Nuclear Matrix in Apoptotic Cell Death and Cell Proliferation. The role of Nuclear Mitotic Apparatus (NuMA) Protein

The nucleus is a membrane enclosed organelle containing most of the genetic information of the cell in the form of chromatin. The nucleus, which can be divided into many sub-organelles such as the nucleoli, the Cajal bodies and the nuclear lamina, is the site for several essential cellular functions such as the DNA replication and its regulation and most of the RNA synthesis and processing. The nucleus is often affected in disease: the size and the shape of the nucleus, the chromatin distribution and the size of the nucleoli have remained the basis for the grading of several cancers. The maintenance of the vertebrate body shape depends on the skeleton. Similarly, in a smaller context, the shape of the cell and the nucleus are mainly regulated by the cytoskeletal and nucleoskeletal elements. The nuclear matrix, which by definition is a detergent, DNase and salt resistant proteinaceous nuclear structure, has been suggested to form the nucleoskeleton responsible for the nuclear integrity. Nuclear mitotic apparatus protein, NuMA, a component of the nuclear matrix, is better known for its mitotic spindle organizing function. NuMA is one of the nuclear matrix proteins suggested to participate in the maintenance of the nuclear integrity during interphase but its interphase function has not been solved to date. This thesis study concentrated on the role of NuMA and the nuclear matrix as structural and functional components of the interphase nucleus. The first two studies clarified the essential role of caspase-3 in the disintegration of the nuclear structures during apoptosis. The second study also showed NuMA and chromatin to co-elute from cells in significant amounts and the apoptotic cleavage of NuMA was clarified to have an important role in the dissociation of NuMA from the chromatin. The third study concentrated on the interphase function of NuMA showing NuMA depletion to result in cell cycle arrest and the cytoplasmic relocalization of NuMA interaction partner GAS41. We suggest that the relocalization of the transcription factor GAS41 may mediate the cell cycle arrest. Thus, this study has given new aspects in the interactions of NuMA, chromatin and the nuclear matrix.

Organisaatioiden ostokäyttäytyminen yliopistollisen aikuiskoulutuksen hankinnassa

Tutkimuksen toimeksiantaja on Lappeenrannan teknillisen yliopiston Koulutus- ja kehittämiskeskus. Tutkimuksen tavoitteena on selvittää miten yliopiston asiakasorganisaatioiden hankintapäätös muodostuu. Pääpaino tutkimuksessa on päätöksentekoyksikön ja päätöksentekokriteerien kartoittamisessa. Teoriaosuus koostuu työn kannalta keskeisimmistä aikuiskoulutuspalveluiden sekä organisaation ostokäyttäytymisen teorioista. Tutkimuksessa käytetään sekä kvalitatiivisia, että kvantitatiivisia tutkimusmenetelmiä. Pääpaino on haastattelututkimuksella ja aineisto analysoidaan laadullisin menetelmin. Otanta koostuu kahdeksasta asiakasorganisaatiosta ja kahdeksasta organisaatiosta, joiden kanssa toivotaan yhteistyötä. Yritykset ovat toimeksiantajan asiakasmatriisista. Tutkimuksen perusteella saatiin selkeä kuva yritysten koulutuksen hankinnasta. Henkilöstön kouluttaminen koetaan yrityksissä tärkeäksi ja siihen panostetaan paljon. Merkittävästi päätöksentekoon yrityksessä ottavat osaa koulutusvastaava ja henkilöstöhallinto. Päätös muodostetaan yhteistyössä asiantuntijan kanssa, joka on usein liiketoimintayksikön esimies. Merkittävimmät päätöksentekoon vaikuttavat kriteerit selkiytyivät koulutuksen tarjoajan, koulutuksen sekä hankintaprosessin osalta sekä asiakasorganisaatioissa että potentiaalisissa yrityksissä. Vaikka tutkimustulosten ja toimenpide-ehdotusten raportointi tapahtuu tässä tutkimuksessa yleisellä tasolla, saa Koulutus- ja kehittämiskeskus tutkimuksen konkreettiset tulokset kuten kontaktoitavat henkilöt, päätöksentekoyksikön jäsenet sekä päätöksentekokriteerit kussakin yrityksessä omaan yksityiseen käyttöönsä. Päätöksentekokriteerit ovat hyödyksi erityisesti toivottavien potentiaalisten organisaatioiden vaatimusten ymmärtämisessä.

