A Model for Integrating the Publication and Preservation of Journal Articles

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Ionic liquid mediated biomass deconstruction: from analysis challenges to fermentable sugars

Ionic liquids, ILs, have recently been studied with accelerating interest to be used for a deconstruction/fractionation, dissolution or pretreatment processing method of lignocellulosic biomass. ILs are usually utilized combined with heat. Regarding lignocellulosic recalcitrance toward fractionation and IL utilization, most of the studies concern IL utilization in the biomass fermentation process prior to the enzymatic hydrolysis step. It has been demonstrated that IL-pretreatment gives more efficient hydrolysis of the biomass polysaccharides than enzymatic hydrolysis alone. Both cellulose (especially cellulose) and lignin are very resistant towards fractionation and even dissolution methods. As an example, it can be mentioned that softwood, hardwood and grass-type plant species have different types of lignin structures leading to the fact that softwood lignin (guaiacyl lignin dominates) is the most difficult to solubilize or chemically disrupt. In addition to the known conventional biomass processing methods, several ILs have also been found to efficiently dissolve either cellulose and/or wood samples – different ILs are suitable for different purposes. An IL treatment of wood usually results in non-fibrous pulp, where lignin is not efficiently separated and wood components are selectively precipitated, as cellulose is not soluble or degradable in ionic liquids under mild conditions. Nevertheless, new ILs capable of rather good fractionation performance have recently emerged. The capability of the IL to dissolve or deconstruct wood or cellulose depends on several factors, (e.g. sample origin, the particle size of the biomass, mechanical treatments as pulverization, initial biomassto-IL ratio, water content of the biomass, possible impurities of IL, reaction conditions, temperature etc). The aim of this study was to obtain (fermentable) saccharides and other valuable chemicals from wood by a combined heat and IL-treatment. Thermal treatments alone contribute to the degradation of polysaccharides (e.g. 150 °C alone is said to cause the degradation of polysaccharides), thus temperatures below that should be used, if the research interest lies on the IL effectiveness. On the other hand, the efficiency of the IL-treatment can also be enhanced to combine other treatment methods, (e.g. microwave heating). The samples of spruce, pine and birch sawdust were treated with either 1-Ethyl-3-methylimidazolium chloride, Emim Cl, or 1-Ethyl-3-methylimidazolium acetate, Emim Ac, (or with ionized water for comparison) at various temperatures (where focus was between 80 and 120 °C). The samples were withdrawn at fixed time intervals (the main interest treatment time area lied between 0 and 100 hours). Double experiments were executed. The selected mono- and disaccharides, as well as their known degradation products, 5-hydroxymethylfurfural, 5-HMF, and furfural were analyzed with capillary electrophoresis, CE, and high-performance liquid chromatography, HPLC. Initially, even GC and GC-MS were utilized. Galactose, glucose, mannose and xylose were the main monosaccharides that were present in the wood samples exposed to ILs at elevated temperatures; in addition, furfural and 5-HMF were detected; moreover, the quantitative amount of the two latter ones were naturally increasing in line with the heating time or the IL:wood ratio.

Design and evaluation of web interface signs to improve web usability : a semiotic framework

