Väitöskirjat

Recent Submissions

  • Kanerva, Kaisa (Helsingin yliopisto, 2019)
    Working memory (WM), a limited cognitive storing and processing mechanism for information, explains individual differences in scholastic learning and, more generally, complex cognition. One dominant view explaining these relationships proposes that variation in WM capacity reflects individual differences in general attentional processes. However, some models propose, that there are also domain-specific aspects in WM that explain variation in cognitive skills. Present series of four studies explored the nature of the mechanisms explaining the close relation between WM and scholastic skills in 5–16-year-old children and adolescents. A total of 1069 subjects participated in the studies. Studies I and II investigated whether the individual differences in the general cognitive capacity are sensitive to external or internal distraction. In Study I the natural environmental noise at the classroom during WM assessment was documented (external distraction). In Study II the complexity of the WM task was manipulated (task’s internal distraction). The contribution of the distraction in the memory scores and in the correlation between WM and scholastic skills was explored. Studies III and IV, in turn, aimed at investigating whether this relationship is causal, that is, whether the training of domain-general WM capacity or domain-specific counting skills, or both, would enhance children's WM and emergent mathematical skills. In two interventions lasting four to five weeks, domains of WM components (verbal WM and short-term memory, STM; visuospatial WM and STM; Study III) and domains of outcome (counting, combined WM and counting; Study IV) were addressed. The results of Studies I and II showed that environmental distraction and task demands contributed the relationship between WM and scholastic skills manifesting the individual differences more clearly. The cognitive constructs assessed appeared to be highly overlapping. However, the results of Studies III and IV indicate that while WM has an important role in scholastic skills, the computerised training of different WM domains did not lead to improvement in numeracy. Despite the lack of such training effects, the group-based interventions addressed to the skill of interest, in this case numeracy, enhanced these skills. Taken together, the present results suggest that while attentional load contributes substantially to individual differences in WM capacity by restricting the mental workspace, the acquired long-term memory representations are needed in order to apply the WM capacity in scholastic learning. The results of the present thesis can be applied in regognising the cognitive deficits that hinders children's scholastic learning, and in developing interventions that benefit scholastic skills.
  • Sun, Yu (Helsingin yliopisto, 2019)
    Fossil evidence suggests that liverworts may have existed already in the Ordovician. The long-standing hypothesis, that widely disjunct geographic ranges of various extant liverwort groups have been largely resulted from vicariance events from fragmentation of widespread ancestors through tectonic plate movements, has been challenged by the recent studies based on molecular data. In this thesis, two groups of the leafy liverworts in the order Jungermanniales were investigated in order to better understand the phylogenetic relationship and biogeography of liverworts. They are the family Schistochilaceae ranging mostly in the Southern Hemisphere, and the cosmopolitan genus Herbertus of family Herbertaceae. Both families possess a diverse morphology and wide disjunct distribution. The phylogeny and biogeographic history of Schistochilaceae and Herbertus were studied by using DNA sequence data of chloroplast and nuclear gene regions. Morphological characters used for species delimitation were also studied and re-evaluated. Schistochilaceae is resolved as monophyletic being one of the early derived leafy liverwort groups. The phylogenetic position of the Chilean endemic Pleurocladopsis simulans is resolved within the genus Schistochila and the new combination Schistochila simulans (C. Massal.) Xiao L. He & Yu Sun is made. Schistochilaceae is inferred to have originated in the Late Cretaceous at c.100 Mya, in an ancestral area including southern South America, West Antarctica and New Zealand. New Zealand was recognized as the early divergence and dispersal center, most dispersals were transoceanic. Herbertus is resolved as a monophyletic group with one clade consisting of the southern hemispheric taxa Herbertus runcinatus, H. oldfieldianus, and H. juniperoideus, and the other including species of H. sendtneri complex and of H. aduncus complex, mostly belonging to the Northern Hemisphere. H. armitanus and H. circinatus were synonymized with H. sendtneri. H. borealis, H. buchii, H. delavayi, H. dicranus, H. kurzii, H. longifissus, H. norenus and H. stramineus were synonymized with H. aduncus. Herbertus is inferred to have originated in the Cenozoic era about 51 Mya, in an ancestral area including southern South America, the Neotropics, Oceania, and Southeast Asia, supporting its Gondwanan origin. In the Southern Hemisphere the distribution pattern of Herbertus is characterized by in situ persistence and did not show further dispersal until the uplift of the Andean Cordillera. Herbertus in the Northern Hemisphere showed more recent diversifications, wide range expansions both north- and southward and repeated recolonizations, and the range shifts had occurred more frequently since the late Miocene. Long-distance dispersal has played an important role in the formation of the global distribution pattern of the genus. Our obtained phylogenies of liverworts all resolved the New Zealand endemic Herzogianthus vaginatus as the first diverged lineage in the Jungermanniales, not supporting its current placement in the Ptilidiales. Our study supports the southern temperate origins for both Schistochilaceae and Herbertus, and most of the diversification occurred in the Cenozoic, a pattern that has been shown to occur also in other leafy liverwort groups. Our results suggest that species with separate sexes do not constrain long-distance dispersal. The causes for the formation of current geographical ranges of liverworts seem to be manifold, likely linked with ecophysiology, lineage age, dispersibility and diversification rate.