Combining Productivity and Renewal in a Production Organization: a Case Study on Organizational Ambidexterity

This case study examined how productivity and renewal are combined in a production organization operating in process industry through the antecedents of organizational ambidexterity; structure, culture, and management. The empirical material consisted of semi-structured interviews, observations and case organization documents. The findings suggest that the case organization structurally separates exploitation and exploration to separate units. However, it was found that the units focusing on exploration also devote resources to exploitation. External networks, such as customers, suppliers, and other factories seemed to play a role in the exploration activities, as well as in learning activities, which were connected to renewal. Productivity was seen as a natural part of a production organization and pursued at manufacturing units. Process management techniques appeared to be spread across the organization and having positive impact on exploitation and negative impact on exploration. The managerial culture and management’s capability to communicate goals, vision and strategy was found to be unsatisfactory. This thesis contributes to the new research paradigm of organizational ambidexterity by providing unique results on how the antecedents of organizational ambidexterity are accomplished in a production organization. Furthermore, the thesis extends the previous research of organizational renewal capability by connecting it to the ambidexterity theory.

Impersonal trust within the organization: what, how and why?

It has been shown in organizational settings that trust is a crucial factor in different kinds of outcomes, and consequently, building employee trust in the employer is a goal for all kinds of organizations. Although it is recognized that trust in organizations operates on multiple levels, at present there is no clear consensus on the concept of trust within the organization. One can have trust in particular people (i.e. interpersonal trust) or in organized systems (i.e. impersonal trust). Until recently organizational trust has been treated mainly as an interpersonal phenomenon. However, the interpersonal approach is limited. Scholars studying organizational trust have thus far focused only on specific dimensions of impersonal trust, and none have taken a comprehensive approach. The first objective in this study was to develop a construct and a scale encompassing the impersonal element of organizational trust. The second objective was to examine the effects of various HRM practices on the impersonal dimensions of organizational trust. Moreover, although the “black box” model of HRM is widely studied, there have been only a few attempts to unlock the box. Previous studies on the HRM-performance link refer to trust, and this work contributes to the literature in considering trust an impersonal issue in the relationship between HRM, trust, and performance. The third objective was thus to clarify the role of impersonal trust in the relationship between HRM and performance. The study is divided into two parts comprising the Introduction and four separate publications. Each publication addresses a distinct sub-question, whereas the Introduction discusses the overall results in the light of the individual sub-questions. The study makes two major contributions to the research on trust. Firstly, it offers a framework describing the construct of impersonal trust, which to date has not been clearly articulated in the research on organizational trust. Secondly, a comprehensive, psychometrically sound, operationally valid scale for measuring impersonal trust was developed. In addition, the study makes an empirical contribution to the research on strategic HRM. First, it shows that HRM practices affect impersonal trust and the contribution is to consider the HRM-trust link in terms of impersonal organizational trust. It is shown that each of the six HRM practices in focus is connected to impersonal trust. A further contribution lies in unlocking the black box. The study explores the impersonal element of organizational trust and its mediating role between HRM practices and performance. The result is the identification of the path by which HRM contributes to performance through the mediator of impersonal trust. It is shown that the effect on performance of HRM designed specifically to enhance employees’ impersonal trust in the organization is positive.

Ambidextrous leadership in customer contact centre organization

In a modern dynamic environment organizations are facing new requirements for success and competitive advantage. This also sets new requirements for leaders. The term of ambidexterity is used in relation with organizations that are able to manage short-term efficiency and long-term innovation simultaneously. Ambidextrous leaders have the same capability at an individual level. They are able to balance between efficiency and flexibility. This study examined the confrontation of these two competing concepts in the leadership perspective. The aim of the study was to understand this recently arisen concept and its antecedents and examine what is currently known about ambidextrous leadership. This was a case study with data collected through theme interviews in a result orientated customer centre organization that has a cultural change at hand when it comes to leadership and empowerment. Organization wants to be efficient and flexible at the same time (a.k.a. ambidextrous) and that requires new type of leadership. In this study the aim was to describe the capabilities and criteria for ambidextrous leader and examine the leadership roles related to ambidextrous leadership in different hierarchical levels. The case organization had also created systematic means to support this cultural change and the effects of the process related to leadership were studied. This study showed that the area is yet widely unexplored and contradictory views are presented. This study contributes to the deprivation of study of ambidexterity in leadership and individuals. The study presents a description of ambidextrous leadership and describes the capabilities of ambidextrous leader. Ambidextrous leaders are able to make cognitive decisions between their leadership style according to situation that requires either leadership related to efficiency such as transactional leadership or leadership related to flexibility such as transformational leadership. Their leadership style supports both short-term and long-term goals. This study also shows that the role of top management is vital and operational leaders rely on their example.

