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  • Ryynänen, Juha (Edita Publishing Oy, 2016)
    The purpose of this study is to answer the following question: How do changes in a construction project affect the contractual relationship between employer and contractor? Traditionally, the contractual balance has been seen as a static equilibrium between reciprocal rights and duties as set forth by the parties at the time their agreement commences. For example, in a sales contract the seller and buyer determine the balance between goods sold and sales price at the time the contracts commences. The traditional view of contractual balance is best suited to a short-term contract, which is agreed under the assumption of perfect information. In contrast to a sales agreement, a construction contract is typically a long-term agreement which is incomplete at its birth. A construction contract is typically subject to changes (changes in works, costs and/or timing) that occur during the construction project after the date the agreement commences. Some of the relevant changes result from unexpected changes in circumstances over which the parties have no control, but some are under their control i.e. variation orders given by the employer. Regardless of its origin, a change may have an impact on works (including impact on the scope, timing and order of the works), contract price and/or contract time. In this study works, price and time are described as the dynamic components of a construction contract. This study proposes a model of contractual balance based on an equilibrium between the dynamic components mentioned above. Changes and the contractual balance are managed through rules of completion. The rules of completion can be divided into primary and secondary rules of completion. The primary rules of completion include those rules agreed to by the parties in the contract, taking into account the limitations of mandatory rules of law and good building practice. The secondary rules of completion apply to situations not covered by the primary rules of completion. This study identifies four secondary rules of completion: the in dubio contra stipulatorem rule, the in dubio minimis rule, the effectlessness rule (fin. vaikutuksettomuusolettama) and the proportionality rule (in Finnish suhteellisuussääntö). The rules of completion and their implementation are discussed in detail, taking into account general terms of contract, especially YSE 1998.
  • Uronen, Ilkka (Helsingin yliopisto, 2016)
    The Finnish television industry has gradually moved from a production-centered to a customer-oriented business. Knowledge of your customer and the ability to react to change are major competitive advantages in a situation where there is an abundant supply of similar content and services. In this research, customer orientation could be defined as a competence requirement, as well as a business culture which helps the company reform its operations. This research evaluates the strategic competence of the Finnish television industry in the early 2000s and in connection with the post-digitalization shift. This research is focused on competence in the television industry, the research question being the relationship between competence and business operations. By looking at the television business environment and competences from various perspectives, this research examines the significance of individual, team, and company level competence in the business operations of TV companies. Furthermore, it discloses factors which have an effect on competence and competence development in a company. The internet, the integration of multichannel distribution, the arrival of formats and pay channels, the internationalization of production companies and general media digitalization all contributed to the shift of the television industry in the early 2000s. The aforementioned factors had an effect on the product and service processes, distribution and competence in the TV industry. The integration of television content and internet distribution has been particularly groundbreaking. The internet has generated a new kind of competitive situation, where competence is a crucial competition factor of the television companies. The research results are mainly based on thematic interviews which were assessed in relation to Michael Porter s competitive strategy. In the research interviews, the competence requirements brought on by digitalization were partly seen as a threat. The fear was that traditional TV business will change unforeseeably, and professional images will become fragmented. However, the new competence requirements were also seen as a major future competition factor and an opportunity to create new types of TV content and services. The analysis also takes advantage of media management research as well as research on competence development, leadership and innovation. Moreover, other research material is used to draw conclusions on the development of the TV industry, as well as the changes in business and competence brought on by digitalization.
  • Peltola, Timo Hannu Tapani (Helsingin yliopisto, 2016)
    The position sensitive silicon particle detectors are widely used in the tracking systems of High Energy Physics experiments such as the CMS at LHC, the world's largest particle accelerator at CERN. The foreseen upgrade of the LHC to its high luminosity (HL) phase, will enable the use of maximal physics potential of the facility. However, after 10 years of operation the expected fluence will result in a radiation environment that is beyond the capacity of the present tracking system design. The required upgrade of the all-silicon central trackers will include higher granularity and radiation hard sensors that can tolerate the increased occupancy and the higher radiation levels. To address this, extensive measurement and simulation studies have been performed to investigate different designs and silicon materials. The work in this thesis has been carried out within the CMS Tracker Upgrade Project and the multi-experiment RD50 Collaboration. Simulations serve a vital role in device structure optimization and predicting the electric fields and trapping in the silicon sensors. The main objective of device simulations is by using professional software to develop an approach to both model and predict the performance of the irradiated silicon detectors. In the course of this thesis, an effective non-uniform defect model is developed using the Sentaurus TCAD simulation framework. The model reproduces both the observed bulk and surface properties and can predict the performance of strip detectors up to HL-LHC fluences. When applied to measurements of the position dependence of Charge Collection Efficiency, the model can provide a means for the parametrization of oxide charge accumulation at the detector s SiO2/Si interface as a function of irradiation dose. TCAD simulations are also applied for a comparative study of a thin p-on-p pixel sensor and a more conventional p-on-n pixel sensor. The simulations are used to provide an explanation to the measured charge collection behavior and for a detailed investigation of the electrical properties of the two sensor types. Finally, the scope of TCAD simulations is extended to GaAs, a compound semiconductor material. By implementing the observed deep donor defect level to the simulation, the resulting electrical properties are in close agreement with the measurements of an epitaxial GaAs radiation detector. Also, the transferred electron effect observed in the transient current measurements is reproduced by the simulation. The combined results of this thesis demonstrate the versatility and power of the TCAD simulations of semiconductor detectors as a tool to bridge the gap from observation to parametrization.