  • Wang, Jinhui (Helsingin yliopisto, 2019)
    The phloem-limited bacterial pathogen ‘Candidatus Liberibacter solanacearum’ is known to cause several economically important plant diseases. Among the distinct haplotypes in ‘Ca. Liberibacter solanacearum’, haplotypes A and B are associated with zebra chip disease in potato, haplotype C is associated with carrot yellowing disease, and haplotypes D and E are associated with disease in carrot and celery. However, the vector-transmitted and unculturable nature of ‘Ca. Liberibacter solanacearum’ has limited the use of many conventional microbiological methods and advanced molecular biological techniques. Current understanding of the pathogenesis of ‘Ca. Liberibacter solanacearum’ and the pathophysiology of infected host plants is still very limited. In this study, a series of experiments were designed and implemented to improve our understanding of those aspects. Multi-omic approaches, high-throughput sequencing technologies and bioinformatic analysis were fully integrated in this research. Metagenomic sequencing was applied to obtain the genome sequence of ‘Ca. Liberibacter solanacearum’ haplotype C in Finland. Two draft genome sequences of haplotype C, FIN114 (1.24 Mbp) and FIN111 (1.20 Mbp), were obtained from carrot psyllids (Trioza apicalis) harbouring ‘Ca. Liberibacter solanacearum’. Genome comparison between haplotypes A, B and C revealed that prophages were involved in most of the genome rearrangement events. Comparison of the gene content between haplotypes revealed that the core and pan-genomes of ‘Ca. Liberibacter solanacearum’ consisted of 885 and 1327 orthologue groups, respectively. Orthologue groups putatively involved in host specificity associated with a certain haplotype were also identified. Twenty-seven orthologue groups were only present in haplotype C, while 11 orthologue groups shared by haplotypes A and B were absent from haplotype C. Based on the obtained genomic sequences, a finer genotyping system was designed and applied to the study of genetic variations of ‘Ca. Liberibacter solanacearum’ in Finland. Two sub-clades of haplotype C were characterized through the MLST approach. One sub-clade was associated with T. anthrisci and its primary host, Anthriscus sylvestris, and the other sub-clade was associated with T. apicalis and carrot. A novel haplotype was identified in the psyllid T. urticae and the stinging nettle Urtica dioica in Finland, named haplotype U. This was the first study to identify the presence of ‘Ca. Liberibacter solanacearum’ in the family Urticaceae. Phylogenetic analysis suggested that haplotype U was closely related to A and D and haplotype D was more closely related to A than to C. Dual RNA-Seq was applied to study the interaction between ‘Ca. Liberibacter solanacearum’ haplotype C and carrot plants at 4, 5 and 9 weeks after inoculation. ‘Ca. Liberibacter solanacearum’ infection significantly suppressed many genes involved in photosynthesis and chloroplast function, while genes related to defence response and phenolic compounds were up-regulated. A gene encoding the master regulator HY5 was constantly down-regulated in all the infected samples. Many genes involved in jasmonate biosynthesis were up-regulated in the infected samples, while genes related to the biosynthesis of other plant hormones showed complex differential expression at different time points. However, ‘Ca. Liberibacter solanacearum’ infection seemed to have a sustained impact on the expression of the key regulators of plant hormone signalling. Key regulators such as JAZs in jasmonate signalling, CTR1 in ethylene signalling and PP2Cs in abscisic acid signalling were all significantly altered by the infection. The bacterial gene encoding salicylate hydroxylase showed stable expression in ‘Ca. Liberibacter solanacearum’ at all the time points, which suggests that the bacteria were able to reduce the concentration of salicyclic acid in the host carrot plants. The proliferation of ‘Ca. Liberibacter solanacearum’ was very active at the early time point, as indicated by the high expression levels of genes related to the basic bacterial cell cycle, including replication, transcription and translation. ‘Ca. Liberibacter solanacearum’ appeared to have reduced mobility and increased adherence at the late time point examined, as the Flp pilus genes were expressed at high levels. A major change in the use of energy sources was identified between the early and late time points in ‘Ca. Liberibacter solanacearum’. A gene involved in the uptake of ATP was more actively expressed at the early time point, whereas genes related to the uptake and metabolism of C4-dicarboxylate were more actively expressed at the late time point, suggesting an adjustment in the acquisition and utilization of energy and carbon sources. This study provides novel information about the genome structure and genetic differences of ‘Ca. Liberibacter solanacearum’ and its interactions with its host plant.
  • Kumar, Ashwini (Helsingin yliopisto, 2019)
    This thesis is comprised of three studies demonstrating the application of different statistical and bioinformatic approaches to address distinct challenges of implementing precision medicine strategies for hematological malignancies. The approaches focus on the analysis of next-generation sequencing data, including both genomic and transcriptomics, to deconvolute disease biology and underlying mechanisms of drug sensitivities and resistance. The outcomes of the studies have clinical implications for advancing current diagnosis and treatment paradigms in patients with hematological diseases. Study I, RNA sequencing has not been widely adopted in a clinical diagnostic setting due to continuous development and lack of standardization. Here, the aim was to evaluate the efficiency of two different RNA-seq library preparation protocols applied to cells collected from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. The poly-A-tailed mRNA selection (PA) and ribo- depletion (RD) based RNA-seq library preparation protocols were compared and evaluated for detection of gene fusions, variant calling and gene expression profiling. Overall, both protocols produced broadly consistent results and similar outcomes. However, the PA protocol was more efficient in quantifying expression of leukemia marker genes and drug targets. It also provided higher sensitivity and specificity for expression-based classification of leukemia. In contrast, the RD protocol was more suitable for gene fusion detection and captured a greater number of transcripts. Importantly, high technical variations were observed in samples from two leukemia patient cases suggesting further development of strategies for transcriptomic quantification and data analysis. Study II, the BCL-2 inhibitor venetoclax is an approved and effective agent in combination with hypomethylating agents or low dose cytarabine for AML patients, unfit for intensive induction chemotherapy. However, a limited number of patients responding to venetoclax and development of resistance to the treatment presents a challenge for using the drug to benefit the majority of the AML patients. The aim was to investigate genomic and transcriptomic biomarkers for venetoclax sensitivity and enable identification of the patients who are most responsive to venetoclax treatment. We found that venetoclax sensitive samples are enriched with WT1 and IDH1/IDH2 mutations. Intriguingly, HOX family genes, including HOXB9, HOXA5, HOXB3, HOXB4, were found to be significantly overexpressed in venetoclax sensitive patients. Thus, these HOX-cluster genes expression biomarkers can be explored in a clinical trial setting to stratify AML patients responding to venetoclax based therapies. Study III, venetoclax treatment does not benefit all AML patients that demands identifying biomarkers to exclude the patients from venetoclax based therapies. The aim was to investigate transcriptomic biomarkers for ex vivo venetoclax resistance in AML patients. The correlation of ex vivo venetoclax response with gene expression profiles using a machine learning approach revealed significant overexpression of S100 family genes, S100A8 and S100A9. Moreover, high expression ofS100A9was found to be associated with birabresib (BET inhibitor) sensitivity. The overexpression of S100A8 and S100A9 could potentially be used to detect and monitor venetoclax resistance. The combination of BCL-2 and BET inhibitors may sensitize AML cells to venetoclax upon BET inhibition and block leukemic cell survival.