A platform for anti-biofilm assays combining viability, biomass and matrix quantifications in susceptibility assessments of antimicrobials against Staphylococcus aureus biofilms

Bacteria can exist as planktonic, the lifestyle in which single cells exist in suspension, and as biofilms, which are surface-attached bacterial communities embedded in a selfproduced matrix. Most of the antibiotics and the methods for antimicrobial work have been developed for planktonic bacteria. However, the majority of the bacteria in natural habitats live as biofilms. Biofilms develop dauntingly fast high resistance towards conventional antibacterial treatments and thus, there is a great need to meet the demands of effective anti-biofilm therapy. In this thesis project it was attempted to fill the void of anti-biofilm screening methods by developing a platform of assays that evaluate the effect that screened compounds have on the total biomass, viability and the extracellular polysaccharide (EPS) layer of the biofilms. Additionally, a new method for studying biofilms and their interactions with compounds in a continuous flow system was developed using capillary electrochromatography (CEC). The screening platform was utilized with a screening campaign using a small library of cinchona alkaloids. The assays were optimized to be statistically robust enough for screening. The first assay, based on crystal violet staining, measures total biofilm biomass, and it was automated using a liquid handling workstation to decrease the manual workload and signal variation. The second assay, based on resazurin staining, measures viability of the biofilm, and it was thoroughly optimized for the strain used, but was then a very simple and fast method to be used for primary screening. The fluorescent resazurin probe is not toxic to the biofilms. In fact, it was also shown in this project that staining the biofilms with resazurin prior to staining with crystal violet had no effect on the latter and they can be used in sequence on the same screening plate. This sequential addition step was indeed a major improvement on the use of reagents and consumables and also shortened the work time. As a third assay in the platform a wheat germ agglutinin based assay was added to evaluate the effect a compound has on the EPS layer. Using this assay it was found that even if compounds might have clear effect on both biomass and viability, the EPS layer can be left untouched or even be increased. This is a clear implication of the importance of using several assays to be able to find “true hits” in a screening setting. In the pilot study of screening for antimicrobial and anti-biofilm effects using a cinchona alkaloid library, one compound was found to have antimicrobial effect against planktonic bacteria and prevent biofilm formation at low micromolar concentration. To eradicate biofilms, a higher concentration was needed. It was also shown that the chemical space occupied by the active compound was slightly different than the rest of the cinchona alkaloids as well as the rest of the compounds used for validatory screening during the optimization processes of the separate assays.

Knowledge sharing in intrafirm networks in organization

The objective of this study was research the shared knowledge and the means of sharing with the help of social network analysis. The purpose of this study was to give descriptive information to case-organization about its situational network status in different units. The premise of the study is the success of organizational competences and networks, especially when it comes to the sharing of knowledge. The research was accomplished in a TEKES –projects, Developing Network-Based Services – The Role of Competences and Networks COMNET –projects case-organization. Lappeenranta School of Business and the case-organization started the project in co-operation. The baseline for the study was organizational competencies and organizational networks as success factors, especially from the knowledge sharing’s point of view. The research was based on triangulation, which included pre-interviews, network analyses accomplished by Webropol –e-mail survey and qualitative interviews. The results indicated that regular unit meetings were experienced to be the most important method of knowledge sharing along with e-mailing, intranet and weekly bulletins. The co-operation between units was also experienced to be important when evaluating knowledge sharing and communication. The intrafirm network was experienced tight. Dispersed units and partly unclear means of information sharing were the biggest obstacles for information communication. Knowledge sharing, communication with others and trainings were seen important in the case-organization.

