probe which provides information on the structure of matter in nanometer lengthscales. Structure in this size scale determines the mechanical and functional properties of materials, and in this thesis, small- and wide-angle X-ray scattering (SAXS and WAXS) have been used to study the structure of biological and biomimetic materials. WAXS gives information on the structures in atomistic scales, while SAXS provides information in the important range above atomistic but below microscale. SAXS was used together with dynamic light scattering and zeta potential measurements to study protein and liposome structures. The S-layer protein of Lactobacillus brevis ATCC 8287 was shown to reassemble on cationic liposomes. The structure of the reassembled crystallite differed from that of the S-layer on native bacterial cell wall fragments, and the crystallite was more stable in the direction of the larger lattice constant than in the direction of the shorter. Liposomes were also used as a biomembrane model to study the interactions of phosphonium-based ionic liquids with cell membrane mimics. All studied ionic liquids penetrated multilamellar vesicles and caused a thinning of the lamellar distance that was dependent on ionic liquid concentration. The ability of the ionic liquids to disrupt membranes was, however, dependent on the length of hydrocarbon chains in the cation. In most cases, ionic liquids with long hydrocarbon chains in the cation induced disorder in the system, but in one case also selective extraction of lipids and reassembly into lamellae was observed. The effects depended both on ionic liquid type, concentration, and lipid composition of the vesicle. WAXS was used as a complementary technique to provide information on the structure-function relationship of a novel biomimicking material composed of a genetically engineered protein, chitin and calcium carbonate, and films composed of hydroxypropylated xylan. The presence of calcium carbonate and its polymorph (calcite) was determined from the biomimetic material. For the xylan films, crystallinity was assessed. In both cases, also the crystallite size was determined. These parameters influence the mechanical properties of the developed materials. In all cases, X-ray scattering provided information on the nanostructure of biological or biomimetic materials. Over a hundred years after the principle behind X-ray scattering was first explained, it still provides information about the properties of matter which is not available by other means.
  • Ilmonen, Klaus (Helsingin yliopisto, 2016)
    The significance of EU level corporate governance regulation has been increasing in the years following the financial crisis. At the same time EU regulatory initiatives in this field have been subject to much criticism. The corporate governance systems in the EU vary significantly and it has been argued that EU initiatives have not been adapted to corporate environments prevalent in member states. This has been argued to have decreased the competitiveness of listed companies and the financial markets in the EU. Several EU corporate governance initiatives have also failed or been subject to considerable political compromise emphasizing the challenging political nature of the EU regulatory system. EU integration represents a model for coordinating interaction between different economies and political systems. Understanding how supranational systems work and developing regulation at this level remains an important venture. More attention is needed to adapt the design of EU regulation to the varied institutional environment across the EU. To be able to develop EU legal strategies and regulatory design in the field of corporate governance, a better understanding of the dynamics of EU policymaking remains important. The goal of the study is to provide a basis for developing legal strategies used in EU corporate governance regulation in light of the challenges of the (i) varied regulatory requirements of different corporate environments in the EU and (ii) the supranational political dynamics of corporate governance regulation. This requires a better awareness of the factors that affect (i) the impact and effectiveness of different legal strategies and regulatory mechanisms in different corporate environments and (ii) the political dynamics of EU policy-making with respect to corporate governance regulation. The study analyses corporate governance regulation in the context of specific environments of corporate governance and corporate ownership. With an emphasis on institutional and political aspects of corporate governance, the study analyses and compares the effects of different legal strategies in these environments; i.e. what the effects of different regulatory mechanisms have been on the relationships between corporate constituencies. The study focuses on corporate governance regulation in the context of concentrated ownership in a Nordic institutional environment. The study also analyses the political dynamics of EU policymaking based on economic theories of regulation and an institutional analysis of EU policy-making. The results of study include a framework for a corporate governance index that incorporates the prevalent institutional dynamic, as well as a qualitative model for developing regulatory policy at the EU level. The study relates to comparative corporate governance research and to political economy analysis of EU regulation.
