Tuning cell motility : roles of nestin and vimentin in cancer cell invasion and motility

The cytoskeleton is a key feature of both prokaryotic and eukaryotic cells. Itis comprised of three protein families, one of which is the intermediate filaments (IFs). Of these, the IFs are the largest and most diverse. The IFs are expressed throughout life, and are involved in the regulation of cell differentiation, homeostasis, ageing and pathogenesis. The IFs not only provide structural integrity to the cell, they are also involved in a range of cellular functions from organelle trafficking and cell migration to signalling transduction. The IFs are highly dynamic proteins, able to respond and adapt their network rapidly in response to intra- and extra- cellular cues. Consequently they interact with a whole host of cellular signalling proteins, regulating function, and activity, and cellular localisation. While the function of some of the better-known IFs such as the keratins is well studied, the understanding of the function of two IFs, nestin and vimentin, is poor. Nestin is well known as a marker of differentiation and is expressed in some cancers. In cancer, nestin is primarily described as is a promoter of cell motility, however, how it fulfils this role remains undefined. Vimentin too is expressed in cancer, and is known to promote cell motility and is used as a marker for epithelial to mesenchymal transition (EMT). It is only in the last decade that studies have addressed the role that vimentin plays in cell motility and EMT. This work provides novel insight into how the IFs, nestin and vimentin regulate cell motility and invasion. In particular we show that nestin regulates the cellular localisation and organisation of two key facilitators of cell migration, focal adhesion kinase and integrins. We identify nestin as a regulator of extracellular matrix degradation and integrin-mediated cell invasion. Two further studies address the specific regulation of vimentin by phosphorylation. A detailed characterisation study identified key phosphorylation sites on vimentin, which are critical for proper organisation of the vimentin network. Furthermore, we show that the bioactive sphingolipids are vimentin network regulators. Specifically, the sphingolipids induced RhoA kinasedependent (ROCK) phosphorylation at vimentin S71, which lead to filament reorganisation and inhibition of cell migration. Together these studies shed new light into the regulation of nestin and vimentin during cell motility.

Networks and partnerships in third party logistics service production

Third party logistics, and third party logistics providers and the services they offer have grown substantially in the last twenty years. Even though there has been extensive research on third party logistics providers, and regular industry reviews within the logistics industry, a closer research in the area of partner selection and network models in the third party logistics industry is missing. The perspective taken in this study was of expanding the network research into logistics service providers as the focal firm in the network. The purpose of the study is to analyze partnerships and networks in the third party logistics industry in order to define how networks are utilized in third party logistics markets, what have been the reasons for the partnerships, and whether there are benefits for the third party logistics provider that can be achieved through building networks and partnerships. The theoretical framework of this study was formed based on common theories in studying networks and partnerships in accordance with models of horizontal and vertical partnerships. The theories applied to the framework and context of this study included the strategic network view and the resource-based view. Applying these two network theories to the position and networks of third party logistics providers in an industrial supply chain, a theoretical model for analyzing the horizontal and vertical partnerships where the TPL provider is in focus was structured. The empirical analysis of TPL partnerships consisted of a qualitative document analysis of 33 partnership examples involving companies present in the Finnish TPL markets. For the research, existing documents providing secondary data on types of partnerships, reasons for the partnerships, and outcomes of the partnerships were searched from available online sources. Findings of the study revealed that third party logistics providers are evident in horizontal and vertical interactions varying in geographical coverage and the depth and nature of the relationship. Partnership decisions were found to be made on resource based reasons, as well as from strategic aspects. The discovered results of the partnerships in this study included cost reduction and effectiveness in the partnerships for improving existing services. In addition in partnerships created for innovative service extension, differentiation, and creation of additional value were discovered to have emerged as results of the cooperation. It can be concluded that benefits and competitive advantage can be created through building partnerships in order to expand service offering and seeking synergies.

