62 resultados para likelihood to publication
Resumo:
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.
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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.
Resumo:
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.
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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.
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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.
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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.
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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.
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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.
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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.
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It has long been known that amino acids are the building blocks for proteins and govern their folding into specific three-dimensional structures. However, the details of this process are still unknown and represent one of the main problems in structural bioinformatics, which is a highly active research area with the focus on the prediction of three-dimensional structure and its relationship to protein function. The protein structure prediction procedure encompasses several different steps from searches and analyses of sequences and structures, through sequence alignment to the creation of the structural model. Careful evaluation and analysis ultimately results in a hypothetical structure, which can be used to study biological phenomena in, for example, research at the molecular level, biotechnology and especially in drug discovery and development. In this thesis, the structures of five proteins were modeled with templatebased methods, which use proteins with known structures (templates) to model related or structurally similar proteins. The resulting models were an important asset for the interpretation and explanation of biological phenomena, such as amino acids and interaction networks that are essential for the function and/or ligand specificity of the studied proteins. The five proteins represent different case studies with their own challenges like varying template availability, which resulted in a different structure prediction process. This thesis presents the techniques and considerations, which should be taken into account in the modeling procedure to overcome limitations and produce a hypothetical and reliable three-dimensional structure. As each project shows, the reliability is highly dependent on the extensive incorporation of experimental data or known literature and, although experimental verification of in silico results is always desirable to increase the reliability, the presented projects show that also the experimental studies can greatly benefit from structural models. With the help of in silico studies, the experiments can be targeted and precisely designed, thereby saving both money and time. As the programs used in structural bioinformatics are constantly improved and the range of templates increases through structural genomics efforts, the mutual benefits between in silico and experimental studies become even more prominent. Hence, reliable models for protein three-dimensional structures achieved through careful planning and thoughtful executions are, and will continue to be, valuable and indispensable sources for structural information to be combined with functional data.
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Intermediate filaments are part of the cytoskeleton and nucleoskeleton; they provide cells with structure and have important roles in cell signalling. The IFs are a large protein family with more than 70 members; each tightly regulated and expressed in a cell type-specific manner. Although the IFs have been known and studied for decades, our knowledge about their specific functions is still limited, despite the fact that mutations in IF genes cause numerous severe human diseases. In this work, three IF proteins are examined more closely; the nuclear lamin A/C and the cytoplasmic nestin and vimentin. In particular the regulation of lamin A/C dynamics, the role of nestin in muscle and body homeostasis as well as the functions and evolutionary aspects of vimentin are investigated. Together this data highlights some less well understood functions of these IFs. We used mass-spectrometry to identify inter-phase specific phosphorylation sites on lamin A. With the use of genetically engineered lamin A protein in combination with high resolution microscopy and biochemical methods we discovered novel roles for this phosphorylation in regulation of lamin dynamics. More specifically, our data suggests that the phosphorylation of certain amino acids in lamin A determines the localization and dynamics of the protein. In addition, we present results demonstrating that lamin A regulates Cdk5-activity. In the second study we use mice lacking nestin to gain more knowledge of this seldom studied protein. Our results show that nestin is essential for muscle regeneration; mice lacking nestin recover more slowly from muscle injury and show signs of spontaneous muscle regeneration, indicating that their muscles are more sensitive to stresses and injury. The absence of nestin also leads to decreased over-all muscle mass and slower body growth. Furthermore, nestin has a role in controlling testicle homeostasis as nestin-/- male mice show a greater variation in testicle size. The common fruit fly Drosophila melanogaster lacks cytoplasmic IFs as most insects do. By creating a fly that expresses human vimentin we establish a new research platform for vimentin studies, as well as provide a new tool for the studies of IF evolution.
