The effects of mutated cationic amino acid transporter y+LAT1 at the cellular and systemic level

y+LAT1 is a transmembrane protein that, together with the 4F2hc cell surface antigen, forms a transporter for cationic amino acids in the basolateral plasma membrane of epithelial cells. It is mainly expressed in the kidney and small intestine, and to a lesser extent in other tissues, such as the placenta and immunoactive cells. Mutations in y+LAT1 lead to a defect of the y+LAT1/4F2hc transporter, which impairs intestinal absorbance and renal reabsorbance of lysine, arginine and ornithine, causing lysinuric protein intolerance (LPI), a rare, recessively inherited aminoaciduria with severe multi-organ complications. This thesis examines the consequences of the LPI-causing mutations on two levels, the transporter structure and the Finnish patients’ gene expression profiles. Using fluorescence resonance energy transfer (FRET) confocal microscopy, optimised for this work, the subunit dimerisation was discovered to be a primary phenomenon occurring regardless of mutations in y+LAT1. In flow cytometric and confocal microscopic FRET analyses, the y+LAT1 molecules exhibit a strong tendency for homodimerisation both in the presence and absence of 4F2hc, suggesting a heterotetramer for the transporter’s functional form. Gene expression analysis of the Finnish patients, clinically variable but homogenic for the LPI-causing mutation in SLC7A7, revealed 926 differentially-expressed genes and a disturbance of the amino acid homeostasis affecting several transporters. However, despite the expression changes in individual patients, no overall compensatory effect of y+LAT2, the sister y+L transporter, was detected. The functional annotations of the altered genes included biological processes such as inflammatory response, immune system processes and apoptosis, indicating a strong immunological involvement for LPI.

Item-level life-cycle model for maintenance network – from cost to additional value

The importance of industrial maintenance has been emphasized during the last decades; it is no longer a mere cost item, but one of the mainstays of business. Market conditions have worsened lately, investments in production assets have decreased, and at the same time competition has changed from taking place between companies to competition between networks. Companies have focused on their core functions and outsourced support services, like maintenance, above all to decrease costs. This new phenomenon has led to increasing formation of business networks. As a result, a growing need for new kinds of tools for managing these networks effectively has arisen. Maintenance costs are usually a notable part of the life-cycle costs of an item, and it is important to be able to plan the future maintenance operations for the strategic period of the company or for the whole life-cycle period of the item. This thesis introduces an itemlevel life-cycle model (LCM) for industrial maintenance networks. The term item is used as a common definition for a part, a component, a piece of equipment etc. The constructed LCM is a working tool for a maintenance network (consisting of customer companies that buy maintenance services and various supplier companies). Each network member is able to input their own cost and profit data related to the maintenance services of one item. As a result, the model calculates the net present values of maintenance costs and profits and presents them from the points of view of all the network members. The thesis indicates that previous LCMs for calculating maintenance costs have often been very case-specific, suitable only for the item in question, and they have also been constructed for the needs of a single company, without the network perspective. The developed LCM is a proper tool for the decision making of maintenance services in the network environment; it enables analysing the past and making scenarios for the future, and offers choices between alternative maintenance operations. The LCM is also suitable for small companies in building active networks to offer outsourcing services for large companies. The research introduces also a five-step constructing process for designing a life-cycle costing model in the network environment. This five-step designing process defines model components and structure throughout the iteration and exploitation of user feedback. The same method can be followed to develop other models. The thesis contributes to the literature of value and value elements of maintenance services. It examines the value of maintenance services from the perspective of different maintenance network members and presents established value element lists for the customer and the service provider. These value element lists enable making value visible in the maintenance operations of a networked business. The LCM added with value thinking promotes the notion of maintenance from a “cost maker” towards a “value creator”.

Future operational-tactical level warfare : challenges and opportunities for the defence of Finland

Finnish Defence Studies is published under the auspices of the National Defence College, and the contributions reflect the fields of research and teaching of the College. Finnish Defence Studies will occasionally feature documentation on Finnish Security Policy. Views expressed are those of the authors and do not necessarily imply endorsement by the National Defence College.

