Immunopathogenesis of Asthma and Atopic Diseases – The specific Role of a selected Panel of Genes in human T helper Cell Differentiation

T helper cell (Th) functions are crucial for proper immune defence against various intra- and extracellular pathogens. According to the specific immune responses, Th cells can be classified into subtypes, Th1 and Th2 cells being the most frequently characterized classes. Th1 and Th2 cells interact with other immune cells by regulating their functions with specific cytokine production. IFN, IL-2 and TNF- are the cytokines predominantly produced by Th1 cells whereas Th2 cells produce Th2-type cytokines, such as IL-4, IL-5 and IL-13. Upon TCR activation and in the presence of polarizing cytokines, Th cells differentiate into effector subtypes from a common precursor cell. IFN and IL-12 are the predominant Th1 polarizing cytokines whereas IL-4 directs Th2 polarization. The cytokines mediate their effects through specific receptor signalling. The differentiation process is complex, involving various signalling molecules and routes, as well as functions of the specific transcription factors. The functions of the Th1/Th2 cells are tightly regulated; however, knowledge on human Th cell differentiation is, as yet, fairly poor. The susceptibility for many immune-mediated disorders often originates from disturbed Th cell responses. Thus, research is needed for defining the molecular mechanisms involved in the differentiation and balanced functions of the Th cells. Importantly, the new information obtained will be crucial for a better understanding of the pathogenesis of immune-mediated disorders, such as asthma or autoimmune diseases. In the first subproject of this thesis, the role of genetic polymorphisms in the human STAT6, GATA3 and STAT4 genes were investigated for asthma or atopy susceptibility in Finnish asthma families by association analysis. These genes code for key transcription factors regulating Th cell differentiation. The study resulted in the identification of a GATA3 haplotype that associated with asthma and related traits (high serum IgE level). In the second subproject, an optimized method for human primary T cell transfection and enrichment was established. The method can be utilized for functional studies for the selected genes of interest. The method was also utilized in the third subproject, which aimed at the identification of novel genes involved in early human Th cell polarization (0-48h) using genome-wide oligonucleotide arrays. As a result, numerous genes and ESTs with known or unknown functions were identified in the study. Using an shRNA knockdown approach, a panel of novel IL-4/STAT6 regulated genes were identified in the functional studies of the genes. Moreover, one of the genes, NDFIP2, with a previously uncharacterized role in the human Th differentiation, was observed to promote IFN production of the differentiated Th1 cells. Taken together, the results obtained have revealed potential new relevant candidate genes serving as a basis for further studies characterizing the detailed networks involved in the human Th cell differentiation as well as in the genetic susceptibility of Th-mediated immune disorders.

EPCM-toimitustapamallin kehittäminen Kvaerner Power Oy:n voimalaitostoimituksiin

Tämän diplomityön päämääränäoli laatia suunnitelma voimalaitoksen toimittamiseksi EPCM-toimitustavalla. Työn keskeisiksi tavoitteiksi asetettiin EPCM-toimitustapaan perustuvan toimitustapakonseptin muodostaminen, toimituksiin liittyvien terminologian selkeyttäminen ja harmonisointi sekä voimalaitoksen suhteellisen kustannusrakenteen laatiminen. Työssä tutkittiin voimalaitostoimituksissa tavanomaisesti käytettyjä sopimustyyppejä, kiinteähintaista sopimusta ja kustannusvoittolisäsopimusta sekä harvinaisemmin käytettyjä kattohinta- ja tavoitekustannussopimusta. Vallitsevat toimitustavat, EPC- ja EPCM-toimitustavat sekä monitoimittajatapa, esiteltiin ja niiden vahvuudet sekä heikkoudet selvitettiin. Projektin ominaisuuksilla, markkinoilla ja tilaajan kyvyllä, asiantuntemuksella sekä resursseilla todettiin olevan vaikutusta toimitustavan valintaan. Lisäksi tehtiin katsaus voimalaitostoimitusten kehitystrendeihin ja projektin riskienhallintaan. Voimalaitoksen laitosjärjestelmäjako kehitettiin ja sitä soveltamalla määritettiin voimalaitoksen suhteellinen kustannusrakenne. Kattilaitoksen osuus voimalaitoksen rakentamiskustannuksista todettiin merkittävimmäksi. Laitosjärjestelmien laitekustannusten havaittiin olevan korkeimmat. EPCM-toimitustapamalli kehitettiin teoriaosan pohjalta ja sen rakenne, organisaatio, sopimustyypit ja -suhteetsekä toimituksen riskien jako kuvattiin. Voimalaitoksen rakentamiskustannuksia vertailtiin eri toimitustavoilla ja EPCM-toimitustapamalli todettiin EPC-toimitustapaa edullisemmaksi.