Technological innovations, the development of the internet, and globalization have increased the number and complexity of web applications. As a result, keeping web user interfaces understandable and usable (in terms of ease-of-use, effectiveness, and satisfaction) is a challenge. As part of this, designing userintuitive interface signs (i.e., the small elements of web user interface, e.g., navigational link, command buttons, icons, small images, thumbnails, etc.) is an issue for designers. Interface signs are key elements of web user interfaces because ‘interface signs’ act as a communication artefact to convey web content and system functionality, and because users interact with systems by means of interface signs. In the light of the above, applying semiotic (i.e., the study of signs) concepts on web interface signs will contribute to discover new and important perspectives on web user interface design and evaluation. The thesis mainly focuses on web interface signs and uses the theory of semiotic as a background theory. The underlying aim of this thesis is to provide valuable insights to design and evaluate web user interfaces from a semiotic perspective in order to improve overall web usability. The fundamental research question is formulated as What do practitioners and researchers need to be aware of from a semiotic perspective when designing or evaluating web user interfaces to improve web usability? From a methodological perspective, the thesis follows a design science research (DSR) approach. A systematic literature review and six empirical studies are carried out in this thesis. The empirical studies are carried out with a total of 74 participants in Finland. The steps of a design science research process are followed while the studies were designed and conducted; that includes (a) problem identification and motivation, (b) definition of objectives of a solution, (c) design and development, (d) demonstration, (e) evaluation, and (f) communication. The data is collected using observations in a usability testing lab, by analytical (expert) inspection, with questionnaires, and in structured and semi-structured interviews. User behaviour analysis, qualitative analysis and statistics are used to analyze the study data. The results are summarized as follows and have lead to the following contributions. Firstly, the results present the current status of semiotic research in UI design and evaluation and highlight the importance of considering semiotic concepts in UI design and evaluation. Secondly, the thesis explores interface sign ontologies (i.e., sets of concepts and skills that a user should know to interpret the meaning of interface signs) by providing a set of ontologies used to interpret the meaning of interface signs, and by providing a set of features related to ontology mapping in interpreting the meaning of interface signs. Thirdly, the thesis explores the value of integrating semiotic concepts in usability testing. Fourthly, the thesis proposes a semiotic framework (Semiotic Interface sign Design and Evaluation – SIDE) for interface sign design and evaluation in order to make them intuitive for end users and to improve web usability. The SIDE framework includes a set of determinants and attributes of user-intuitive interface signs, and a set of semiotic heuristics to design and evaluate interface signs. Finally, the thesis assesses (a) the quality of the SIDE framework in terms of performance metrics (e.g., thoroughness, validity, effectiveness, reliability, etc.) and (b) the contributions of the SIDE framework from the evaluators’ perspective.

From genes to communities : stress tolerance in eelgrass (Zostera marina)

Shallow coastal areas are dynamic habitats that are affected by a variety of abiotic and biotic factors. In addition to the natural environmental stress, estuarine and coastal seagrass ecosystems are exposed to effects of climate change and other anthropogenic impacts. In this thesis the effect of different abiotic (shading stress, salinity and temperature) and biotic stressors (presence of co-occurring species) and different levels and combinations of stressors on the performance and survival of eelgrass (Zostera marina) was assessed. To investigate the importance of scale for stress responses, varying levels of biological organization (genotype, life stage, population and plant community) were studied in field and aquarium experiments. Light limitation, decreased salinity and increased temperature affected eelgrass performance negatively in papers I, II and III, respectively. While co-occurring plant species had no notable effect on eelgrass in paper IV, the presence of eelgrass increased the biomass of Potamogeton perfoliatus. The findings in papers II and III confirmed that more extreme levels of salinity and temperature had stronger impacts on plant performance compared to intermediate levels, but intermediate levels also had more severe effects on plants when they were exposed to several stressors, as illustrated in paper II. Thus, multiple stressors had negative synergetic effects. The results in papers I, II and III indicate that future changes in light climate, salinity and temperature can have serious impacts on eelgrass performance and survival. Stress responses were found to vary among genotypes, life stages and populations in papers I, II and III, respectively, emphasizing the importance of study scale. The results demonstrate that while stress in general affects seagrass productivity negatively, the severity of effects can vary substantially depending on the studied scale or level of biological organization. Eelgrass genotypes can differ in their stress and recovery processes, as observed in paper I. In paper II, eelgrass seedlings were less prone to abiotic stress compared to adult plants, but stress also decreased their survival considerably. This indicates that recruitment and re-colonization through seeds might be threatened in the future. Variation among population responses observed in paper III indicates that long-term local adaptation under differing selection pressures has caused divergence in salinity tolerance between Baltic eelgrass populations. This variability in stress tolerance observed in papers I and III suggests that some eelgrass genotypes and populations have a better capacity to adapt to changes and survive in a changing environment. Multiple stressors and biological level-specific responses demonstrate the uncertainty in predicting eelgrass responses in a changing environment. As eelgrass populations may differ in their stress tolerance both within and across regions, conservation strategies at both local and regional scales are urgently needed in order to ensure the survival of these important ecosystems.

