Väitöskirjat

Recent Submissions

  • Cole, Elizabeth (Helsingin yliopisto, 2017)
    The universe is populated with magnetically active stars. This magnetic activity is thought to be generated by dynamos operating in turbulent stellar convection zones, a process by which kinetic energy is converted into magnetic energy. The solar dynamo is but one dynamo type possible for stars. Rapidly rotating late-type stars are observed to have large spots, activity cycles, flip-flops, and active longitudes, all indicating a different dynamo mechanism may be responsible. Numerical simulations provide a tool for better understanding some of the mechanisms responsible for these dynamos. In this thesis, direct numerical simulations in spherical wedges are used to study dynamo mechanisms in the stellar convection zone. These spherical wedges are used to investigate the dependence of the resulting magnetic field on input parameters such as the density stratification and rotation rate. Mean-field models are used to evaluate the assumption that the wedges can be used to approximate full spheres. As rotation increases, differential rotation decreases in the models, in agreement with observations where more rapidly rotating stars have smaller estimates for differential rotation. As density stratification approaches more realistic values, a lat- itudinal dynamo wave with equatorward propagation is found. The impact of the domain size in the azimuthal direction on the results is explored. When the domain size is increased to 2pi in the azimuthal direction, a non-axisymmetric m = 1 mode is excited. This non-axisymmetry is reminiscent of the field configurations of rapidly rotating late-type stars. The azimuthal dynamo wave rotates nearly independently of latitude and depth, and its rotation rate is slower than that of the mean rotation of the model. This azimuthal dynamo can provide a possible explanation for the observed rotational difference of spots from the mean rotation observed on stars. The wedges use the perfect conductor boundary conditions at the latitudinal boundary to compensate for the omission of polar regions due to the time step becoming prohibitively small there. Simple mean-field models with only a latitudinal extent and perfectly conducting boundaries do not oscillate when the model is extended to the poles. Thus oscillations near the polar region may be an artifact of the boundary condition. However, when the alpha effect from mean-field dynamo theory and magnetic diffusivity are concentrated towards lower latitudes, oscillatory solutions with equatorward migration are found. When sufficient shear is added, oscillatory solutions are again found, and the Parker-Yoshimura rule for latitudinal dynamo wave propagation is obeyed. It is concluded that numerical simulations where the alpha effect and diffusivity are found to be stronger at lower latitudes and simulations with sufficient shear are considered good approximations of full spheres. These numerical simulations are put into context with stellar observations. Two young solar analogs are selected, V352 Canis Majoris and LQ Hydrae. V352 CMa is considered an active star, while LQ Hya is classified as a super-active star. The continuous period search method is applied to the low-amplitude light curves of V352 CMa. Stable active longitudes with rotation periods of 7.157 days are found. This is faster than the mean rotation of 7.24 days. Such active longitudes may be due to the underlying magnetic structure with azimuthal dynamo waves competing with differential rotation. LQ Hya rotates even more rapidly with a rotation period of only 1.600 days. A carrier period is selected of 1.605 days using the D2 statistical analysis. Primary and secondary light curve minima are found with the carrier fit analysis. No stable active longitudes are found, instead, there is only a short period spanning a few years where an active longitude may exist, but the rotation period is poorly defined. Several possible flip-flop events are identified. The azimuthal dynamo waves in numerical simulations with comparable rotation rates have a similar chaotic nature. The Doppler Imaging technique is applied to LQ Hya to examine the latitudinal spot structure. Spots at high and low latitudes are in agreement with the bimodal structure of the D2 statistic used in the carrier fit analysis. Temperature maps of LQ Hya spanning four years show an increase and a decrease in spot coverage, but no cycle can be found. Because LQ Hya is a rapidly rotating star, differential rotation is estimated to be very small. The azimuthal dynamo wave presents a new possible explanation for the jumps and trends of the spots in observations of this star.
  • Mölsä, Markos (Maanpuolustuskorkeakoulu, 2016)
    Rapid and accurate detection and diagnosis of infectious agents is crucial in preparedness for diseases and biothreats. Due to a lack of rapid diagnostic capabilities, diseases and outbreaks may remain undetected. Currently available point-of-care tests often lack the sensitivity to directly detect pathogens in samples, thus there is a need for quick and robust solutions for identification of pathogens in order to mount appropriate responses. The spread of infectious diseases is a global challenge and outbreaks and epidemics place great strains to healthcare and economy. Several of the pathogens causing these diseases are not only major public health issues but pose also potential biothreats. This thesis describes the performance of field-capable gene amplification methods in the detection of three bacterial pathogens (Francisella tularensis, Bacillus anthracis, and Yersinia pestis) and a viral pathogen causing respiratory infections (influenza A virus). The methods include on-site nucleic-acid extraction and rapid real-time PCR amplification of selected gene regions in these pathogens occurring in animal tissue and human nasopharyngeal samples. Results confirm that currently-available portable thermocyclers can generate highly accurate diagnostic results in field. Furthermore, genetic characterization of a common respiratory pathogen, adenovirus is presented by investigating adenoviruses circulating in Finnish garrisons with molecular sequence analysis. Genetic characterization of a pathogen is also an important tool in investigations of alleged use of biological weapons. The presented methodology and workflow serves as an effective tool for decision makers in biothreat preparedness and in case of deliberate spread of pathogens.