Analysis of the voltage source inverter with small DC-link capacitor

IIn electric drives, frequency converters are used to generatefor the electric motor the AC voltage with variable frequency and amplitude. When considering the annual sale of drives in values of money and units sold, the use of low-performance drives appears to be in predominant. These drives have tobe very cost effective to manufacture and use, while they are also expected to fulfill the harmonic distortion standards. One of the objectives has also been to extend the lifetime of the frequency converter. In a traditional frequency converter, a relatively large electrolytic DC-link capacitor is used. Electrolytic capacitors are large, heavy and rather expensive components. In many cases, the lifetime of the electrolytic capacitor is the main factor limiting the lifetime of the frequency converter. To overcome the problem, the electrolytic capacitor is replaced with a metallized polypropylene film capacitor (MPPF). The MPPF has improved properties when compared to the electrolytic capacitor. By replacing the electrolytic capacitor with a film capacitor the energy storage of the DC-linkwill be decreased. Thus, the instantaneous power supplied to the motor correlates with the instantaneous power taken from the network. This yields a continuousDC-link current fed by the diode rectifier bridge. As a consequence, the line current harmonics clearly decrease. Because of the decreased energy storage, the DC-link voltage fluctuates. This sets additional conditions to the controllers of the frequency converter to compensate the fluctuation from the supplied motor phase voltages. In this work three-phase and single-phase frequency converters with small DC-link capacitor are analyzed. The evaluation is obtained with simulations and laboratory measurements.

Osteoclastic tartrate-resistant acid phosphatase 5b. Diagnostic use and biological significance in bone physiology

The skeleton undergoes continuous turnover throughout life. In women, an increase in bone turnover is pronounced during childhood and puberty and after menopause. Bone turnover can be monitored by measuring biochemical markers of bone resorption and bone formation. Tartrate-resistant acid phosphatase (TRACP) is an enzyme secreted by osteoclasts, macrophages and dendritic cells. The secreted enzyme can be detected from the blood circulation by recently developed immunoassays. In blood circulation, the enzyme exists as two isoforms, TRACP 5a with an intact polypeptide chain and TRACP 5b in which the polypeptide chain consists of two subunits. The 5b form is predominantly secreted by osteoclasts and is thus associated with bone turnover. The secretion of TRACP 5b is not directly related to bone resorption; instead, the levels are shown to be proportional to the number of osteoclasts. Therefore, the combination of TRACP 5b and a marker reflecting bone degradation, such as C-terminal cross-linked telopeptides of type I collagen (CTX), enables a more profound analysis of the changes in bone turnover. In this study, recombinant TRACP 5a-like protein was proteolytically processed into TRACP 5b-like two subunit form. The 5b-like form was more active both as an acid phosphatase and in producing reactive oxygen species, suggesting a possible function for TRACP 5b in osteoclastic bone resorption. Even though both TRACP 5a and 5b were detected in osteoclasts, serum TRACP 5a levels demonstrated no change in response to alendronate treatment of postmenopausal women. However, TRACP 5b levels decreased substantially, demonstrating that alendronate decreases the number of osteoclasts. This was confirmed in human osteoclast cultures, showing that alendronate decreased the number of osteoclats by inducing osteoclast apoptosis, and TRACP 5b was not secreted as an active enzyme from the apoptotic osteoclasts. In peripubertal girls, the highest levels of TRACP 5b and other bone turnover markers were observed at the time of menarche, whereas at the same time the ratio of CTX to TRACP 5b was lowest, indicating the presence of a high number of osteoclasts with decreased resorptive activity. These results support the earlier findings that TRACP 5b is the predominant form of TRACP secreted by osteoclasts. The major source of circulating TRACP 5a remains to be established, but is most likely other cells of the macrophage-monocyte system. The results also suggest that bone turnover can be differentially affected by both osteoclast number and their resorptive activity, and provide further support for the possible clinical use of TRACP 5b as a marker of osteoclast number.

Conservation Genetics of Exploited Finnish Salmonid Fishes

Genetic diversity is one of the levels of biodiversity that the World Conservation Union (IUCN) has recognized as being important to preserve. This is because genetic diversity is fundamental to the future evolution and to the adaptive flexibility of a species to respond to the inherently dynamic nature of the natural world. Therefore, the key to maintaining biodiversity and healthy ecosystems is to identify, monitor and maintain locally-adapted populations, along with their unique gene pools, upon which future adaptation depends. Thus, conservation genetics deals with the genetic factors that affect extinction risk and the genetic management regimes required to minimize the risk. The conservation of exploited species, such as salmonid fishes, is particularly challenging due to the conflicts between different interest groups. In this thesis, I conduct a series of conservation genetic studies on primarily Finnish populations of two salmonid fish species (European grayling, Thymallus thymallus, and lake-run brown trout, Salmo trutta) which are popular recreational game fishes in Finland. The general aim of these studies was to apply and develop population genetic approaches to assist conservation and sustainable harvest of these populations. The approaches applied included: i) the characterization of population genetic structure at national and local scales; ii) the identification of management units and the prioritization of populations for conservation based on evolutionary forces shaping indigenous gene pools; iii) the detection of population declines and the testing of the assumptions underlying these tests; and iv) the evaluation of the contribution of natural populations to a mixed stock fishery. Based on microsatellite analyses, clear genetic structuring of exploited Finnish grayling and brown trout populations was detected at both national and local scales. Finnish grayling were clustered into three genetically distinct groups, corresponding to northern, Baltic and south-eastern geographic areas of Finland. The genetic differentiation among and within population groups of grayling ranged from moderate to high levels. Such strong genetic structuring combined with low genetic diversity strongly indicates that genetic drift plays a major role in the evolution of grayling populations. Further analyses of European grayling covering the majority of the species’ distribution range indicated a strong global footprint of population decline. Using a coalescent approach the beginning of population reduction was dated back to 1 000-10 000 years ago (ca. 200-2 000 generations). Forward simulations demonstrated that the bottleneck footprints measured using the M ratio can persist within small populations much longer than previously anticipated in the face of low levels of gene flow. In contrast to the M ratio, two alternative methods for genetic bottleneck detection identified recent bottlenecks in six grayling populations that warrant future monitoring. Consistent with the predominant role of random genetic drift, the effective population size (N_e) estimates of all grayling populations were very low with the majority of N_e estimates below 50. Taken together, highly structured local populations, limited gene flow and the small N_e of grayling populations indicates that grayling populations are vulnerable to overexploitation and, hence, monitoring and careful management using the precautionary principles is required not only in Finland but throughout Europe. Population genetic analyses of lake-run brown trout populations in the Inari basin (northernmost Finland) revealed hierarchical population structure where individual populations were clustered into three population groups largely corresponding to different geographic regions of the basin. Similar to my earlier work with European grayling, the genetic differentiation among and within population groups of lake-run brown trout was relatively high. Such strong differentiation indicated that the power to determine the relative contribution of populations in mixed fisheries should be relatively high. Consistent with these expectations, high accuracy and precision in mixed stock analysis (MSA) simulations were observed. Application of MSA to indigenous fish caught in the Inari basin identified altogether twelve populations that contributed significantly to mixed stock fisheries with the Ivalojoki river system being the major contributor (70%) to the total catch. When the contribution of wild trout populations to the fisheries was evaluated regionally, geographically nearby populations were the main contributors to the local catches. MSA also revealed a clear separation between the lower and upper reaches of Ivalojoki river system – in contrast to lower reaches of the Ivalojoki river that contributed considerably to the catch, populations from the upper reaches of the Ivalojoki river system (>140 km from the river mouth) did not contribute significantly to the fishery. This could be related to the available habitat size but also associated with a resident type life history and increased cost of migration. The studies in my thesis highlight the importance of dense sampling and wide population coverage at the scale being studied and also demonstrate the importance of critical evaluation of the underlying assumptions of the population genetic models and methods used. These results have important implications for conservation and sustainable fisheries management of Finnish populations of European grayling and brown trout in the Inari basin.