The effect of focal point parameters in fiber laser welding of structural steel

In this thesis the effect of focal point parameters in fiber laser welding of structural steel is studied. The goal is to establish relations between laser power, focal point diameter and focal point position with the resulting quality, weld-bead geometry and hardness of the welds. In the laboratory experiments, AB AH36 shipbuilding steel was welded in an I-butt joint configuration using IPG YLS-10000 continuous wave fiber laser. The quality of the welds produced were evaluated based on standard SFS-EN ISO 13919-1. The weld-bead geometry was defined from the weld cross-sections and Vickers hardness test was used to measure hardness's from the middle of the cross-sections. It was shown that all the studied focal point parameters have an effect on the quality, weld-bead geometry and hardness of the welds produced.

Structural dynamics in the global pulp and paper industry

The pulp and paper industry is currently facing broad structural changes due to global shifts in demand and supply. These changes have significant impacts on national economies worldwide. Planted forests (especially eucalyptus) and recovered paper have quickly increased their importance as raw material for paper and paperboard production. Although advances in information and communication technologies could reduce the demand for communication papers, and the growth of paper consumption has indeed flattened in developed economies, particularly in North America and Western Europe, the consumption is increasing on a global scale. Moreover, the focal point of production and consumption is moving from the Western world to the rapidly growing markets of Southeast Asia. This study analyzes how the so-called megatrends (globalization, technological development, and increasing environmental awareness) affect the pulp and paper industry’s external environment, and seeks reliable ways to incorporate the impact of the megatrends on the models concerning the demand, trade, and use of paper and pulp. The study expands current research in several directions and points of view, for example, by applying and incorporating several quantitative methods and different models. As a result, the thesis makes a significant contribution to better understand and measure the impacts of structural changes on the pulp and paper industry. It also provides some managerial and policy implications.

The nature and role of trust in temporary virtual problem-solving teams

The objective of this study is to increase understanding of the nature and role of trust in temporary virtual problem-solving teams engaged in real-life co-creation activities, while much of previous research has been conducted in student settings. The different forms and bases of trust, possible trust barriers and trust building actions, and perceived role of trust in knowledge sharing and collaboration are analyzed. The study is conducted as a qualitative case study in case company. Data includes interviews from 24 people: 13 from 3 different project teams that were going on during the study, 8 from already finalized project teams, and 3 founders of case company. Additional data consists of communication archives from three current teams. The results indicate that there were both knowledge-based and swift trust present, former being based on work-related personal experiences about leaders or other team members, and latter especially on references, disposition to trust and institution-based factors such as norms and rules, as well as leader and expert action. The findings suggest that possible barriers of trust might be related to lack of adaptation to virtual work, unclear roles and safety issues, and nature of virtual communication. Actions that could be applied to enhance trust are for example active behavior in discussions, work-related introductions communicating competence, managerial actions and face-to-face interaction. Finally, results also suggest that trust has a focal role as an enabler of action and knowledge sharing, and coordinator of effective collaboration and performance in temporary virtual problem-solving teams.

Financial working capital - management and measurement

Unexpected changes in cash flow have started to occur more frequently after the financial crisis. The capital structures of companies have also changed, and financial flexibility as well as flexible asset management have therefore become more important. This thesis aims at presenting financial working capital management, a part of flexible asset management, as a possibility to gain financial flexibility and survive the changes. This thesis operates in the interface of corporate finance, strategic management and management accounting, and it has two main objectives: to examine financial working capital management and to develop measures of financial working capital. The research in this thesis has been conducted using archival research and design science. Qualitative comparative analysis and model building are used to formulate tools and strategies for financial working capital management. The tools are tested with simulations, case studies and statistical analysis. The empirical data is collected from companies listed in the Helsinki Stock Exchange. The results of this thesis indicate that there are several possible financial working capital management strategies. FOCAL matrix is created in the thesis to assist in the selection of a strategy. The results also imply that profitability can be improved by reducing financial working capital, which creates a need to change the financial working capital management strategy. Financial flow cycle, and its modification, is developed in this thesis to measure financial working capital. Financial working capital as a concept is presented in this thesis with an orientation towards the management view. New dimensions have also been produced to financial management and working capital management, while providing a holistic approach to financial flexibility. Financial working capital management strategies are presented to managers and practical tools are provided for decision-making.