Simplified sample handing in mass spectrometry based protein research - focus on protein phosphorylation

The human genome comprises roughly 20 000 protein coding genes. Proteins are the building material for cells and tissues, and proteins are functional compounds having an important role in many cellular responses, such as cell signalling. In multicellular organisms such as humans, cells need to communicate with each other in order to maintain a normal function of the tissues within the body. This complex signalling between and within cells is transferred by proteins and their post-translational modifications, one of the most important being phosphorylation. The work presented here concerns the development and use of tools for phosphorylation analysis. Mass spectrometers have become essential tools to study proteins and proteomes. In mass spectrometry oriented proteomics, proteins can be identified and their post-translational modifications can be studied. In this Ph.D. thesis the objectives were to improve the robustness of sample handling methods prior to mass spectrometry analysis for peptides and their phosphorylation status. The focus was to develop strategies that enable acquisition of more MS measurements per sample, higher quality MS spectra and simplified and rapid enrichment procedures for phosphopeptides. Furthermore, an objective was to apply these methods to characterize phosphorylation sites of phosphopeptides. In these studies a new MALDI matrix was developed which allowed more homogenous, intense and durable signals to be acquired when compared to traditional CHCA matrix. This new matrix along with other matrices was subsequently used to develop a new method that combines multiple spectra from different matrises from identical peptides. With this approach it was possible to identify more phosphopeptides than with conventional LC/ESI-MS/MS methods, and to use 5 times less sample. Also, phosphopeptide affinity MALDI target was prepared to capture and immobilise phosphopeptides from a standard peptide mixture while maintaining their spatial orientation. In addition a new protocol utilizing commercially available conductive glass slides was developed that enabled fast and sensitive phosphopeptide purification. This protocol was applied to characterize the in vivo phosphorylation of a signalling protein, NFATc1. Evidence for 12 phosphorylation sites were found, and many of those were found in multiply phosphorylated peptides

A comparison of one- and two-compartment neighbourhoods in heuristic search with spatial forest management goals

Abstract

The Reflections of Strategic Orientation on profitability - A resource-based study in pulp and paper industry

Tutkielman tavoitteena oli analysoida erilaisia strategisia orientaatioita sellu- ja paperiteollisuudessa. Sellu- ja paperiteollisuus on kohtaamassa strategisia haasteita, jotka ulottuvat syvälle sen rakenteisiin. Yritykset ovat valinneet erilaisia lähestymistapoja organisoidessaan tuotantoa ja kansainvälistä arvoketjuaan tässä muuttuvassa ympäristössä. Tutkimukseen valittiin 30 suurinta sellu- ja paperiteollisuudessa toimivaa yritystä ja mahdollisia syitä kannattavuuseroihin yritysten välillä analysoitiin. Yritysten strategista orientaatiota tarkasteltiin vertailemalla muun muassa seuraavia tekijöitä: vertikaalinen integraatioaste, tuotevalikoiman laajuus, tuotantokapasiteetin levinneisyys ja tuotantokapasiteetin ikä. Kannattavuutta mitattiin erilaisilla talouden tunnusluvuilla (liikevoitto, oman pääoman tuotto-%, koko pääoman tuotto-%). Tulosten mukaan yrityksiä voidaan ryhmitellä strategisen orientaation perusteella ja ryhmien välillä on kannattavuuseroja.

Intraorganizational Benefits of Customer Orientation in International Businesses - Empirical Evidence fromFinnish Service Exporters

This research concentrates to find out whether service employees' customer orientation has positive consequences relating to job attitudes in international context. A literature review is conducted in order to define the essential concepts and to see what kind of results researchers have found between customer orientation and job attitudes. The job attitudes researched in this research arejob satisfaction, role ambiguity, role conflict and commitment. This research differs from the previous customer orientation and job attitudes researchers with its international context. International services are thus discussed. Upon the previous literature and findings, four hypotheses are formed. They are tested with data from Finnish service exporters. Three hypotheses are supported, indicating that customer orientation has positiveeffect on job attitudes also in international context. Upon this research and literature review, future research recommendations are presented as well as managerial implications.

Market Orientation in Rapidly Internationalizing Small Companies — Evidence from the Software Industry

For more than a decade, researchers have been aware of the increased pace of small-firm internationalization and the greater effect of these rapidly growing small businesses on the wealth, international trade, and job-creation opportunities of countries. Due to the small size of the home market, Finnish companies have been generally considered highly interested in internationalization. One particular domain in which rapid internationalization has been considered feasible is the global software business, with its knowledge-intensive nature and high growth potential. However, over time the failure rate of small entrepreneurial firms has remained especially high in high-technology markets. One of the reasons for this seems to lie in the fact that these companies are often formed by people with a strong technological background but limited competences in other areas. Further, research on the marketing capabilities of rapidly internationalizing high-tech firms has been scarce thus far. In addition, while there is much research on the first years of operations of rapidly internationalizing companies, it is not well known what becomes of them later on. Therefore, there is a need for more investigation into the managerial mindset, competences and decision-making in these small companies, especially from the perspective of how they acquire and exploit market knowledge, and enhance their networking capabilities in order to promote international expansion. The present study focuses on market orientation in small software firms that internationalize their operations rapidly in global software markets. It builds on qualitative data to illustrate how these companies develop their market-oriented product-market strategies during the process of increasing international commitment. It also shows how they manage their network relationships in order to be able to offer better customer service and to thrive in the fierce global competition. The study was conducted in the empirical context of Finnish small software companies, and the main data consists of interviews with top managers in these businesses. The interviews were designed to cover a minimum period of five years of the company's international operations, thus offering a retrospective in-depth perspective on market orientation, internationalization and partnerships in the given context. One particular focus is on less successfully internationalized software companies, and the challenges they face when approaching international markets. This study makes a significant contribution to the literature on market orientation for several reasons. First, building on data from the software industry, it clarifies the existing theory in the context of rapid internationalization and network relationships. Secondly, it provides a good body of evidence on market orientation in both successfully and less successfully internationalized companies, and identifies the key related differences between the two company groups. Thirdly, it highlights the importance of inter-firm networks in the rapid internationalization of small software firms, providing companies with important market knowledge and, in some cases, management challenges. Fourthly, this investigation clarifies market orientation in the context of different software-product strategies, thus, combining the perspectives of market orientation in both manufacturing and services. In sum, the results of the study are significant for both small software firms and public-policy makers since they shed light on the market-oriented managerial mindset and the market-information gathering and sharing processes that are needed in successful rapid internationalization.