  • Katajamäki, Sakari (ntamo, 2016)
    Kukunor. Dream and the tradition of nonsense literature in Lauri Viitaʼs long poem This study examines Lauri Viita s (1916 1965) long poem Kukunor. Satu ihmislapsille [‛Koko Nor. A fairy tale for human children ] (1949) and its dream features from the perspective of the European tradition of literary nonsense. Here nonsense literature is defined as language-centred and play- or game-like literature, which balances meaning or a multiplicity of meaning with an absence of meaning. Usually, nonsense literature is topsy-turvy and self-reflective and it frequently represents emotions that are at odds with current events. In addition to earlier research on nonsense literature, the present study uses the three most canonical European nonsense writers Edward Lear, Lewis Carroll and Christian Morgenstern as the corpus for defining and analysing this literary genre. This study analyses the kind of relations Kukunorʼs dream features (i.e., structures and themes connected with dreaming) have with its nonsensical features. It examines Viitaʼs long poem from several structural and thematic perspectives. Most of the essential structural phenomena analysed in this survey include topsy-turvydom, palimpsest structures, and autocentricity. Other topics of analysis include epistemological matters and the instability of the subject or its identity. The main linguistic research themes of this study focus on anomalies regarding referentiality and arbitrariness, the concreteness of language and literature, and linguistic generation. The epithet dream has seen repeated use in the context of nonsense literature, and many surveys have dealt with the relations between dreaming and nonsense, though not in depth. Thus, this study is both an analysis of Viitaʼs long poem and a survey of the interrelation between dreams and nonsensicality in the European canon of literary nonsense. The present study argues that many confusing or incoherent features in Kukunor embody many structures of dreams and nonsense literature. The survey of these intertwining structural, stylistic and thematic characteristics helps to perceive Viitaʼs long poem and the relations between its parts in new ways. Contrary to the view of Elizabeth Sewellʼs eminent book The Field of Nonsense (1952), the key features of the nonsense genre correspond in various ways with many characteristics of dreaming. In Kukunor, Lauri Viita masters both the structural features of dreaming and the poetics of nonsense literature. Kukunor is exceptional among Viita s literary works, but analysing it offers new perspectives for understanding Viita s entire oeuvre.
  • Dashkevich, Alexey (Helsingin yliopisto, 2016)
    The primary goal of the conducted research was to analyse the role of lymphatic endothelial cell in heart failure as well as in the setting of heart and lung transplantation. Our observations of lymphatic phenotype after heart and lung transplantation in human patients are the first of their kind and provide the evidence, that acute allograft rejection is associated with significant changes of lymphatic endothelial phenotype. In experimental studies, we demonstrated that ischemia-reperfusion injury activated the lymphatic endothelium in cardiac allografts. The process was mediated by interaction in the VEGF-C and VEGFR-3 axis and had direct consequences for the development of alloimmune responses. Furthermore, specific perioperative single-dose VEGF-C inhibition demonstrated beneficial effects on lymphatic vessel activation, antigen-presenting cell transport and subsequent alloimmune responses in cardiac allografts. The results of the studies, thus, demonstrate the significance of VEGF-C-VEGFR-3 signaling in promotion of alloimmunity and suggest VEGF-C/D inhibiting strategies as an alternative clinically feasible lymphatic vessel targeted immunomodulatory approach.
  • Pääkkönen, Tarja (Helsingin yliopisto, 2016)
    Although the immature brain reportedly is more prone to seizure activity than the mature brain, there are no previous reports on well-defined juvenile epilepsy syndromes in dogs. This study describes a novel juvenile epilepsy syndrome in Lagotto Romagnolo (LR) dogs, namely benign familial juvenile epilepsy (BFJE). We studied the clinical characteristics of this novel syndrome in 25 affected dogs, while healthy littermates of the affected dogs served as controls. The mean age at onset of focal seizures is 6 weeks, and spontaneous remission of seizures usually occurs by the age of 4 months. Between the seizure episodes, most of the affected puppies are neurologically normal, but puppies with the most severe seizure episodes exhibit some neurological deficits interictally. These deficits also resolve with remission of seizures. Interictal electroencephalography (EEG) shows focal abnormalities, including sharp waves and spikes, in most (88%) of the affected dogs. Conventional imaging examinations, including magnetic resonance imaging (MRI), show no remarkable focal abnormalities in dogs with BFJE. Positron emission tomography (PET) is a nuclear neuroimaging modality that is able to detect abnormal metabolism in the epileptic focus of the brain. We investigated glucose metabolism of the brain in 6 affected and 5 control dogs using radiolabeled glucose, namely 2-[18F]fluoro-2-deoxy-D-glucose (FDG), as a tracer. In dogs with BFJE, FDG-PET shows areas of hypometabolism with good correspondence to focal EEG findings, thus supporting the area of abnormal metabolism being the epileptic zone. Furthermore, we performed a follow-up study by utilizing two previously validated questionnaires on impulsivity and activity levels in dogs, and additionally, we telephone-interviewed the owners of the affected dogs. We evaluated the results based on the data collected for 25 dogs with a history of BFJE and 91 control dogs. We utilized principal component analysis to explore the factorial structure of the questionnaire. Although the life span of affected dogs seems to be comparable with that of healthy control dogs and recurrence of seizures after remission is rare, the dogs with a history of BFJE exhibit abnormalities in behavior reminiscent of attention deficit hyperactivity disorder (ADHD) in humans. This study also reveals the mode of inheritance and the genetic defect behind BFJE. Based on pedigree analysis, we found that BFJE is inherited in a recessive Mendelian form. We further found that a mutation in the gene encoding for protein LGI2 is responsible for BFJE. LGI2, as well as LGI1, interacts with neuronal membrane proteins, namely ADAM22 and ADAM23, in synaptic transmission. LGI1, ADAM22, and ADAM23 have previously been shown to be important in the development of epilepsy, and this study reveals the importance of LGI2 in epileptogenesis of BFJE.
