JNK, a versatile regulator of kinesin-1 transport and cytoskeleton dynamics

C-Jun N-terminal kinase (JNK) is traditionally recognized as a crucial factor in stress response and inducer of apoptosis upon various stimulations. Three isoforms build the JNK subfamily of MAPK; generally expressed JNK1 and JNK2 and brain specific JNK3. Degenerative potency placed JNK in the spotlight as potential pharmacological option for intervention. Unfortunately, adverse effects of potential drugs and observation that expression of only JNK2 and JNK3 are induced upon stress, restrained initial enthusiasm. Notably, JNK1 demonstrated atypical high constitutive activity in neurons that is not responsive to cellular stresses and indicated existence of physiological activity. This thesis aimed at revealing the physiological functions of JNK1 in actin homeostasis through novel effector MARCKS-Like 1 (MARCKSL1) protein, neuronal trafficking mediated by major kinesin-1 motor protein and microtubule (MT) dynamics via STMN2/SCG10. The screen for novel physiological JNK substrates revealed specific phosphorylation of C-terminal end of MARCKSL1 at S120, T148 and T183 both ex vivo and in vitro. By utilizing site-specific mutagenesis, various actin dynamics and migrations assays we were able to demonstrate that JNK1 phosphorylation specifically facilitates F-actin bundling and thus filament stabilisation. Consecutively, this molecular mechanism was proved to enhance formation of filopodia; cell surface projections that allow cell sensing surrounding environment and migrate efficiently. Our results visualize JNK dependent and MARCKSL1 executed induction of filopodia in neurons and fibroblast indicating general mechanism. Subsequently, inactivation of JNK action on MARCKSL1 shifts cellular actin machinery into lamellipodial dynamic arrangement. Tuning of actin cytoskeleton inevitably melds with cell migration. We observed that both active JNK and JNK pseudo-phosphorylated form of MARCKSL1 reduce actin turnover in intact cells leading to overall diminished cell motility. We demonstrate that tumour transformed cells from breast, prostate, lung and muscle-derived cancers upregulate MARCKSL1. We showed on the example of prostate cancer PC-3 cell line that JNK phosphorylation negatively controls MARCKSL1 ability to induce migration, which precedes cancer cell metastasis. The second round of identification of JNK physiological substrates resulted in detection of predominant motor protein kinesin-1 (Kif5). Mass spectrometry detailed analysis showed evident endogenous phosphorylation of kinesin-1 on S176 within motor domain that interacts with MT. In vitro phosphorylation of bacterially expressed kinesin heavy chain by JNK isoforms displayed higher specificity of JNK1 when compared to JNK3. Since, JNK1 is constitutively active in neurons it signified physiological aspect of kinesin-1 regulation. Subsequent biochemical examination revealed that kinesin-1, when not phosphorylated on JNK site, exhibits much higher affinity toward MTs. Expression of the JNK non-phosphorable kinesin-1 mutant in intact cells as well as in vitro single molecule imaging using total internal reflection fluorescence microscopy indicated that the mutant loses normal speed and is not able to move processively into proper cellular compartments. We identify novel kinesin-1 cargo protein STMN2/SCG10, which along with known kinesin-1 cargo BDNF is showing impaired trafficking when JNK activity is inhibited. Our data postulates that constitutive JNK activity in neurons is crucial for unperturbed physiologically relevant transport of kinesin-1 dependant cargo. Additionally, my work helps to validate another novel physiological JNK1 effector STMN2/SCG10 as determinant of axodendritic neurites dynamics in the developing brain through regulation of MT turnover. We show successively that this increased MT dynamics is crucial during developmental radial migration when brain layering occurs. Successively, we are able to show that introduction of JNK phosphorylation mimicking STMN2/SCG10 S62/73D mutant rescues completely JNK1 genetic deletion migration phenotype. We prove that STMN2/SCG10 is predominant JNK effector responsible for MT depolymerising activity and neurite length during brain development. Summarizing, this work describes identification of three novel JNK substrates MARCKSL1, kinesin-1 and STMN2/SCG10 and investigation of their roles in cytoskeleton dynamics and cargo transport. This data is of high importance to understand physiological meaning of JNK activity, which might have an adverse effect during pharmaceutical intervention aiming at blocking pathological JNK action.

