935 resultados para Functional Requirements for Authority Data (FRAD)
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TMPRSS2–ERG is the most frequent type of genomic rearrangement present in prostate tumors, in which the 5- prime region of the TMPRSS2 gene is fused to the ERG oncogene. TMPRSS2, containing androgen response elements (AREs), is regulated by androgens in the prostate. The truncated TMPRSS2-ERG fusion transcript is overexpressed in half of the prostate cancer patients. The formation of TMPRSS2-ERG transcript is an early event in prostate carcinogenesis and previous in vivo and in vitro studies have shown ectopic ERG expression to be associated with increased cell invasion. However, the molecular function of ERG and its role in cell signaling is poorly understood. In this study, genomic rearrangement of ERG with TMPRSS2 was studied by using comparative genomic hybridization (CGH) in prostate cancer samples. The biological processes associated with the ERG oncogene expression in prostate epithelial cells were studied, and the results were compared with findings observed in clinical prostate tumor samples. The gene expression data indicated that increased WNT signaling and loss of cell adhesion were a characteristic of TMPRSS2- ERG fusion positive prostate tumor samples. Up- regulation of WNT pathway genes were present in ERG positive prostate tumors, with frizzled receptor 4 (FZD4) presenting with the highest association with ERG overexpression, as verified by quantitative reverse transcription-PCR, immunostaining, and immunoblotting in TMPRSS2-ERG positive VCaP prostate cancer cells. Furthermore, ERG and FZD4 silencing increased cell adhesion by inducing active β1-integrin and E-cadherin expression in VCaP cells. Furthermore, we found a novel inhibitor, 4-(chloromethyl) benzoyl chloride which inhibited the WNT signaling and induced similar phenotypic effects as observed after ERG or FZD4 down regulation in VCaP cells. In conclusion, this work deepens our understanding on the complex oncogenic mechanisms of ERG in prostate cancer that may help in developing drugs against TMPRSS2-ERG positive tumors.
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Background: Atherosclerosis begins in early life progressing from asymptomatic to symptomatic as we age. Although substantial progress has been made in identifying the determinants of atherosclerosis in middle to older age adults at increased cardiovascular risk, there is lack of data examining determinants and prediction of atherosclerosis in young adults. Aims: The current study was designed to investigate levels of cardiovascular risk factors in young adults, subclinical measures of atherosclerosis, and prediction of subclinical arterial changes with conventional risk factor measures and novel metabolic profiling of serum samples. Subjects and Methods: This thesis utilised data from the follow-ups performed in 2001 and 2007 in the Cardiovascular Risk in Young Finns study, a Finnish population-based prospective cohort study that examined 2,204 subjects who were aged 30-45 years in 2007. Subclinical atherosclerosis was studied using noninvasive ultrasound measurements of carotid intima-media thickness (IMT), carotid arterial distensibility (CDist) and brachial flow-mediated dilation (FMD). Measurements included conventional risk factors and metabolic profiling using highthroughput nuclear magnetic resonance (NMR) methods that provided data on 42 lipid markers and 16 circulating metabolites. Results: Trends in lipids were favourable between 2001 and 2007, whereas waist circumference, fasting glucose, and blood pressure levels increased. To study the stability of noninvasive ultrasound markers, 6-year tracking (the likelihood to maintain the original fractile over time) in 6 years was examined. IMT tracked more strongly than CDist and FMD. Cardiovascular risk scores (Framingham, SCORE, Finrisk, Reynolds and PROCAM) predicted subclinical atherosclerosis equally. Lipoprotein subclass testing did not improve the prediction of subclinical atherosclerosis over and above conventional risk factors. However, circulating metabolites improved risk stratification. Tyrosine and docosahexaenoic acid were found to be novel biomarkers of high IMT. Conclusions: Prediction of cardiovascular risk in young Finnish adults can be performed with any of the existing risk scores. The addition of metabonomics to risk stratification improves prediction of subclinical changes and enables more accurate targeting of prevention at an early stage.