  • Rosti, Katja Marjukka (Helsingin yliopisto, 2016)
    This thesis work comprises the characterization of proteins from two different neuronal membrane receptor protein families: the growth factor receptor -type (GFRa) of protein, growth arrest specific-1 (GAS1) and the synaptic leucine rich repeat adhesion proteins, leucine-rich-repeat transmembrane-2 (LRRTM2), and synaptic adhesion-like molecules 1 and 5 (SALM1 and SALM5). The GAS1 project has focused on the structural characterization of the recombinant human GAS1 protein, and on the possible interaction and effect of GAS1 on the tyrosine kinase receptor protein, re-arranged during transfection (RET), signaling. GAS1 has two different types of interactions, GAS1-RET signaling participates in neuronal survival and maintenance and GAS1-Patched1-Sonic hedgehog (SHH) signaling is needed both for cell survival and in the development of the enteric nervous system during early development. As a conclusion GAS1 has very different structure from other members of the protein family and can interact directly with RET unlike the other GFRa co-receptors. Indicating a different biological role. The study of leucine-rich-repeat transmembrane proteins (LRRTMs), and the synaptic adhesion-like molecules (SALMs) concentrated characterization of an engineered variant of LRRTM2, SALM1 and SALM5. These proteins are involved in neurite outgrowth, branching and synapse formation. They are mainly expressed in brain, and their malfunction is connected to familial schizophrenia, bipolar disorder and autism. We developed a new strategy for protein structure solution and utilized a statistical sequence-based protein engineering method for generation of a stabilized protein for structural studies. We believe this method will have wider use in structural studies of difficult proteins. The goals of this thesis work were to produce these proteins, solve their structures, test their interactions with ligands and do functional characterization studies using a variety of methods. The results will contribute to a better understanding of the molecular structure and the roles these proteins in neuronal tissue, and possibly generate new research into the cellular phenomena, including diseases, linked to these proteins, and aid in future drug development.
  • Havula, Essi (Helsingin yliopisto, 2017)
    SUMMARY Sugars, amino acids and lipids provide the energy and building blocks for growth and maintenance in all animals. However, animal species display great variation in their dietary preferences. The optimal diet of even closely related species can vary tremendously. Also human populations and individuals vary in their dietary behavior and physiological responses to dietary interventions. Moreover, the high amounts of refined sugars in the modern human diet are suggested to contribute to the development of metabolic diseases such as metabolic syndrome and type 2 diabetes. Multicellular animals sense and control their energy homeostasis continuously by integrating nutritional, hormonal and neuronal inputs from their internal and external environment. For example, the counteracting hormones Insulin and Glucagon maintain the levels of circulating glucose constant during fluctuating nutritional conditions. At the cellular level, macronutrients are sensed by distinct mechanisms. The nutrient sensors and their downstream signaling pathways are activated in response to specific nutrients, and they ensure the metabolic homeostasis. Sugars are sensed by highly conserved transcription factor paralogs ChREBP (Carbohydrate-responsive element-binding protein) and MondoA, which share the same heterodimerization partner Mlx. ChREBP/MondoA-Mlx heterodimers regulate the majority of sugar-induced transcription in mammals, including genes of the glycolytic and lipogenic pathways. Dysregulation of ChREBP has been associated with the development of type 2 diabetes, and polymorphisms of ChREBP with circulating triglyceride levels and increased risk of coronary artery disease. The Drosophila genome encodes single orthologues for ChREBP/MondoA and Mlx called Mondo and Mlx, respectively. The function of the mammalian ChREBP/MondoA-Mlx has been largely studied in vitro. The aim of this thesis was to characterize the in vivo function of Drosophila Mondo-Mlx and to identify its target genes and their roles in regulating sugar metabolism. Due to the lack of genetic redundancy and with the extensive toolkit available, the Drosophila provides an optimal in vivo model for studying the role of Mondo-Mlx in nutrient sensing and metabolism. In this thesis, I demonstrate the physiological importance of Mondo-Mlx for organismal sugar tolerance. The mlx null mutant animals display severe sugar intolerance and a gene expression profile that confirms the role of Mondo-Mlx as a key regulator of glycolytic and lipogenic genes also in Drosophila. Furthermore, we expand the role of Mondo-Mlx as a metabolic regulator by showing that it directly controls the expression of several key enzymes of lipid storage, pentose phosphate pathway and amino acid metabolism in response sugars. We also show that Mondo-Mlx is a master regulator of a gene regulatory network composed of a secondary tier of transcriptional effectors including GLI similar transcription factor Sugarbabe and Krüppel-like factor Cabut. The metabolic profiling of the mlx null mutant animals revealed that in addition to being hyperglycaemic, the mutants show signs of amino acid catabolism and elevated ceramide levels that indicate lipotoxicity. This thesis demonstrates the use of Drosophila in studying the genetic basis of dietary sugar tolerance and metabolism. It reveals a number of new metabolic pathways and downstream effectors regulated by Mondo-Mlx, broadening its role as a master regulator of sugar-induced transcription.