  • Nieminen, Eeva-Liisa (Helsingin yliopisto, 2016)
    In this study, students' discourse of science learning is explored with a special focus on interest in learning. The research group is an optional science class. The data consist of 20 interviews. The entire collection of interviews served as data for searching discourses, which further led to closer case studies. A portrait of the class is created, first searching dominant discourses and then taking a closer look at students who exemplify influential discourses contributing to interest generation in the whole class. The research starts from individual narratives and follows the idea of Roth and Lucas (1997) that individuals belonging to a community represent the discourses of that community. Qualitative content analysis is used inductively to trace categories, which represent the interpretive repertoires of the students. By further abstraction, the latent contents of these discourses are abstracted to more general concepts in order to find recurrent patterns. Eventually, based on the created concepts and then deductively drawing on the theoretical models of Vygotsky, interest development, self-regulation and affective neuroscience, a model of the students interest generation is formed. The science class context offers the students possibilities to make choices. Students experience a feeling of succeeding when they understand the subject contents. This, in turn, creates a zeal for school and learning. Interest in learning seems to derive from a desire to succeed in life; a constant search for that which is new, exciting and fun; picking one's own handbag of choices; taking one's own action and feeling success; interest in the subject; and togetherness and identification with the science class. From the students' experiences, a twofold image appears: students like projects, practical work and other student-centred methods, but they are not considered superior to the traditional teacher explanation, which in itself promotes understanding, leading to a feeling of succeeding. A clear division between students appears: those who expect firm teacher guidance and those who prefer independent working. Belonging to a special class reinforces self-regulation. I construct a pattern, a pyramid of learning, where emotions, play and fun along with togetherness form the foundation for motivation. Learning and gaining experience contribute to increasing independence and the mastery of situations. One's own effort, attention and concentration make it possible to advance in learning and independence. The degree of teacher involvement needed depends on the individual student's position on this pyramid: on the bottom, more control and teacher guidance are needed, whereas students situated on the top of the pyramid are able to work on their own. Through a process of development aided by cultural and social influence, the students move in steps from bottom to top on the pyramid. These students are searching for their identities, picking up what is useful for them and building a set of knowledge and skills within the limits the school. I identify the science class as a community of the practice of science, where the how-aspect of science is conveyed from the science community through its practices and artefacts and is embraced and developed further by students through their social relations and communication. Keywords: science education, interest, discourse, interpretive repertoire, zest, enthusiasm, community of practice, identity, seeking
  • Hyvärinen, Satu (Helsingin yliopisto, 2016)
    The complement system is a network of over 30 plasma proteins that act in, for example, protecting the body against invading microbes and removing damaged self cells. Complement activation proceeds in a cascade-like fashion, resulting in deposition of certain protein fragments on cell surfaces and liberation of others to the fluid nearby. Due to the destructive nature of complement attacks, it is imperative that this system be stringently controlled. When regulation fails, deleterious complement activation on self cells follows. This is the case for example in atypical hemolytic uremic syndrome (aHUS), a rare thrombotic microangiopathy characterized by hemolysis, thrombocytopenia and renal impairment. In roughly two thirds of aHUS patients, abnormalities in complement genes can be detected. A frequent observation is a mutation in the regulator factor H (FH). The majority of FH mutations in aHUS cluster in the two C-terminal domains of the protein, i.e. FH19-20. These are critical for directing FH onto cell surfaces under complement attack. Several important aspects of the syndrome have been uncovered, but the mechanisms underlying aHUS pathogenesis remain incompletely understood. The general aim of this work was to better explain the molecular events leading to aHUS. First it was asked, whether disturbances in the recently described interactions between FH19-20 and malondialdehyde (MDA) adducts could be involved in aHUS. To study this, binding assays employing MDA-modified proteins and wt and mutant FH19-20 fragments were performed. FH19-20 binding was observed only if a high density of MDA adducts on the surface