6 resultados para tRNA-like structure

em Doria (National Library of Finland DSpace Services) - National Library of Finland, Finland


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The Swedish public health care organisation could very well be undergoing its most significant change since its specialisation during the late 19th and early 20th century. At the heart of this change is a move from using manual patient journals to electronic health records (EHR). EHR are complex integrated organisational wide information systems (IS) that promise great benefits and value as well as presenting great challenges to the organisation. The Swedish public health care is not the first organisation to implement integrated IS, and by no means alone in their quest for realising the potential benefits and value that it has to offer. As organisations invest in IS they embark on a journey of value-creation and capture. A journey where a costbased approach towards their IS-investments is replaced with a value-centric focus, and where the main challenges lie in the practical day-to-day task of finding ways to intertwine technology, people and business processes. This has however proven to be a problematic task. The problematic situation arises from a shift of perspective regarding how to manage IS in order to gain value. This is a shift from technology delivery to benefits delivery; from an ISimplementation plan to a change management plan. The shift gives rise to challenges related to the inability of IS and the elusiveness of value. As a response to these challenges the field of IS-benefits management has emerged offering a framework and a process in order to better understand and formalise benefits realisation activities. In this thesis the benefits realisation efforts of three Swedish hospitals within the same county council are studied. The thesis focuses on the participants of benefits analysis projects; their perceptions, judgments, negotiations and descriptions of potential benefits. The purpose is to address the process where organisations seek to identify which potential IS-benefits to pursue and realise, this in order to better understand what affects the process, so that realisation actions of potential IS-benefits could be supported. A qualitative case study research design is adopted and provides a framework for sample selection, data collection, and data analysis. It also provides a framework for discussions of validity, reliability and generalizability. Findings displayed a benefits fluctuation, which showed that participants’ perception of what constituted potential benefits and value changed throughout the formal benefits management process. Issues like structure, knowledge, expectation and experience affected perception differently, and this in the end changed the amount and composition of potential benefits and value. Five dimensions of benefits judgment were identified and used by participants when finding accommodations of potential benefits and value to pursue. Identified dimensions affected participants’ perceptions, which in turn affected the amount and composition of potential benefits. During the formal benefits management process participants shifted between judgment dimensions. These movements emerged through debates and interactions between participants. Judgments based on what was perceived as expected due to one’s role and perceived best for the organisation as a whole were the two dominant benefits judgment dimensions. A benefits negotiation was identified. Negotiations were divided into two main categories, rational and irrational, depending on participants’ drive when initiating and participating in negotiations. In each category three different types of negotiations were identified having different characteristics and generating different outcomes. There was also a benefits negotiation process identified that displayed management challenges corresponding to its five phases. A discrepancy was also found between how IS-benefits are spoken of and how actions of IS benefits realisation are understood. This was a discrepancy between an evaluation and a realisation focus towards IS value creation. An evaluation focus described IS-benefits as well-defined and measurable effects and a realisation focus spoke of establishing and managing an on-going place of value creation. The notion of valuescape was introduced in order to describe and support the understanding of IS value creation. Valuescape corresponded to a realisation focus and outlined a value configuration consisting of activities, logic, structure, drivers and role of IS.