  • Holopainen, Jani (Helsingin yliopisto, 2017)
    Bone is a fibrous nanocomposite material with a complex hierarchical system of different macro-, micro- and nanostructures. The structure elegantly supports the bone cell functions and facilitates bone remodeling by cellular activity. Injuries and diseases, e.g. osteoporosis, can cause bone fractures and loss that need to be treated with orthopedic implants. The global orthopedic market was estimated at $30 500 000 000 in 2012 and predicted to grow rapidly. A substantial amount of this goes to revision surgery due to implant failures. This not only causes unnecessary costs and work but reduces the quality of life for patients. The key for improving the performance of current implants lies in optimizing both the surface chemistry and structure from macro- to nanoscale. At best bone defects can be treated with bone scaffolds that induce formation of new bone via cellular functions and are degraded by the body thus evading the need for implant removal surgery. However, combining the favorable mechanical, structural and chemical properties poses challenges for the design and preparation methods used for bone implants and scaffolds. The aim of this work was to investigate the preparation of thin film and fibrous biomaterials for bone implants and scaffolds. New processes were developed for various biomaterials and their properties were thoroughly characterized. A method to convert CaCO3 nanostructures to nanocrystalline hydroxyapatite (HA) by treatment in phosphate solution was used to prepare HA thin films and fibers from atomic layer deposited (ALD) and electrospun CaCO3, respectively. HA fibers were also fabricated conventionally by annealing electrospun composite fibers that incorporated Ca and P precursors. Biocomposite fibers of HA nanoparticles and polylactic acid (nHA/PLA) were directly electrospun. These different nanofibers are highly interesting for bone scaffolds owing to their high surface area and the structural similarity to the fibrous nanostructure found in bone. However, conventional electrospinning is limited by its modest production rate. A needleless twisted wire electrospinning (NTWE) setup was developed to increase the production rate and was studied for the preparation of HA fibers for the bone scaffolds. Solution blow spinning (SBS) and electroblowing (EB) of HA were studied as other upscaling alternatives. Promising results were obtained in cell culture studies with the different materials. The electrospun materials could find use in fibrous bone scaffolds. The HA fibers were found out to be very interesting from a biological standpoint, but the fragility of the fibers limits their usability as such and therefore methods to incorporate bioceramic fibers into more rigid support structures should be developed. The method to prepare nanocrystalline HA by the conversion of CaCO3 proved to be highly conformal as evidenced by its ability to preserve the original shape of the ALD films and electrospun fibers. NTWE and EB were shown to be capable of producing high quality nanofibers and to provide a viable upscaling route to conventional electrospinning. In contrast, the quality of the SBS fibers needs improvement. Further work would be required to conclude if EB and NTWE are upscalable to industrial scale production levels.
  • Kuuluvainen, Soila (Helsingin yliopisto, 2016)
    Accurate perception of speech sound features forms the basis of language and oral communication. Cortical speech processing consists of sound identification, feature extraction, and change discrimination, all occurring within a few hundred milliseconds timescale, and leading to conscious perception of sounds in their context. When these processes do not work optimally, speech perception is hampered, which can lead to problems in academic achievement or social interaction. Therefore, in this thesis, the processing of sublexical syllables and changes if their five features (consonant, vowel, vowel duration, fundamental frequency (F0), and intensity) were compared to the processing of complex nonspeech sounds in adults and six-year-old children, using event-related potentials (ERPs). Overall, larger ERP amplitudes or stronger magnetic mismatch negativity (MMNm) sources were found for speech than nonspeech stimuli. Stronger responses in the speech than the nonspeech condition were seen in both groups for changes in consonants, vowels, vowel duration and vowel F0. This is consistent with their role in Finnish: in addition to phonemic changes, vowel duration and F0 changes co-signal vowel quantity, which differentiates word meaning. Furthermore, children, but not adults, had larger left-lateralized responses for speech than nonspeech intensity changes, which is possibly beneficial for word segmentation and learning. Moreover, children's cortical measures were associated with neurocognitive skills. The overall pattern of larger speech than nonspeech responses was associated with better reasoning skills. Furthermore, larger left than right hemisphere ERP amplitudes for speech stimuli were associated with better performance in language tasks. Finally, the early responses (P1, early differentiating negativity, EDN) were associated with phonological and prereading skills, and later responses (N2, N4, late differentiating negativity, LDN) with verbal short-term memory and naming speed. The results suggest that speech and nonspeech sounds are processed by at least partially different neural substrates in preschoolers and adults. Furthermore, intra-individual differences in ERP amplitudes between conditions and hemispheres might be a useful tool in assessing cortical auditory functioning in children without the requirement of attention or motivation to carry out tasks.