  • Tomberg, Eemeli (Helsingin yliopisto, 2019)
    Cosmic inflation is a hypothetical period in the early universe, where the expansion of space accelerated. Inflation explains many properties of the observed universe, but its cause is not known. Higgs inflation is a model where inflation is caused by the Higgs field of the Standard Model of particle physics, coupled non-minimally to gravity. In this thesis, we study various aspects of cosmology with Higgs inflation. Inflation leaves marks on the cosmic microwave background radiation, and these marks can be used to distinguish inflationary models from each other. We study hilltop Higgs inflation, a model where quantum corrections produce a local maximum into the Higgs potential, and show that there the predicted tensor-to-scalar ratio is less than or equal to 1.2 × 10^-3. This is smaller than the prediction of tree-level Higgs inflation by a factor of four or more and can be probed by next-generation microwave telescopes. We also study reheating, the process where the universe transitions from inflation to radiation domination with a thermal bath of relativistic Standard Model particles. We show that in Higgs inflation, reheating is particularly efficient in the Palatini formulation of general relativity, because there Higgs bosons are produced violently by a tachyonic instability. The duration of reheating affects, for example, the predicted spectral index of the primordial perturbations. Finally, we discuss the production of primordial black holes in Higgs inflation. We show that large quantities of such black holes can be produced, but in order to satisfy observational constraints on large scales, they must be so small that they would have evaporated by now by Hawking radiation. However, if the evaporating black holes left behind Planck mass relics, these could constitute part or all of the dark matter, the dominant, unknown matter component of the universe. Together, these studies show that even though the ingredients that go into Higgs inflation are simple, they lead to a rich phenomenology and offer valuable insights into inflation, gravitational degrees of freedom and the origin of dark matter.
  • Leinonen, Jaakko (Helsingin yliopisto, 2019)
    Over the past decade, advances in genetics have led to identification of thousands of genetic loci in the human genome that contribute to complex traits such as the timing of pubertal onset. Following genome-wide association studies (GWAS), we currently know how a large proportion of the heritability of complex traits can be explained by common genetic variation in these loci. However, in many instances, we understand relatively little about the biology behind these genetic associations, and functional characterization of genetic variation has become a new bottleneck for genetic research. Prior to this thesis project, sequence variants nearby lin-28 homolog B (LIN28B) had become associated with pubertal timing in the general population. Remarkably, compared to all other common genetic variants, the variants in the LIN28B locus appeared to exert relatively large effects on pubertal timing: one pubertal timing advancing allele associating with ~1,5 months advancement in age at menarche (AAM) in females. Yet, the gene showed little evidence of affecting the established mechanisms behind pubertal onset. Exploring the molecular mechanisms by which LIN28B affects puberty therefore became the focus of this thesis, which is is founded on three original studies addressing the function of LIN28B. To move beyond the original GWAS results, we first utilized Finnish population cohorts to assess the potential pleiotropy of the gene in terms of body size and adult health. The second original study combined human gene expression data from the GTEx database with zebrafish models, evaluating the consequences of transient dysregulation of lin28b during embryogenesis. For the third study, we first created lin28b knockout zebrafish with CRISPR-Cas9 technology to evaluate the effects of permanent lin28b knockout, and utilized the GTEx data and the UK biobank resource to study whether LIN28B contributes to sex steroid signaling in humans. The results presented in this thesis suggest that LIN28B has pleiotropic actions on vertebrate phenotypes and may contribute to the timing and tempo of human growth in more complex ways than originally thought. Our studies demonstrate that the gene associates with variation in several body size parameters in adult humans, although showing little evidence of affecting metabolism. The results also suggest that the effects that LIN28B has on body size are evolutionarily conserved. Overexpression of lin28b during embryogenesis appears to stimulate zebrafish growth, and, intriguingly, lin28b knockout zebrafish show similar growth patterns as humans that carry sequence variants linked with lower LIN28B expression. Importantly, the data presented in this thesis indicates that the sequence variants associating with pubertal timing affect LIN28B expression mostly in the hypothalamus and the pituitary of adult humans. These changes in the LIN28B expression level may have further consequences: LIN28B expression at the hypothalamic-pituitary (HP) axis seems to correlate positively with the expression of several hormonal genes like ESR1 and POMC. Highlighting the gene’s potential to contribute to sex steroid signaling, we finally associated LIN28B with the regulation of testosterone levels in adult humans, which might be relevant in terms of explaining many of the GWAS associations including pubertal timing. Overall, the results presented in this thesis offer novel insight into LIN28B function in pubertal timing, disease and development, the project simultaneously serving as an example for follow-up studies of GWAS loci in general.
  • Iyer, Siddharth (Helsingin yliopisto, 2019)
    Understanding the gas-phase chemistry of secondary organic aerosol (SOA) formation is critical for accurate estimation of the effect of these aerosol on Earth's radiative balance. Additionally, the direct detection of the precursor molecules involved in these chemical reactions at atmospheric pressure without pre-treatment is valuable. In this work, computational and experimental methods are employed to 1) elucidate the thermodynamics and the mechanisms of selected key radical-radical reactions in the atmosphere and 2) investigate the efficiency of some of the chemical ionization mass spectrometry methods in detecting the atmospherically relevant acids and precursor compounds involved in the formation of SOA. The main oxygen containing radical species in our atmosphere, and also the key focus of this study, are hydroxy (OH), hydroperoxy (HO2), alkoxy (RO) and peroxy (RO2) radicals. Our computational study on the favorability of the radical recycling product channels of RO2 + HO2 and RO2 + RO2 reactions (RO + OH + O2 and RO + RO + O2, respectively) for RO2s derived from the oxidation of a set of the highest globally emitted monoterpenes showed that the two reactions were thermodynamically favorable for all the studied systems, and that for some of them, especially the O3 oxidized systems, the rate-limiting transition state energies can be low enough to render the reactions competitive in atmospheric conditions. Peroxy radical reactions with the atmospheric oxidant OH and alkoxy radicals RO were found to first form a trioxide adduct (ROOOH and ROOOR, respectively). While the former rapidly decompose to RO + HO2 and R(O)OH + O2 products for the model β-oxo and acetyl RO2 systems, respectively, the ROOOR adducts from the latter can have lifetimes in the range of 10 - 100 s (for the homo and hetero alkyl and β-oxo systems). If the reacting RO2 and RO radicals are sufficiently large and oxidized, the product adducts can directly be involved in SOA formation. The modeling of iodide-based chemical ionization mass spectrometer (iodide-CIMS) using computational methods showed that relatively low-level computational theory can produce reasonable correlation between molecule•I- cluster binding enthalpies and iodide-CIMS instrumental sensitivities. While some outliers were observed (lower than expected binding enthalpies for clusters that were detected at the maximum possible sensitivity of the instrument, for example), the method outlined in our study can be a quick indicator of the detectibility of an analyte by an iodide-CIMS. Additionally, the direct detection of the HO2 radical experimentally using an iodide-CIMS was demonstrated. The comparison of iodide- and nitrate-CIMS spectra for a cyclohexene ozonolysis experiment showed that the iodide-CIMS method was capable of detecting the less oxidized (oxygen:carbon O/C ratio of 0.5 - 0.66) molecules more efficiently than nitrate-CIMS. Higher oxidized molecules (O/C ratio 1 - 1.5) were detected equally well by both methods. Finally, the use of a new chemical ionization inlet (Multi-scheme chemical IONization inlet, MION, Karsa Ltd, Helsinki, Finland), which is capable of switching between two different reagent ions, bromide and nitrate, in 1 s timescales was demonstrated and used to detect the ozonolysis products of cyclohexene and α-pinene. The successful demonstration of the MION inlet opens up the possibility to use multiple CIMS methods concurrently and detect a widest possible range of volatile organic compound (VOC) oxidation products.
