998 resultados para Key, Emil, 1822-1892.


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Luettelo Kansalliskirjastossa olevan Emil Länsiön arkiston sisällöstä

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

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The melanocortin system is an important regulator of feeding, energy metabolism,and cardiovascular function and it consists of the pro-opiomelanocortin (POMC) derived melanocyte stimulating hormones (α-, β- and γ-MSH) and their endogenous melanocortin receptors, MC1R to MC5R. In the hypothalamus, α-MSH reduces food intake, and increases energy expenditure and sympathetic tone by binding to MC4R. Mutations affecting the MC4R gene lead to obesity in mammals. On the other hand, the metabolic effects of MC3R stimulation using agonists such as the endogenously expressed γ-MSH have been less extensively explored. The main objective of this study was to investigate the long-term effects of increased melanocortin tone in key areas of metabolic regulation in the central nervous system (CNS) in order to investigate the sitespecific roles of both α-MSH and γ-MSH. The aim was to stereotaxically induce local overexpression of single melanocortin peptides using lentiviral vectors expressing α-MSH (LVi-α-MSH-EGFP) and γ-MSH (LVi-γ-MSH-EGFP). The lentiviral vectors were shown to produce a long-term overexpression and biologically active peptides in cell-based assays. The LVi-α-MSHEGFP was targeted to the arcuate nucleus in the hypothalamus of diet induced obese mice where it reduced weight gain and adiposity independently of food intake. When the nucleus tractus solitarus in the brainstem was targeted, the LVi-α-MSH-EGFP treatment was shown to cause a small decrease in adiposity, which did not impact weight development. However, the α-MSH treatment increased heart rate, which was attenuated by adrenergic receptor blockade indicative of increased sympathetic activity. The LVi-γ-MSH-EGFP was targeted to the hypothalamus where it decreased fat mass in mice eating the standard diet, but the effect was abated if animals consumed a high-fat Western type diet. When the diet induced obese mice were subjected again to the standard diet, the LVi-γ-MSH-EGFP treated animals displayed increased weight loss and reduced adiposity. These results indicate that the long-term central anti-obesity effects of α-MSH are independent of food intake. In addition, overexpression of α-MSH in the brain stem efficiently blocked the development of adiposity, but increased sympathetic tone. The evidence presented in this thesis also indicates that selective MC3R agonists such as γ-MSH could be potential therapeutics in combination with low fat diets.

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The present review describes recent research on the regulation by glutamate and Ca2+ of the phosphorylation state of the intermediate filament protein of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP), in immature hippocampal slices. The results of this research are discussed against a background of modern knowledge of the functional importance of astrocytes in the brain and of the structure and dynamic properties of intermediate filament proteins. Astrocytes are now recognized as partners with neurons in many aspects of brain function with important roles in neural plasticity. Site-specific phosphorylation of intermediate filament proteins, including GFAP, has been shown to regulate the dynamic equilibrium between the polymerized and depolymerized state of the filaments and to play a fundamental role in mitosis. Glutamate was found to increase the phosphorylation state of GFAP in hippocampal slices from rats in the post-natal age range of 12-16 days in a reaction that was dependent on external Ca2+. The lack of external Ca2+ in the absence of glutamate also increased GFAP phosphorylation to the same extent. These effects of glutamate and Ca2+ were absent in adult hippocampal slices, where the phosphorylation of GFAP was completely Ca2+-dependent. Studies using specific agonists of glutamate receptors showed that the glutamate response was mediated by a G protein-linked group II metabotropic glutamate receptor (mGluR). Since group II mGluRs do not act by liberating Ca2+ from internal stores, it is proposed that activation of the receptor by glutamate inhibits Ca2+ entry into the astrocytes and consequently down-regulates a Ca2+-dependent dephosphorylation cascade regulating the phosphorylation state of GFAP. The functional significance of these results may be related to the narrow developmental window when the glutamate response is present. In the rat brain this window corresponds to the period of massive synaptogenesis during which astrocytes are known to proliferate. Possibly, glutamate liberated from developing synapses during this period may signal an increase in the phosphorylation