  • Shirokova, Vera (Helsingin yliopisto, 2016)
    Development of the organ and its regeneration in adulthood are highly related events and are often guided by similar molecular cues. The hair follicle undergoes repetitive cycles of growth and represents an ideal model for studying both development and regeneration. Hair follicle is an ectodermally-derived organ formed trough interaction of embryonic epithelium and mesenchyme. Once morphogenesis is accomplished, hair follicle undergoes subsequent cycles of growth, regression and rest. Hair regeneration is ensured by the population of hair follicle stem cells which are set aside early during embryonic development. The most quiescent stem cells reside in the bulge, while the stem cells fated for the new growth are in the hair germ. Transcription factors control gene expression and regulate the variety of cell fate choices. Transcription factor Foxi3 is a causative gene for hairless phenotype in several dog breeds, but little else is known about its function in the hair follicle. In this thesis work, I have studied the role of Foxi3 in hair follicle development and postnatal regeneration. To address this question, several Foxi3-deficient mouse lines were used, as well as gene expression analysis, tissue culture techniques and molecular biology methods. Foxi3 is expressed in the developing hair follicle and in the hair germ, exclusively in the activated stem cells. Foxi3 is essential for specification of the hair follicle stem cells and for their activation at the beginning of the hair growth. Foxi3-deficient mice have delayed hair follicle downgrowth during embryogenesis. In the absence of Foxi3, postnatal natural hair regeneration and hair regrowth after depilation are both impaired due to poor activation of stem cells and decrease in their number. Genome-wide profiling, quantitative PCR and immunostaining showed downregulation of several stem cell associated genes upon Foxi3 loss. Thus, Foxi3 is a novel regulator of hair follicle stem cell specification, maintenance and activation.
  • Cheng, Jing (Helsingin yliopisto, 2016)
    The interactions between a host and his/her microbiota have co-evolved over time and they exert profound effects on each other. Intestinal microbiota has been linked with a number of diseases, such as irritable bowel syndrome; it is considered to be a major etiopathological factor since it can alter intestinal homeostasis. However, the role of intestinal microbiota, especially commensals, is unclear in celiac disease. To date, most efforts for detecting potential microbial changes affected by celiac disease have focused on adult individuals and have examined fecal materials, although it is known that early life is the critical period for the microbiota to colonize and establish their niche in the human intestine. At this time in healthy individuals, there is continuing cross-talk with the host e.g. via the immune system, leading to the establishment of homeostasis in both metabolic and immunological programming. Since the intestinal epithelium is the main interface for host- microbe interactions, the role of mucosa-associated microbiota may be distinct from that of fecal microbiota, but both the normal fluctuations in intestinal microbiota and the composition of duodenal mucosa-associated microbiota are still not fully clarified. The aims of thesis were to characterize the development and stability of intestinal microbiota in healthy young children and to compare the microbial features between children and adults. Furthermore, the aim was to investigate host-microbe interactions in celiac disease by studying duodenal mucosa-associated microbial signatures and mucosal gene expression in healthy children and their counterparts with celiac disease. The microbiota profiles were characterized by using the human intestinal tract chip (HITChip), which is a bacterial phylogenetic microarray. The amounts of Bifidobacterium spp. in children and adults were verified with real time qPCR. The levels of mucosal gene expressions were quantified with reverse transcriptase quantitative PCR. The results showed that intestinal microbiota is not fully matured at the age of five in children. A common core microbiota, including several butyrate-producing bacteria, was identified in children and it was developing towards core microbiota found in adults. The different progression pattern of major bacterial taxa may reflect the physiological development steps in children. Moreover, differences were observed between healthy- and celiac disease- associated microbial signatures. The differences may reflect changes in epithelial integrity associated with the disease. On the other hand, the studies on both microbiota and mucosal gene expression indicated that the persistently enhanced Th1 type immune responsiveness in subjects with celiac disease after treating with gluten-free diet might result from the increased expression of TLR9, which recognizes unmethylated CpG motifs in bacterial DNA via the direct stimulation of immune cells and/or intestinal epithelial cells. The results of this thesis project suggest that specific symbiotic and dysbiotic microbial signatures may provide potential functional diagnostic or therapeutic targets for promoting healthy/natural microbiota development. Long-term studies in a controlled environment with an adequate number of participants will be necessary to decode the disturbed microbial signatures. These trials should be combined with systematic pathological surveillance to reveal how the changes in the microbiota influence the onset of disease.