Planning and control of internal development projects in a fast changing environment: Case study

Tutkimuksen tarkoituksena on kuvata ja ymmärtää kuinka sisäisiä kehityshankkeita voidaan hallita onnistuneesti kun toimitaan nopeasti muuttuvassa ympäristössä. Tutkimus kuvailee etenkin projekteille tärkeitä menestymistekijöitä, kuten suunnittelu, kontrollointi ja päätöksenteko. Tutkimus selvittää yleisimmät ongelma-alueet case-organisaation sisäisten kehityshankkeiden hallinnassa. Tutkimus on luonteeltaan laadullinen tutkimus, jossa tutkimusmenetelmänä on käytetty tapaustutkimusta. Empiirisessa osassa käsittellään case-organisaation sisäisiä informaatioteknologia-hankkeita (IT) ja uusien konseptien kehityshankkeita (NCD). iSisäisten kehityshankkeiden erilaisuuden ymmärtäminen oli tutkimuksen tärkein tulos. Tutkimuksen empiirinen osio osoitti sen, että epävarmuudella on erittäin suuri vaikutus projektihallintaan sekä projektin kontrollointiin. Case-organisaation IT-projektien onnistuminen riippuu organisaatiomuu-toksen onnistumisesta. Asiakkaisiin ja markkinoihin liittyvät epävarmuudet ovat vaikuttavimmat NCD projektien epävarmuuksista. Näillä epävarmuuk-sil­la on vaikutusta projektihallintaan jonka myötä NCD projektit juuttuvat useim­mi­ten noidankehiin tai ne lopetetaan jo aikaisessa vaiheessa.

The use of branched ketenedimers in solving the deposit problems related to the internal sizing of uncoated fine paper

Alkyl ketene dimers (AKD) are effective and highly hydrophobic sizing agents for the internal sizing of alkaline papers, but in some cases they may form deposits on paper machines and copiers. In addition, alkenyl succinic anhydrides (ASA)- based sizing agents are highly reactive, producing on-machine sizing, but under uncontrolled wet end conditions the hydrolysis of ASA may cause problems. This thesis aims at developing an improved ketene dimer based sizing agent that would have a lower deposit formation tendency on paper machines and copiers than a traditional type of AKD. The aim is also to improve the ink jet printability of a AKD sized paper. The sizing characteristics ofketene dimers have been compared to those of ASA. A lower tendency of ketene dimer deposit formation was shown in paper machine trials and in printability tests when branched fatty acids were used in the manufacture of a ketene dimer basedsizing agent. Fitting the melting and solidification temperature of a ketene dimer size to the process temperature of a paper machine or a copier contributes to machine cleanliness. A lower hydrophobicity of the paper sized with branched ketene dimer compared to the paper sized with traditional AKD was discovered. However, the ink jet print quality could be improved by the use of a branched ketene dimer. The branched ketene dimer helps in balancing the paper hydrophobicity for both black and color printing. The use of a high amount of protective colloidin the emulsification was considered to be useful for the sizing performance ofthe liquid type of sizing agents. Similar findings were indicated for both the branched ketene dimer and ASA.

The Development of an Internal Testing Process for a Bluetooth Product

BlueGiga Technologies on uusi Bluetooth -teknologiaa soveltava pk-yritys. Yrityksen tuotekehitysprosessia täydentämään tarvittiin testausprosessi. Testausprosessin luominen oli haastavaa, koska Bluetooth -teknologia on uutta ja yritys on vielä nuori. Lisäksi se integroi kovo- ja ohjelmistokomponentteja tuotteissaan. Testaus aloitettiin evaluoimalla standardinmukaista tapaa dokumentoida testit. Tämän jälkeen tutkittiin BlueGigan ohjelmistokehitysprosessin suhdetta olemassa oleviin ohjelmistokehitysprosesseihin. Samanaikaisesti perehdyttiin Bluetooth -kvalifikaation testaukselle asettamiin vaatimuksiin. Tämän seurauksena TTCN:ää kokeiltiin helppolukuisen testitapauksen määrittelyssä. Käyttötapauksiin perustuvan testauksen sopivuutta Wireless Remote Access Platform:in (WRAP) testaamiseen arvioitiin kokeilemalla sitä Man-to-Machine -käyttötapauksen testaamisessa. Yllämainittujen tehtävien aikana kerätyn tiedon ja hankittujen kokemusten pohjalta laadittiin testausprosessi, joka kattaa yksikkö-, integraatio- ja järjestelmätason testauksen. Painopiste on järjestelmätason testauksessa. Prosessi määrittelee myös vastuuhenkilön tai -henkilöt eri testaustasoille.

