Integration in project business : mechanisms for integrating customers and the project network during the life-cycle of industrial projects

This thesis focuses on integration in project business, i.e. how projectbased companies organize their product and process structures when they deliver industrial solutions to their customers. The customers that invest in these solutions run their businesses in different geographical, political and economical environments, which should be acknowledged by the supplier when providing solutions comprising of larger and more complex scopes than previously supplied to these customers. This means that the suppliers are increasing their supply range by taking over some of the activities in the value chain that have traditionally been handled by the customer. In order to be able to provide the functioning solutions, including more engineering hours, technical equipment and a wider project network, a change is needed in the mindset in order to be able to carry out and take the required responsibility that these new approaches bring. For the supplier it is important to be able to integrate technical products, systems and services, but the supplier also needs to have the capabilities to integrate the cross-functional organizations and departments in the project network, the knowledge and information between and within these organizations and departments, along with inputs from the customer into the product and process structures during the lifecycle of the project under development. Hence, the main objective of this thesis is to explore the challenges of integration that industrial projects meet, and based on that, to suggest a concept of how to manage integration in project business by making use of integration mechanisms. Integration is considered the essential process for accomplishing an industrial project, whereas the accomplishment of the industrial project is considered to be the result of the integration. The thesis consists of an extended summary and four papers, that are based on three studies in which integration mechanisms for value creation in industrial project networks and the management of integration in project business have been explored. The research is based on an inductive approach where in particular the design, commissioning and operations functions of industrial projects have been studied, addressing entire project life-cycles. The studies have been conducted in the shipbuilding and power generation industries where the scopes of supply consist of stand-alone equipment, equipment and engineering, and turnkey solutions. These industrial solutions include demanding efforts in engineering and organization. Addressing the calls for more studies on the evolving value chains of integrated solutions, mechanisms for inter- and intra-organizational integration and subsequent value creation in project networks have been explored. The research results in thirteen integration mechanisms and a typology for integration is proposed. Managing integration consists of integrating the project network (the supplier and the sub-suppliers) and the customer (the customer’s business purpose, operations environment and the end-user) into the project by making use of integration mechanisms. The findings bring new insight into research on industrial project business by proposing integration of technology and engineering related elements with elements related to customer oriented business performance in contemporary project environments. Thirteen mechanisms for combining products and the processes needed to deliver projects are described and categorized according to the impact that they have on the management of knowledge and information. These mechanisms directly relate to the performance of the supplier, and consequently to the functioning of the solution that the project provides. This thesis offers ways to promote integration of knowledge and information during the lifecycle of industrial projects, enhancing the development towards innovative solutions in project business.

Identification and characterization of CIP2A as a novel oncogenic inhibitor of PP2A

Inhibition of the tumor suppressor protein phosphatase 2A (PP2A) activity has been identified as one of the five key alterations required for human cell transformation. Regardless of this crucial role in human cancer development, the detailed mechanisms by which PP2A inhibition occurs in human cancers remain largely uncharacterized. PP2A regulates a plethora of cellular signaling cascades. One of the targets of PP2A is Myc oncoprotein, which is destabilized and degraded in response to PP2A-mediated dephosphorylation of Myc serine 62. In this study we identify Cancerous Inhibitor of PP2A (CIP2A) as a previously uncharacterized endogenous inhibitor of PP2A in human cancer cells. CIP2A inhibits PP2A activity leading to subsequent stabilization of the Myc protein. CIP2A promotes malignant growth of cancer cells in vitro and xenograft tumor formation in vivo and is overexpressed in cancer. Moreover, we explored the effect of CIP2A on global transcriptional profiles and validated a CIP2A-dependent transcriptional signature. Analysis of the CIP2A signature revealed both Myc-dependent and -independent functions for CIP2A. Importantly, we demonstrate that the CIP2A signature has clinical relevance in human breast cancer subtypes. Finally, we identify the genes potentially mediating the long-term growth suppression in CIP2A depleted cancer cells. Taken together, this work identifies CIP2A as a novel human oncoprotein and describes its function in cancer cells. These results may open novel possibilities for patient stratification and therapeutic intervention of cancer.