DPS-Like Peroxide Resistance Protein: Structural and Functional Studies on a Versatile Nanocontainer
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Oxidative stress is a constant threat to almost all organisms. It damages a number of biomolecules and leads to the disruption of many crucial cellular functions. It is caused by reactive oxygen species (ROS), such as hydrogen peroxide (H
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Tämä diplomityö tutkii moduloinnilla saavutettavaa hyötyä kuljetinliiketoiminnassa. Johdanto-osassa kerrotaan yrityksen taustasta ja projektiliiketoiminnan kehitysnäkymistä, hihnakuljetinjärjestelmien historiasta ja nykyisestä kilpailutilanteesta. Lisäksi siinä on mainittu työn tavoitteet, sekä tutkimuksen rajaus. Hihnakuljetinjärjestelmien modulointia käsittelevässä osassa selvitetään moduloinnin historiaa ja on kerrottu siihen liittyviä käsitteitä ja menettelytapoja. Tutkimusosan alussa on esitetty tutkimuskysymykset. Tutkimusmenetelmänä on tapaustutkimus ja siinä on verrattu kahta CASE- tapausta keskenään haastattelujen avulla, sekä pyydetty osallistuneilta jatkotoimenpide-ehdotuksia, koskien modulointia. Toiminnallisen viitekehyksen osassa kuvataan ne tavat, joilla modulointi yrityksessä toteutetaan asiakasvaatimukset ja palveluhallinta huomioiden. Lisäksi siinä kuvataan osaamisen kehittämisen menettely. Tutkimustuloksien tarkastelun yhteydessä on kerrottu CASE- tapauksien perustiedot ja tiedon keräämisen tapa. Tutkimustuloksien analysointi on suoritettu siten, että tuloksista on nostettu esille moduloinnin kannalta oleelliset vastaukset ja ne on analysoitu. Tämän jälkeen suoritettiin pohdinta ja johtopäätökset niistä analysoiduista vastauksista, jotka ovat tärkeitä moduloinnin ja yrityksen kehityksen kannalta. Jatkotoimenpiteet on jaettu kolmeen pääryhmään, joista ensimmäisenä on toiminnan kehittäminen moduloimalla. Toisessa on tarkasteltu sisäisen toiminnan kannalta tärkeitä kohteita ja ehdotettu toimenpiteitä toiminnan tehostamiseksi. Kolmantena ryhmänä ovat tutkimusaiheet, joiden avulla pyritään selvittämään puutteet tai epäkohdat nykyisessä toiminnassa. Yhteenvedossa on tarkasteltu yrityksen strategisten tavoitteiden toteutumista suhteessa hypoteesiin. Siinä on myös esitetty tulevaisuuden haasteita ympäristönsuojelun asettamat vaatimukset huomioiden.
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One of the most crucial tasks for a company offering a software product is to decide what new features should be implemented in the product’s forthcoming versions. Yet, existing studies show that this is also a task with which many companies are struggling. This problem has been claimed to be ambiguous and changing. There are better or worse solutions to the problem, but no optimal one. Furthermore, the criteria determining the success of the solution keeps changing due to continuously changing competition, technologies and market needs. This thesis seeks to gain a deeper understanding of the challenges that companies have reportedly faced in determining the requirements for their forthcoming product versions. To this end, product management related activities are explored in seven companies. Following grounded theory approach, the thesis conducts four iterations of data analysis, where each of the iterations goes beyond the previous one. The thesis results in a theory proposal intended to 1) describe the essential characteristics of organizations’ product management challenges, 2) explain the origins of the perceived challenges and 3) suggest strategies to alleviate the perceived challenges. The thesis concludes that current product management approaches are becoming inadequate to deal with challenges that have multiple and conflicting interpretations, different value orientations, unclear goals, contradictions and paradoxes. This inadequacy continues to increase until current beliefs and assumptions about the product management challenges are questioned and a new paradigm for dealing with the challenges is adopted.