Internal material logistics development in customer-driven production

Työn tavoitteena oli synkronoida yleinen materiaalivirta tuotannon kanssa. Pyrkimyksenä oli virtaviivaistaa materiaalivirta, jotta materiaalin määrä, sekä turhat työvaiheet tuotantoalueella vähenisivät. Päämääränä oli vähentää materiaalilavojen määrää lattialla, sekä parantaa materiaalitoimitusten OTD (On-Time-Delivery) prosenttia.Teoreettinen osa käsittelee nykypäivän toimitusketjun tärkeimpiä elementtejä. Keskeisenä asiana perehdytään materiaalivirtaan ja sen tehokkaaseen hallintaan. Työ esittelee myös synkronisen johtamismallin periaatteet, sekä materiaalivirran synkronoimisen tuotannon kanssa.Empiirinen osuus kuvaa yrityksen materiaalihallinnan nykypäivän tilanteen, sen keskeiset ongelmat, sekä uuden toimintamalliehdotuksen. Työ esittelee kaksi pilottia, joiden tulokset varmistivat uuden virtaviivaistetun materiaalivirran ja täydennysmallin toimivuuden.Työn tulokset osoittavat, miten uusi materiaalin täydennysmalli vähentää materiaalilavojen, sekä jalostamattoman työn määrää tuotantoalueella.

Managing material flows and improving performance in a component supplier’s internal supply chain

Tämä diplomityö tehtiin osana Componenta Cast Componentsin kolmivuotista toimitusketjujen kehitysprojektia. Työn tavoitteena oli kuvata tyypillinen yrityksen sisäinen toimitusketjuprosessi ja tehdä alustava suorituskykyanalyysi valimon ja konepajan väliseen logistiseen prosessiin liittyen. Tarkoituksena oli myös löytää kehityskohteita materiaali- ja tietovirtojen hallinnassa näiden tuotantoyksiköiden välillä. Logistiikkaan, toimitusketjujen hallintaan ja toimitusketjun suorituskyvyn mittaamiseen liittyvän kirjallisuustutkimuksen sekä käytännön perusteella valittiin sopivat analyysimenetelmät. Näitä menetelmiä hyödynnettiin tilaustoimitus – prosessin kuvaamisessa sekä suorituskyvyn analysoinnissa yrityksen sisäisessä toimitusketjussa. Luonnollisena jatkona kehitettiin ja pantiin käytäntöön toimitusketjua synkronoiva imutyyppinen tuotannon- ja materiaalinohjausmenetelmä. Diplomityöprojektin aikana kehitettiin myös apuvälineet käyttöönotetun menetelmän asianmukaista hyödyntämistä varten. Diplomityöprojektissa otettiin ensimmäiset askeleet kohti integroitua sisäistä toimitusketjua. Uuden tuotannon- ja materiaalinohjausmenetelmän standardisointi muihin menetelmiin yhdistettynä, sekä toimitusketjun avainmittarien jatkokehitys on jo alkanut. Läpimenoaikoja lyhentämällä ja synkronoidun, läpinäkyvän kysyntä-tarjontaketjun avulla integroitumisen astetta voidaan nostaa edelleen. Poikkiorganisatorinen kehitys ja johtaminen toimitusketjussa on avainedellytys menestykseen.

Critical reflection on the evaluation plan of the VARPUNEN project

Abstract: Critical reflection on the evaluation plan of the VARPUNEN project

Customer-Related Internal Communication in a Global Matrix Organization

The objective of the thesis was to explore the nature and characteristics of customer-related internal communication in a global industrial matrix organization during a specific customer relationship, and how it could be improved. The theoretical part of the study views the field of the concepts of intra-organizational information and knowledge sharing. The theoretical part also views the internal communications influences to customer relationships, its problematic, and the suggestions to improve internal communication in literature. The empirical part of the study was conducted with the Content Analysis and the Social Network Analysis as research methods. The data was collected by interviews and a questionnaire. Internal communication was observed first generally within the organization from the point of view of a certain business, and secondly, during a specific customer relationship at personal level and at departmental level. The results of the study describe the nature and characteristics of internal communication in the organization. The results give 13 suggestions for improving internal communication in the organization. Although the study has been done in one specific organization, it also offers insights for other organizations as well as managers to improve their internal communication.

Developing A Knowledge Management Process Model for Internal IT Organization, Case: Stora Enso Oyj, Corporate IT

The objectives of this Master’s Thesis were to find out what kind of knowledge management strategy would fit best an IT organization that uses ITIL (Information Technology Infrastructure Library) framework for IT Service Management and to create a knowledge management process model to support chosen strategy. The empirical material for this research was collected through qualitative semi-structured interviews of a case organization Stora Enso Corporate IT. The results of the qualitative interviews indicate that codification knowledge management strategy would fit best for the case organization. The knowledge management process model was created based on earlier studies and a literature of knowledge management. The model was evaluated in the interview research and the results showed that the created process model is realistic, useful, and it responds to a real life phenomenon.