Spiritual Gifts according to C. Peter Wagner

Nådegåvorna eller de andliga gåvorna är en betydande drivkraft hos en del kristna församlingar. Lekmän attraheras till församlingar i ökande grad av nådegåvornas dragkraft och detta är en global trend. C. Peter Wagner som tidigare arbetat som professor vid Fuller Theological Seminary har skrivit ovanligt många publikationer, både akademiska och allmänna, som behandlar nådegåvor. Han representerar den neokarismatiska kristendomen och den så kallade nya apostoliska reformationen. Jag har undersökt strukturer och grundläggande principer i Wagners tänkande. En central fråga i avhandlingen är att dryfta vilka styrkor och svagheter som kan påvisas i hans uppfattning om församlingslivet. En ytterligare målsättning är att hitta länkar mellan nådegåvorna och församlingens tillväxt. Vidare har jag undersökt förhållandet mellan den neokarismatiska kristendomen och den nya apostoliska reformationen till tidigare karismatiska rörelser, till exempel till neopentekostalismen och den klassiska pentekostalismen? I denna avhandling kommer dessa frågor och några andra att diskuteras. Kännetecknande för Wagners församlingslära är att han kombinerar metoder och element från businessvärlden och kristliga tron. Avhandlingen presenterar de centrala elementen i Wagners teologi. Wagner har tidigare karakteriserats av klart evangelikalt tänkande. Hans teologi har dock under senare år utvecklats i karismatisk riktning. Hans senare produktion tar upp bl.a. sådana teman som postmillennial eskatologi. Wagner uppskattar grunderna i den klassiska pentekostalismen men vidareutvecklar många läror. Hans tänkande skiljer sig från den klassiska pentekostalismen bl.a. i det att han ser likheter mellan nådegåvorna och de naturliga begåvningarna. Den kraftiga betoningen av apostelns funktion och den hierarki som detta medför i församlingen har väckt anstöt hos somliga ledare i den klassiska pingströrelsen. Wagern anser, i motsats till den klassiska pingströrelsens syn, att en kristen människa kan vara besatt av onda andar. Wagner indelar nådegåvorna i två olika viktiga kategorier. Till de för församlingen centrala nådegåvorna hör de apostoliska och profetiska nådegåvorna som tillsammans utgör de grundläggande gåvorna. Vidare betonar han betydelsen av ledarskap och trons nådegåva samt den så kallade "power evangelism", som omfattar övertygande evangelisation, helande och under. Vidare betonar Wagner vikten av de nådegåvor som behövs vid andlig krigföring: förmågan att skilja mellan olika andar, frigöring från unda andar och förbön. De nådegåvor som har med tjänande och själavård att göra får en mer perifer plats i hans tänkande. De andliga gåvor som befrämjar församlingens tillväxt och förkristnande av samhället betraktas som de viktigaste. Wagners teologi nyanseras ytterligare av kopplingar till postmillenial rekonstruktivism, den så kallade "Kingdom Now" teologin och rörelsen Word of Faith. Wagerns postmilleniala syn förpliktar de kristina att anta en aktiv roll vid förverkligandet av Guds rike på jorden före parusi. Wagner har fått kritik för det att han ger kristendomen marknadsekonomiska drag. Dessa element kommer till synes i bl.a. i hans tanke om att Gud belönar de kristna med förmögenhet som tas från de icke-kristna. Wagners ställning som teolog är omdiskuterad. Han förbinder sig vid den kristna tronbekännelsen och är på sitt sätt bibeltrogen, men de animistiska dragen och kapitalismens inflytande i hans teologi gör honom till en omstridd person.

Nordic alcohol policy in Europe: the adaptation of Finland’s, Sweden’s and Norway’s alcohol policies to a new policy framework, 1994-2013