  • Kaira, Terhi (Helsingin yliopisto, 2019)
    This doctoral dissertation in the sociology of the church examines strategic thinking in the Evangeli-cal Lutheran Church of Finland since the turn of the millennium. The dissertation answers the following research questions: What kind of strategic thinking can be seen in the Evangelical Lutheran Church of Finland? How has this strategic thinking evolved? What are the opportunities for and obstacles to strategic thinking? The research material comprises 39 approved strategy documents of the church and aggregated survey data from two parish vicars. The study focuses on the church as a whole, its areas of work, dioceses, and parishes. The study adopts a classical strategy theory approach. Particular attention is paid to the strategies’ content. The study’s results present a material analysis of the characteristics of the church’s strategic thinking as a whole, consisting of 29 different elements. Each element of strategic thinking describes the church’s identity, strategic choices or strategy processes. The results show that the church is striving through its strategies to justify, reinforce, and maintain the essential features of its community identity. Through its visions and choices, the church’s strategic thinking attaches itself to an understanding of the dynamism and emergent causes of reality. In making its strategic choices, the church appears to be following its own timetable and seeking reform. The study suggests that the church’s strategic thinking is characterised by trust in leadership and protection. There is a hopeful attitude concerning the future. Strategy processes have evolved over the reviewed period in a more open direction. The church’s common strategy serves as a framework for other church administration strategies. Although a common strategy clearly guides its overall planning process, the church’s strategic thinking is characterised by each actor’s freedom and a broad strategic leeway. The study reveals that the church’s strategic thinking not only evinces a strongly classical approach to strategy but also a processual, systemic, and evolutionary approach. The study therefore reinforces the notion that strategy-theoretical approaches do not appear to be distinct, but rather blend with and complement one another. Keywords: strategic thinking, the church’s community identity, future work, vision and choices, change.
  • Karkulahti, Ossi Mikael (Helsingin yliopisto, 2019)
    The amount of user-generated web content has grown drastically in the past 15 years and many social media services are exceedingly popular nowadays. In this thesis we study social media content creation and consumption through large volume measurements of three prominent social media services, namely Twitter, YouTube, and Wikipedia. Common to the services is that they have millions of users, they are free to use, and the users of the services can both create and consume content. The motivation behind this thesis is to examine how users create and consume social media content, investigate why social media services are as popular as they are, what drives people to contribute on them, and see if it is possible to model the conduct of the users. We study how various aspects of social media content be that for example its creation and consumption or its popularity can be measured, characterized, and linked to real world occurrences. We have gathered more than 20 million tweets, metadata of more than 10 million YouTube videos and a complete six-year page view history of 19 different Wikipedia language editions. We show, for example, daily and hourly patterns for the content creation and consumption, content popularity distributions, characteristics of popular content, and user statistics. We will also compare social media with traditional news services and show the interaction with social media, news, and stock prices. In addition, we combine natural language processing with social media analysis, and discover interesting correlations between news and social media content. Moreover, we discuss the importance of correct measurement methods and show the effects of different sampling methods using YouTube measurements as an example.
  • Rapo-Pylkkö, Susanna (Helsingin yliopisto, 2019)
    Background Chronic pain is a common reason for primary care consultations in older community-dwelling adults. Chronic pain is often related with multimorbidity and may compromise patient’s independency and quality of life. Neuropathic pain (NP) causes a more severe burden than nociceptive pain in patients. Prognosis of chronic pain and NP in older adults is unknown. As the population is ageing, the cost and impact of chronic pain are becoming increasingly significant. Objective The focus of this study was to map the occurrence, characteristics and consequences of chronic pain and neuropathic pain in community-dwelling older adults in three age groups (75, 80 and 85 year olds). Methods Independently living older adults were screened for chronic pain during preventive home visits in 2009-2013 in Kirkkonummi, Finland. Patients with chronic pain (duration > 3 months) with average pain intensity and / or interference of > 4 on the NRS 0-10 scale during the week prior to the visit were invited to participate in the study. During the preventive home visits, 106 patients were recruited to the study. During the clinical study visit, a nurse interviewed the patients regarding their pain. The geriatrician then performed a clinical evaluation. One-year postal follow-up survey was conducted afterwards. Results Based on the data collected during the preventive home visits, older adults with chronic pain rated their health and mobility worse, and felt sadder, lonelier and more tired than those living without chronic pain. However, older adults with chronic pain rated their life satisfaction similarly to those without chronic pain. Most of the participants had more than one pain state, and the worst pain in 83% was musculoskeletal. The worst pain was purely nociceptive in 58% and combined nociceptive and NP or purely NP in 40% of participants. Regular pain medication, most commonly paracetamol or NSAIDs, were used by 77%. Only a fifth of the patients with NP were taking recommended medication. Use of non-pharmacological treatments was also common; 75% named at least one non-pharmacological method to alleviate pain. Chronic pain did not compromise participant independence in the one-year follow-up. Conclusions Chronic pain is often a combination of multiple conditions in community-dwelling older adults. Subjective health and mobility are impacted and worsened in those with chronic pain, however life satisfaction remains similar to those without pain.