Fiktiivisen kirjallisuuden maailmasta monikulttuuriseen Suomeen. Ennakointikertomus kirjallisuudenopetuksen ja monikulttuurisuuskasvatuksen välineenä

From the world of fiction literature into multi-cultural Finland. Anticipatory story as an educational tool in teaching of literature and multiculturalism The research clarifies the relationship between reading fiction literature and multicultural value education in basic education. The research focuses on the subject didactics of mother tongue and literature and on the literature teaching in particular. The objective is to develop a method that is easily transferable into a teaching context so as to intensify the educational discussion based on fiction literature. In essence, understanding fiction literature and the ethical and moral thinking resemble one another, because both of them aim at empathizing with the thinking of a person or with a situation foreign to oneself. For this reason fiction literature is ideally suited for the discussion on ethical and moral values within a subject entity in the basic education. The empirical unit of the research consists of two parts. The first part explains how youth novels published in the years 1993 – 2007 describe multiculturalism in Finnish society. Books on multiculturalism are still few in number within youth literature, and people with a foreign background are mainly minor or background characters in such literary works. Nevertheless, youth novels serve well as a starting point for an educational discussion about multicultural issues. More often than not characters in youth novels are stereotypes and even opposite to each other. The juxtaposing makes a young reader question the stereotypes associated with immigrants. Besides the stereotype, reference to a prototype or a model is possible. The second part tests the usefulness of an anticipatory story based on a fictive text for an educational discussion about multicultural issues. The empirical material was collected from the eighth-grade teaching groups in basic education as follows: one teaching group was an immigrant group, the second one a group of Finns with experience of immigrants while the third group of students had hardly any experience of immigrants. The anticipatory stories were written on the basis of extracts from youth novels with multicultural themes. The material collected for a total of 120 anticipatory stories was analysed by using meaning cue analysis. Using the meaning cue analysis, the anticipatory stories were divided into three groups: stories with predominantly positive meaning cues of interculturalism, ambivalent stories with both positive and negative meaning cues of interculturalism and the stories with predominantly negative meaning cues of interculturalism. The meaning cues produced by girls and boys differ from one another, in particular, by the negative meaning cues of interculturalism. For girls, the predominant meaning cue is fear whereas for boys, it is that of violence. It would also seem that the students, in particular, boys with little experience of immigrants produce more negative meaning cues of interculturalism than do immigrants or Finnish students with experience of immigrants. Further still, it seems that active reading of fiction literature affects the meaning cues of interculturalism in an ambivalent direction. In the way of youth novels this is understandable, because youth novels in general are made up of opposite characters and meaning cues. The less the student takes an interest in reading, the more he used meaning cues from outside the parent text for his anticipatory story. No doubt it would be possible to use fiction literature in the literature education to a much higher extent than it is being used today whereby the literature could be used in basic education for reviewing subject entities or study contents of other study subjects. By way of an anticipatory story and the meaning cue analysis, it is possible to intensify the educational discussions based on fiction literature. However, using fiction literature in the literature education requires consideration of the specific genre of fiction literature.

Emancipating and developing learning activity: Systemic intervention and re-instrumentation in higher education.