The purpose of this thesis is to study how and to which extent Finland, Sweden and Norway have adapted their alcohol policies to the framework imposed to them by the EU and the European Economic Area (EEA) since the mid-1990s. This is done by studying the underlying mechanisms that have influenced the formation of alcohol policy in the Nordic countries in that period. As a part of this analysis main differences in alcohol policies and alcohol consumption between the three countries are assessed and the phenomenon of cross-border trade with alcohol is discussed. The study examines also the development of Finnish, Norwegian and Swedish alcohol policies between 1994 and 2012 and compares the Nordic alcohol policies with other alcohol policies in Europe as the situation was in 2012. The time frame of the study spans from the mid-1990s to the end of 2013 and is divided into three phases. Studying the role of the Europeanisation process on the formation of alcohol policies has a key role in the analysis. Besides alcohol policies, the analyses comprise the development of alcohol consumption and cross-border trade with alcohol. In addition, a quantitative scale constructed to measure the strictness of alcohol policies is utilised in the analyses. The results from the scale are used to substantiate the qualitative analysis and to test whether the stereotypical view of a strict Nordic alcohol policy is still true. The results from the study clearly corroborate earlier findings on the significance of Europeanisation and the Single Market for the development of alcohol policies in the Nordic countries. Free movement of goods and unhindered competition have challenged the principle of disinterest and enabled private profit seeking in alcohol trade. The Single Market has also contributed to the increase in availability of alcohol and made it more difficult for the Nordic EU member states to maintain restrictive alcohol policies. All in all, alcohol policies in the Nordic countries are more liberal in 2013 than they were in 1994. Norway, being outside the EU has, however, managed to maintain a stricter alcohol policy than Finland and Sweden. Norway has also been spared from several EU directives that have affected Finland and Sweden, the most remarkable being the abolishment of the travellers’ import quotas for alcohol within the EU. Due to its position as a non-EU country Norway has been able to maintain high alcohol taxes without being subjected to a ”race to the bottom” regarding alcohol taxes the same way as Finland and Sweden. Finland distinguishes as the country that has liberalised its alcohol policy most during the study period. The changes in alcohol policies were not only induced by Europeanisation and the Single Market, but also by autonomous decision-making and political processes in the individual countries. Furthermore, the study shows that alcohol policy measures are implemented more widely in Europe than before and that there is a slow process of convergence going on regarding alcohol policy in Europe. Despite this, alcohol policies in the Nordic countries are still by far the strictest in all of Europe. From a Europeanisation perspective, the Nordic countries were clearly on the receiving end during the first two study phases (1994–2007), having more to adjust to rules from the EU and the Single Market than having success in uploading and shaping alcohol policy on the European and international field. During the third and final study phase (2008–2013), however, the Nordic countries have increasingly succeeded in contributing to shape the alcohol policy arena in the EU and also more widely through the WHOs global alcohol strategy. The restrictive Nordic policy tradition on which the current alcohol policies in Finland, Sweden and Norway were built on has still quite a solid evidence base. Although the basis of the restrictive alcohol policy has crumbled somewhat during the past twenty years and the policies have become less effective, nothing prevents it from being the base for alcohol policy in the Nordic countries even in the long term. In the future, all that is needed for an effective and successful alcohol policy is a solid evidence base, enough political will and support from the general public.

Catalytic upgrading of biomass extractives to fine chemicals over supported ionic liquid catalysts (SILCAs)

Behovet av förnyelsebar energi ökar ständigt eftersom det finns en strävan att minska beroendet av fossila bränslen. Dessutom är tillgångar av fossila bränslen begränsade. Miljövänliga processer för bioraffinaderier erbjuder en stor möjlighet för produktion av energi, bränslen och kemikalier. Den finska och svenska skogsindustrin har en lång tradition i utnyttjandet av skogsbiomassor. Bioraffinaderier som integreras med pappers- och cellulosaindustrin kan frambringa både ekonomiska och ekologiska fördelar i framställning av traditionella och biobaserade produkter. I doktorsarbetet studerades omvandling av extraktivämnen till finkemikalier som kan användas t.ex. av läkemedelsindustrin. Extraktivämnen fås ur biomassa. I forskningsarbetet framställdes biobaserade finkemikalier med hjälp av katalysatorer som baserar sig på joniska vätskor. Biomassan består av cellulosa, hemicellulosa, lignin och extraktivämnen, vilka huvudsakligen är terpener, vaxer och fettsyror. Extraktivämen är vedens komponenter, som kan separeras ur vedmaterialet med hjälp av neutrala lösningsmedel. Joniska vätskekatalysatorer som var immobiliserade på fasta bärare utnyttjades för isomerisering av α,β-pinenoxider samt hydrogenering citral. Inverkan av joniska vätskor på katalysatorns aktivitet och reaktionernas produktfördelning undersöktes under varierande reaktionsbetingelser. Kinetiska modeller för pinenoxidens isomeriseringsreaktioner beskrev väl experimentellt upptäckta skillnader mellan olika katalysatorer. --------------------------------------------------- Uusiutuvan energian tarve on kasvussa, koska riippuvuutta fossiilisista polttoaineista pyritään vähentämään. Tämän lisäksi fossiilisten polttoaineiden varannot ovat rajalliset. Ympäristöystävälliset biojalostusprosessit ovat näin ollen suuri mahdollisuus energian, polttoaineiden ja kemikaalien tuotannossa. Suomen ja Ruotsin metsäteollisuudella on pitkät perinteet metsäbiomassojen hyödyntämisessä. Paperi- ja selluteollisuuden yhteyteen integroiduilla biojalostamoilla voidaan luoda taloudellisia ja ympäristöllisiä etuja sekä perinteisten että biopohjaisten tuotteiden valmistuksessa. Väitöstyössä on tutkittu biomassan uuteaineiden kemiallista muuntamista hienokemikaaleiksi, joita voidaan käyttää esimerkiksi lääkeaineteollisuudessa. Biopohjaisia hienokemikaaleja on valmistettu biomassan uuteaineista ionisiin nesteisiin perustuvilla katalyyteillä. Biomassa koostuu selluloosasta, hemiselluloosasta, ligniinistä sekä uuteaineista, jotka ovat pääosin terpeenejä, vahoja tai rasvahappoja. Uuteaineet ovat puun komponentteja, jotka voidaan erottaa puusta neutraalien liuottimien avulla. Kiinteän kantajan päälle immobilisoituja ionisia nestekatalyyttejä (Supported Ionic Liquid Catalyst) hyödynnettiin α,β-pineenioksidien isomerisointireaktioissa sekä sitraalin vedytysreaktioissa. Ionisten nesteiden vaikutusta katalyyttien aktiivisuuteen sekä reaktioiden tuotejakaumaan tutkittiin erilaisissa reaktio-olosuhteissa. Pineenioksidien isomerisointireaktioiden kineettiset mallit kuvasivat hyvin kokeellisesti todettuja katalyyttien eroavaisuuksia.