New perspectives on the melanocortins and their cardiovascular effects: Potential implications for the treatment of cardiovascular diseases with melanocortin analogues

The melanocortin peptides, including melanocyte-stimulating hormones, α-, β- and γ-MSH, are derived from the precursor peptide proopiomelanocortin and mediate their biological actions via five different melanocortin receptors, named from MC1 to MC5. Melanocortins have been implicated in the central regulation of energy balance and cardiovascular functions, but their local effects, via yet unidentified sites of action, in the vasculature, and their therapeutic potential in major vascular pathologies remain unclear. Therefore, the main aim of this thesis was to characterise the role of melanocortins in circulatory regulation, and to investigate whether targeting of the melanocortin system by pharmacological means could translate into therapeutic benefits in the treatment of cardiovascular diseases such as hypertension. In experiments designed to elucidate the local effects of α-MSH on vascular tone, it was found that α-MSH improved blood vessel relaxation via a nitric oxide (NO)-dependent mechanism without directly contracting or relaxing blood vessels. Furthermore, α-MSH was shown to regulate the expression and function of endothelial NO synthase in cultured human endothelial cells via melanocortin 1 receptors. In keeping with the vascular protective role, pharmacological treatment of mice with α-MSH analogues displayed therapeutic efficacy in conditions associated with vascular dysfunction such as obesity. Furthermore, α-MSH analogues elicited marked diuretic and natriuretic responses, which together with their vascular effects, seemed to provide protection against sodium retention and blood pressure elevation in experimental models of hypertension. In conclusion, the present results identify novel effects for melanocortins in the local control of vascular function, pointing to the potential future use of melanocortin analogues in the treatment of cardiovascular pathologies.

Strategic communication : practice, ideology and dissonance

This dissertation approaches the manifestations of ideology in U.S. Strategic Communication. The discussion approaches Strategic Communication by relating it to the Enlightenment narratives and suggesting these narratives maintain similar social and political functions. This dissertation aims to address the key contents and mechanisms of Strategic Communication by covering the perspectives of (i) communication as leadership as well as (ii) communication as discourse , i.e. practice and contents. Throughout the empirical part of the dissertation, the communication theoretical discussion is supported by a methodological framework that bridges Critical Discourse Analysis (CDA) and functional language theory. According to the principles of CDA, Strategic Communication is treated as ideological, hegemonic discourse that impacts social order. The primary method of analysis is transitivity analysis, which is concerned with how language and its patterns construe reality. This analysis is complemented with a discussion on the rituals of production and interpretation, which can be treated as visual extensions of textual transitivity. The concept of agency is the key object of analysis. From the perspective of leadership, Strategic Communication is essentially a leadership model through which the organization defines itself, its aims and legitimacy. This dissertation arrives to the conclusion that Strategic Communication is used not only as a concept for managing Public Relations and information operations. It is an esse ntial asset in the inter-organization management of its members. The current developments indicate that the concept is developing towards even heavier measures of control. From the perspective of language and discourse, the key narratives of Strategic Communication are advocated with the intrinsic values of democracy and technological progress as the prerequisites of ethics and justice. The transitivity patterns reveal highly polarized agency. The agency of the Self is typically outsourced to technology. Further, the transitivity pa tterns demonstrate how the effects-centric paradigm of warfare has created a lexicon that is ideologically exclusive. It has led to the development of two mutually exclusive sets of vocabulary, where the desc riptions of legitimate ac tion exclude Others by default. These ideological discourses have become naturalized in the official vocabulary of strategic planning and le adership. Finally, the analysis of the images of the captures and deaths of Saddam Hussein, Osama bin Laden and Muammar Gaddafi bring the discussion back to the themes of the Enlightenment by demonstrating how democracy is framed to serve political purposes. The images of democracy are essentially images of violence. Contrary to the official, instrumental and humanitari an narratives of Strategic Communication, it is the grammar of expressive, violent rituals that serve as the instrument of unity.