  • Li, Ma (Helsingin yliopisto, 2016)
    Interactions between the brain and the immune system provide a complex microenvironment for brain development. Furthermore, these interactions cause behavioral changes in rodents and humans. Multiple molecules of the immune system in the brain can regulate neural development. Microglia, the resident phagocytes in the central nervous system (CNS), dynamically survey their microenvironment to maintain brain homeostasis. Microglia also actively respond to neuroinflammation induced by insults such as stress, injury, or infection. A dysfunctional immune system in the brain may cause aberrant brain development and adulthood behavior. Dysfunctional immune regulation has also been implicated in the pathophysiological progression of neuropsychiatric disorders in rodents and humans. The major goal of my thesis is to characterize brain immune genes, gene networks, and neuropeptides in inbred mouse strains. These factors might contribute to mouse anxiety- and sociability-like behavior related to symptoms in generalized anxiety disorder and schizophrenia, as inbred strains such as C57BL/6J(N) (C57BL/6J and C57BL/6N) and DBA/2J differ in their anxiety-, sociability- and sensorimotor gating-related behaviors. In this thesis, we utilized eight inbred mouse strains 129S1/SvImJ, A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J, FVB/NJ, and SJL/J to investigate the contributions of brain immune genes and gene networks to social behavioral phenotypes. We first analyzed brain transcriptomics from eight inbred strains to detect differentially expressed immune genes. By correlation analysis, we then predicted the associations of these genes of interest with the animal behavior and brain morphology. Compared to female C57BL/6N mice, we observed high expression of cortical Il1b and Il6 and reduced expression of Cx3cl1 in female DBA/2J mice. Furthermore, male DBA/2J mice had lower levels of C1qb and H2-d1 in the brain compared to male C57BL/6J mice. Interestingly, the hippocampal mRNA level of C1qb was positively correlated with the time spent in social interaction processes in male DBA/2J mice but not C57BL/6J mice. We also investigated differences in cytokine expression and microglial signature gene (for M1-M2 polarization) expression among male C57BL/6J, FVB/N, DBA/2J and 129S2/Sv mice following systemic LPS challenge. Il1b, Il6, and Tnf were highly expressed in the hypothalamus of DBA/2J mice without LPS stimulation. After LPS challenge, the microglial proinflammatory M1-type signature gene Nos2 was highly expressed in the hypothalamus of DBA/2J mice compared to the mouse strains FVB/N, DBA/2J, and 129S2/Sv. We further found that social stress modulated anxiety-like and social behavior in female C57BL/6N and DBA/2J mice in a different manner. The experimental mice were divided into three groups: separate-housed C57BL/6N mice, separate-housed DBA/2J mice, and mix-housed C57BL/6N and DBA/2J mice. Mixed housing made socially active C57BL/6N mice more vulnerable to anxiety and social deficits compared to socially withdrawn DBA/2J mice. Furthermore, expression of glucocorticoid receptor Nr3c1 was attenuated in the hippocampus and cortex of mix-housed C57BL/6N mice compared to the separate-housed C57BL/6N mice. Mix-housed C57BL/6N mice also had a higher level of cortical Avpr1a, but a lower level of hippocampal Oxtr than mix-housed DBA/2J mice. Separate-housed DBA/2J mice had a higher level of hypothalamic Oxtr compared to the separate-housed C57BL/6N mice. These results imply a significant differential impact of social intervention on anxiety-like and social behavior between C57BL/6N mice and DBA/2J mice. In conclusion, my thesis revealed that brain immune genes and neuropeptides are associated with neuropsychiatric-like (anxiety-like and social deficits) behavior in mice. These observations may provide insight on the potential pathogenic molecular mechanisms of neuropsychiatric disorders.
  • Rundgren, Heta (Helsingin yliopisto, 2016)
    Situated at the intersection between comparative literature and gender studies, this dissertation theorizes what I term the postnormâle novel. It deploys readings of four contemporary European novels along with a corpus of literary and feminist theory. The novels include Doris Lessing s The Golden Notebook (1962), Märta Tikkanen's Manrape (1975), Stieg Larsson's Millenium trilogy or The Girl with the Dragon Tattoo (2005-2007) and Virginie Despentes's Apocalypse baby (2010). My analysis of these texts examines the way in which the postnormâle novel reclaims social discourses of sexual difference for a mass audience while subtly displacing realist conventions in order to inscribe women s or lesbians experience of sexual conflict into the text. A four step process is used to study the work. First, I anchor the novels to a realist real , and study the function of detail within the postnormâle aesthetic. Then I chart the sociogram feminism in the novels and their reception. Thirdly, I read the narrative of what I call counter-rape , and lastly the inscription of woman-desire and the figuration the constitution even of entr elles, a feminist space. The perspective of my study is postmodern, which implies a suspension but not a disbelief of the twofold question of literary status and literary evaluation, in order to focus on texts in their contexts. In this process, I aim to rethink the link between the notions of the feminine and the queer in light of contemporary feminist and lesbian perspectives.