The role of organization-level factors on informal learning process

This study discusses the nature of informal learning process in business organizations, and the importance of different organization-level factors in this process. The purpose of this study is to understand the role of organization-level factors on informal learning process with three subquestions: how informal learning process takes place in business organizations, what organization-level factors affects informal learning process, and how informal learning process is affected by organizational-level factors. The theoretical background of this study includes literatures on the concept of informal learning, its process, and organization-level factors that can affect informal learning process. The empirical research has been conducted in this study by face-to-face interviews. The interviews were conducted between June and August 2015 in Dhaka, Bangladesh. Thirteen interviews were made with the employees from different hierarchical levels from four freight forwarding MNCs in Bangladesh. Constant comparative analysis has been used to process the collected data until reaching a level of saturation. The empirical research found that all the phases in an informal learning process are not linear and sequential, and the role of organization-level factors on each phase varies with the degree and nature of each factor. In addition, the results also revealed that all the organization-level factors do not interact with each other while playing their role on informal learning process. The findings of this study considerably extend our understanding of the important role of HRD, manager, colleague, culture, and work structure on informal learning process in the workplace. However, future research in different organizational contexts is required to generalize the findings of this study.

Investigating the Existence of Business-IT Alignment Trap in Finnish IT Organizations

The overall purpose of this master's thesis is to investigate the existence of business-IT alignment trap in Finnish IT organizations. The alignment trap refers to the inability of IT investments to deliver the expected business benefits. The basis for this investigation is due to the previous knowledge that high level of IT alignment practice with very low efficacy in an organization can lead to alignment trap. The theory which was established on the dimensions of IT-alignment and efficacy of IT as a whole with considerations for cost reduction and revenue growth benefits. This study explored the same dimensions with the previous study but identified additional benefit (profitability). The study was conducted using the Finnish IT barometer data from different IT organizations. A quantitative research method was used in conducting this study which was built on positivist philosophical stance. The empirical data is based on survey data, an excerpt from the Finnish IT barometer data that captured the annual survey results of IT significance to Finnish organizations as evaluated by business and IT professionals. The survey data comprised of 249 respondents and their responses were categorized into high and low IT intensive which form the basis of the statistical analysis conducted. Overall, five analyses were conducted using the variables of cost reductions, revenue growth and profitability in the 2x2 matrix dimensions of IT alignment and efficacy of IT, grouped into alignment trap, maintenance zone, well-oiled IT and IT-enabled growth. The empirical results, revealed a partial existence of alignment trap in Finnish IT organizations. This is due to a very minute number of organizations that were ensnared in the alignment trap zone on the analyses conducted. Although they recorded considerable high performances in terms of revenue growth rate with IT spending below the average companies, their profitability was considered very low. Generally it was observed that Finnish IT organizations with high efficacy of IT practices had good performances, while those with low efficacy of IT experienced low performances, especially in the aspect of profitability, regardless of the degree of IT alignment. The study proposes that organizations should improve on practices that enhance effectiveness of IT more in order for them to realize the full benefits of IT and to avoid alignment trap.

The role of organization-level factors on informal learning process

This study discusses the nature of informal learning process in business organizations, and the importance of different organization-level factors in this process. The purpose of this study is to understand the role of organization-level factors on informal learning process with three subquestions: how informal learning process takes place in business organizations, what organizationlevel factors affects informal learning process, and how informal learning process is affected by organizational-level factors. The theoretical background of this study includes literatures on the concept of informal learning, its process, and organization-level factors that can affect informal learning process. The empirical research has been conducted in this study by face-to-face interviews. The interviews were conducted between June and August 2015 in Dhaka, Bangladesh. Thirteen interviews were made with the employees from different hierarchical levels from four freight forwarding MNCs in Bangladesh. Constant comparative analysis has been used to process the collected data until reaching a level of saturation. The empirical research found that all the phases in an informal learning process are not linear and sequential, and the role of organization-level factors on each phase varies with the degree and nature of each factor. In addition, the results also revealed that all the organization-level factors do not interact with each other while playing their role on informal learning process. The findings of this study considerably extend our understanding of the important role of HRD, manager, colleague, culture, and work structure on informal learning process in the workplace. However, future research in different organizational contexts is required to generalize the findings of this study.