Regulation of self-renewal and detection of karyotypic changes of pluripotent human embryonic stem cells

Human embryonic stem cells are pluripotent cells capable of renewing themselves and differentiating to specialized cell types. Because of their unique regenerative potential, pluripotent cells offer new opportunities for disease modeling, development of regenerative therapies, and treating diseases. Before pluripotent cells can be used in any therapeutic applications, there are numerous challenges to overcome. For instance, the key regulators of pluripotency need to be clarified. In addition, long term culture of pluripotent cells is associated with the accumulation of karyotypic abnormalities, which is a concern regarding the safe use of the cells for therapeutic purposes. The goal of the work presented in this thesis was to identify new factors involved in the maintenance of pluripotency, and to further characterize molecular mechanisms of selected candidate genes. Furthermore, we aimed to set up a new method for analyzing genomic integrity of pluripotent cells. The experimental design applied in this study involved a wide range of molecular biology, genome-wide, and computational techniques to study the pluripotency of stem cells and the functions of the target genes. In collaboration with instrument and reagent company Perkin Elmer, KaryoliteTM BoBsTM was implemented for detecting karyotypic changes of pluripotent cells. Novel genes were identified that are highly and specifically expressed in hES cells. Of these genes, L1TD1 and POLR3G were chosen for further investigation. The results revealed that both of these factors are vital for the maintenance of pluripotency and self-renewal of the hESCs. KaryoliteTM BoBsTM was validated as a novel method to detect karyotypic abnormalities in pluripotent stem cells. The results presented in this thesis offer significant new information on the regulatory networks associated with pluripotency. The results will facilitate in understanding developmental and cancer biology, as well as creating stem cell based applications. KaryoliteTM BoBsTM provides rapid, high-throughput, and cost-efficient tool for screening of human pluripotent cell cultures.

How to increase brand quality perception with audiovisual content? : Exploring the role of emotions in B2C and B2B contexts

This study discusses how audiovisual content can influence brand quality perceptions. The purpose of this study is to explore how audiovisual content creation can increase brand quality perceptions. This research problem is addressed with three sub questions, which aim at clarifying the role of emotions between content marketing and brand quality perception, explaining how different functions of audiovisual content can increase brand quality perception, and by identifying and comparing the key differences in content creation in business-to-consumer and business-to-businesscontexts. The theoretical background of the study is in brand personality, consumer emotions, consumerbrand relationships, content marketing and B2B branding literature. The empirical research part includes a single-case study. The case company was a Swiss startup that wished to build a highquality brand for both B2C and B2B segments. The empirical data was collected in September 2014. Eight interviews were conducted; seven with target segment representatives and one with an existing customer of the case company. The empirical findings were analyzed with thematic analysis and finally a 5-stage framework was created based on the findings of the research, offering a guideline for high-quality content creation. This study finds that emotions play an important role in brand quality perceptions. Psychological processes, emotion, cognition and conation, influence the engagement process of the target segment which ultimately can lead to activation and electronic word-of-mouth. Brand quality perception is the result of the overall emotion of the brand. The overall emotion derives from brand personality, brand concept, product attributes and utilitarian benefits of the brand. The entertaining and educational functions of the audiovisual content can target and evoke these emotional processes, and result in increased quality perceptions. In the B2B context, emotions are found to play a relatively smaller role in the quality perception processes. However, the significance of emotions cannot be ignored, since they can emphasize the value for the buying organization, and build on the trust and loyalty among the potential customers. The final framework presents five stages of content creation that ultimately improve brand quality perceptions. These stages help marketers to design and implement their content and evoke positive emotions in their target segment as part of a quality-based marketing strategy. Further research is warranted to quantitatively test the generalizability of the framework. Further research is also suggested to make the framework adaptable to different stages of the brand life cycle.