CFD Simulation of Two-phase and Three-phase Flows in Internal-loop Airlift

Airlift reactors are pneumatically agitated reactors that have been widely used in chemical, petrochemical, and bioprocess industries, such as fermentation and wastewater treatment. Computational Fluid Dynamics (CFD) has become more popular approach for design, scale-up and performance evaluation of such reactors. In the present work numerical simulations for internal-loop airlift reactors were performed using the transient Eulerian model with CFD package, ANSYS Fluent 12.1. The turbulence in the liquid phase is described using κ- ε the model. Global hydrodynamic parameters like gas holdup, gas velocity and liquid velocity have been investigated for a range of superficial gas velocities, both with 2D and 3D simulations. Moreover, the study of geometry and scale influence on the reactor have been considered. The results suggest that both, geometry and scale have significant effects on the hydrodynamic parameters, which may have substantial effects on the reactor performance. Grid refinement and time-step size effect have been discussed. Numerical calculations with gas-liquid-solid three-phase flow system have been carried out to investigate the effect of solid loading, solid particle size and solid density on the hydrodynamic characteristics of internal loop airlift reactor with different superficial gas velocities. It was observed that averaged gas holdup is significantly decreased with increasing slurry concentration. Simulations show that the riser gas holdup decreases with increase in solid particle diameter. In addition, it was found that the averaged solid holdup increases in the riser section with the increase of solid density. These produced results reveal that CFD have excellent potential to simulate two-phase and three-phase flow system.

Reflexive model of research-based theatre – processing innovation at the crossroads of theatre, reflection and practice-based innovation activities

Contemporary organisations have to embrace the notion of doing ‘more with less’. This challenges knowledge production within companies and public organisations, forcing them to reorganise their structures and rethink what knowledge production actually means in the context of innovation and how knowledge is actually produced among various professional groups within the organisation in their everyday actions. Innovations are vital for organisational survival, and ‘ordinary’ employees and customers are central but too-often ignored producers of knowledge for contemporary organisations. Broader levels of participation and reflexive practices are needed. This dissertation discusses the missing links between innovation research conducted in the context of industrial management, arts, and culture; applied drama and theatre practices (specifically post-Boalian approaches); and learning – especially organising reflection – in organisational settings. This dissertation (1) explores and extends the role of research-based theatre to organising reflection and reflexive practices in the context of practice-based innovation, (2) develops a reflexive model of RBT for investigating and developing practice-based organisational process innovations in order to contribute to the development of a tool for innovation management and analysis, and (3) operationalises this model within private- and publicsector organisations. The proposed novel reflexive model of research-based theatre for investigating and developing practice-based organisational process innovations extends existing methods and offers a different way of organising reflection and reflexive practices in the context of general innovation management. The model was developed through five participatory action research processes conducted in four different organisations. The results provide learning steps – a reflection path – for understanding complex organisational life, people, and relations amid renewal and change actions. The proposed model provides a new approach to organising and cultivating reflexivity in practice-based innovation activities via research-based theatre. The results can be utilised as a guideline when processing practice-based innovation within private or public organisations. The model helps innovation managers to construct, together with their employees, temporary communities where they can learn together through reflecting on their own and each others’ experiences and to break down assumptions related to their own perspectives. The results include recommendations for practical development steps applicable in various organisations with regard to (i) application of research-based theatre and (ii) related general innovation management. The dissertation thus contributes to the development of novel learning approaches in knowledge production. Keywords: practice-based innovation, research-based theatre, learning, reflection, mode 2b knowledge production

On Innovative Search: the use of internal and external sources of innovation among Finnish innovators