  • Mäkelä, Sanna (Helsingin yliopisto, 2016)
    Influenza viruses are human respiratory pathogens that cause seasonal epidemics and pandemics. The host restricts the virus infection by inducing immune responses aiming at virus clearance. The immune response has two arms. The innate immunity is the first line defense mechanism that is activated immediately after the recognition of the pathogen. The adaptive immunity, which consists of humoral and cell-mediated immunity, takes more time to develop. The epithelial cells of the respiratory tract and innate immune cells, such as macrophages and dendritic cells, are equipped with a plethora of receptors and signaling molecules that are designed for pathogen recognition. These receptors include Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs). The pathogen recognition by these receptors leads to the activation of complex cellular signaling cascades that culminate in the production of cytokines, small proteins that mediate the communication between cells. In influenza infection, one important class of cytokines is interferons (IFNs) which induce the production of antiviral proteins that are able to inhibit virus infection. On the other hand, influenza viruses are capable of evading innate immune surveillance and there are differences between influenza virus types or strains in their immune evasion mechanisms. In this thesis work influenza virus-induced IFN responses were studied in human macrophages and dendritic cells in vitro. Firstly, we showed that in macrophages influenza B virus infection induced a very early IFN-β and IFN-λ1 gene expression that coincided with the nuclear entry of the virus and the activation and nuclear import of IFN regulatory factor 3 (IRF3). This early activation did not take place in influenza A virus-infected cells. Furthermore, our study indicated that RIG-I receptor was essential for the early IFN gene expression. Secondly, we compared the cytokine responses induced by pandemic H1N1 influenza A virus to the ones induced by seasonal influenza A viruses in human macrophages and dendritic cells. We showed that the pandemic influenza A virus induced weak IFN responses but was highly sensitive to the antiviral actions of IFNs. During the infection, different types of microbial structures are present and can be recognized by different cellular receptors. Another aim of this thesis was to elucidate the mechanism of receptor cooperation in inducing synergistic cytokine production. We confirmed the previous findings that TLR3 or TLR4 together with TLR7/8 induces synergistic interleukin (IL)-12 and IFN gene expression in human dendritic cells. We studied, which regulatory factors bound to IL-12 and IFN-λ1 gene promoters during a synergistic stimulation and which cell signaling pathways took part in the cytokine production. We conclude that at the transcriptional level, several different IRF proteins and cell signaling pathways cooperate in the synergistic IL-12 and IFN-λ gene expression. In addition, we propose that IFNs produced after stimulation of the TLR3 pathway induce the expression of TLR7 receptor and other cell signaling components that create a positive feedback loop that further augments the cytokine and IFN production during synergistic stimulation. This thesis discusses the host-pathogen interactions in the human system and clarifies the cell signaling pathways leading to synergistic cytokine gene expression. Moreover, the early events in influenza B virus infection and IFN responses induced by pandemic H1N1 influenza A virus are described. More detailed knowledge of the human innate immune responses induced by host-pathogen interactions is needed for the development of effective vaccines and antiviral treatments against influenza virus.
  • Nenonen, Olga (Helsingin yliopisto, 2016)
    Phonetic development in Russian-Finnish bilinguals of pre-primary age The doctoral dissertation addresses the phonetic development in Russian-Finnish bilingual children of pre-primary age. The study combines qualitative and quantitative methods in the framework of child language development studies, and contrastive and contact linguistics. It also takes into account language therapy approaches. The data were collected through an articulation test specially designed for Russian and Finnish. The research is based on the results of both longitudinal and cross-sectional studies. The longitudinal study observes the evidence from 6 normally developing bilingual children in a 2.5-year time period. The sample of the cross-sectional study consists of 126 children divided into three groups: (1) 46 typically developing Russian-Finnish bilinguals; (2) 40 typically developing Russian monolinguals and 20 typically developing Finnish monolinguals; and (3) 20 Russian-Finnish bilinguals with Specific Language Impairment (SLI). The participant s production of target words in the articulation test was transcribed and phonetic errors were analysed. Despite considerable individual variation in phonetic production, the findings suggest that bilinguals acquire Russian and Finnish phonetic inventories later than their monolingual pairs. The difference is visible both in the speed of acquisition and in the number and nature of errors. With regard to the nature of mispronunciation, four types of bilingual mistakes were distinguished: (1) common developmental mistakes made by bilinguals and monolinguals; (2) language-specific mistakes made by monolinguals and bilinguals, however the latter group makes considerably more mistakes, especially at an older age; (3) cross-linguistic interference mistakes caused by the differences in Russian and Finnish phonetic systems, made only by bilinguals, resembling the mistakes of second language learners; and (4) unpredictable mistakes common in bilingual normally developing and bilingual SLI children. The analysis reveals that from a longitudinal perspective, phonetic development is faster and easier for bilinguals in Finnish than in Russian. However, relatively simple Russian vocalism is acquired faster than Finnish vocalism, whereas the complex system of Russian consonants takes longer to develop than the Finnish consonant system. Furthermore, language-specific features appear to be the most problematic for acquisition. The research shows the evidence of language interaction in bilingual phonetic development, e.g. in the form of cross-language phonetic interference. As a result, some bilingual children may have either a Russian or a Finnish accent. However, this accent tends to gradually disappear.