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Integrins are heterodimeric, signaling transmembrane adhesion receptors that connect the intracellular actin microfilaments to the extracellular matrix composed of collagens and other matrix molecules. Bidirectional signaling is mediated via drastic conformational changes in integrins. These changes also occur in the integrin αI domains, which are responsible for ligand binding by collagen receptor and leukocyte specific integrins. Like intact integrins, soluble αI domains exist in the closed, low affinity form and in the open, high affinity form, and so it is possible to use isolated αI domains to study the factors and mechanisms involved in integrin activation/deactivation. Integrins are found in all mammalian tissues and cells, where they play crucial roles in growth, migration, defense mechanisms and apoptosis. Integrins are involved in many human diseases, such as inflammatory, cardiovascular and metastatic diseases, and so plenty of effort has been invested into developing integrin specific drugs. Humans have 24 different integrins, four of which are collagen receptor (α1β1, α2β1, α10β1, α11β1) and five leukocyte specific integrins (αLβ2, αMβ2, αXβ2, αDβ2, αEβ7). These two integrin groups are quite unselective having both primary and secondary ligands. This work presents the first systematic studies performed on these integrin groups to find out how integrin activation affects ligand binding and selectivity. These kinds of studies are important not only for understanding the partially overlapping functions of integrins, but also for drug development. In general, our results indicated that selectivity in ligand recognition is greatly reduced upon integrin activation. Interestingly, in some cases the ligand binding properties of integrins have been shown to be cell type specific. The reason for this is not known, but our observations suggest that cell types with a higher integrin activation state have lower ligand selectivity, and vice versa. Furthermore, we solved the three-dimensional structure for the activated form of the collagen receptor α1I domain. This structure revealed a novel intermediate conformation not previously seen with any other integrin αI domain. This is the first 3D structure for an activated collagen receptor αI domain without ligand. Based on the differences between the open and closed conformation of the αI domain we set structural criteria for a search for effective collagen receptor drugs. By docking a large number of molecules into the closed conformation of the α2I domain we discovered two polyketides, which best fulfilled the set structural criteria, and by cell adhesion studies we showed them to be specific inhibitors of the collagen receptor integrins.

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The Baltic Sea is unique by its biological, geochemical and physical features. The number of species of larger organisms is small and the species composition is distinctive. On the contrary microbial communities are diverse. Because of the low salinity levels, bacterial communities differ from the ones in the oceans. Knowing the structure of these communities better and how they response to different environmental conditions helps us to estimate how different factors affect the balance and function of the Baltic Sea ecosystem. Bacteria are the key players when it comes to natural biogeochemical processes and human-induced phenomena like eutrophication, oil spills or disposal of other harmful substances to the sea ecosystem. In this thesis, bacterial community structure in the sea surface microlayer and subsurface water of the Archipelago Sea were compared. In addition, the effect of diatom derived polyunsaturated aldehydes on bacterial community structure was studied by a mesocosm experiment. Diesel, crude oil and polycyclic aromatic hydrocarbon degradation capacity of the Baltic Sea bacteria was studied in smaller scale microcosm experiments. In diesel oil experiments bacteria from water phase of the Archipelago Sea was studied. Sediment and iron manganese concretions collected from the Gulf of Finland were used in the crude oil and polycyclic aromatic hydrocarbon experiments. The amount of polycyclic aromatic hydrocarbon degradation genes was measured in all of the oil degradation experiments. The results show how differences in bacterial community structure can be seen in the sea surface when compared to the subsurface waters. The mesocosm experiment demonstrated how diatom-bacteria interactions depend on other factors than diatom derived polyunsaturated aldehydes, which do not seem to have an effect on the bacterial community structure as has been suggested in earlier studies. The dominant bacterial groups in the diesel microcosms differed in samples taken from a pristine site when compared to a site with previous oil exposure in the Archipelago Sea area. Results of the study with sediment and iron-manganese concretions indicate that there are diverse bacterial communities, typical to each bottom type, inhabiting the bottoms of the Gulf of Finland capable to degrade oil and polycyclic aromatic hydrocarbon compounds.  