The central theme of this thesis is the emancipation and further development of learning activity in higher education in the context of the ongoing digital transformation of our societies. It was developed in response to the highly problematic mainstream approach to digital re-instrumentation of teaching and studying practises in contemporary higher education. The mainstream approach is largely based on centralisation, standardisation, commoditisation, and commercialisation, while re-producing the general patterns of control, responsibility, and dependence that are characteristic for activity systems of schooling. Whereas much of educational research and development focuses on the optimisation and fine-tuning of schooling, the overall inquiry that is underlying this thesis has been carried out from an explicitly critical position and within a framework of action science. It thus conceptualises learning activity in higher education not only as an object of inquiry but also as an object to engage with and to intervene into from a perspective of intentional change. The knowledge-constituting interest of this type of inquiry can be tentatively described as a combination of heuristic-instrumental (guidelines for contextualised action and intervention), practical-phronetic (deliberation of value-rational aspects of means and ends), and developmental-emancipatory (deliberation of issues of power, self-determination, and growth) aspects. Its goal is the production of orientation knowledge for educational practise. The thesis provides an analysis, argumentation, and normative claim on why the development of learning activity should be turned into an object of individual|collective inquiry and intentional change in higher education, and why the current state of affairs in higher education actually impedes such a development. It argues for a decisive shift of attention to the intentional emancipation and further development of learning activity as an important cultural instrument for human (self-)production within the digital transformation. The thesis also attempts an in-depth exploration of what type of methodological rationale can actually be applied to an object of inquiry (developing learning activity) that is at the same time conceptualised as an object of intentional change within the ongoing digital transformation. The result of this retrospective reflection is the formulation of “optimally incomplete” guidelines for educational R&D practise that shares the practicalphronetic (value related) and developmental-emancipatory (power related) orientations that had been driving the overall inquiry. In addition, the thesis formulates the instrumental-heuristic knowledge claim that the conceptual instruments that were adapted and validated in the context of a series of intervention studies provide means to effectively intervene into existing practise in higher education to support the necessary development of (increasingly emancipated) networked learning activity. It suggests that digital networked instruments (tools and services) generally should be considered and treated as transient elements within critical systemic intervention research in higher education. It further argues for the predominant use of loosely-coupled, digital networked instruments that allow for individual|collective ownership, control, (co-)production, and re-use in other contexts and for other purposes. Since the range of digital instrumentation options is continuously expanding and currently shows no signs of an imminent slow-down or consolidation, individual and collective exploration and experimentation of this realm needs to be systematically incorporated into higher education practise.

JNK, a versatile regulator of kinesin-1 transport and cytoskeleton dynamics

C-Jun N-terminal kinase (JNK) is traditionally recognized as a crucial factor in stress response and inducer of apoptosis upon various stimulations. Three isoforms build the JNK subfamily of MAPK; generally expressed JNK1 and JNK2 and brain specific JNK3. Degenerative potency placed JNK in the spotlight as potential pharmacological option for intervention. Unfortunately, adverse effects of potential drugs and observation that expression of only JNK2 and JNK3 are induced upon stress, restrained initial enthusiasm. Notably, JNK1 demonstrated atypical high constitutive activity in neurons that is not responsive to cellular stresses and indicated existence of physiological activity. This thesis aimed at revealing the physiological functions of JNK1 in actin homeostasis through novel effector MARCKS-Like 1 (MARCKSL1) protein, neuronal trafficking mediated by major kinesin-1 motor protein and microtubule (MT) dynamics via STMN2/SCG10. The screen for novel physiological JNK substrates revealed specific phosphorylation of C-terminal end of MARCKSL1 at S120, T148 and T183 both ex vivo and in vitro. By utilizing site-specific mutagenesis, various actin dynamics and migrations assays we were able to demonstrate that JNK1 phosphorylation specifically facilitates F-actin bundling and thus filament stabilisation. Consecutively, this molecular mechanism was proved to enhance formation of filopodia; cell surface projections that allow cell sensing surrounding environment and migrate efficiently. Our results visualize JNK dependent and MARCKSL1 executed induction of filopodia in neurons and fibroblast indicating general mechanism. Subsequently, inactivation of JNK action on MARCKSL1 shifts cellular actin machinery into lamellipodial dynamic arrangement. Tuning of actin cytoskeleton inevitably melds with cell migration. We observed that both active JNK and JNK pseudo-phosphorylated form of MARCKSL1 reduce actin turnover in intact cells leading to overall diminished cell motility. We demonstrate that tumour transformed cells from breast, prostate, lung and muscle-derived cancers upregulate MARCKSL1. We showed on the example of prostate cancer PC-3 cell line that JNK phosphorylation negatively controls MARCKSL1 ability to induce migration, which precedes cancer cell metastasis. The second round of identification of JNK physiological substrates resulted in detection of predominant motor protein kinesin-1 (Kif5). Mass spectrometry detailed analysis showed evident endogenous phosphorylation of kinesin-1 on S176 within motor domain that interacts with MT. In vitro phosphorylation of bacterially expressed kinesin heavy chain by JNK isoforms displayed higher specificity of JNK1 when compared to JNK3. Since, JNK1 is constitutively active in neurons it signified physiological aspect of kinesin-1 regulation. Subsequent biochemical examination revealed that kinesin-1, when not phosphorylated on JNK site, exhibits much higher affinity toward MTs. Expression of the JNK non-phosphorable kinesin-1 mutant in intact cells as well as in vitro single molecule imaging using total internal reflection fluorescence microscopy indicated that the mutant loses normal speed and is not able to move processively into proper cellular compartments. We identify novel kinesin-1 cargo protein STMN2/SCG10, which along with known kinesin-1 cargo BDNF is showing impaired trafficking when JNK activity is inhibited. Our data postulates that constitutive JNK activity in neurons is crucial for unperturbed physiologically relevant transport of kinesin-1 dependant cargo. Additionally, my work helps to validate another novel physiological JNK1 effector STMN2/SCG10 as determinant of axodendritic neurites dynamics in the developing brain through regulation of MT turnover. We show successively that this increased MT dynamics is crucial during developmental radial migration when brain layering occurs. Successively, we are able to show that introduction of JNK phosphorylation mimicking STMN2/SCG10 S62/73D mutant rescues completely JNK1 genetic deletion migration phenotype. We prove that STMN2/SCG10 is predominant JNK effector responsible for MT depolymerising activity and neurite length during brain development. Summarizing, this work describes identification of three novel JNK substrates MARCKSL1, kinesin-1 and STMN2/SCG10 and investigation of their roles in cytoskeleton dynamics and cargo transport. This data is of high importance to understand physiological meaning of JNK activity, which might have an adverse effect during pharmaceutical intervention aiming at blocking pathological JNK action.