  • Leisti, Tuomas (Helsingin yliopisto, 2019)
    Academic psychology has traditionally considered subjective explanations for judgments and decisions unreliable or even fabricated. Additionally, explanations have been shown to interfere with judgment and decision making processes, which can degrade the quality of choices. These phenomena have been attributed to the lack of conscious access to the decision making processes. Explaining is assumed to shift the processing from the non-conscious mode into a more verbalized and conscious mode, leading to either fabrication or interference. This dissertation examines these effects by assuming that subjective experience is a highly relevant intermediate processing stage in decision making, whereas subjective explanations reflect the contents of socially oriented conscious thought, which originates from the metacognitive understanding related to the judgment and decision-making processes. When subjective experience and conscious thought are dissociated, interference or fabrication can occur. The dissertation presents the ideas underlying the Interpretation-Based Quality (IBQ) method, which emphasizes the special nature of subjective experience in judgments and decisions: Every individual has his or her own subjective point of view, from which the world is interpreted. In the context of preferential judgment and decision making, these differences between individuals, arising from different ways of experiencing the world, are easily regarded as measurement error. The IBQ method approaches these differences by asking research participants to explain their decisions in their own words. These explanations have been further analyzed qualitatively in order to find the relevant subjective dimensions on which decisions are based. As subjective explanations are used as data, the use of the IBQ method must respond to claims concerning unreliability, fabrication and interference. Therefore, four studies were conducted to test these claims in the evaluation of high image quality. As explaining has been found to shift processing into a more conscious mode, these studies also inform about the role of conscious thought in judgments and decisions. The general finding of this research was that conscious thought, evoked by the requirement to explain judgments, can also enhance the decision maker’s performance in cases that require tradeoffs, effortful information search and consistency over several decisions. The results suggest that when conscious thought and subjective experience work in concert, subjective explanations can provide highly useful qualitative data about the dimensions of subjective experience that are relevant in judgments and decisions. These dimensions are dependent on personal and contextual factors and cannot be predicted from physical data alone. The importance of conscious thought in decision making appears to be its ability to bring relevant information into consciousness by means of voluntary attention. This happens particularly in conflicts and when the decisions are novel. In these situations conscious thought and an analytic approach is activated automatically. This mechanism derives from metacognitive understanding, which is learned gradually in similar judgment and decision-making situations.
  • Väyrynen, Katja (Helsingin yliopisto, 2019)
    Late first-row transition metals, namely copper, nickel, and cobalt, are pivotal materials in many modern and future applications. Because of its low resistivity, Cu has for long been the metal of choice for interconnects in microelectronic devices. Co is needed in the smallest features of the 10-nm technology node interconnects, as it is more robust than Cu toward electromigration, a phenomenon causing damage to the interconnects. Being ferromagnetic, Co and Ni are in the focal point of developing faster and more durable magnetic memories capable of handling the exponentially increasing amounts of data being generated annually. The development of faster yet smaller electronic devices requires a constant increase in computational power. To improve the performance without increasing device size, the components on integrated circuits should be shrunk and packed more closely. The shrinking is achieved by using thin films with nanoscale thicknesses preferably arranged in three-dimensional forms. For downscaling to continue, accurate thin film deposition methods are needed. Atomic layer deposition (ALD) provides atomic level accuracy and is thus the number one thin film deposition technique for modern and future devices. ALD is based on a cyclically repeated alternate supply of gaseous precursors that react on a substrate and form a uniform layer of material, atom by atom, even on complex three-dimensional structures. ALD is based solely on chemistry; to benefit from the many advantages the method has to offer, suitable precursors must first be found for each of the desired materials. ALD has been employed to deposit a myriad of materials ranging from pure elements to, for example, oxides, nitrides, and chalcogenides, but the deposition of metals has been hindered by a lack of reactive precursors and reducing agents. Thermal ALD processes exist mostly for noble metals, but mere thermal activation has often proven insufficient for the reduction of the late first-row transition metals. The aim of this thesis was to find and develop new precursors and processes for the ALD of high-quality Cu, Ni, and Co thin films, thus promoting the development of better microelectronics. Within the scope of this thesis, several new metal precursors for the ALD of the late first-row transition metals were developed and tested. Out of all of them, the diamine adducts of Co(II) and Ni(II) chlorides showed the best performance in the ALD experiments. In addition to the new metal precursors, the focus of this thesis was also on finding more efficient alternatives for the conventional reducing agents, H2 and NH3. Tert-butylhydrazine showed high reactivity to produce Cu and Ni3N by ALD, providing significant improvement on film purity and resistivity over the existing processes. Tributyltin hydride, another powerful reducing agent, was studied for the ALD of Co and Ni. Instead of producing metallic Co or Ni, intermetallic Co3Sn2 and Ni3Sn2 were deposited unveiling a new field of ALD: the ALD of intermetallics. The same approach was also applied to the ALD of Ni2Ge thin films. Postdeposition reduction of the corresponding metal oxides and nitrides was also explored as an alternative route for the preparation of metal thin films.