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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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Tutkimus sai innoituksensa, kun tutkija huomasi tarpeen liiketaloudelliselle, ajantasaiselle ja realistiselle tutkimukselle Pohjois-Korean markkinoista, joka kuvailisi markkinoiden olemassaolevia ja puuttuvia rakenteita sekä tutkisi mahdollisuuksia ylittää puuttuvat rakenteet. Institutionaalinen teoria valittiin sopivaksi viitekehykseksi kuvailla ja tutkia markkinarakennetta. Tutkimuskysymys muotoiltiin seuraavasti: “Miten ulkomaiset yritykset voivat reagoida puuttuviin markkinarakenteisiin Pohjois-Koreassa?”. Tutkimuskysymys jaettiin kolmeen osakysymykseen: (1) Millainen on Pohjois-Korean markkinoiden institutionaalinen ympäristö? (2) Mitkä ovat merkittävimmät puuttuvat markkinarakenteet Pohjois-Koreassa? (3) Mitä mahdollisuuksia ulkomaisilla yrityksillä voisi olla reagoida puuttuviin markkinarakenteisiin? Tutkimus toteutettiin kvalitatiivisena, koska tutkimuskysymys on deskriptiivinen. Aineisto kerättiin asiantuntijahaastattelun ja kvalitatiivisen sisällönanalyysin keinoin. Primääriaineiston muodostavat 2 asiantuntijahaastattelua ja sekundääriaineiston muodostavat 95 artikkelia, jotka kerättiin 40 lähteestä. Aineisto analysoitiin kvalitatiivisen sisällönanalyysin keinoin. Aineisto koodattiin, luokiteltiin ja esitettiin kokonaisuuksina luokittelurungon avulla, joka laadittiin tutkimusta varten muodostetun teoreettisen viitekehyksen mukaan. Tulokset ja johtopäätökset voidaan tiivistää seuraavasti. (1) Pohjois-Korean markkinan instituutioihin vaikuttaa kaksoisrakenne, jossa muodollinen, sosialistinen rakenne ja epämuodollinen, markkinalähtöinen rakenne toimivat päällekkäin. (2) Puuttuvia rakenteita on sekä markkinan kontekstissa että markkinatasolla. Puutteet ovat osittain seurausta vanhojen rakenteiden korvaantumisesta uusilla, jotka eivät ole institutionalisoituneet. (3) Yritykset voivat käyttää samoja mahdollisuuuksia reagoida puuttuviin markkinarakenteisiin Pohjois-Koreassa, joita kehittyvien markkinoiden yhteydessä on esitetty. Sen tulkittiin vähentävän käsitystä, jonka mukaan Pohjois-Korean markkina on liian erikoinen yritystoiminnalle. (4) Kasvava keskiluokka sekä yrittäjyyden ja naisten yhä merkittävämpi rooli liike-elämässä aiheuttavat alhaalta ylöspäin suuntautuvaa kehitystä markkinoilla. Nämä ovat merkkejä viimeaikaisesta kehityksestä, jotka eivät ole saaneet laajaa huomiota länsimaisessa mediassa. Se korostaa tarvetta liiketaloudelliselle, ajantasaiselle jatkotutkimukselle Pohjois-Korean markkinoista.

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The research was sparked by an exchange in South Korea, as the author identified a gap in research that provides economic, up to date and realistic information about the North Korean market in English language. A need for a research was identified that would describe the market’s existing and missing market structures and explore possibilities to overcome the missing market structures. Institutional theory was chosen as a suitable framework to describe and explore the market. The research question was formulated as follows: “How can foreign companies overcome institutional voids in the North Korean market?”. To answer the research question, it was divided into three sub-questions as follows: (1) What is the institutional environment in North Korea like? (2) What are the major institutional voids in the North Korean market? (3) What possibilities do foreign companies have to overcome institutional voids? The research is qualitative by nature due to the descriptive and exploratory nature of the research question. Data collection consisted of expert interview and content analysis, resulting in primary data of two interviews and secondary data of 95 articles from 40 different sources. The data was analyzed with the systematical technique of content analysis. The data was coded, classified and presented as concepts with the help of a classification system that was build following the theoretical framework adapted for this study. The findings can be summarized as follows. (1) The market institutions are characterized by an overlapping dual system of formal, socialist structures and informal, market-oriented structures. (2) Institutional voids prevail on both the market’s contextual and on the market level. They are partly result of old institutions being replaced by new institutions that lack institutionalization. (3) Identified possibilities to overcome institutional voids correspond with possibilities drawn from previous research. This decreases the image of North Korea as an impossibly unique market to operate in. (4) Emerging middle class, rapidly growing entrepreneurial activities and women’s increasing role in business drive a down-to-up change in the market. This signals the recent development of the market, yet has been overlooked in the Western media. Thus there is a need for further economic, up to date research concerning North Korea.