This dissertation explores the use of internal and external sources of knowledge in modern innovation processes. It builds on a framework that combines theories such as a behavioural theory of the firm, the evolutionary theory of economic change, and modern approaches to strategic management. It follows the recent increase in innovation research focusing on the firm-level examination of innovative activities instead of traditional industry-level determinants. The innovation process is seen as a problem- and slack- driven search process, which can take several directions in terms of organizational boundaries in the pursuit of new knowledge and other resources. It thus draws on recent models of technological change, according to which firms nowadays should build their innovative activities on both internal and external sources of innovation rather than relying solely on internal resources. Four different research questions are addressed, all of which are empirically investigated via a rich dataset covering Finnish innovators collected by Statistics Finland. Firstly, the study examines how the nature of problems shapes the direction of any search for new knowledge. In general it demonstrates that the nature of the problem does affect the direction of the search, although under resource constraints firms tend to use external rather than internal sources of knowledge. At the same time, it shows that those firms that are constrained in terms of finance seem to search both internally and externally. Secondly, the dissertation investigates the relationships between different kinds of internal and external sources of knowledge in an attempt to find out where firms should direct their search in order to exploit the potential of a distributed innovation process. The concept of complementarities is applied in this context. The third research question concerns how the use of external knowledge sources – openness to external knowledge – influences the financial performance of firms. Given the many advantages of openness presented in the current literature, the focus is on how it shapes profitability. The results reveal a curvilinear relationship between profitability and openness (taking an inverted U-shape), the implication being that it pays to be open up to a certain point, but being too open to external sources may be detrimental to financial performance. Finally, the dissertation addresses some challenges in CISbased innovation research that have received relatively little attention in prior studies. The general aim is to underline the fact that comprehensive understanding of the complex process of technological change requires the constant development of methodological approaches (in terms of data and measures, for example). All the empirical analyses included in the dissertation are based on the Finnish CIS (Finnish Innovation Survey 1998-2000).

From network pictures to network insight in solution business – the role of internal communication

Operating in business-to-business markets requires an in-depth understanding on business networks. Actions and reactions made to compete in markets are fundamentally based on managers‘ subjective perceptions of the network. However, an amalgamation of these individual perceptions, termed a network picture, to a common company level shared understanding on that network, known as network insight, is found to be a substantial challenge for companies. A company‘s capability to enhance common network insight is even argued to lead competitive advantage. Especially companies with value creating logics that require wide comprehension of and collaborating in networks, such as solution business, are necessitated to develop advanced network insight. According to the extant literature, dispersed pieces of atomized network pictures can be unified to a common network insight through a process of amalgamation that comprises barriers/drivers of multilateral exchange, manifold rationality, and recursive time. However, the extant body of literature appears to lack an understanding on the role of internal communication in the development of network insight. Nonetheless, the extant understanding on the amalgamation process indicates that internal communication plays a substantial role in the development of company level network insight. The purpose of the present thesis is to enhance understanding on internal communication in the amalgamation of network pictures to develop network insight in the solution business setting, which was chosen to represent business-to-business value creating logic that emphasizes the capability to understand and utilize networks. Thus, in solution business the role of succeeding in the amalgamation process is expected to emphasize. The study combines qualitative and quantitative research by means of various analytical methods including multiple case analysis, simulation, and social network analysis. Approaching the nascent research topic with differing perspectives and means provides a broader insight on the phenomenon. The study provides empirical evidence from Finnish business-to-business companies which operate globally. The empirical data comprise interviews (n=28) with managers of three case companies. In addition the data includes a questionnaire (n=23) collected mainly for the purpose of social network analysis. In addition, the thesis includes a simulation study more specifically achieved by means of agent based modeling. The findings of the thesis shed light on the role of internal communication in the amalgamation process, contributing to the emergent discussion of network insights and thus to the industrial marketing research. In addition, the thesis increases understanding on internal communication in the change process to solution business, a supplier‘s internal communication in its matrix organization structure during a project sales process, key barriers and drivers that influence internal communication in project sales networks, perceived power within industrial project sales, and the revisioning of network pictures. According to the findings, internal communication is found to play a substantial role in the amalgamation process. First, it is suggested that internal communication is a base of multilateral exchange. Second, it is suggested that internal communication intensifies and maintains manifold rationality. Third, internal communication is needed to explicate the usually differing time perspectives of others and thus it is suggested that internal communication has role as the explicator of recursive time. Furthermore, the role of an efficient amalgamation process is found to be emphasized in solutions business as it requires a more advanced network insight for cross-functional collaboration. Finally, the thesis offers several managerial implications for industrial suppliers to enhance the amalgamation process when operating in solution business.

Heat transfer inside internal combustion engine: modelling and comparison with experimental data

The paper is devoted to study specific aspects of heat transfer in the combustion chamber of compression ignited reciprocating internal combustion engines and possibility to directly measure the heat flux by means of Gradient Heat Flux Sensors (GHFS). A one – dimensional single zone model proposed by Kyung Tae Yun et al. and implemented with the aid of Matlab, was used to obtain approximate picture of heat flux behavior in the combustion chamber with relation to the crank angle. The model’s numerical output was compared to the experimental results. The experiment was accomplished by A. Mityakov at four stroke diesel engine Indenor XL4D. Local heat fluxes on the surface of cylinder head were measured with fast – response, high – sensitive GHFS. The comparison of numerical data with experimental results has revealed a small deviation in obtained heat flux values throughout the cycle and different behavior of heat flux curve after Top Dead Center.