Prognostic Factors In Breast Cancer. With Special Reference to Cyclins A, B1, D1 and E, MMP-1 and Decorin

Breast cancer is a highly heterogenous malignancy, which despite of the similar histological type shows different clinical behaviour and response to therapy. Prognostic factors are used to estimate the risk for recurrence and the likelihood of treatment effectiveness. Because breast cancer is one of the most common causes of cancer death in women worldwide, identification of new prognostic markers are needed to develop more specific and targeted therapies. Cancer is caused by uncontrolled cell proliferation. The cell cycle is controlled by specific proteins, which are known as cyclins. They function at important checkpoints by activating cyclin-dependent kinase enzymes. Overexpression of different cyclins has been linked to several cancer types and altered expression of cyclins A, B1, D1 and E has been associated with poor survival. Little is known about the combined expression of cyclins in relation to the tumour grade, breast cancer subtype and other known prognostic factors. In this study cyclins A, B1 and E were shown to correlate with histological grade, Ki-67 and HER2 expression. Overexpression of cyclin D1 correlated with receptor status and non-basal breast cancer suggesting that cyclin D1 might be a marker of good prognosis. Proteolysis in the surrounding tumour stroma is increased during cancer development. Matrix metalloproteinases (MMPs) are proteolytic enzymes that are capable of degrading extracellular matrix proteins. Increased expression and activation of several MMPs have been found in many cancers and MMPs appear to be important regulators of invasion and metastasis. In this study MMP-1 expression was analysed in breast cancer epithelial cells and in cancer associated stromal cells. MMP-1 expression by breast cancer epithelial cells was found to carry an independent prognostic value as did Ki-67 and bcl-2. The results suggest that in addition to stromal cells MMP-1 expression in tumour cells control breast cancer progression. Decorin is a small proteoglycan and an important component of the extracellular matrix. Decorin has been shown to inhibit growth of tumour cells and reduced decorin expression is associated with a poor prognosis in several cancer types. There has been some suspicion wheather different cancer cells express decorin. In this study decorin expression was shown to localize only in the cells of the original stroma, while breast cancer epithelial cells were negative for decorin expression. However, transduction of decorin in decorin-negative human breast cancer cells markedly modulated the growth pattern of these cells. This study provides evidence that targeted decorin transduction to breast cancer cells could be used as a novel adjuvant therapy in breast malignancies.