  • Tuominen, Pekka (Helsingin yliopisto, 2016)
    This study examines the moral qualities of urban space in the Beyoğlu district of Istanbul, looking particularly into how its transformation is understood as interaction between layers of historical consciousness and reproduction of its physical and symbolic boundaries. It focusses on how significant places in Istanbul carry different meanings to people, how the life-worlds of its neighbourhoods are separated from the urban sphere by contextually shifting boundaries and how the notions of public space and the spatial makeup of the city are rapidly changing, motivated by negotiations of appropriate values, appearances and practices. The research is based on a long-term ethnographic fieldwork in Beyoğlu, concentrating on the dynamics between the effective urban centre around Istiklal Street and Taksim Square and the impoverished neighbourhoods of Tarlabaşı and Tophane in its close proximity. The analysis focusses on moral ambiguities of everyday life; I discuss the spatially ordered sense of sociality, dealing with the notions of individual and community, freedom and tolerance, in relation to moral frameworks of Istanbul s urbanity coexisting in different spaces. I explore the shifts between morally appropriate practices across sociocultural boundaries to study how they demand reflective adaptation from the inhabitants to reproduce the mental mappings of the city with internalized, albeit often contradictory, notions of the proper rules of the conduct. These questions were extremely important in the everyday lives of my central informants, underemployed men living in Istanbul s inner-city neighbourhoods who were struggling to live moral lives in an environment characterized by discrimination and exclusion. This is also a study of Turkish modernity. I investigate the historical consciousness of modernity in present-day Istanbul as constant reorganization of historical trajectories, spatial arrangements, mentalities and senses of selfhood in the city. I draw from diverse historical materials, illustrating both official histories and vernacular accounts, to show how the debates over desired modernity at different periods are brought into the present and how they are expressed in the moral landscape of Istanbul. In my fieldwork I have concentrated on participant observation of everyday life, especially in situations and spaces where questions of morality arise. In Istanbul, there are countless struggles over urban space at different levels, fractured along often crosscutting lines of social difference: the issues of class, ethnicity, urbanity, gender and religion derive from encounters between people and assessment of their conduct. These are intimately linked with the extensive rearrangements of urban space in Istanbul that are redrawing the boundaries within the city. In the study, these transformations are studied as both material and embodied, in a way that acknowledges their historical specificities.
  • Yrjölä, Jukka (2016)
    Jukka Yrjölä: A bridge of faith across the Gulf of Finland: Ecclesiastical connections between Finns and Estonians from 1918 to 1939 The independence of Finland and Estonia created the conditions for the emergence and development of ecclesiastical connections between the two countries. Initially, these connections were established primarily by associations that represented various ecclesiastical operations. Such associations had already been set up in Finland during the period of autonomy (1809−1917), but similar activities did not begin in Estonia until the country s independence in 1918. The first connections were created by missionary workers, the YMCA, Suomen Kirkon Seurakuntatyön Keskusliitto (the Central Association for Parish Work of the Church of Finland) and the Laestadian new revival movement. The initial difficulties of the Church of Estonia meant that more organised forms of contact were not established until the late 1920s, when the collaboration expanded to include parish youth work, Sunday schools, Christian student activities and the Christian work of the railway mission. Other efforts included the Finnish diaspora activities in Narva and Tallinn as well as the meetings of clergymen in the recreational groups at Finno-Ugric cultural conferences and the convocations of Finnish and Estonian clergy. For the Finns, the rise of nationalism and the resulting interest in kindred peoples, the Finno-Ugrians, provided the ideological basis for developing connections. The ecclesiastical connections to Estonia were not motivated by a single goal. Whereas the Finnish Evangelical Lutheran Mission shared an operational basis with the YMCA, the railway mission and Sunday schools, the connections of the Laestadian new revival movement were rooted in the revivalist movement, and the contacts of Finnish university students and the Finnish Christian Youth Organisation developed on the same basis from the late 1920s onwards by incorporating national revivalist efforts with the then-prevalent ideas of the Norwegian revivalist preacher Ole Hallesby. The recreational groups at Finno-Ugric cultural conferences, the Finnish-Estonian convocations of the Suomen Kirkon Pappisliitto (the Clerical Association of the Church of Finland), the Hungarian-organised Finno-Ugric convocation in Budapest, and the Lappeenranta kindred peoples camp represented the connection that was perhaps most genuinely inspired by the kindred peoples ideology. The symbols of the kindred connection between the churches included common roots, blood relations, cultural heritage, people s suffering and the Evangelical faith. Separate from the kindred peoples activities per se, the activities of the Herättäjä-Yhdistys (the Awakening Society) in Estonian Ingria had such a strong Finnish nationalist tone that they led to a head-on confrontation with the Estonian regime headed by Konstantin Päts.
  • Liu, Xinxin (Helsingin yliopisto, 2016)
    The worldwide use of triazines as pesticides has resulted in their widespread occurrence in groundwater. Within the northern boreal region in Southern Finland, 30% of groundwater sampling points contained pesticides, and acceptable drinking water limits were exceeded in 11%. Atrazine and its degradation products were among the most common pesticides observed. Chemical pesticide degradation in soil is slower than microbial degradation. Biodegradation often decreases with increasing depth. Nutritional factors and soil physicochemical properties affect microbial pesticide degradation. However, their effects on separate microorganisms, and the genetic basis of these responses, are not well documented. The aim of this thesis was to isolate and characterize atrazine-degrading microorganisms, and to find appropriate microbial, physicochemical, and nutritional demands for pesticide degradation. Microbial community composition was studied in farmland, forested farmland, and primary forest soils by pyrosequencing and in gardens, groundwater deposits, and vadose zone sediments by cultivation on mineral medium with atrazine or terbutryn as the nitrogen source. Atrazine dissipation efficiency was additionally compared under stagnant and circulating water conditions. The dominant phyla that increased in atrazine-treated farmland, gardens, deposits, and sediments were Proteobacteria and Actinobacteria. The overlap in genera was less than in phyla, while the isolated Pseudomonas strains only slightly overlapped between isolates from surface soils and subsurface deposits and sediments. Atrazine dissipation was better in circulating than in stagnant water, and aerobic microbes from genera known to have atrazine degradation genes, all from phyla Proteobacteria and Actinobacteria, were simultaneously enriched,. Based on the results, the application of microbial remediation of atrazine and terbutryn requires special attention to soil physicochemical properties and selection of proper microbial strains.