  • Wang, Liang (Helsingin yliopisto, 2019)
    Mitochondria are a powerhouse for cells and a hub for numerous signaling pathways. Mitochondria are highly dynamic organelles, frequently changing their shape by shifting the balance of fusion and fission. Dysregulation in mitochondrial function or dynamics causes many human diseases. The sub-mitochondrial localization and biological function of 13 mtDNA-encoded proteins have been clearly characterized, while many novel nuclear-encoded mitochondrial proteins are yet to be discovered. To comprehensively determine the mechanisms of mitochondrial-related diseases, it is imperative to reveal cellular functions of key mitochondrial proteins essential for mitochondrial biogenesis, structure, function, and dynamics. In this thesis, we have identified two novel nuclear-encoded mitochondrial proteins in mammalian cells: the Bin-Amphiphysin-Rvs (BAR) protein FAM92A1 essential for regulation of mitochondrial membrane ultrastructure, and the GTP-binding protein GTPBP8 required for mitochondrial translation. Due to the critical roles of mitochondria in cell signaling and cell survival, mitochondria, especially mitochondrial proteins, are the potential drug targets for treatment of a wide spectrum of diseases. Thus, prickly zinc-doped copper oxide (Zn-CuO) nanoparticles (prickly NPs) are designed and synthesized for cancer therapy. In paper I, FAM92A1 localizes to the matrix side of the mitochondrial inner membrane through an N-terminal mitochondrial targeting sequence. Loss of FAM92A1 causes a severe disruption to mitochondrial morphology, ultrastructure, and membrane dynamics, impairing organelle bioenergetics. Furthermore, the purified recombinant FAM92A1 protein binds to model membranes through preferential binding to negatively charged phospholipids. After insertion into a lipid bilayer, FAM92A1 transforms spherical liposomes into narrow tubules. Importantly, the aberrant mitochondrial morphology and function caused by depletion of FAM92A1 can be rescued by wild-type FAM92A1, but only partially rescued by the FAM92A1 mutants with defects in membrane binding and remodeling activity. In paper III, GTPBP8 localizes to the mitochondrial matrix associated with the mitochondrial inner membrane. The N-terminal 46aa is indispensable for the mitochondrial localization of GTPBP8. Importantly, GTPBP8 exclusively interacts with the large subunit of mitochondrial ribosome. Genetic knockdown of GTPBP8 causes a significant reduction in the level of mitoribosomes, inducing defects in mitochondrial translation and mitochondrial bioenergetics. In paper II, the prickly NPs are very effective in inducing cell death of 3T3 and MCF-7 cancer cell lines. The prickly NPs efficiently accumulate in mitochondria, resulting in severe mechanic disruption to mitochondria and inducing cell apoptosis. Collectively, these studies reveal the biological functions of two previously uncharacterized mitochondrial proteins and an efficient nanoparticle cancer treatment by targeting mitochondria. These new findings elucidate the crucial relation between mitochondrial form and function, and hence, contribute to establishing the concept of membrane-mediated signaling in mitochondria. Furthermore, mitochondrial gene expression is critical for maintaining cellular homoeostasis. Therefore, the mitochondrial proteins and mitochondria per se are valuable potential drug targets for overcoming many mitochondrial diseases.
  • Saaripuu, Tuire (Helsingin yliopisto, 2019)
    In Finland, provisions concerning the identification of a person were laid down as recently as in 2009 when the Act on Strong Electronic Identification and Digital Signatures was enacted. Until then, the identification of a person had not been a recognised legal concept. Instead, it had served as one of the functionalities in various judicial transactions. The importance to identify a certain person has always been a relevant element for example in the law of obligation to ensure that responsible parties and their personal legal obligations in a legal act are recognised. In today’s world, it is important that the end users of electronic services can be identified and it is therefore essential that applicable legislation be put in place. The identification of a person is now defined in the context of strong electronic identification. In lex specialis, provisions are also given on requirements pertaining to electronic identification, digital signatures and other trust services. In many cases, the enacted standard level of strong identification is required. In electronic transactions based on identification, various judicial relationships can be recognised. Data protection and the protection of privacy are essential in and compulsory prerequisites of electronic transactions and they must be provided for in legislation. Service providers also keep registers of personal information and, according to European Union and Finnish legislation, they may be held liable in case any corrupt practices are discovered. This demand applies also to enacted strict liability. Parties’ legal positions are defined in the regulations and legal principles of contract law and tort liability law. A typical online transaction involves several parties operating simultaneously either in a contractual or some other legally binding relationship. Non-contractual relationships exist, too. In certain cases, compensation of financial loss is covered under the Tort Liability Act, in contractual relationships according to contractual liability. In electronic transactions, typical parties include the service provider issuing the identification and signature service, a customer using the service and a third party, in many cases a non-contractual party trusting the identity or signature the service provider. The third party, such as an end-user web service, is very often a party in a contractual relationship with the primary end user and special liability expectations have been enacted in the relationship towards the service provider. Liability questions vary and they can be recognised as strict liability, fault liability, contractual liability, or tort liability. In addition, administrative law plays an important role because public administration is responsible for issuing digital services. Identification and trust services are based on standardised and audited legal and technical requirements, which determine the status and obligations of the Trusted Third Party, digital trust services and the minimum level of cross-border identification on European level. The dissertation examines in detail legal issues concerning strong electronic identification and signatures and end-user services using these standardised methods. Most legal requirements are based on Regulation (EU) No 910/2014 of the European Parliament and the Council of 23 July 2014 on electronic identification and trust services for electronic transactions in the internal market and repealing Directive 1999/93/EC as well as on Finnish Act on Strong Electronic Identification and Trust Services (617/2009).
  • Sanmark, Enni (Helsingin yliopisto, 2019)
    Peritonsillar abscess (PTA) is the most common deep head and neck infection. PTA is considered to be a purulent complication of acute tonsillitis (AT), although the correlation between these two has not been proven. In recent decades, infection of minor peritonsillar salivary glands has been proposed to be behind the development of PTA. Smoking has been known to predispose patients to PTA, and poor dental hygiene has been hypothesised to control the course of the disease. Clarifying the aetiology of PTA would help physicians differentiate better the subtypes of PTA and plan the best treatment for the patient. Diagnostic tools to achieve this are lacking. Diagnosis of PTA is clinical and is based on a patient’s symptoms and clinical examination. No blood tests or imaging has been used routinely. Bacterial culture is a slow method and is not used in clinical decision-making. In the first study of this thesis, we compared bacterial findings of PTA between patients who had had a renewal and those who had not. Streptococcus anginosus group (SAG) was detected more often in the patients with renewal, compared to those without; however, no group A streptococcus was reported in patients with renewal. In addition, male patients over 40 years old had renewal episodes after a shorter period than other patients. In the second study, we histologically analysed the presence of peritonsillar minor salivary glands and inflammation patterns from the removed tonsils. In most (67.5%) of the tonsil specimens, minor salivary glands were identified, and we observed a greater periductal inflammation in patients with PTA compared to AT and chronic tonsillitis groups. In the third study, we collected AT and PTA patients and found a subgroup of PTA patients without any clinical signs of AT. PTA patients without tonsillar findings had significantly lower C-reactive protein (CRP) levels than PTA patients with tonsillar findings. They were also older than other patients suffering from PTA. In the fourth study, we compared salivary samples of the patients with AT, peritonsillitis, and PTA between themselves, and with healthy volunteers. No differences between groups were observed which could imply that the composition of oral bacterial microbiota may not have a significant effect on the development of PTA. Alcohol consumption, oral hygiene and smoking had no significant effect either on numbers or distribution of saliva bacteria. Our studies suggest that tonsillar infection is not always a pre-stage of PTA and support the hypothesis that infection of minor salivary glands, in some cases, causes PTA. We also showed that SAG predicts renewal of PTA, and it is found in older male patients with rapidly proceeding disease. By understanding the aetiology of PTA better, we could also identify patients with different aetiological factors and target treatment more accurately.