A phonological and tonal analysis of Samue using Optimality Theory

The topic of the present doctoral dissertation is the analysis of the phonological and tonal structures of a previously largely undescribed language, namely Samue. It is a Gur language belonging to the Niger-Congo language phulym, which is spoken in Burkina Faso. The data were collected during the fieldwork period in a Sama village; the data include 1800 lexical items, thousands of elicited sentences and 30 oral texts. The data were first transcribed phonetically and then the phonological and tonal analyses were conducted. The results show that the phonological system of Samue with the phoneme inventory and phonological processes has the same characteristics as other related Gur languages, although some particularities were found, such as the voicing and lenition of stop consonants in medial positions. Tonal analysis revealed three level tones, which have both lexical and grammatical functions. A particularity of the tonal system is the regressive Mid tone spreading in the verb phrase. The theoretical framework used in the study is Optimality theory. Optimality theory is rarely used in the analysis of an entire language system, and thus an objective was to see whether the theory was applicable to this type of work. Within the tonal analysis especially, some language specific constraints had to be created, although the basic Optimality Theory principle is the universal nature of the constraints. These constraints define the well-formedness of the language structures and they are differently ranked in different languages. This study gives new insights about typological phenomena in Gur languages. It is also a fundamental starting point for the Samue language in relation to the establishment of an orthography. From the theoretical point of view, the study proves that Optimality theory is largely applicable in the analysis of an entire sound system.

Gut Microbiota and Metabolic Disorders

Obesity and its co-morbidities, such as metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, have increased over the last few decades like an epidemic. So far the mechanisms of many metabolic diseases are not known in detail and currently there are not enough effective means to prevent and treat them. Several recent studies have shown that the unbalanced gut microbiota composition (GMC) and activity have an influence on the fat accumulation in the body. Further, it seems that the GMC of obese individuals differs from the lean. The aim of this study was to investigate whether there are differences between the GMC of metabolically impaired overweight/obese (MetS group), metabolically healthy overweight/obese and normal-weight individuals. In addition, the mechanisms by which the gut bacteria as well as their specific structures, such as flagellin (FLG) that stimulates the Toll-like receptor 5 (TLR5) affect metabolism, were investigated both in vivo and in vitro in human adipocytes and hepatocytes. The results of this study show that the abundance of certain gram-positive bacteria belonging to the Clostridial cluster XIV was higher in the MetS group subjects compared to their metabolically healthy overweight/obese and lean counterparts. Metabolically impaired subjects tended to also have a greater abundance of potentionally inflammatory Enterobacteria in their gut and thus seemed to have aberrant GMC. In addition, it was found that subjects with a high hepatic fat content (HHFC group) had less Faecalibacterium prausnitzii in their gut than individuals with low hepatic fat content. Further gene expression analysis revealed that the HHFC group also had increased inflammation cascades in their adipose tissue. Additionally, metabolically impaired individuals displayed an increased expression of FLG-recognizing TLR5 in adipose tissue, and the TLR5 expression levels associated positively both with liver fat content and insulin resistance in humans. These changes in the adipose tissue may further contribute to the impaired metabolism observed, such as insulin resistance and dyslipidemia. In vitro -studies showed that the FLG-induced TLR5 activation in adipocytes enhanced the hepatic fat accumulation by decreasing insulin signaling and mitochondrial functions and increasing triglyceride synthesis due to increased glycerol secretion from adipocytes. In conclusion, the findings of this study suggest that it may be possible that the novel prevention and personalized treatment strategies based on GM modulation will succesfully be developed for obesity and metabolic disorders in the future.