  • Jokinen, Riikka (Helsingin yliopisto, 2016)
    Mitochondrial DNA (mtDNA) is a small extra-nuclear genome present in all nucleated cells of the body and important for mitochondrial function. The mtDNA is a present in hundreds to thousands of copies per cell and therefore arising mutations cause heteroplasmy: the co-existence of two or more distinct mtDNA variants in the same cell. Because of these features mtDNA variants segregate mitotically in the tissues of an individual, which can lead to time-dependent changes in the relative proportions of the mtDNA variants. Mutations in the mtDNA cause diseases and most pathogenic mtDNA mutations are heteroplasmic. In heteroplasmic situations a certain threshold proportion of the mutant mtDNA must be exceeded prior to onset of symptoms. Somatic mtDNA segregation of mtDNA mutations affect whether the threshold is exceeded, and can thus be a factor in determining disease onset and severity. Some pathogenic mtDNA mutations exhibit tissue-specific mtDNA segregation patterns, but the genes and mechanisms involved in this process are unknown. The aim of this thesis was to uncover genetic regulators of tissue-specific mtDNA segregation and study their properties to gain insight into the mechanisms involved in this process. We investigated tissue-specific mtDNA segregation in a mouse model that segregates two neutral mtDNA variants. These mtDNA variants display tissue-specific mtDNA segregation in three tissue types: the liver, kidney and hematopoietic tissues. In these tissues there is selection for one mtDNA variant over the other. Using this mouse model we identified and verified Gimap3 as a modifying gene for mtDNA segregation in the hematopoietic tissues. In a follow-up study we further studied Gimap3 and a functionally related gene Gimap5. We uncovered a novel subcellular localization to the endoplasmic reticulum for the Gimap3 protein. Moreover we established Gimap5, which encodes a lysosomal protein, as another genetic modifier of mtDNA segregation in hematopoietic tissues. Taken together these results demonstrated the involvement of other organelles in the segregation of mtDNA. To study tissue-specific mtDNA segregation from another aspect we investigated the role of mitochondrial fission in this process. Mitochondrial fission has been implicated to play a role in mtDNA segregation in yeast. We utilized a dominant-negative mouse model for Dnm1l, a master regulator of mitochondrial fission. We demonstrated that expression of the dominant-negative Dnm1l modulated the mtDNA segregation specifically in the hematopoietic tissues. In conclusion, we were able discover the first genetic modifiers for tissue-specific mtDNA segregation in mammals. These findings can be utilized to guide future research aiming to uncover the molecular mechanisms of this process, which can ultimately elucidate the genetics of pathogenic human mtDNA mutations.
  • Kivelä, Juhani (Väittelijä, 2016)
    Abstract Silent alarm how incidents in society have been managed between 2012 and 2014 According to the government resolution on comprehensive security of 2012, situation snapshots are among of the most important bases of decision-making at all levels of operations. The resolution finds that preparedness arrangements related to Finnish security are well-functioning and do not require large-scale reforms; neither is there any reason to develop regulations related to specific procedures or incident management systems. In 2000s prior to 2010 and subsequently numerous regulatory and structural reforms applying to all security operators. The point of departure of the study was the researcher s view based on administrative experiences that the decision-makers lacked knowledge about the effects of reforms in the practical management of incidents. The aim of the study was to update the situation snapshot presented in the government resolution with the perspective of competent practical security operators. Incident management is a new concept and used as a sub-area of security management in government resolutions in the 2010s. The upper framework of the study is the framework of the management of overall security, which includes the security management of normal circumstances, incidents and war-time conditions. The main question posed by the study is: What did the state of incident management look like from the perspective of competent authorities after the administrative reforms and changes in the security environment that took place in the 2000s at the end of 2014? The empirical study focused on years 2012 2014. The study was a qualitative case study. The study object was selected as the macro and operative micro level of practical operations. At both levels, the aim was to gather comprehensive empirical data. In all 130 security operators were interviewed for the study. The micro level data comprises in all 79 interviews of emergency centre, rescue, police, border guard and municipal employees. These are supplemented by 11 regional level interviews with Regional State Administrative Agency and Centre for Economic Development, Transport and the Environment employees. The macro level interview data comprises 38 interviews with the management of ministries, central government and NGOs. The document sources at macro level comprise government programmes, government resolutions, committee reports, regulative and structural reform decisions made in the 2000s and investigation reports of crisis and incident situations experienced. The interpretation of the sources is based on theory-based content analysis, for the purpose of which a loose interpretative framework based on international research literature was created. Its strategic management analyses are derived from T.E. Drabek s strategic management roadmap as well as concepts belonging to L. Johnston and C. Shearing s management theory. Operative management criteria are based on concepts formulated by Johnson and Shearing, which have been supplemented with H. de Bruijn and E.F. ten Heuvelhof s hybrid management criteria. Finally, the study observations have been analysed from the perspective of Drabek s main concept related to incident situations; coordination. Based on the analyses performed, the answer to the main question of the study, can be summarised as follows: 1.From the perspective of the competent authorities, incident management during the study period was administratively disorganised. The view presented in the 2012 resolution about the functioning of the arrangements during normal circumstances did not correspond to the management demands in 2012, or at the end of 2014. 2. The state of management exhibited significant deficiencies in both the strategic management coordination capabilities at the end of 2014. The hierarchical and network management arrangements related to incidents did not correspond to the hybrid management requirements of the incidents. 3. During the study period, the threats related to incidents increased and their management became an increasingly important area of comprehensive security. The deficiencies found in the study also weakened the management preconditions of comprehensive security. The practical conclusion of the study is that the management of incidents and comprehensive security require significant corrective measures and reforms. Moreover, the study revealed that the necessary reforms do not require large additional resources; some of the corrective measures can be performed with existing resources and some by reallocating resources. Based on the study findings, it appears that the loose theoretical framework created for content analysis seemed to suit the object of study and the analysis of data collected for it. Keywords: Comprehensive security, incident management, coordination, strategic, operative, hierarchical, network and hybrid management
  • Hiivala, Nora (Helsingin yliopisto, 2016)