How (not) to interview children : interviews with young children in sexual abuse investigations in Finland

The present thesis had two main objectives: The first was to assess how child sexual abuse (CSA) interviews in Finland are conducted through analysing the interviewing techniques applied and the language used by the interviewers, as well as to suggest ways to improve interviews if they were found to have deficiencies. The second main aim was to contribute to the growing research corpus concerning CSA interviews, in particular, by addressing how interviewers follow up information provided by the child, by analysing whether child health care professionals would use childadapted language, and by studying the kind of modifications in the verbal behaviour of interviewers and children that were associated with a) repeated interviews, b) a support person’s presence at the interview, and c) the use of anatomically detailed dolls. Two complementary samples of CSA interviews were analysed. The first one was composed of child interviews with 3-12-year-old children (N = 27) that had been considered problematic by lawyers or other involved professionals (Studies I and IV). The second sample consisted of unselected interviews (N = 43) with children aged 3 to 8 years conducted in a number of hospitals in different parts of the country (Studies II and III). Study I: The verbal interaction between interviewer and child was analysed in a sample of interviews that had been considered to be problematic by involved professionals. Results showed that interviewers used inappropriate questioning techniques, relying on option-posing, specific suggestive and unspecific suggestive questions to a significant extent, these comprising around 50% of all interviewer utterances. The proportion of invitations, which the research community recommends interviewers to rely on, was strikingly low. Invitations and directive utterances were associated with an increase in informative responses by the child in terms of response type, number of new details reported, as well as length of response. The opposite was true for option-posing and suggestive utterances. Longer questions by the interviewer (in number of words) often rendered no reply from the child, whereas shorter questions were followed by descriptive answers. Even after the child had provided an informative answer, interviewers failed to follow up the information in an adequate way and instead continued to rely on focused and leading questions. Study II: Due to the possible bias of the sample analysed in Study I, the most important analyses were rerun with the unselected sample and reported separately. Results were quite similar between the two studies, indicating that the problems observed in Study I, with interviewers relying on option-posing and suggestive questions to a significant extent, are likely to be general and not specific for those interviews. Even if suggestive questions were slightly less and invitations slightly more common in this sample than in the previous study, almost half of the interviewer questions were still optionposing or suggestive, and also in this sample, interviewers failed to follow up information by the child in a facilitating manner. Differentiating between judicial and contextual details showed that while facilitators, invitations, and directive utterances elicited more contextual than judicial details, the opposite was true for specific suggestive utterances. These results might be explained by the reluctance of children to describe sexual details related to the abuse events. Alternatively, they may also be due to children describing incorrect sexual details as a result of suggestive interviewing techniques. Study III: This study examined features of the language used by the interviewers. Interviewer utterances included multiple questions, long statements, complicated grammar and concepts, as well as unclear references to persons and situations. More than a fifth of the interviewer utterances were coded as belonging to at least one of these categories. The results suggest that even professionals who are experienced in interacting with children may have difficulties in using a child-sensitive language, adding to the pool of studies showing similar problems to occur in legal hearings with children conducted by lawyers. As children rarely comment on, or even recognise, their lack of comprehension, the use of a language that is too complex can have detrimental consequences for the outcomes of investigative interviews. Interviewers used different approaches to introduce the topic of abuse. While 15% of the children spontaneously addressed the topic of abuse, probably indicating that they felt confident with the interviewer and the situation, in almost 50% of the cases, the interviewer introduced the topic of abuse in a way that can be considered leading. Interviews were characterised by a lack of structure, apparent in frequent rapid switches of topic by the interviewer. This manner was associated with a decrease in the number of new details provided by the children. Study IV: This study analysed possible changes in the interview dynamics associated with repeated interviewing, the presence of a support person (related to the child), and the use of anatomically detailed (AD) dolls. Repeated interviewing, in combination with suggestive questions, has previously been found to seriously contaminate children’s accounts. In the present material, interviewers used significantly more suggestive utterances in the repeated condition, thus endangering the reliability of the children’s reports. Few studies have investigated the effects of a support person’s presence at the interview. The results of the present study showed that interviewers talked more and children provided less information when a support person was present. Supporting some earlier findings regarding the use of AD dolls, the present results showed that using AD dolls was associated with longer interviewer utterances and shorter, less responsive, and less detailed child responses. Interviewers used up to five times more unspecific suggestive utterances when dolls were used, for instance through repeatedly asking the child to show “what really happened” with the dolls. Conclusion: The results indicate that CSA interviews in Finland are not conducted in a manner that follows best practice as defined by the research community and as stated in a number of guidelines. When comparing these questioning strategies with the recommendations, which have been predominant in the field for more than ten years now, it can be concluded that the interviews analysed were conducted in a manner that undermines the possibility to elicit an uncontaminated and accurate narrative from the children. A particularly worrying finding was the fact that interviewers did not follow up relevant information by the children in an adequate way. A number of clinical implications can be drawn from the results, particularly concerning the need for improvement in the quality of CSA interviews. There is convincing research regarding how to improve CSA interviews, notably through training forensic child interviewers to use a structured interviewing protocol, and providing them with continuous supervision and feedback. Allocating appropriate resources to improve the quality of forensic child interviews is a matter of protecting the rights of all persons involved in CSA investigations, in particular those of the children.