Role of fibroblast growth factors and their receptors in prostate cancer

Prostate cancer (PCa) is the most common non-cutaneous malignant disease among males in the developed countries. Radical prostatectomy (RP) is an effective therapy for most PCa patients with localized or locally invaded tumors but in some cases the cancer recurs after RP. PCa is a heterogeneous disease, which is regulated by many factors, such as androgen receptor (AR), estrogen receptors and  (ER and ER), fibroblast growth factors (FGFs) and their receptors (FGFRs). In this study, the role of ERβ, FGF8, FGF13 and FGFRL1 was investigated in PCa. Previous studies have suggested that ER is protective against PCa whereas FGF8 has been shown to induce PCa in transgenic mice. FGF13 and FGFRL1 are poorly understood members of the FGF and FGFR families, respectively. Transgenic mouse models were used to investigate the ability of inactivated ERβ to facilitate FGF8-induced prostate tumorigenesis. Human PCa tissue microarrays (TMAs) were used to study the expression pattern of FGF13 and FGFRL1 in PCa and the results were correlated to corresponding patient data. The targets and biological functions of FGF13 and FGFRL1 were characterized using experimental in vivo and in vitro models. The results show that deficiency of ERβ, which had been expected to have tumor suppressing capacity, seemed to influence epithelial differentiation but did not affect FGF8-induced prostate tumorigenesis. Analysis of the TMAs showed increased expression of FGF13 in PCa. The level of cytoplasmic FGF13 was associated with the PCa biochemical recurrence (BCR), demonstrated by increasing serum PSA value, and was able to act as an independent prognostic biomarker for PCa patients after RP. Expression of FGFRL1, the most recently identified FGFR, was also elevated in PCa. Cytoplasmic and nuclear FGFRL1 was associated with high Gleason score and Ki67 level whereas the opposite was true for the cell membrane FGFRL1. Silencing of FGFRL1 in PC-3M cells led to a strongly decreased growth rate of these cells as xenografts in nude mice and the experiments with PCa cell lines showed that FGFRL1 is able to modulate the FGF2- and FGF8-induced signaling pathways. The next generation sequencing (NGS) experiments with FGFRL1-silenced PC-3M cells revealed candidates for FGFRL1 target genes. In summary, these studies provide new data on the FGF/FGFR signaling pathways in normal and malignant prostate and suggest a potential role for FGF13 and FGFRL1 as novel prognostic markers for PCa patients. Keywords: FGF8, FGF13, FGFRL1, ERβ, prostate cancer, prognostic marker

Relay card for capacitance measurements

In this bachelor's thesis a relay card for capacitance measurements was designed, built and tested. The study was made for the research and development laboratory of VTI Technologies, which manufactures capacitive silicon micro electro mechanical accelerometers and pressure sensors. As the size of the sensors is decreasing the capacitance value of the sensors also decreases. The decreased capacitance causes a need for new and more accurate measurement systems. The technology used in the instrument measuring the capacitance dictates a framework how the relay card should be designed, thus the operating principle of the instrument must be known. To achieve accurate results the measurement instrument and its functions needed to be used correctly. The relay card was designed using printed circuit board design methods that minimize interference coupling to the measurement. The relay card that was designed in this study is modular. It consists of a separate CPU card, which was used to control the add-on cards connected to it. The CPU card was controlled from a computer through a serial bus. Two add-on cards for the CPU card were designed in this study. The first one was the measurement card, which could be used to measure 32 capacitive sensors. The second add-on card was the MUX card, which could be used to switch between two measurement cards. The capacitance measurements carried out through the MUX card and the measurement cards were characterized with a series of test measurements. The test measurement data was then analysed. The relay card design was confirmed to work and offer accurate measurement results up to a measurement frequency of 10 MHz. The length of the measurement cables limited the measurement frequency.