  • Dimitrova, Maria (Helsingin yliopisto, 2019)
    Magnetic fields alter the properties of molecules, affecting the electron distribution, the electron configuration and the molecular geometry. In weak magnetic fields, the changes are subtle. Electrons as charged particles placed in magnetic field start following specific pathways, giving rise to magnetically induced ring currents. They follow the contour of the molecule, as well as form vortices around certain molecular rings and chemical bonds. Strong ring currents arise near atomic nuclei due to the core electrons. Magnetically induced currents are a unique fingerprint of the molecular structure but they also serve as an indicator for electron delocalisation, aromatic properties and applicability in optoelectronics. Various organic molecules were investigated using the gauge-including magnetically-induced current density approach. It has been demonstrated that heteroatoms alter the ring-current pathways and the current strength, and thereby affect molecular aromaticity.The topology of Möbius systems has been shown to depend both on the twist of the molecular rings of a series of [40]annulenes, as well as on their spatial folding (writhe). The investigation of a series of toroidal carbon nanotubes showed helical current flow in one of the chiral molecules in the study, which is a pre-requisite for the generation of anapole moment when the molecule is placed in a magnetic field. Very strong magnetic fields beyond achievable on Earth cause major changes in the electron configuration of atoms and molecules. Orbitals with high angular momentum and high-spin configurations become lower in energy than the typical zero-field occupation. Weak magnetic fields can be studied as a perturbation to the zero-field Hamiltonian. However, as the field strength increases, the magnetic interaction becomes equally strong as the electrostatic one. The explicit treatment of the magnetic field strength involves the angular momentum operator in the \schr, thus leading to complex orbitals. Therefore, new quantum chemistry software is necessary. A benchmark study for the performance of a traditional implementation based on Gaussian-type orbitals versus a fully numerical code has been done at the \acl{hf} level. After determining the accuracy of the method, small hydrocarbon molecules have been investigated, which showed that they exist as bound molecules in high-spin configurations where only the core electrons of the carbon atom are paired.
  • Karsisto, Virve (Helsingin yliopisto, 2019)
    Wintertime weather conditions can be hazardous for road traffic. Icy roads and poor visibility caused by snowfall increase the accident risk. Accurate forecasting of road conditions is important, because reliable and precise forecasts help the road maintenance personnel to plan their operations accordingly. Well timed maintenance operations increase safety and enable economical savings as unnecessary actions can be avoided. Drivers can also adjust their route plan and driving behaviour appropriately when warnings of hazardous conditions are given well beforehand. Road conditions are forecasted in the Finnish Meteorological Institute (FMI) with specialized road weather model. Before executing the actual forecast, the model is first initialized by feeding it with observation data. The quality of this data is essential for forecast accuracy, as the forecast is greatly dependent of the initial model state. Road weather stations have traditionally been one of the main sources of information, but their density is sparse especially in rural areas. Road surface temperature can vary considerably across the road network, so observations should be done in dense enough spatial scale. Nowadays it is possible to gather real time information from vehicles. Mobile sources provide observations with high spatial density and thus facilitate detecting the road stretches most prone to freezing. However, the quality of mobile observations should be assessed before implementing them to the road weather forecasting systems. This dissertation aims to answer to two research questions. Firstly, it has been studied how to best use available surface temperature observations in the road weather model initialization. Secondly, it has been studied how differences in two road weather models' physics affect to the surface temperature forecast accuracy. A method called coupling was implemented to the FMI road weather model. The main idea of the method is to adjust the incoming radiation flux so that the modelled surface temperature fits to the last observed value. The results show that this method improves considerably the short range surface temperature forecasts. Mobile surface temperature observations done with Teconer RTS411 were compared to road weather station measurements to assess the mobile data quality. According to the results, the mobile observations were on average 0.62 ͦC warmer than the road weather station measurements at 0 ͦC and in dry conditions. It was found out that the difference between mobile observations and road weather station measurements was dependent on the road status. A calibration equation for mobile observations was developed using linear mixed models to get mobile observations more in line with road weather station measurements. The effect of the mobile observations to the road surface temperature forecast accuracy was studied. According to the results, using the mobile observations calibrated with the developed equation improved the accuracy of road surface temperature forecasts compared to a theoretical situation where there would not be other surface temperature observations available. However, for an area with a dense road weather station network the accuracy of forecasts assimilating mobile observations with correction were on par with the accuracy of forecast assimilating interpolated surface temperature values. Studying model physics and comparing behaviour of different models is beneficial for model development. In this work, the verification results of the FMI's and the Royal Netherlands Meteorological institute's (KNMI) road weather models were compared to each other. In addition, the model physics were studied to find out the reasons for differences in the surface temperature forecasts. The forecasts of the KNMI model were found to be slightly more accurate than the forecasts of the FMI model. Although the core physics of the models were rather similar, there were large differences in some physical parameters and the number and the thickness of the ground layers. Individual reason for the better performance of the KNMI model could not be found, as the effects of different physical properties eventually sum up to surprisingly similar modelled surface temperature values.