Strategic management of value networks: how to create value in cross-sector collaboration and partnerships

Cross-sector collaboration and partnerships have become an emerging and desired strategy in addressing huge social and environmental challenges. Despite its popularity, cross-sector collaboration management has proven to be very challenging. Even though cross-sector collaboration and partnership management have been widely studied and discussed in recent years, their effectiveness as well as their ability to create value with respect to the problems they address has remained very challenging. There is little or no evidence of their ability to create value. Regarding all these challenges, this study aims to explore how to manage cross-sector collaborations and partnerships to be able to improve their effectiveness and to create more value for all partners involved in collaboration as well as for customers. The thesis is divided into two parts. The first part comprises an overview of relevant literature (including strategic management, value networks and value creation theories), followed by presenting the results of the whole thesis and the contribution made by the study. The second part consists of six research publications, including both quantitative and qualitative studies. The chosen research strategy is triangulation, as the study includes four types of triangulation: (1) theoretical triangulation, (2) methodological triangulation, (3) data triangulation and (4) researcher triangulation. Two publications represent conceptual development, which are based on secondary data research. One publication is a quantitative study, carried out through a survey. The other three publications represent qualitative studies, based on case studies, where data was collected through interviews and workshops, with participation of managers from all three sectors: public, private and the third (nonprofit). The study consolidates the field of “strategic management of value networks,” which is proposed to be applied in the context of cross-sector collaboration and partnerships, with the aim of increasing their effectiveness and the process of value creation. Furthermore, the study proposes a first definition for the strategic management of value networks. The study also proposes and develops two strategy tools that are recommended to be used for the strategic management of value networks in cross-sector collaboration and partnerships. Taking a step forward, the study implements the strategy tools in practice, aiming to show and to demonstrate how new value can be created by using the developed strategy tools for the strategic management of value networks. This study makes four main contributions. (1) First, it brings a theoretical contribution by providing new insights and consolidating the field of strategic management of value networks, also proposing a first definition for the strategic management of value networks. (2) Second, the study makes a methodical contribution by proposing and developing two strategy tools for value networks of cross-sector collaboration: (a) value network mapping, a method that allows us to assess the current and the potential value network and (b) the Value Network Scorecard, a method of performance measurement and performance prediction in cross-sector collaboration. (3) Third, the study has managerial implications, offering new solutions and empirical evidence on how to increase the effectiveness of cross-sector collaboration and also allow managers to understand how new value can be created in cross-sector partnerships and how to get the full potential of collaboration. (4) And fourth, the study also has practical implications, allowing managers to understand how to use in practice the strategy tools developed in this study, providing discussions on the limitations regarding the proposed tools as well as general limitations involved in the study.

The collective dimension of freedom of religion or belief in international law : the application of findings to the case of Turkey

Pertinent domestic and international developments involving issues related to tensions affecting religious or belief communities have been increasingly occupying the international law agenda. Those who generate and, thus, shape international law jurisprudence are in the process of seeking some of the answers to these questions. Thus the need for reconceptualization of the right to freedom of religion or belief continues as demands to the right to freedom of religion or belief challenge the boundaries of religious freedom in national and international law. This thesis aims to contribute to the process of “re-conceptualization” by exploring the notion of the collective dimension of freedom of religion or belief with a view to advance the protection of the right to freedom of religion or belief. The case of Turkey provides a useful test case where both the domestic legislation can be assessed against international standards, while at the same time lessons can be drawn for the improvement of the standard of international review of the protection of the collective dimension of freedom of religion or belief. The right to freedom of religion or belief, as enshrined in international human rights documents, is unique in its formulation in that it provides protection for the enjoyment of the rights “in community with others”.1 It cannot be realized in isolation; it crosses categories of human rights with aspects that are individual, aspects that can be effectively realized only in an organized community of individuals and aspects that belong to the field of economic, social and cultural rights such as those related to religious or moral education. This study centers on two primary questions; first, what is the scope and nature of protection afforded to the collective dimension of freedom of religion or belief in international law, and, secondly, how does the protection of the collective dimension of freedom of religion or belief in Turkey compare and contrast to international standards? Section I explores and examines the notion of the collective dimension of freedom of religion or belief, and the scope of its protection in international law with particular reference to the right to acquire legal personality and autonomy religious/belief communities. In Section II, the case study on Turkey constitutes the applied part of the thesis; here, the protection of the collective dimension is assessed with a view to evaluate the compliance of Turkish legislation and practice with international norms as well as seeking to identify how the standard of international review of the collective dimension of freedom of religion or belief can be improved.