  • Styrman, Avril (Helsingin yliopisto, 2016)
    This doctoral dissertation introduces economical unification as a method of analysis and shows how it is applied in dealing with some topics that are central in contemporary philosophy. The method resembles a production line that consists of three successive elements which are interconnected in two stages: Economy > Ontology > Applications In the first stage, an economically unified ontology is explicated by applying the principle of economy, which is an evaluation criterion of alternative ontologies. An economically unified ontology is an empirically sufficient, metaphysically minimal and generally virtuous world-view or a belief system of a human being. In the second stage everything else is dealt with in terms of the ontology. The central argument is that economical unification is a more progressive method than plain conceptual analysis which proceeds in the absence of an economically unified ontology and without the principle of economy. Its progressiveness results from having economy as an unambiguous evaluation criterion, which enables explicating a stable and minimal unified ontology which functions as a common base for all topics, and which enables defining and disambiguating meanings of concepts, thereby facilitating their genuine understanding and resolving problems around them, more efficiently than without an economically unified ontology, and without an unambiguous evaluation criterion that would enable explicating it. The progressiveness of the method is substantiated by applying it in disambiguating some of the central concepts that are dealt with in contemporary philosophy such as time, truth and possibility, and in resolving problems around them. The method works: unification efficiently resolves problems whose central source is disunification itself. In other words, the absence of an economically unified ontology is a central source of problems and ambiguities in contemporary philosophy; in economical unification such problems are resolved by removing their source; their source is removed by replacing the absence of an economically unified ontology by bringing it in the center of the analysis. The holistic method that handles special topics in the top-down order by relying on an understandable world-view, is very different from traditional conceptual analysis that proceeds in the absence of an economically unified ontology, and even in the absence of having it as the goal, i.e., without economy or the degree of virtuousness as the criterion. Moreover, the method was formulated in order to systematically overcome those limitations of plain conceptual analysis which result from their absence. Traditional conceptual analysis proceeds typically by investigating isolated topics and various angles to them, but this does not manage to interconnect the isolated topics and thus does not resolve problems which are due to the isolation itself. It is practically impossible to unify many things by concentrating on one thing only, and the optimal rate of progress in philosophy and in science in general cannot be achieved if the analysis is limited into investigating isolated fragments. In order to achieve the optimal rate of progress, unification is needed in counterbalancing specialization. By looking at many individual pieces together, one can start streamlining them into a functional totality. In this process much is revealed about what kinds of parts are needed in the totality and what are not. The totality consists of interrelated parts, but in economical unification the overall picture of reality guides the development of its parts at least as strongly as the requirements for the parts guide the development of the totality. Economical unification can thus be seen merely as the project getting hold of the natural order where the totality and its parts interact, and whose alternative is to keep on investigating details of isolated parts blindfolded without worrying about their roles in a totality, for all parts that are applicable do have a role in a totality. One can and one should scrutinize any suggested totality and replace it when a better one is available, but not before a better one has been presented. This holds for contemporary paradigmatic theories and for everything that comes after them. This brings the focus to the question of what is the objective meaning of better. The suggested answer is: the more economically unified, the better. The most important starting point in the project of economical unification is the acceptance of the principle of economy or the degree of virtuousness as the evaluation criterion, for without a commonly accepted and acknowledged criterion the path towards consensus is unnecessarily long and painful. The easiest way of accepting economy as the criterion is understanding that its general acceptance would accelerate the progress rate of science, including philosophy: virtuousness as the criterion of theories likely results into more virtuous science, faster than without it. Once we have a common criterion, people no longer have to settle on agreeing to disagree, but people have leaped forward into evaluating which theory is objectively better. Everything can be scrutinised, including economy, but rejecting it without replacing it with a more progressive criterion means that one does not fully appreciate progress.
  • Lampinen, Anita (Helsingin yliopisto, 2016)
    Angiogenesis, the growth of new blood vessels, is essential during embryonic development, but it is also involved in numerous human diseases, including cancer. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), as well as angiopoietin growth factors (Ang1, Ang2) together with their Tie1 and Tie2 tyrosine kinase receptors are essential regulators of angiogenesis and lymphangiogenesis. These endothelial specific pathways also control vascular permeability. Ang1 stimulates the translocation of Tie receptors into endothelial cell-cell contacts resulting in endothelial stabilization, while Ang2 stimulates tumor angiogenesis, metastasis and vascular leakage, and Ang2 expression is elevated in several diseases, including cancer. VEGF-targeted therapies have been in clinical use for more than a decade, whereas Ang-Tie targeted drugs are in clinical development for cancer. However, problems with anti-angiogenic therapies are associated with drug related resistance, and biomarkers that would predict patient responses are lacking. In this study, we focused to discover molecular mechanisms that regulate the Ang-Tie signalling system, and how this pathway functions during tumor metastasis and endotoxemia. Second, we sought to investigate Ang2 expression in human metastatic renal cell carcinoma (mRCC), and its potential as a biomarker for anti-angiogenic therapies. In summary, our results demonstrate that Tie1 is essential for angiopoietin signalling and vascular remodelling, by interacting with Tie2, within a distance of 10 nm, and regulating the subcellular trafficking of Tie2. Tie1-Tie2 interaction is dependent on the EC-extracellular matrix (ECM) adhesion receptor, alpha5beta1-integrin, and silencing of alpha5beta1-integrin inhibited also Tie receptor activation and downstream signalling. Second, a therapeutic anti-Ang2 antibody was found to promote vessel integrity and inhibit tumor metastasis, by inhibiting Ang2 binding to Tie2 and inducing internalization of the Ang2-Tie2 signalling complexes in ECs. Third, Ang2 expression was determined in the vasculature of RCC tumors, and correlated with clinical parameters, including response to anti-angiogenic therapy and survival. These results advance the current understanding of the function of the Ang-Tie pathway in the vasculature, and call for more thorough studies of Ang2 in human RCC.