    Until recently research on patient safety (PS) focused on secondary care, and little was known about the risks that patients face in primary care and especially in dental care. Only few studies have hitherto focused on the understanding of either the patients or their families about safety in dentistry. The objectives of this thesis were to identify types of dental patient safety incidents (PSIs), the contributory factors that played a role on the origin, development of PSIs, or identify the factors that increased the risk of PSIs, the mitigating factors against PSI, suggested by dentists and PS practices in use in their clinics. Furthermore, this thesis aimed at exploring whether patients or their families are able to observe PSIs in their own dental care. The study findings were derived from two datasets: 1) The first dataset was obtained from an internet-based questionnaire, sent in 2010 that requested practicing dentists to respond to questions on any PSIs that had occurred during the preceding year and any incident mitigating factors. A total of 1041 dentists responded (response rate 54%) and almost one third reported PSI(s) (n=872). 2) The second dataset was compiled from national data on patients or their family complaints and other notifications made against individual dental practitioners or dental practice units (n=948) for six Regional State Administrative Agencies (AVIs) and also from the National Supervisory Authority for Welfare and Health (Valvira) in Finland from 2000 to 2012 inclusive. The study used quantitative and qualitative research methods. Qualitative analyses (root cause analysis and document analysis) aimed to find emergent themes of dental PSIs and the factors related to them. The quantitative analyses examined several variables related to incident types, which included the contributing factors, the mitigating factors and their associations with dentists characteristics. The detected dental incident types in Finland are in many ways identical to reports from other countries. The two datasets provided somewhat different pictures of PSIs in dentistry. The dentists incident reports mostly captured incidents with relatively low severity, whereas patient complaints and supervisory data of healthcare regulators captured rarer but more serious events. This study showed that PS in dentistry is a complex and multidimensional issue and it relates to all aspects of care; diagnostics, treatment, devices and premises, medications, leadership and management, infection control, teamwork, communication, practitioner characteristics and patient characteristics. All dental PSIs in both datasets had a broad array of contributing factors including both human factors and latent system-factors. Compared to the total number of annual dental visits in Finland, severe dental PSIs are rare. However, less severe PSIs are more common, especially in prosthetics, dental surgery, endodontic and restorative treatments. According to dentist reports no significant difference existed in the incident rate between public and private dental practice. Yet two thirds (68%) of all studied patient complaints and other notifications concerned private professionals, whereas one third concerned public dental providers (32%). Most patients or family lodged complaints were lodged against individual dental professionals and only a minority was issued against dental practices or organizations. Nine out of ten complaints were made against dentists, the majority being general dental practitioners. Most (83%) dental professionals were complained about only once during the study period, however, a small number of dentists were responsible for a notable proportion of complaints from patients or received notifications concerning dentistry. These complaint-prone dentists carried a significantly higher risk for PSIs than did other dentists. The study also showed that patients and their families can be observant and are capable of identifying several incidents and hazardous circumstances in their dental care. Even serious safety risks that were otherwise probably not captured can be detected. The results show a relatively high prevalence of preventable incidents in Finnish dentistry. On the other hand, several mitigating factors had already implemented every day dental practice to safeguard patients in Finland. The problem is that the active use of novel methods varies between individuals and organizations. Patient protection in dentistry can be further enhanced by creating a more open PS culture. Such a culture should include improved incident reporting and should focus on learning from adverse events and also near misses. Anonymous, easy-to-use and blame-free reporting systems tailored for the specific features of dentistry might facilitate reporting. Development of proactive ways to intervene against complaint-prone dentists early and effectively to prevent an escalation of problems is also needed. PS issues should be implemented in undergraduate, post-graduate and continuing professional training. Further research should use different datasets, target groups (health care professionals, patients and their families), several PS research methods and include physical, emotional, social and economic consequences of dental incidents. Keywords: Patient safety, dentistry, incident type, degree of harm, prevention, patient complaints, malpractice
  • Peltola, Olli (Helsingin yliopisto, 2016)
    Methane (CH4) is a strong greenhouse gas and its surface mixing ratio has increased by 150 % since the pre-industrial era. The aggregated atmospheric CH4 budget is relatively well-constrained, however the contribution of different sources/sinks to the overall budget is not. The exchange of matter and energy between the atmosphere and different ecosystems can be studied with eddy covariance (EC) technique. Recently, instrumentation suitable for EC measurements of CH4 fluxes have become available, however, measurement and data processing methodologies are yet to be standardised. By including instrument and software intercomparisons, this thesis is aimed to advance the harmonisation of EC CH4 flux measurement and data processing methodologies. Data from two sites are utilized: Siikaneva fen in Southern Finland and Cabauw agricultural peatland in the Netherlands. Improvement in CH4 instrumentation was exemplified in this work by the decrease in the signal noise: the new CH4 gas analysers showed approximately 10-times lower noise levels than the older models. Cumulative CH4 emissions agreed within 7 % which suggests that there was no significant bias between the instruments. Another possible source of uncertainty is EC data processing. Two widely used EC data processing programs computed comparable CH4 fluxes for different instrument and data processing combinations and thus the data processing routines were implemented similarly. The significance of careful EC data processing was demonstrated by the fact that occasionally the flux corrections contributed over 100 % of the measured signal. EC CH4 fluxes showed high spatial variability in an agricultural peatland ecosystem, considerably higher than the other fluxes. The variability hinders the scalability of EC CH4 fluxes to larger spatial scales and scaling is needed if the CH4 balance of the whole landscape is evaluated. Therefore, the usability of tall flux tower to measure the landscape fluxes directly was also explored. While the results from this exercise were encouraging, the morning and evening transition periods proved to be difficult for the tall flux tower system. This thesis sets a benchmark for the precision and accuracy of EC CH4 data by evaluating instrumentation and data processing tools. Further, the thesis raises awareness of possible problems when upscaling short tower EC CH4 measurements due to flux variability within the landscape. Finally, the findings can be used by researches in the future to evaluate the reliability of their EC CH4 data and thus the thesis contributes to the harmonisation of EC CH4 methodologies.