Selection of patients for myocardial perfusion scintigraphy based on fuzzy sets theory applied to clinical-epidemiological data and treadmill test results

Coronary artery disease (CAD) is a worldwide leading cause of death. The standard method for evaluating critical partial occlusions is coronary arteriography, a catheterization technique which is invasive, time consuming, and costly. There are noninvasive approaches for the early detection of CAD. The basis for the noninvasive diagnosis of CAD has been laid in a sequential analysis of the risk factors, and the results of the treadmill test and myocardial perfusion scintigraphy (MPS). Many investigators have demonstrated that the diagnostic applications of MPS are appropriate for patients who have an intermediate likelihood of disease. Although this information is useful, it is only partially utilized in clinical practice due to the difficulty to properly classify the patients. Since the seminal work of Lotfi Zadeh, fuzzy logic has been applied in numerous areas. In the present study, we proposed and tested a model to select patients for MPS based on fuzzy sets theory. A group of 1053 patients was used to develop the model and another group of 1045 patients was used to test it. Receiver operating characteristic curves were used to compare the performance of the fuzzy model against expert physician opinions, and showed that the performance of the fuzzy model was equal or superior to that of the physicians. Therefore, we conclude that the fuzzy model could be a useful tool to assist the general practitioner in the selection of patients for MPS.

Transformation of carbon dioxide to diethyl carbonate over ceria and ceria-supported catalysts

Carbon dioxide is regarded, nowadays, as a primary anthropogenic greenhouse gas leading to global warming. Hence, chemical fixation of CO2 has attracted much attention as a possible way to manufacture useful chemicals. One of the most interesting approaches of CO2 transformations is the synthesis of organic carbonates. Since conventional production technologies of these compounds involve poisonous phosgene and carbon monoxide, there is a need to develop novel synthetic methods that would better match the principles of "Green Chemistry" towards protection of the environment and human health. Over the years, synthesis of dimethyl carbonate was under intensive investigation in the academia and industry. Therefore, this study was entirely directed towards equally important homologue of carbonic esters family namely diethyl carbonate (DEC). Novel synthesis method of DEC starting from ethanol and CO2 over heterogeneous catalysts based on ceria (CeO2) was studied in the batch reactor. However, the plausible drawback of the reaction is thermodynamic limitations. The calculated values revealed that the reaction is exothermic (ΔrHØ298K = ─ 16.6 J/ ) and does not occur spontaneously at rooms temperature (ΔrGØ 298K = 35.85 kJ/mol). Moreover, co-produced water easily shifts the reaction equilibrium towards reactants excluding achievement of high yields of the carbonate. Therefore, in-situ dehydration has been applied using butylene oxide as a chemical water trap. A 9-fold enhancement in the amount of DEC was observed upon introduction of butylene oxide to the reaction media in comparison to the synthetic method without any water removal. This result confirms that reaction equilibrium was shifted in favour of the desired product and thermodynamic boundaries of the reaction were suppressed by using butylene oxide as a water scavenger. In order to obtain insight into the reaction network, the kinetic experiments were performed over commercial cerium oxide. On the basis of the selectivity/conversion profile it could be concluded that the one-pot synthesis of diethyl carbonate from ethanol, CO2 and butylene oxide occurs via a consecutive route involving cyclic carbonate as an intermediate. Since commercial cerium oxide suffers from the deactivation problems already after first reaction cycle, in-house CeO2 was prepared applying room temperature precipitation technique. Variation of the synthesis parameters such as synthesis time, calcination temperature and pH of the reaction solution turned to have considerable influence on the physico-chemical and catalytic properties of CeO2. The increase of the synthesis time resulted in high specific surface area of cerium oxide and catalyst prepared within 50 h exhibited the highest amount of basic sites on its surface. Furthermore, synthesis under pH 11 yielded cerium oxide with the highest specific surface area, 139 m2/g, among all prepared catalysts. Moreover, CeO2─pH11 catalyst demonstrated the best catalytic activity and 2 mmol of DEC was produced at 180 oC and 9 MPa of the final reaction pressure. In addition, ceria-supported onto high specific surface area silicas MCM-41, SBA-15 and silica gel were synthesized and tested for the first time as catalysts in the synthesis of DEC. Deposition of cerium oxide on MCM-41 and SiO2 supports resulted in a substantial increase of the alkalinity of the carrier materials. Hexagonal SBA-15 modified with 20 wt % of ceria exhibited the second highest basicity in the series of supported catalysts. Evaluation of the catalytic activity of ceria-supported catalysts showed that reaction carried out over 20 wt % CeO2-SBA-15 generated the highest amount of DEC.