Palvelusopimukset tienpidon hankinnoissa

Infrarakentamisen toimintaympäristö on muuttumassa. Aikaisemmin julkinen sektori hallitsi toimialaa, mutta markkinat ovatavautumassa. Teknologian kehittäminen siirtyy julkiselta tilaajataholta yksityisille ja osaaminen yritysten kilpailutekijänä korostuu. Julkisen sektorin tehtävänä on luoda edellytyksiä tällaiselle toiminnalle. Toimintoja tullaan Tiehallinnossa ulkoistamaan yhä enemmän. Uusissa palvelusopimusmalleissa yhdistetään tieverkon tai tuotteen kunnon hallinta, toimenpiteiden ohjelmointi sekä palvelujen hankinta. Tästä muodostuu yhtenäinen prosessi, josta palvelun tuottaja vastaa. Nykyisin käytössä olevassa hankintamallissa edellä mainitut toiminnot on hajautettu useammalle eri vastuutaholle. Tämän työn tavoitteena on tarkastella palvelusopimusmallin soveltuvuutta hankintamenettelyjen eräänä vaihtoehtona. Lähtökohtana on tehdä ajallisesti pidempiä, sisällöllisesti laajempia sopimuksia. Palvelusopimusmallia voidaan soveltaa moniin hankintoihin. Tässä työssä tarkastellaan palvelusopimusmallia päällystetyn tieverkon ylläpidon hankinnassa. Uusien toimintatapojen käyttöönotossa on tärkeää saada alan toimijat yhdessä kehittämään näitä malleja. Työssä on haastateltu alan toimijoita ja heidän mielipiteet on otettu huomioon suunniteltaessa palvelusopimuksen sisältöä. Uusi sopimusmalli motivoi innovatiivisiin ratkaisuihin. Niiden syntymistä edesauttaa yritysten verkostomainen toiminatapa ja kumppanuuden syventäminen. Jokainen yritys voi tällöin keskittyä omaan ydinosaamiseensa. Samalla toimintojen kokonaistuottavuutta voidaan parantaa. Riskien hallinta on eräs tärkeimmistä asioista palvelusopimusmallin mukaisen toiminnan onnistumiselle. Riskien tunnistaminen ja niiden jakaminen eri osapuolten kesken oikeuden mukaisesti tulee sopimusmallissa hallita. Merkittävänä riskitekijöinä nousivat tässä työssä esiin, vaikeasti hallittavat, pitkän sopimusajan tuomat uhat.

Tuotannonsuunnittelun analysointi ja kehittäminen eräällä sahalaitoksella

Diplomityön tavoitteena oli analysoida ja kehittää työn toimeksiantajan UPM-Kymmene Wood Oy Korkeakosken sahan tuotannonsuunnittelua. Työn tärkein tavoite on saada selkeä toimintamalli tuotannonsuunnitteluun, jonka avulla pystytään läpäisemään 300 000 m3:n tai jopa tulevaisuudessa 320 000 m3:n vuosituotanto. Tuotannonsuunnittelulle asetettavat perusvaatimukset ovat raaka-aineen, tuotannon ja myynnin yhteensovittaminen, tilausten oikea-aikainen valmistus ja toimitus, asiakastyytyväisyys, laadun tasaisuus, reklamaatioiden minimointi ja ajosarjojen pituuden maksimointi. Tuotannon suunnittelussa on tärkeää tuntea raaka-aine- ja tuotejakaumat, varastot sekä materiaalivirrat. Tärkeitä osa-alueita tässä tutkimuksessaovat raaka-aine- sekä väli- ja valmisvarastojen seuranta, kierto sekä tuotannonohjaus. Tutkimuksessa perehdytään tuotantoon ja tuotannonsuunnittelun nykyiseen toimintaan ja apuvälineisiin. Tutkimuksen tuloksena kehitettiin tuotannonsuunnitteluun toimintamalli. Se vaatii tuotannonsuunnittelijalta tarkkaa analysointia ja tuotteiden läpimenoaikojen tuntemusta sekä kuivauksen maksimikapasiteetin hyödyntämistä.