  • Lehtomaa, Jaakko (Helsingin yliopisto, 2016)
    This book is about heavy-tailed random variables and the phenomena they induce to mathematical models. It has become clear that the classical models employing light-tailed variables have an inherent tendency to underestimate the magnitude of extremal events. Recent developments in the financial world (financial crises) suggest that such shortcomings are not merely theoretical curiosities, but game-changing phenomena that can solely determine the fate of an agent. To overcome the obstacles set by the classical lines of thought an agent must consider ways to improve the way risk is modelled and assessed. The book proposes two ways to do this. Firstly, the existing models are reconfigured to include the effects of different types of risks. Secondly, heavy-tailed effects such as the principle of a single big jump are made more transparent by a detailed investigation. The mathematical theory of this book is based on the theory of random walks and their generalisations. Special attention is paid to randomly weighted random walks and randomly stopped random walks that are commonly encountered in the field of insurance mathematics.
  • Rasimus-Sahari, Stiina (Helsingin yliopisto, 2016)
    Humans are exposed to microbes and microbial compounds continuously via environmental exposure and food in addition to our own microbiome. This thesis reports new empirical findings concerning the types of mitochondrial toxins present in food and indoor air and the effects of these toxins on mammalian cells. Dust and aerosolized compounds collected from moisture-damaged buildings were shown to have mitochondriotoxic effects detectable with a boar sperm motility inhibition (BSMI) assay. Toxin-producing bacteria isolated from the dusts and aerosols included producers of the mitochondrial toxins amylosin, cereulide, and valinomycin. In addition, aerosolized valinomycin and toxic chemical compounds emitted from building materials were detected using boar spermatozoa, demonstrating that the BMSI assay could be used to screen for mitochondrial toxicity in indoor air. Amylosin, a mitochondriotoxin produced by Bacillus spp. from indoor air and food, was shown to be immunotoxic: exposure of human primary macrophages to nanomolar concentrations of amylosin stimulated the release of inflammatory cytokines interleukin 1β and interleukin 18. Amylosin is the first bacterial channel-forming ionophore toxin reported to have this effect. Low amounts of amylosin caused significant dose-dependent potassium ion efflux from human somatic cells and boar spermatozoa. Potassium efflux may be the trigger causing the observed cytokine release from macrophages after amylosin exposure. Amylosin also displayed antifungal and antibacterial activity which may give its producers a competitive advantage in mixed microbial communities. Two previously unreported food safety hazards were identified from cereal grains. A novel heat-stable mitochondrial toxin named paenilide, similar to cereulide biochemically and in mode of action, was found to be produced by Paenibacillus tundrae isolated from barley grains. This finding shows that the genus Paenibacillus cannot be considered harmless for human health. Paenilide consisted of two components with molecular masses equal to those of cereulide and homocereulide but with longer chromatographic retention times, indicating more hydrophobic structures than those of the cereulide compounds. Paenilide acted as a lipophilic potassium ionophore, causing depolarization, swelling, uncoupling of oxidative phosphorylation, and loss of respiratory control in isolated rat liver mitochondria. Paenilide accelerated glucose consumption in porcine kidney epithelial cells, causing metabolic acidosis, and was cytotoxic to porcine and murine cells. Paenilide was as toxic as cereulide at nanomolar amounts, making it a possibly potent food poisoning agent. Paenilide was produced at incubation temperatures down to +5°C, indicating potential toxin formation in chilled foods. The second novel finding connected to cereal grains was the discovery of toxin-producing Streptomyces spp. in healthy-looking grains of barley and spring wheat. The barley grain isolates, belonging to the Streptomyces albidoflavus group, produced the mitochondriotoxic macrolide antimycin A, a known disrupter of oxidative phosphorylation. The cause of the mitochondrial toxicity of the spring wheat grain isolates, most closely related to Streptomyces sedi, remained unidentified. The toxicity of the isolates and grains was detected using the BSMI assay, which was sensitive enough to detect nanomolar contamination corresponding to 2 ng of antimycin A per barley grain. Antimycin A was more toxic towards porcine kidney epithelial cells than the mycotoxin enniatin B but less toxic than cereulide or paenilide. Exposure of porcine kidney epithelial cells to these four toxins accelerated glucose consumption and caused mitochondrial depolarization, indicating upregulation of glycolysis. Pancreatic insulin-producing beta cells, however, are not able to switch to glycolytic ATP production and undergo necrotic cell death upon exposure to mitochondrial toxins. Thus, consumption of grains contaminated with mitochondrial toxins may especially affect pancreatic functions. In conlusion, the results of this thesis show that chronic exposure via indoor air or food to sub-lethal concentrations of mitochondriotoxins produced by spore-forming bacteria may be more common than known so far. This exposure may connect to the increasing worldwide incidence of western lifestyle diseases, such as diabetes, asthma, and allergies as well as cardiovascular and neurological disorders. The studied toxins are all heat-stable and produced by spore-formers able to withstand harsh environmental conditions, highlighting that preventing their presence and endurance in food and indoor environments is problematic.
  • Kangas, Jonna (Helsingin yliopisto, 2016)
    Children's participation in early childhood education has raised concern and discussion in the international researches lately. Young children have been considered to have lack of participation experiences in early education settings because of institutional policies, social understanding about childhood and perspectives of educators (Bae, 2009; Emilson and Folkesson, 2006; Smith, 2002). Focus of children as active agents of their own development through sociocultural learning paradigm the approach of participatory learning has been considered important in early childhood education and research (Berthelsen, Brownlee and Johansson, 2009). This approach of children's learning views participation as a developing and dynamic cultural phenomenon. This research is focusing on the educators' perspectives and the conceptions of children's participation in everyday pedagogic practices and is based on a survey conducted in early childhood education in Metropolitan area of Helsinki in 2010. The survey was realized in the VKK-Metro development and research project funded by the Ministry of Social and Health affairs. The participants represented 1114 working teams from 350 kindergartens. The working teams included 3721 educators taking care of 19 907 children. The analytical framework of research is based on an abductive approach conducted with mixed methods. The findings indicate that children's voice was considered important by educators. Also opportunities to make independent initiatives and choices were considered as a right and an item of learning and of developing of skills of participation. However children's chances to participate in decision making process and pedagogical processes were weak because of challenges of children's participation experienced by educators. These challenges were connected to both institutional issues, such as routines and adult-child-ratios, and professional skills and beliefs about children's competence. According to findings of this research children's participation is understood to include such aspects as having opportunities to have an influence in their learning and the culture of kindergartens, becoming respected and listened to by educators and having chances to practice responsibility and self-regulation. The role of educators as facilitators of children's participation is found essential and the research builds knowledge of children's participation through framework of participatory pedagogy in early education context. Through this framework the challenges of children's participation could be reflected and a culture of developing participation built in co-operation between educators, children and political and social environment of early childhood education.