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Tässä diplomityössä on käsitelty ydinvoimalaitoksen rakentamisprosessin aikaista viran-omaistoimintaa, viranomaisten vaatimuksia sekä rakentamiseen liittyvää riskienhallintaa julkisesti saatavissa olevan materiaalin pohjalta. Ensin on käyty läpi johdannon ja tavoitteiden lisäksi ydinvoiman historiaa ja nykyhetkeä Suomessa. Tämän jälkeen työssä on käsitelty riskienhallintaa sekä siihen liittyvää yleistä teoriaa. Teoria toimii lisätukena viranomaisvaatimusten tarkastelussa sekä niiden toimien ymmärtämisessä. Ennen viranomaisvaatimuksia on tarkasteltu kuitenkin itse viranomaisia, niiden välisiä kytköksiä sekä sitä, mitkä eri viranomaiset vaikuttavat ydinvoimalaitoksen rakentamiseen. Tässä osiossa on tarkasteltu myös politiikan vaikutusta viranomaistoimintaan. Viranomaisten toimintaa ja vaatimuksia käsittelevässä osiossa on käyty läpi yleisesti ydinvoimalaitokseen liittyviin toimituksiin kuuluvat vaatimukset sekä yksityiskohtaisempia vaatimuksia aihealueittain. Tässä osiossa on myös käsitelty esimerkkejä Olkiluoto 3 –projektissa tehdyistä havainnoista ja toteutuneista riskeistä. Tämän jälkeen työssä on tehty tarvittavat johtopäätökset tutkimuskysymyksiin läpikäydyn materiaalin pohjalta. Johtopäätöksissä on myös käsitelty ydinvoimalaitokseen liittyvään toimitukseen sisältyviä riskejä sekä niiden hallintaa. Viranomaistyöstä korostuivat läpikäydyssä materiaalissa erityisesti suomalaisen viranomaistoiminnan tinkimättömyys ja korkea vaatimustaso. Tärkeimmiksi seikoiksi työssä nousivat ydinvoimalaitoksen rakentamiseen olennaisena osana kuuluva korkea turvallisuuskulttuuri sekä sen seurauksena yritysten toimivat johtamisjärjestelmät. Lisäksi hyvin tehty esi- ja perussuunnittelu helpottavat projektin eri osa-alueita. Huomioimalla nämä kolme seikkaa pystytään ydinvoimalaitoksen rakentamisen ja käytön aikaisia riskejä hallitsemaan tehokkaimmalla tavalla.
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Unsuccessful mergers are unfortunately the rule rather than the exception. Therefore it is necessary to gain an enhanced understanding of mergers and post-merger integrations (PMI) as well as learning more about how mergers and PMIs of information systems (IS) and people can be facilitated. Studies on PMI of IS are scarce and public sector mergers are even less studied. There is nothing however to indicate that public sector mergers are any more successful than those in the private sector. This thesis covers five studies carried out between 2008 and 2011 in two organizations in higher education that merged in January 2010. The most recent study was carried out two years after the new university was established. The longitudinal case-study focused on the administrators and their opinions of the IS, the work situation and the merger in general. These issues were investigated before, during and after the merger. Both surveys and interviews were used to collect data, to which were added documents that both describe and guide the merger process; in this way we aimed at a triangulation of findings. Administrators were chosen as the focus of the study since public organizations are highly dependent on this staff category, forming the backbone of the organization and whose performance is a key success factor for the organization. Reliable and effective IS are also critical for maintaining a functional and effective organization, and this makes administrators highly dependent on their organizations’ IS for the ability to carry out their duties as intended. The case-study has confirmed the administrators’ dependency on IS that work well. A merger is likely to lead to changes in the IS and the routines associated with the administrators’ work. Hence it was especially interesting to study how the administrators viewed the merger and its consequences for IS and the work situation. The overall research objective is to find key issues for successful mergers and PMIs. The first explorative study in 2008 showed that the administrators were confident of their skills and knowledge of IS and had no fear of having to learn new IS due to the merger. Most administrators had an academic background and were not anxious about whether IS training would be given or not. Before the merger the administrators were positive and enthusiastic towards the merger and also to the changes that they expected. The studies carried out before the merger showed that these administrators were very satisfied with the information provided about the merger. This information was disseminated through various channels and even negative information and postponed decisions were quickly distributed. The study conflicts with the theories that have found that resistance to change is inevitable in a merger. Shortly after the merger the (third) study showed disappointment with the fact that fewer changes than expected had been implemented even if the changes that actually were carried out sometimes led to a more problematic work situation. This was seen to be more prominent for routine changes than IS changes. Still the administrators showed a clear willingness to change and to share their knowledge with new colleagues. This knowledge sharing (also tacit) worked well in the merger and the PMI. The majority reported that the most common way to learn to use new ISs and to apply new routines was by asking help from colleagues. They also needed to take responsibility for their own training and development. Five months after the merger (the fourth study) the administrators had become worried about the changes in communication strategy that had been implemented in the new university. This was perceived as being more anonymous. Furthermore, it was harder to get to know what was happening and to contact the new decision makers. The administrators found that decisions, and the authority to make decisions, had been moved to a higher administrative level than they were accustomed to. A