Customer profitability measurement in a not-for-profit organization

The objective of this study was to find out the factors that affect customer profitability in the not-for-profit case company. The customer profitability was examined in two different segments of the customer base. The effects that price, cost and the amount of services provided have on the profit margin were studied. The distribution of profitability among the customers and the effect of certain characteristics, such as size of the customer measured in services purchased, on the profitability were analyzed. The theoretical framework was built around customer profitability and the use of customer profitability information in a not-for-profit organization. The present use of customer profitability information and the possibilities of using the results of this research in the case company were presented. Quantitative research methods were used in the empirical part of the study. The results indicate that the two customer segments have differences in their buying behaviors which affect the profitability and thus the measures taken to improve the profitability should be considered with the different characteristics of the customers in mind. Finally the limitations of the study were discussed as possible further research topics.

Integrins on the move

Cancer is a leading cause of death worldwide accounting for 13% of all deaths in 2005. The spread of cancer and formation of metastases is the major cause of mortality among cancer patients. The spread of cancer is based on the cancer cell’s ability to break away from the surrounding tissue and to migrate into new areas in the body. The ability of cells to bind its surroundings and to move is controlled by the mechanical cell surface adhesion receptors called the integrins. Integrins have a critical role in cell adhesion, cell motility and tissue homeostasis. By communicating with ECM, integrins transmit signals from the surrounding environment inside the cell and modulate the function of many important signalling pathways involved in cell survival, development, gene expression, proliferation, motility and cytoskeletal organization. During cell migration integrin-matrix adhesions are formed in front of the cell while rear-adhesions are released during migration. Integrins are endocytosed from the plasma-membrane into the cytoplasm and partly recycled back to new adhesion sites in a process called integrin trafficking. Also, the cell cytoskeleton and protrusions are important in cell migration. Finger-like actin protrusions called filopodia display an interesting cancer relevant cooperation with integrins that is required for cell migration. The expression and function of integrins changes markedly as cells acquire carcinogenic properties. Changed integrin function is partly responsible for detachment of tumor cells from neighbouring cells and for providing enhanced invasive capabilities for tumor cells to disseminate. Similarly, the formation of filopodia is increased in cancer. High myosin-10 expression is related to poor outcome in breast cancer and increased cell migration. The proper function of myosin-10 induced filopodia needs association with β1 integrins. The importance of integrin trafficking and filopodia formation is becoming increasingly more recognized in cancer. This thesis focusses on the role of integrins, integrin trafficking and myosin-10 induced filopodia cancer cell migration.

Knowledge, processes and relationships in organizational change: Understanding how to facilitate management of intellectual capital in diverse organization structures and cultures.

This study examined relationships of organizational dependencies, change management and developed intellectual knowledge resources, in different intellectual capital based development programs on ICT-sector. Study was carried out in a research context, where high degree of external organizational contingencies existed and lots of changes in several development programs had taken place in the last years. From a scientific perspective the main contribution was that evidence between relationships of organizational dependencies, change model portfolio and developed knowledge resources could be suggested. From managerial perspective the primary implication was that in situations where sustainable competitive advantage is pursued by means of increasing knowledge based productivity of labor, firms should seek to pursue organizational settings where external dependencies have minimal amount of effect.

Matrix Mind : on managerial reframing in multidimensional problem solving

Det är inte ovanligt att man i organisationer ställs inför problem som inte kan hanteras inom befintlig organisationsstruktur. Skälen kan vara att frågorna har många – ibland konflikterande – dimensioner och perspektiv som samtidigt måste beaktas. I den här avhandlingen studeras vilka tankemönster och föreställningar som fanns när grupper av chefer försökte lösa komplexa problem, som inte hade en naturlig organisatorisk hemvist och hur de omsatte dessa tankemönster i handling. Vad kännetecknade det ledarskap som utövades under problemlösningsprocessen? Avhandlingens empiri hämtas från ledarutvecklingsprogram i två internationellt verksamma företag i Sverige, och omfattar 14 verkliga affärsproblem i dessa företag och den process varigenom de löstes. De 14 seminarierna utgör exempel på hur mångdimensionella frågeställningar framgångsrikt hanteras utanför den befintliga organisationsstrukturen. Studien ger, genom att adressera frågor kring tankesätt och ledningsprocesser, en djupare förståelse för förutsättningarna för detta, och lyfter särskilt fram betydelsen av ett ledarskap som inbegriper begreppen intervention, förmåga och omtolkning. Som ett samlat begrepp introduceras bilden att utöva ledarskapet utifrån ett matrix mind. Att påverka strukturer (i vid mening) och därigenom de förmågor som utvecklas, är del i detta ledarskap. Det sker genom interventioner (ingrepp som påverkar relationer i t ex en grupp) och baserades i den aktuella empirin på uppfattningar om värdet av problematisering, erfarenhetsutbyte och av ett språk, som både beskriver och anger inriktning för aktiviteter. Interventioner i strukturer (och till dem knutna processer) beskriver dock bara delvis detta ledarskap. Att leda med ett matrix mind innefattar också ett nyfiket och kreativt förhållningssätt, och att utifrån detta leda omtolkning av problem. I empirin finns flera exempel på detta. Avhandlingen avser att ge ett bidrag inom såväl organisations- som ledarskapsteori.