was present. Since such extensive MDA modification of cell surface proteins is improbable in vivo, it was concluded that disturbed recognition of MDA adducts on cells by FH is unlikely to be relevant in aHUS. Next, the hypothesis of plasminogen to regulate propagation of the complement cascade on cell surfaces was tested. Serum complement was activated on erythrocytes, endothelial cells, and platelets with or without added plasminogen, and complement activation determined as cell lysis or deposition of C5b-9 or C3b. Plasminogen was observed to cause only a very minor inhibition of complement activation on platelets. It was concluded that reduced complement control by plasminogen does not properly explain the recent association of plasminogen deficiency with aHUS. The final aim of this work was to determine the role of sialic acid in FH-mediated regulation on not only erythrocytes, but also on endothelial cells and platelets. To this end, the abilities of several FH19-20 fragments carrying aHUS-associated mutations to antagonize FH function on different types of cells was compared. Flow cytometry detection of FH binding and C3b deposition revealed identical patterns of FH19-20 function on all types of cells. Removal of sialic acid from cells impaired FH function on them. With the help of recent structural data, it was concluded that mutations impair simultaneous binding of the C-terminus of FH to surface sialic acid and C3b, providing a unifying explanation for association between the C-terminus mutations of FH and the clinical disease aHUS. In conclusion, the work presented in this thesis improves our understanding of the pathogenic mechanisms involved in aHUS. Most importantly, the results show that in aHUS, the underlying common defect of various FH C-terminus mutations is the inability to simultaneously bind sialic acid and C3b on cells under complement attack.
  • Paolini, Gianluca (Helsingin yliopisto, 2016)
    The subject of this doctoral thesis is the mathematical theory of independence, and its various manifestations in logic and mathematics. The topics covered in this doctoral thesis range from model theory and combinatorial geometry, to database theory, quantum logic and probability logic. This study has two intertwined centres: - classification theory, independence calculi and combinatorial geometry (papers I-IV); - new perspectives in team semantics (papers V-VII). The first topic is a classical topic in model theory, which we approach from different directions (implication problems, abstract elementary classes, unstable first-order theories). The second topic is a relatively new logical framework where to study non-classical logical phenomena (dependence and independence, uncertainty, probabilistic reasoning, quantum foundations). Although these two centres seem to be far apart, we will see that they are linked to each others in various ways, under the guiding thread of independence.
  • Kallonen, Aki (Helsingin yliopisto, 2016)
    X-ray tomography is a widely used and powerful tool; its significance to diagnostics was recognized with the Nobel award, and tomographic imaging has also become a large contributor to several fields of science, from material physics to biological and palaeontological sciences. Current technology enables tomography on the micrometre scale, microtomography, in the laboratory. This provides a non-destructive three-dimensional microscope to probe the internal structure of radiotranslucent objects, which has obvious implications towards its applicability. Further, x-rays may be utilized for x-ray scattering experiments, which probes material properties on the ångström-scale. Crystallographic studies on various forms of matter, not least of which famously being the DNA molecule, have also been awarded the Nobel. In this thesis, the construction of a combined experimental set-up for both x-ray microtomography and x-ray scattering is documented. The device may be used to characterize materials on several levels of their hierarchical structure, and the microtomography data may be used as a reference for targeting the crystallographic experiment. X-ray diffraction tomography is demonstrated. An algorithm for x-ray tomography from sparse data is presented. In many scenarios, the amount of data collected for a tomogram is not sufficient for traditional algorithms, and would benefit from more robust computational schemes. Real x-ray data was used for computing a tomographic reconstruction from a data set two orders of magnitude smaller than what is conventionally used with set-ups such as the one presented in the thesis. Additionally, x-ray microtomography was utilized for morphological studies in developmental and evolutionary biology, evo-devo for short. The fossil record shows vast changes in morphology as more complex forms of life evolved, while the morphology of any given individual organism is the product of its developmental process. Understanding both evolution and development is essential for a comprehensive view on the history of life. In this thesis, two studies on teeth and their development are discussed. In both, dental morphology was investigated with high-resolution x-ray tomography.