Kelvin Probe Force Microscopy (KPFM) characterization of lanthanum lutetium oxide high-k dielectric thin films

Lanthanum lutetium oxide (LaLuO3) thin films were investigated considering their perspective application for industrial microelectronics. Scanning probe microscopy (SPM) techniques permitted to visualize the surface topography and study the electric properties. This work compared both the material properties (charge behavior for samples of 6 nm and 25 nm width) and the applied SPM modes. Particularly, Kelvin probe force microscopy (KPFM) was applied to characterize local potential difference with high lateral resolution. Measurements showed the difference in morphology, chargeability and charge dissipation time for both samples. The polarity effect was detected for this material for the first time. Lateral spreading of the charged spots indicate the diffusive mechanism to be predominant in charge dissipation. This allowed to estimate the diffusion coefficient and mobility. Using simple electrostatic model it was found that charge is partly leaking into the interface oxide layer.

Terpenoid transformations over gold catalysts

Nowadays biomass transformation has a great potential for the synthesis of value-added compounds with a wide range of applications. Terpenoids, extracted from biomass, are inexpensive and renewable raw materials which often have a biological activity and are widely used as important organic platform molecules in the development of new medicines as well as in the synthesis of fine chemicals and intermediates. At the same time, special attention is devoted to the application of gold catalysts to fine chemical synthesis due to their outstanding activity and/or selectivity for transformations of complex organic compounds. Conversion of renewable terpenoids in the presence of gold nanoparticles is one of the new and promising directions in the transformation of biomass to valuable chemicals. In the doctoral thesis, different kinds of natural terpenoids, such as α-pinene, myrtenol and carvone were selected as starting materials. Gold catalysts were utilized for the promising routes of these compounds transformation. Investigation of selective α-pinene isomerization to camphene, which is an important step in an industrial process towards the synthesis of camphor as well as other valuable substrates for the pharmaceutical industry, was performed. A high activity of heterogeneous gold catalysts in the Wagner-Meerwein rearrangement was demonstrated for the first time. Gold on alumina carrier was found to reach the α-pinene isomerization conversion up to 99.9% and the selectivity of 60-80%, thus making this catalyst very promising from an industrial viewpoint. A detailed investigation of kinetic regularities including catalyst deactivation during the reaction was performed. The one-pot terpene alcohol amination, which is a promising approach to the synthesis of valuable complex amines having specific physiological properties, was investigated. The general regularities of the one-pot natural myrtenol amination in the presence of gold catalysts as well as a correlation between catalytic activity, catalyst redox treatment and the support nature were obtained. Catalytic activity and product distribution were shown to be strongly dependent on the support properties, namely acidity and basicity. The gold-zirconia (Au/ZrO2) catalyst pretreated under oxidizing atmosphere was observed to be rather active, resulting in the total conversion of myrtenol and the selectivity to the corresponding amine of about 53%. The reaction kinetics was modelled based on the mechanistic considerations with the catalyst deactivation step incorporated in the mechanism. Carvone hydrogenation over a gold catalyst was studied with the general idea of investigating both the activity of gold catalysts in competitive hydrogenation of different functional groups and developing an approach to the synthesis of valuable carvone derivatives. Gold was found to promote stereo- and chemoselective carvone hydrogenation to dihydrocarvone with a predominant formation of the trans-isomer, which generally is a novel synthetic method for an industrially valuable dihydrocarvone. The solvent effect on the catalytic activity as well as on the ratio between trans- and cis-dihydrocarvone was evaluated.

Creating an open-books implementation framework for a maintenance-related value-based life-cycle model