  • Tapiovaara, Laura (Helsingin yliopisto, 2016)
    Upper respiratory infections are among the most common ailments in humans. Evidence for mechanisms suggests that specific probiotic bacteria could reduce the risk and symptoms of these infections. However, the clinical evidence of probiotics in the upper respiratory tract, especially when colonization and the etiological effects are considered, is sparse. In addition, the safety of probiotics requires constant assessment. This thesis investigated the recovery of probiotic Lactobacillus rhamnosus GG (L. GG) from the upper respiratory tract and its effects on pathogens in this tract. In addition, the thesis assessed the adverse events of L. GG alone or in combination with other probiotics (Bifidobacterium lactis BB-12 [BB12], or Lactobacillus rhamnosus Lc705 [Lc705], Propionibacterium freudenreichii JS [PJS], and/or Bifidobacterium breve 99 [BB99]). In a randomized, double-blinded, placebo-controlled study, 40 children consumed per oral L. GG or a placebo (1:1) prior to surgery in which their adenoids were removed and a possible middle ear effusion (MEE) was collected. L. GG was recovered from both the adenoid tissue and MEE, but it did not affect the findings of human rhinovirus (HRV) or enterovirus (EV) in the samples compared to the placebo. In addition, the analysis of the bacterial pathogens in the MEE showed similarities in both intervention groups. No differences between the groups emerged in respiratory or gastrointestinal (GI) symptoms prior to the surgery or in pain or bleeding after the surgery. In another randomized, double-blinded, placebo-controlled trial, an experimental HRV infection model was used in 59 healthy adult volunteers to investigate the effects of the oral consumption of live, heat-inactivated L. GG on the HRV load in nasopharyngeal lavage samples. The correlation of the HRV load to the subjects clinical symptom scores was assessed. The use of live or inactivated L. GG did not result in statistical differences in the HRV load, but a tendency to lower loads in the L. GG groups was noted. The HRV load positively correlated with the total symptom scores on day 2 and day 5 after inoculation. In the fourth study, individual participant data from six randomized placebo-controlled probiotic studies were analyzed for adverse events (AEs), as distributed by the Common Terminology Criteria of Adverse Events (CTCAE). Data on 1,909 healthy subjects, including children, young adults, and elderly participants, revealed no statistical differences in AEs between the groups that consumed L. GG alone, L. GG in combination, or the placebo. A detailed analysis of three specific categories (respiratory diseases, gastrointestinal diseases, and infections) did not yield any statistical differences in AEs between the probiotic and placebo groups. Based on the results, we concluded that L. GG was able to colonize the upper respiratory tract, but it had no effects on the levels of viral or bacterial pathogens or on the frequency of clinical symptoms in the subjects during either the intervention or the follow-up period. The nasopharyngeal HRV load was positively correlated with the subjects total symptom score. The use of L. GG alone or in combination did not result in AEs in the population of healthy children, young adults, and elderly participants.
  • Saurus, Pauliina (Helsingin yliopisto, 2016)
    Background: Diabetic nephropathy (DN) is a renal complication of diabetes and a common cause of end-stage renal disease (ESRD). DN presents in its earliest stage with low levels of albumin in the urine (microalbuminuria) and develops into overt albuminuria as the disease progresses. Podocyte loss due to detachment or apoptosis has a central role in the pathogenesis of DN, but the mechanisms are not fully understood. The studies in this thesis aimed to increase the knowledge of the pathophysiological mechanisms and molecular pathways leading to podocyte apoptosis in DN by studying three molecules that are expressed in podocytes, SH2-domain-containing inositol polyphosphate 5-phosphate 2 (SHIP2), 3-phosphoinositide-dependent kinase 1 (PDK1) and cyclindependent kinase 2 (CDK2). Results: Lipid phosphatase SHIP2 was identified as an interaction partner of CD2AP, a protein known to be involved in the regulation of apoptosis in podocytes. We found that overexpression of SHIP2 in cultured podocytes reduced the phosphorylation of the major cell survival kinase Akt in response to insulin and increased apoptosis. We also observed that the expression of SHIP2 was upregulated in glomeruli of insulin resistant obese Zucker rats prior to the onset of proteinuria, suggesting a role for SHIP2 in the development of podocyte injury. In contrast, we found that the expression of PDK1 and CDK2 was downregulated in obese Zucker rats before they had developed proteinuria. We also observed that treatment of human podocytes with sera from normoalbuminuric type 1 diabetic (T1D) patients with high lipopolysaccharide (LPS) activity downregulated the expression of PDK1 and CDK2. LPS treatment of mice in vivo also reduced PDK1 and CDK2 expression. LPS-induced downregulation of PDK1 and CDK2 was prevented both in vitro and in vivo by inhibition of the toll-like receptor (TLR) pathway using immunomodulatory agent GIT27. Knockdown of either PDK1, or CDK2 inhibited antiapoptotic Akt pathway, stimulated the proapoptotic p38 MAPK pathway and increased podocyte apoptosis. Conclusions: Given the central role of the PI3K-dependent Akt signaling pathway in regulating cell survival, our findings suggest that SHIP2, PDK1 and CDK2 regulate apoptosis in podocytes by modulating the activity of the PI3K-dependent Akt signaling pathway.