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This study focuses on understanding the internationalisation of small and medium-sized enterprises (SMEs) from an emerging market to a developed market. In particular, it examines the internationalisation process of a firm in the clothing and textile manufacturing industry in Ghana. Theoretically, the study is limited to the network internationalisation approach (e.g. Johanson & Mattsson, 1988; Johanson & Vahlne, 2009) and the industrial network approach (Håkansson & Snehota, 1995). Methodologically, a qualitative abductive case study approach is employed. The research process relies on a longitudinal method involving primary and secondary data and critical event analysis. Primary data has been collected from relevant informants at two different times in the internationalisation process. The research findings highlight the significance of both domestic and foreign business relationships in the internationalisation of an SME from an emerging African market to a developed country market. They show the greater importance of exogenous critical events than has been found in the research regarding firms in developed countries. Institutional actors were essential in the network and as sources of exogenous critical events. In addition, the successful SME should possess unique resources in the form of an entrepreneurial spirit, sufficient knowledge of internationalisation, and specific product knowledge. Theoretically, the present study contributes to business network research through providing an understanding of the process of developing network relationships and their impact in an African context. By focusing on SMEs, a contribution has been made in relation to the advancement of SME research. This research reveals empirical insight into SME internationalisation in a setting where an SME is internationalising to a developed country market from a newly emerging African market. Methodologically, the study provides an example of longitudinal research based on abductive methodology. The results provide implications for firms, managers, and policy-makers within the industry, especially on how to manage and use network relationships to promote SME internationalisation from newly emerging markets.
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This study focuses on teacher practices in publicly funded music schools in Finland. As views on the aims of music education change and broaden, music schools across Europe share the challenge of developing their activities in response. In public and scholarly debate, there have been calls for increased diversity of contents and concepts of teaching. In Finland, the official national curriculum for state-funded music schools builds on the ideal that teaching and learning should create conditions which promote ‘a good relationship to music’. The meaning of this concept has been deliberately left open in order to leave room for dialogue, flexibility, and teacher autonomy. Since what is meant by ‘good’ is not defined in advance, the notion of ‘improving’ practices is also open to discussion. The purpose of the study is to examine these issues from teachers’ point of view by asking what music school teachers aim to accomplish as they develop their practices. Methodologically, the study introduces a suggestion for building empirical research on Alperson’s ‘robust’ praxial approach to music education, a philosophical theory which is strongly committed to practitioner perspectives and musical diversity. A systematic method for analysing music education practices, interpretive practice analysis, is elaborated with support from interpretive research methods originally used in policy analysis. In addition, the research design shows how reflecting conversations (a collaborative approach well-known in Nordic social work) can be fruitfully applied in interpretive research and combined with teacher inquiry. Data have been generated in a collaborative project involving five experienced music school teachers and the researcher. The empirical material includes transcripts from group conversations, data from teacher inquiry conducted within the project, and transcripts from follow-up interviews. The teachers’ aspirations can be understood as strivings to reinforce the connection between musical practices and various forms of human flourishing such that music and flourishing can sustain each other. Examples from their practices show how the word ‘good’ receives its meaning in context. Central among the teachers’ concerns is their hope that students develop a free and sustainable interest in music, often described as inspiration. I propose that ‘good relationships to music’ and ‘inspiration’ can be understood as philosophical mediators which support the transition from an indeterminate ‘interest in music’ towards specific ways in which music can become a (co-)constitutive part of living well in each person’s particular circumstances. Different musical practices emphasise different aspects of what is considered important in music and in human life. Music school teachers consciously balance between a variety of such values. They also make efforts to resist pressure which might threaten the goods they think are most important. Such goods include joy, participation, perseverance, solid musical skills related to specific practices, and a strong sense of vitality. The insights from this study suggest that when teachers are able to create inspiration, they seem to do so by performing complex work which combines musical and educational aims and makes general positive contributions to their students’ lives. Ensuring that teaching and learning in music schools remain as constructive and meaningful as possible for both students and teachers is a demanding task. The study indicates that collaborative, reflective and interdisciplinary work may be helpful as support for development processes on both individual and collective levels of music school teacher practices.