From genotype to phenotype : diversity and population structure of Flavobacterium psychrophilum

Flavobacterium psychrophilum is the etiological agent of bacterial cold-water disease (BCWD) causing high fish mortalities and significant economic losses to the freshwater salmonid aquaculture industry around the world. Today BCWD outbreaks are mainly treated with environmentally hazardous antimicrobial agents and alternative preventative measures are urgently needed in order to ensure the well-being of animals and the sustainability of aquaculture. The diversity of pathogenic bacteria challenges the development of universal control strategies and in many cases the pathogen population structure, i.e. the total genetic diversity of the species must be taken into account. This work integrates the tools of modern molecular biology and conventional phenotypic microbiology to gain knowledge about the diversity and population structure of F. psychrophilum. The present work includes genetic characterization of a large collection of isolates collected from diverse origins and years, from aquaculture in a whole region including different countries, and provides the first international validation of a universal multilocus sequence typing (MLST) approach for unambiguous genetic typing of F. psychrophilum. Population structure analyses showed that the global F. psychrophilum population is subdivided into pathogenic species-specific clones, of which one particular genetic lineage, clonal complex CC-ST2, has been responsible for the majority of BCWD outbreaks in rainbow trout (Oncorhynchus mykiss) in European aquaculture facilities over several decades. Genotypic and phenotypic population heterogeneity affecting antimicrobial resistance in F. psychrophilum within BCWD outbreaks was discovered. Specific genotypes were associated with severe infections in farmed rainbow trout and Atlantic salmon (Salmo salar), and in addition to high adherence, antimicrobial resistance was strongly associated with outbreak strains. The study brought additional support for the hypothesis of an epidemic F. psychrophilum population structure, where recombination is an important force for the generation and maintenance of genetic diversity, and a significant contribution towards mapping the genetic diversity of this important fish pathogen. Evidence indicating dissemination of virulent strains with commercial movement of fish and fish products was strengthened.

To divide or differentiate? : nestin-mediated regulation of Cdk5 in cell fate decisions

The molecular functions of the non-cell cycle-related Cyclin-dependent kinase 5 (Cdk5) have been of primary interest within the neuroscience field, but novel undertakings are constantly emerging for the kinase in tissue homeostasis, as well as in diseases such as diabetes and cancer. Although Cdk5 activation is predominantly regulated by specific non-cyclin activator protein binding, additional mechanisms have proved to orchestrate Cdk5 signaling in cells. For example, the interaction between the intermediate filament protein nestin and Cdk5 has been proposed to determine cellular fate during neuronal apoptosis through nestin-dependent adjustment of the sensitive balance and turnover of Cdk5 activators. While nestin constitutes a crucial regulatory scaffold for appropriate Cdk5 activation in apoptosis, Cdk5 itself phosphorylates nestin with the consequence of filament reorganization in both neuronal progenitors and differentiating muscle cells. Interestingly, the two proteins are often found coexpressed in various tissues and cell types, proposing that nestin-mediated scaffolding of Cdk5 and its activators may be applicable to other tissue systems as well. In the literature, the molecular functions of nestin have remained in the shade, as it is mostly exploited as a marker protein for progenitor cells. In light of these studies, the aim of this thesis was to assess the importance of the nestin scaffold in regulation of Cdk5 actions in cell fate decisions. This thesis can be subdivided into two major projects: one that studied the nature of the Cdk5-nestin interplay in muscle, and one that assessed their role in prostate cancer. During differentiation of a myoblast cell line, the filament formation properties of nestin was found to be crucial in directing Cdk5 activity, with direct consequences on the process of differentiation. Also the genetic knockout of nestin was found to influence Cdk5 activity, although differentiation per se was not affected. Instead, the genetic ablation of nestin had broad consequences on muscle homeostasis and regeneration. While the nestin-mediated regulation of Cdk5 in muscle was found to act in multiple ways, the connection remained more elusive in cancer models. Cdk5 was, however, established as a significant determinant of prostate cancer proliferation; a behavior uncharacteristic for this differentiation-associated kinase. Through complex and simultaneous regulation of two major prostate cancer pathways, Cdk5 was placed upstream of both Akt kinase and the androgen receptor. Its action on proliferation was nonetheless mainly exerted through the Akt signaling pathway in various cancer models. In summary, this thesis contributed to the knowledge of Cdk5 regulation and functions in two atypical settings; proliferation (in a cancer framework) and muscle differentiation, which is a poorly understood model system in the Cdk5 field. This balance between proliferation and differentiation implemented by Cdk5 is ultimately regulated (where present) by the dynamics of the cytoskeletal nestin scaffold.