  • Karjalainen, Riikka (Helsingin yliopisto, 2019)
    Acute myeloid leukemia (AML) is a clonal disease of immature hematopoietic cells. Treatment of AML patients is based on conventional chemotherapy and stem cell transplantation, but the majority of patients still suffer from relapse and poor overall survival. A growing body of evidence suggests that the BM microenvironment plays an important role in protecting leukemic cells from drug-induced apoptosis, which consequently leads to accumulation of residual leukemic cells and eventual relapse. Although several factors are involved in leukemic cell-BM interactions, the exact mechanisms of these interactions and comprehensive knowledge of their impact on the activity of different drug classes is lacking. Better understanding of the molecular mechanisms of drug resistance could facilitate the development of improved treatment strategies, and means to monitor patients who are at risk for developing drug resistance. Modern technologies, such as RNA sequencing and proteomics, are widening our possibilities to learn more about the molecular basis of AML and to discover predictive biomarkers for therapy resistance. In study I, we evaluated the effect of stromal cell secreted soluble factors on ex vivo drug responses in AML. We comprehensively evaluated how mononuclear cells (MNCs) collected from AML patients respond to 304 different inhibitors in stromal cell-conditioned medium compared to standard cell culture medium. From this study, we discovered that the stroma-derived factors altered response to 12% (36/304) of the drugs. Amongst the drugs, sensitivity to BCL-2 inhibitor venetoclax was significantly reduced by the stromal conditions. In follow-up experiments, we found that this effect could be overcome by inhibition of activated JAK/STAT signaling. In study II, we investigated gene expression profiles that were associated with resistance to BCL-2 inhibitor venetoclax. Ex vivo and in vitro analyses of AML showed that high expression of S100A8 and S100A9 calcium binding family genes correlates positively with venetoclax resistance. In contrast, BET (bromodomain and extraterminal) inhibitor OTX-015 acted synergistically with venetoclax in resistant AML cell lines and patient samples. In study III, our aim was to determine the applicability of proteins in biomarker discovery. We compared marker panels from proteomic and microarray transcriptomic assays using reproducibility optimized test statistic (ROTS) in the context of AML dysregulated processes and networks. The analysis led to discovery of protein markers specific for AML using LC-MS/MS derived data. In summary, this thesis shows that JAK/STAT inhibitors can counteract BM stroma-mediated resistance to the BCL-2 inhibitor venetoclax. Furthermore, we discovered a gene expression profile that correlates with ex vivo venetoclax resistance in AML and provide evidence of AML-related biomarkers from a proteomics dataset.
  • Slavcheva, Adriana (Helsingin yliopisto, 2019)
    Academic networks and international academic mobility at every level are on the rise, yet the success of study time or research periods abroad are crucially dependent on appropriate communicative and social skills in the language of the target community, especially in spoken language. From the perspective of teaching German as a Foreign Language (GFL), one important issue is to determine what kind of linguistic and communicative skills and competences in academic German are required of somebody in order for him/her to be able to participate successfully in a foreign-language academic setting and how these skills and competences can be best acquired. The design and the implementation of appropriate target-oriented methodical-didactical approaches and materials for the development of those competences, however, require a detailed empirical research on academic German, also in comparison with other languages. With Bachmann/Palmer (1996), the textual competence can be considered as one basic component of the oral communicative language competence. From the perspective of the foreign language teaching, the use of connectors as cohesion-creating linguistic means is of particular relevance since they often cause difficulties for non-native speakers. Yet, there is still little empirical research on that crucial linguistic aspect in spoken academic language that could allow for systematic language training. One of the reasons for this was the lack of an empirical database. The corpus resources available for larger empirical research on spoken academic German were practically non-existent in the German corpus landscape at the beginning of this Ph.D. project. The dissertation aims at making a first step towards remedying this situation by analyzing the use of connectors in the spoken academic German based on comparable corpora. On the one hand, it discusses central questions of corpus methodology, information technology and legal issues regarding the construction of comparable multimodal and multilingual corpora, based on the scientific research done within the project GeWiss – German in comparison to English and Polish, and thus aims to provide orientation for the following corpus projects. On the other hand, it presents empirical studies on the use of connectors in the spoken academic language by native and non-native speakers of German based on the GeWiss corpus, which are expected to have far-reaching consequences for the teaching of GFL at universities. The results of the analysis show that – in contrast to textbooks, grammars and dictionaries for GFL – verbal connector functions clearly dominate monological academic texttypes and are partly used for specific scientific purposes in academic language. Deficits in dealing with these spoken-language functions in academic communication represent a possible explanation for the general underuse of connectors in spoken academic language among non-native speakers of German compared to the native speakers’ data. This makes it urgently necessary to deal with the specifics of spoken language, also when teaching and assessing the communicative language competence in German as a foreign academic language – in preparatory or study-integrated language courses, in the design of appropriate teaching materials and, not least, in the development of reliable models for the assessment of foreign language proficiency for university access.
  • Sundholm, Johnny (Helsingin yliopisto, 2019)
    Very-high resolution ultrasound (VHRU, 25-55MHz) is a recently developed method for non-invasive assessment of vascular structures. With its increased ultrasound frequency, the method allows for noninvasive examination of the vascular wall in vivo with an axial resolution in the range of tens of micrometers. These characteristics make it a feasible method to determine vascular dimensions of superficial arteries and arteries in the pediatric population. The aim of this thesis was the following: 1. To study the application of a semi-automatic border detection software to improve measurement characteristics of the arterial wall layers, 2. To assess accuracy, precision and feasibility of the VHRU method in assessing superficial arterial wall layers in preterm and term neonates, 3. To validate the VHRU method to assess age-related intimal thickening of the arterial wall, and 4. To determine the potential to implement the method as a noninvasive tool in the bedside diagnosis of giant-cell arteritis of the temporal artery. This Thesis shows that there is no significant difference in the technical precision or bias of arterial wall layer dimension measurements using a semi-automated border detection software compared to electronical calipers, but time of analysis is significantly shorter using the automated border detection software. VHRU is feasible, accurate and precise in the measurement of arterial layer thickness (intima-media and intima-media-adventitia thickness) of proximal conduit arteries, such as carotid, brachial and femoral, in preterm and term neonates. The resolution of VHRU is insufficient in the assessment of more peripheral conduit arteries such as the radial artery. VHRU is feasible and able to detect a thickened intimal layer, seen as a four-line pattern of the arterial far wall in the ultrasound image, in superficial peripheral muscular conduit arteries with intima thickness >0.06mm. Measurements leading-to-leading edge of the intimal layer are accurate compared with histological thickness. VHRU is feasible, accurate and precise in assessing transmural inflammation related intimal thickening in patients with giant-cell arteritis of the temporal artery. The method was however not useful in patients with inflammation limited to the adventitia or without inflammation on histology. In conclusion, very-high resolution ultrasound is an emerging method for the assessment of superficial vascular wall layer structures. The harmless and non-invasive method can detect near-microscopical changes in the vascular wall in human subjects from the newborn stage to old age. Very-high resolution ultrasound has a clinical potential in the non-invasive assessment of vascular health and disease related pathology.

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