This study is a qualitative action research by its nature with elements of personal design in the form of a tangible model implementation framework construction. Utilized empirical data has been gathered via two questionnaires in relation to the arranged four workshop events with twelve individual participants. Five of them represented maintenance customers, three maintenance service providers and four equipment providers respectively. Further, there are two main research objectives in proportion to the two complementary focusing areas of this thesis. Firstly, the value-based life-cycle model, which first version has already been developed prior to this thesis, requires updating in order to increase its real-life applicability as an inter-firm decision-making tool in industrial maintenance. This first research objective is fulfilled by improving appearance, intelligibility and usability of the above-mentioned model. In addition, certain new features are also added. The workshop participants from the collaborating companies were reasonably pleased with made changes, although further attention will be required in future on the model’s intelligibility in particular as main results, charts and values were all reckoned as slightly hard to understand. Moreover, upgraded model’s appearance and added new features satisfied them the most. Secondly and more importantly, the premises of the model’s possible inter-firm implementation process need to be considered. This second research objective is delivered in two consecutive steps. At first, a bipartite open-books supported implementation framework is created and its different characteristics discussed in theory. Afterwards, the prerequisites and the pitfalls of increasing inter-organizational information transparency are studied in empirical context. One of the main findings was that the organizations are not yet prepared for network-wide information disclosure as dyadic collaboration was favored instead. However, they would be willing to share information bilaterally at least. Another major result was that the present state of companies’ cost accounting systems will definitely need implementation-wise enhancing in future since accurate and sufficiently detailed maintenance data is not available. Further, it will also be crucial to create supporting and mutually agreed network infrastructure. There are hardly any collaborative models, methods or tools currently in usage. Lastly, the essential questions about mutual trust and predominant purchasing strategies are cooperation-wise important. If inter-organizational activities are expanded, a more relational approach should be favored in this regard. Mutual trust was also recognized as a significant cooperation factor, but it is hard to measure in reality.

Spontaneous Focusing on Numerosity in the Development of Early Mathematical Skills

The aim of the present set of longitudinal studies was to explore 3-7-year-old children.s Spontaneous FOcusing on Numerosity (SFON) and its relation to early mathematical development. The specific goals were to capture in method and theory the distinct process by which children focus on numerosity as a part of their activities involving exact number recognition, and individual differences in this process that may be informative in the development of more complex number skills. Over the course of conducting the five studies, fifteen novel tasks were progressively developed for the SFON assessments. In the tasks, confounding effects of insufficient number recognition, verbal comprehension, other procedural skills as well as working memory capacity were aimed to be controlled. Furthermore, how children.s individual differences in SFON are related to their development of number sequence, subitizing-based enumeration, object counting and basic arithmetic skills was explored. The effect of social interaction on SFON was tested. Study I captured the first phase of the 3-year longitudinal study with 39 children. It was investigated whether there were differences in 3-year-old children.s tendency to focus on numerosity, and whether these differences were related to the children.s development of cardinality recognition skills from the age of 3 to 4 years. It was found that the two groups of children formed on the basis of their amount of SFON tendency at the age of 3 years differed in their development of recognising and producing small numbers. The children whose SFON tendency was very predominant developed faster in cardinality related skills from the age of 3 to 4 years than the children whose SFON tendency was not as predominant. Thus, children.s development in cardinality recognition skills is related to their SFON tendency. Studies II and III were conducted to investigate, firstly, children.s individual differences in SFON, and, secondly, whether children.s SFON is related to their counting development. Altogether nine tasks were designed for the assessments of spontaneous and guided focusing on numerosity. The longitudinal data of 39 children in Study II from the age of 3.5 to 6 years showed individual differences in SFON at the ages of 4, 5 and 6 years, as well as stability in children.s SFON across tasks used at different ages. The counting skills were assessed at the ages of 3.5, 5 and 6 years. Path analyses indicated a reciprocal tendency in the relationship between SFON and counting development. In Study III, these results on the individual differences in SFON tendency, the stability of SFON across different tasks and the relationship of SFON and mathematical skills were confirmed by a larger-scale cross-sectional study of 183 on average 6.5-year-old children (range 6;0-7;0 years). The significant amount of unique variance that SFON accounted for number sequence elaboration, object counting and basic arithmetic skills stayed statistically significant (partial correlations varying from .27 to .37) when the effects of non-verbal IQ and verbal comprehension were controlled. In addition, to confirm that the SFON tasks assess SFON tendency independently from enumeration skills, guided focusing tasks were used for children who had failed in SFON tasks. It was explored whether these children were able to proceed in similar tasks to SFON tasks once they were guided to focus on number. The results showed that these children.s poor performance in the SFON tasks was not caused by their deficiency in executing the tasks but on lacking focusing on numerosity. The longitudinal Study IV of 39 children aimed at increasing the knowledge of associations between children.s long-term SFON tendency, subitizing-based enumeration and verbal counting skills. Children were tested twice at the age of 4-5 years on their SFON, and once at the age of 5 on their subitizing-based enumeration, number sequence production, as well as on their skills for counting of objects. Results showed considerable stability in SFON tendency measured at different ages, and that there is a positive direct association between SFON and number sequence production. The association between SFON and object counting skills was significantly mediated by subitizing-based enumeration. These results indicate that the associations between the child.s SFON and sub-skills of verbal counting may differ on the basis of how significant a role understanding the cardinal meanings of number words plays in learning these skills. The specific goal of Study V was to investigate whether it is possible to enhance 3-year old children.s SFON tendency, and thus start children.s deliberate practice in early mathematical skills. Participants were 3-year-old children in Finnish day care. The SFON scores and cardinality-related skills of the experimental group of 17 children were compared to the corresponding results of the 17 children in the control group. The results show an experimental effect on SFON tendency and subsequent development in cardinality-related skills during the 6-month period from pretest to delayed posttest in the children with some initial SFON tendency in the experimental group. Social interaction has an effect on children.s SFON tendency. The results of the five studies assert that within a child.s existing mathematical competence, it is possible to distinguish a separate process, which refers to the child.s tendency to spontaneously focus on numerosity. Moreover, there are significant individual differences in children.s SFON at the age of 3-7 years. Moderate stability was found in this tendency across different tasks assessed both at the same and at different ages. Furthermore, SFON tendency is related to the development of early mathematical skills. Educational implications of the findings emphasise, first, the importance of regarding focusing on numerosity as a separate, essential process in the assessments of young children.s mathematical skills. Second, the substantial individual differences in SFON tendency during the childhood years suggest that uncovering and modeling this kind of mathematically meaningful perceiving of the surroundings and tasks could be an efficient tool for promoting young children.s mathematical development, and thus prevent later failures in learning mathematical skills. It is proposed to consider focusing on numerosity as one potential sub-process of activities involving exact number recognition in future studies.