Project Resource Management in R&D Public Sector Organization

In R&D organizations multiple projects are executed concurrently. Problems arises in managing shared resources since they are needed by multiple projects simultaneously. The objective of this thesis was to study how the project and resource management could be developed in a public sector R&D organization. The qualitative research was carried out in the Magnetic Measurements section at CERN where the section measures magnets for particle accelerators and builds state of the art measurement devices for various needs. Hence, the R&D and measurement projects are very time consuming and very complex. Based on the previous research and the requirements from the organization the best alter- native for resource management was to build a project management information system. A centralized database was constructed and on top of it was built an application for interacting and visualizing the project data. The application allows handling project data, which works as a basis for resource planning before and during the projects are executed. It is one way to standardize the work-flow of projects, which strengthens the project process. Additionally, it was noted that the inner customer’s database, the measurement system and the new application needed to be integrated. Further integration ensures that the project data is received efficiently from customers and available not only within the application but also during the concrete work. The research results introduced a new integrated application, which centralizes the project information flow with better visibility.

Design structure matrix ja sen hyödyntäminen ohjelmistotuotannossa

Työn tarkoituksena on selvittää, miten DSM ja siihen liittyvät analyysit toimivat. Työssä selvitetään myös, miten DSM:a voidaan hyödyntää tuotekehityksessä ja ohjelmistotuotannon kohtaamissa ongelmissa. DSM-neliömatriisiin sijoitetaan tarkasteltavan kohteen osat riveihin ja kolumneihin identtisessä järjestyksessä. Matriisin soluihin merkitään osien väliset riippuvuudet, joilla selvitetään kunkin osan lähettämä ja vastaanottama data suhteessa muihin osiin. DSM-analyysissa osien järjestystä muutetaan suoritus- tai toteutusjärjestyksen mukaisesti parhaaseen järjestykseen. Osat ryhmitellään moduuleihin, jolloin esimerkiksi tuotekehitys ohjautuu automaattisesti modulaarisuuteen. Tuotekehitysprojekteihin DSM on kompaktin muodon, yksinkertaisuuden ja automaattisen järjestelyn ansiosta erinomainen työkalu, jolla voidaan mallintaa käytännössä mitä tahansa, mikä voidaan jakaa toisistaan riippuviin osiin. DSM voi vähentää projektien suunnitteluun vaadittua työmäärää ja avustaa realististen budjettien ja aikataulujen luontia suurissa projekteissa.

Study of the advancement of innovations in communications industry. Case study: Russian Post Company

This study attempted to provide a project based on the already tested and successful results of foreign business which can help to contain the final price of innovation on desired levels. The research will attempt to dig out most of available information related to aforementioned definitions and thus completing theoretical background. Next author will explain used methodology and the process of evidence collection. After that the study will show the analysis of collected data in order to obtain results which are going to be compared with stated objectives in the final part. The conclusion of the research and proposed possibilities for additional work will be given in the last part. For this study author has chosen the qualitative model because it performs very well for analysis of small scale of data. The case study method was used because it gave author an opportunity to make an in-depth analysis of the collected information about particular organization so it became possible to analyze system's details in comparison. The results have been early considered valid and applicable to other studies. As the result thesis has proposed undertakings which reflect researches aimed on solving problems with provision of services and development of communications. In addition thesis has proposed formulation of database of postal service for Russian Post when (by request) customer possess an account where he or she can access postal services via PC or info table in postal office and order delivery of postal products which will be given private identification code. Project's payoff period has been calculated as well.