  • Stolt, Sofia (Helsingin yliopisto, 2016)
    Finding the final grade - A study of evaluative remarks in grading comments for matriculation examination essays in Swedish as a mother tongue and literature The main purpose of the study is to illuminate evaluative remarks and an institutional interaction in a social context. The overall focus is on qualitatively demonstrating patterns of expression that censors, through attitude remarks, use in their grading of good and excellent matriculation examination essays in Swedish as a mother tongue and literature, as well as how these remarks fulfill an interpersonal function in the grading process. The matriculation examination in Finland constitutes an institutionalized writing practice and the censors can be seen as authoritative graders in this context. Through evaluative remarks in interaction with each other the censors show qualities of the matriculation examination essay or the author of the essay, which they as graders want to bring to light. Theoretically and methodically, the study follows the appraisal system, which makes it possible to analyse and examine rhetorical elements in texts as well as to look at the relation between the author and the reader. In this study appraisal is used to examine the censors comments on matriculation examination essays and the relations between grading comments. The study shows established patterns of writing practices and the result of the study should be seen as indicators of connections in grading comments. The results of the analysis shows that censors in their comments do not express their own emotions (AFFECT) but express values through the subsystems ENGAGEMENT and ATTITUDE mainly through appreciative remarks on the matriculation examination essay. In a dialogue with the other censors, they reference external sources such as standardized policy documents and the teacher s scoring; consensus in their grading is reached by collegial dialogue. Keywords: writing practice, institutional writing practice, grading, summative grading, evaluative remarks, appraisal, censor evaluative comments as dialogue, Swedish with a didactic alignment.
  • Kumpu, Minna (Helsingin yliopisto, 2016)
    Respiratory tract infections account for significant part of total illness episodes, physician consultations and days off from day care, school or work, thus incurring a significant personal and socio-economic burden. Viruses cause most of the acute infections of the respiratory tract, and there is lack of effective preventive and treatment options available against almost all of the over 200 different viral pathogens. Nutritional interventions are an increasingly researched option for reducing the infection burden, and of these probiotics are among the ones shown most promise. The aim of this work, consisting of three double-blind randomized controlled clinical trials in children and adults, was to investigate whether probiotic Lactobacillus rhamnosus GG would reduce the symptoms of respiratory tract infections and nasopharyngeal presence of respiratory viruses, as well as to explore factors hypothesized to have an impact on probiotic efficacy: the pharyngeal colonization of L. rhamnosus GG and the viability of the probiotic strain. In young adult tonsillectomy patients, L. rhamnosus GG was analysed from palatine tonsil samples and results compared to the faecal recovery of GG after three weeks daily consumption of placebo or L. rhamnosus GG as a single strain or as a part of a multispecies combination. L. rhamnosus GG was recovered in the tonsil tissue of 40% of the subjects in the GG group, 41% in the multispecies group and 30% in the placebo group. The results suggest that individual variation exists in the ability of the probiotic to adhere to the tonsil tissue, as the compliance of study product consumption was confirmed by the analysis of the faecal recovery of the strain and counting of leftover study products. Most of the subjects in the control group with L. rhamnosus GG harboured from the tonsil tissue had the strain recovered from the faecal sample already at the start of the intervention, indicating that persistent colonization could be a factor behind positive tonsillar recoveries in the control group. In a 28-week prospective trial on children aged 2 6 years attending day care in Finland, milk supplemented with L. rhamnosus GG was not able to reduce respiratory tract infections compared to the control group. Analysis on the completed cases subgroup, excluding subjects with intestinal L. rhamnosus GG colonization originating from outside the trial, suggested that children in the probiotic group had one day less per month with respiratory symptoms compared to the control group, but this exploratory finding warrants further research for confirmation. In a subgroup of children who visited the study physician due to an infection during the trial, the presence of 14 respiratory viruses was analysed from nasopharyngeal swab samples. L. rhamnosus GG did not reduce the occurrence of respiratory viruses, or the number of infection symptoms observed at the time of the viral findings. In this subgroup of more symptomatic children, subjects in the probiotic group had fewer days with respiratory symptoms than children in the control group, but number of study physician visits was not different between the groups, thus suggesting that L. rhamnosus GG might be able to reduce only the symptoms of the less severe infections treated at home in the more symptomatic subjects. The potential of the experimental rhinovirus challenge model in studying probiotic efficacy in viral infections was tested in a 6-week trial on live and inactivated L. rhamnosus GG in adults. In this pilot study, the subjects were intranasally inoculated with experimental rhinovirus mid-intervention. Occurrence and severity of cold symptoms and number of subjects with positive rhinovirus culture and rhinovirus infection were the lowest in the group receiving live L. rhamnosus GG, but differences were not statistically significant. Taken together, L. rhamnosus GG was overall not effective in reducing the symptoms of respiratory tract infections, or occurrence of respiratory viruses in the nasopharynx of symptomatic children, but appeared to reduce symptoms in specific subgroups within the study cohort. It was demonstrated that L. rhamnosus GG can be recovered from the tonsil tissue of some but not all subjects after oral consumption, thus warranting future research on the role of the probiotic recovery in infection outcomes. The experimental rhinovirus model was demonstrated a potential controlled approach to studying the efficacy of probiotics, and the pilot study on the model indicated that live L. rhamnosus GG was more promising than the inactivated strain in reducing respiratory infections, but further research is needed to confirm the preliminary findings.