Advanced analysis and design methods for preparative chromatographic separation processes

Preparative liquid chromatography is one of the most selective separation techniques in the fine chemical, pharmaceutical, and food industries. Several process concepts have been developed and applied for improving the performance of classical batch chromatography. The most powerful approaches include various single-column recycling schemes, counter-current and cross-current multi-column setups, and hybrid processes where chromatography is coupled with other unit operations such as crystallization, chemical reactor, and/or solvent removal unit. To fully utilize the potential of stand-alone and integrated chromatographic processes, efficient methods for selecting the best process alternative as well as optimal operating conditions are needed. In this thesis, a unified method is developed for analysis and design of the following singlecolumn fixed bed processes and corresponding cross-current schemes: (1) batch chromatography, (2) batch chromatography with an integrated solvent removal unit, (3) mixed-recycle steady state recycling chromatography (SSR), and (4) mixed-recycle steady state recycling chromatography with solvent removal from fresh feed, recycle fraction, or column feed (SSR–SR). The method is based on the equilibrium theory of chromatography with an assumption of negligible mass transfer resistance and axial dispersion. The design criteria are given in general, dimensionless form that is formally analogous to that applied widely in the so called triangle theory of counter-current multi-column chromatography. Analytical design equations are derived for binary systems that follow competitive Langmuir adsorption isotherm model. For this purpose, the existing analytic solution of the ideal model of chromatography for binary Langmuir mixtures is completed by deriving missing explicit equations for the height and location of the pure first component shock in the case of a small feed pulse. It is thus shown that the entire chromatographic cycle at the column outlet can be expressed in closed-form. The developed design method allows predicting the feasible range of operating parameters that lead to desired product purities. It can be applied for the calculation of first estimates of optimal operating conditions, the analysis of process robustness, and the early-stage evaluation of different process alternatives. The design method is utilized to analyse the possibility to enhance the performance of conventional SSR chromatography by integrating it with a solvent removal unit. It is shown that the amount of fresh feed processed during a chromatographic cycle and thus the productivity of SSR process can be improved by removing solvent. The maximum solvent removal capacity depends on the location of the solvent removal unit and the physical solvent removal constraints, such as solubility, viscosity, and/or osmotic pressure limits. Usually, the most flexible option is to remove solvent from the column feed. Applicability of the equilibrium design for real, non-ideal separation problems is evaluated by means of numerical simulations. Due to assumption of infinite column efficiency, the developed design method is most applicable for high performance systems where thermodynamic effects are predominant, while significant deviations are observed under highly non-ideal conditions. The findings based on the equilibrium theory are applied to develop a shortcut approach for the design of chromatographic separation processes under strongly non-ideal conditions with significant dispersive effects. The method is based on a simple procedure applied to a single conventional chromatogram. Applicability of the approach for the design of batch and counter-current simulated moving bed processes is evaluated with case studies. It is shown that the shortcut approach works the better the higher the column efficiency and the lower the purity constraints are.

Finnish doctoral dissertations of nursing education research

Nursing education research has confirmed its place in the discipline of nursing and caring sciences being one of the most central research areas. However, extensive and systematic analysis of nursing education research has been lacking both nationally and internationally. The aim of this study was to describe the focus of nursing education research in Finnish doctoral dissertations in the field of nursing and caring sciences between the years 1990–2014. In addition, the characteristics (i.e. methods, study informants and reporting of validity, reliability, and research ethics) of the dissertations were described. Also, international reviews (N=39) focusing on nursing education research were analysed for a background literature. A literature review was carried out. Altogether 51 (=N) Finnish doctoral dissertations of nursing and caring sciences in the field of nursing education research were included in the final analysis. The data for this research was collected from the open publication lists of each university offering education in nursing and caring sciences in Finland. The dissertations were published in 1990–2014. The data were analysed by content analysis both deductively and inductively. This study consists of a scientific article manuscript and a background literature review. Nursing education research has focused both nationally and internationally on four main areas: structural factors in nursing education, nurse teacherhood, teaching activities, and learning and learning outcomes in nursing education. In Finland, the most central focus area was learning (84.3 %) whereas nurse teacherhood and structural factors in nursing education were studied the least. Students were the predominant study informant group while nurse staff including nurse mentors were next and nurse educators only the third. Surveys and interviews were the most common data collection methods. In the findings there were a lot of similarities with international reviews of nursing education research. Finnish nursing education research has been very student-centred yet studies focusing on the education of other nursing based professions or different levels of education are rare. Future research about nurse teacherhood, curricula and structural factors in nursing education is recommended. There is also a need for experimental designs. In addition, nursing education research should focus on the central phenomena of nursing education and working life. All in all, more nursing education research is needed. Nursing education dissertations cover only 12.3 % of all the dissertations of nursing and caring sciences in Finland.