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Vaccination of mice with radiation-attenuated cercariae of Schistosoma mansoni induces a high level of protection against challenge with normal larvae. The immune effector mechanism, which operates in the lungs, is a cell-mediated delayed-type hypersensitivity response and involves the formation of a tight focus of mononuclear cells around embolised larvae. CD4+ T cells with Th1 characteristics are a major component of the infiltrate. They secrete abundant interferon gamma (IFNg) upon antigen stimulation in vitro, whilst in vivo neutralisation of the cytokine results in 90% abrogation of immunity. IFNg can induce a large number of genes and an attempt has been made to identify the ones which are essential components of the effector mechanism. Inducible nitric oxide synthase (iNOS) is such a candidate and nitric oxide (NO) is produced by cultures of airway leucocytes from the lungs of vaccinated mice post-challenge. However, the continued resistance of mice with a disrupted iNOS gene indicates that NO has only a minor role in the protective response. Mice with a disrupted IFNg receptor gene have been used to dissect the role of the cytokine. After vaccination and challenge, CD4+ T cells from the pulmonary interstitium have reduced levels of ICAM-1 and LFA-1 expression, compared to wild-type animals, which coincides with a reduced cohesiveness of foci. However, immunity is not significantly impaired in mice with a disrupted ICAM-1 gene, and focus formation is normal. Similarly, a role has not been found for CD2/CD48 interactions in cell aggregation. Possible IFNg-inducible molecules yet to be fully investigated include other ligand-receptor pairs, chemokines, and tumour necrosis factor a.

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Galectins are a family of evolutionarily conserved animal lectins, widely distributed from lower invertebrates to mammals. They share sequence and structure similarities in the carbohydrate recognition domain and specificity for polylactosamine-enriched glycoconjugates. In the last few years significant experimental data have been accumulated concerning their participation in different biological processes requiring carbohydrate recognition such as cell adhesion, cell growth regulation, inflammation, immunomodulation, apoptosis and metastasis. In the present review we will discuss some exciting questions and advances in galectin research, highlighting the significance of these proteins in immunological processes and their implications in biomedical research, disease diagnosis and clinical intervention. Designing novel therapeutic strategies based on carbohydrate recognition will provide answers for the treatment of autoimmune disorders, inflammatory processes, allergic reactions and tumor spreading.

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In recent decade customer loyalty programs have become very popular and almost every retail chain seems to have one. Through the loyalty programs companies are able to collect information about the customer behavior and to use this information in business and marketing management to guide decision making and resource allocation. The benefits for the loyalty program member are often monetary, which has an effect on the profitability of the loyalty program. Not all the loyalty program members are equally profitable, as some purchase products for the recommended retail price and some buy only discounted products. If the company spends similar amount of resources to all members, it can be seen that the customer margin is lower on the customer who bought only discounted products. It is vital for a company to measure the profitability of their members in order to be able to calculate the customer value. To calculate the customer value several different customer value metrics can be used. During the recent years especially customer lifetime value has received a lot of attention and it is seen to be superior against other customer value metrics. In this master’s thesis the customer lifetime value is implemented on the case company’s customer loyalty program. The data was collected from the customer loyalty program’s database and represents year 2012 on the Finnish market. The data was not complete to fully take advantage of customer lifetime value and as a conclusion it can be stated that a new key performance indicator of customer margin should be acquired in order to profitably drive the business of the customer loyalty program. Through the customer margin the company would be able to compute the customer lifetime value on regular basis enabling efficient resource allocation in marketing.

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Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

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Several companies are trying to improve their operation efficiency by implementing an enterprise resource planning (ERP) system that makes it possible to control the resources of the company in real time. However, the success of the implementation project is not a foregone conclusion; a significant part of these projects end in a failure, one way or another. Therefore it is important to investigate ERP system implementation more closely in order to increase understanding about factors influencing ERP system success and to improve the probability of a successful ERP implementation project. Consequently, this study was initiated because a manufacturing case company wanted to review the success of their ERP implementation project. To be exact, the case company hoped to gain both information about the success of the project and insight for future implementation improvement. This study investigated ERP success specifically by examining factors that influence ERP key-user satisfaction. User satisfaction is one of the most commonly applied indicators of information system success. The research data was mainly collected by conducting theme interviews. The subjects of the interviews were six key-users of the newly implemented ERP system. The interviewees were closely involved in the implementation project. Furthermore, they act as representative users that utilize the new system in everyday business processes. The collected data was analyzed by thematizing. Both data collection and analysis were guided by a theoretical frame of reference. This frame was based on previous research on the subject. The results of the study aligned with the theoretical framework to large extent. The four principal factors influencing key-user satisfaction were change management, contractor service, key-user’s system knowledge and characteristics of the ERP product itself. One of the most significant contributions of the research is that it confirmed the existence of a connection between change management and ERP key-user satisfaction. Furthermore, it discovered two new sub-factors influencing contractor service related key-user satisfaction. In addition, the research findings indicated that in order to improve the current level of key-user satisfaction, the case company should pay special attention to system functionality improvement and enhancement of the key-users’ knowledge. During similar implementation projects in the future, it would be important to assure the success of change management and contractor service related processes.