  • Luoma, Samrit (Helsingin yliopisto, 2016)
    This thesis clarifies the potential impacts of climate change and sea-level rise under future climate scenarios on groundwater recharge and surface leakage, and consequently on the groundwater vulnerability of a shallow, unconfined, low-lying coastal sedimentary aquifer in southern Finland. The study utilised multiple approaches, including field investigations, well monitoring, three-dimensional (3D) geological modelling, 3D groundwater flow modelling, multivariate statistical approaches (principal component analysis (PCA) and hierarchical cluster analysis (HCA)), the stable isotopes δ2H and δ18O, conventional hydrogeochemistry and groundwater intrinsic vulnerability assessment methods. The UZF1 model was coupled with the 3D groundwater MODFLOW model to simulate flow from the unsaturated zone through the aquifer. The well-calibrated groundwater flow model was used to simulate and predict the potential impacts of climate change on groundwater recharge under future climate and sea-level rise scenarios. The results indicate changes in the groundwater recharge patterns during the years 2071 2100, with recharge occurring earlier in winter and early spring. Because the aquifer is located in a cold snow-dominated region, the seasonal impacts of climate change on groundwater recharge were more significant, with land surface overflow resulting in flooding during the winter and early spring and drought during the summer. Rising sea levels would cause some parts of the aquifer to be submerged under the sea, compromising groundwater quality due to the intrusion of seawater. This, together with increased groundwater recharge, would raise the groundwater level and consequently contribute to more surface leakage. The groundwater geochemistry of the coastal aquifer in Hanko is very similar to that of inland shallow aquifers generally in Finland, where the groundwater is mainly of the Ca HCO3 type, with low dissolved element concentrations, low pH and alkalinity, and low Ca and Mg concentrations due to rapid percolation or the short residence time. The stable isotopes δ2H and δ18O clearly suggest that the Hanko aquifer recharges directly from meteoric water (snowmelt and rainfall), with minor or insignificant contributions from the Baltic Sea and surface water. However, the geochemistry of the groundwater suggests sulphate reduction in the mixed zone between freshwater and seawater, indicating that local seawater intrusion may temporarily take place, although the contribution of seawater was found to be very low. Further inland, the influence of surface water could be observed from higher levels of KMnO4 consumption in wells near the lake above the aquifer. The findings also demonstrated that the use of stable isotopes δ2H and δ18O alone to identify seawater aquifer interaction is not sufficient to determine the rate of water exchange. The high temporal variation in groundwater chemistry directly corresponded to groundwater recharge. With an increase in groundwater recharge, KMnO4 consumption, EC, alkalinity and Ca concentrations also increased in most wells, while Fe, Al, Mn and SO4 were occasionally increased during the spring after snowmelt under specific geological conditions. Based on the future climate scenarios, precipitation in the Hanko area is expected to increase and the Baltic Sea level to rise. This could cause increased recharge of the aquifer from surface water, but also some seawater intrusion due to the sea-level rise and storm surges, as well as increased groundwater abstraction. An increase in the concentrations of some dissolved elements and changes in groundwater geochemistry along the coastline can be expected in the future. Thus, in coastal aquifers with low hydraulic gradients, the hydrogeochemistry should be used to confirm the intrusion of seawater. The PCA and HCA multivariate statistical approaches are useful tools to extract the main components that are able to identify the vulnerable areas of the aquifer impacted by natural or human activities, either on regional or site-specific scales. The integration of PCA and HCA with conventional classification of groundwater types, as well as with the hydrogeochemical data, provided an understanding of the complex groundwater flow systems, supporting aquifer vulnerability assessment and groundwater management in the future. The degree of groundwater vulnerability in the Hanko aquifer has been greatly impacted by seasonal variations in groundwater recharge during the year, and will also vary depending on climate change variability in the long term. The potential for high groundwater vulnerability to contamination from sources on the ground surface occurs during the period with a high groundwater recharge rate after snowmelt, while high vulnerability to seawater intrusion could occur when there is a low groundwater recharge rate in the dry season. This thesis study highlighted the importance of the integration of groundwater vulnerability assessment methods for shallow, unconfined, low-lying coastal aquifers from a comparison of three intrinsic vulnerability mapping methods: the AVI, a modified version of SINTACS and the GALDIT method. The modified SINTACS could be used as a guideline for groundwater vulnerability assessment of glacial and deglacial deposits in inland aquifers, and in combination with GALDIT, it could provide a useful tool for assessing groundwater vulnerability to both contamination from sources on the ground surface and to seawater intrusion for shallow, unconfined, low-lying coastal aquifers under future climate change.