directive management style is recommended in mergers in order to achieve a quick transition without distracting from the core business. A merger process may be tiresome and require considerable effort from the participants. In addition, not everyone can make their voice heard during a merger and consensus is not possible in every question. It is important to find out what is best for the new organization instead of simply claiming that the tried and tested methods of doing things should be implemented. A major problem turned out to be the lack of management continuity during the merger process. Especially problematic was the situation in the IS-department with many substitute managers during the whole merger process (even after the merger was carried out). This meant that no one was in charge of IS-issues and the PMI of IS. Moreover, the top managers were appointed very late in the process; in some cases after the merger was carried out. This led to missed opportunities for building trust and management credibility was heavily affected. The administrators felt neglected and that their competences and knowledge no longer counted. This, together with a reduced and altered information flow, led to rumours and distrust. Before the merger the administrators were convinced that their achievements contributed value to their organizations and that they worked effectively. After the merger they were less sure of their value contribution and effectiveness even if these factors were not totally discounted. The fifth study in November 2011 found that the administrators were still satisfied with their IS as they had been throughout the whole study. Furthermore, they believed that the IS department had done a good job despite challenging circumstances. Both the former organizations lacked IS strategies, which badly affected the IS strategizing during the merger and the PMI. IS strategies deal with issues like system ownership; namely who should pay and who is responsible for maintenance and system development, for organizing system training for new IS, and for effectively run IS even during changing circumstances (e.g. more users). A proactive approach is recommended for IS strategizing to work. This is particularly true during a merger and PMI for handling issues about what ISs should be adopted and implemented in the new organization, issues of integration and reengineering of IS-related processes. In the new university an ITstrategy had still not been decided 26 months after the new university was established. The study shows the importance of the decisive management of IS in a merger requiring that IS issues are addressed in the merger process and that IS decisions are made early. Moreover, the new management needs to be appointed early in order to work actively with the IS-strategizing. It is also necessary to build trust and to plan and make decisions about integration of IS and people.
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PURPOSE: To assess the chemotactic activity and phagocytic response of neutrophilic polymorphonuclear leukocytes among women in the first five days postpartum.METHODS: A prospective, cross-sectional clinical-laboratory study was conducted. Data of 31 postpartum women during the first five days after vaginal delivery were compared with those of 24 healthy non-pregnant non-postpartum women matched for age. The inclusion criteria were postpartum, clinically and obstetrically healthy women; vaginal delivery, singleton pregnancy carried to term; non-hypertensive, hyperglycemic, allergic, malnourished or with autoimmune or neoplastic diseases; not having received vaccines or blood products in the last three months. The Control Group was chosen according to the same inclusion criteria but involving non-pregnant non-postpartum women. The chemotactic activity of neutrophilic polymorphonuclear leukocytes was assessed by determining the distance from directed migration to bacterial lipopolysaccharide, in three Boyden chamber assays. The phagocytic response was identified by assessing the Zymosan particles' ingestion in three assays carried out in Leighton tubes. The Student's t-test was used in the statistical analysis, adopting a 5% level of significance.RESULTS: The chemotactic activity of neutrophilic polymorphonuclear leukocytes from postpartum women in the presence of homologous (73.2±6.9) and autologous (78.6±13.9) sera showed a significant increase compared to the values observed in the Control Group (64.1±4.1 and 66.6±5.4). Both chemotactic response and phagocytosis ingestion phase of neutrophilic polymorphonuclear leukocytes were significantly increased (p<0.05) in postpartum women compared to healthy non-pregnant and non-postpartum women.CONCLUSION: There was an increase in the chemotactic activity and phagocytic response of neutrophilic polymorphonuclear leukocytes during the first five days after vaginal delivery in women.
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Diplomityö tehtiin kunnallisessa omistuksessa olevaan kiinteistö- ja palveluyhtiöön. Työn tavoitteena oli suunnitella ja luoda uusi budjetointimalli, jota kohdeyritys pystyy hyödyntämään talousjohtamisessa. Mallin keskeisiä ominaisuuksia on tulevan tilikauden toiminnan rahamääräinen ennustaminen, jonka avulla yritys pystyy hinnoittelemaan kiinteistöjen ylläpitovastikkeet ja palvelukokonaisuudet. Työn teoriaosuudessa esitellään budjetoinnin keskeiset tehtävät sekä budjetointi-järjestelmän sisältö; budjetin rakenne, budjetointiprosessin vaiheet, erilaiset menetelmät ja sovellukset sekä sen kehittämiseen liittyvät edellytykset. Työssä on esitetty perinteiseen budjetointiin kohdistunutta kritiikkiä, joiden huomioiminen on tärkeää toimivan budjetointimallin luomisessa. Empiirisessä osiossa kuvataan mallin kehittämisen vaiheita, budjetointiprosessia sekä siihen luotuja ominaisuuksia. Mallin ominaisuuksiin kuuluvat budjetointilomakkeet, niiden väliset yhteydet sekä kuluvan tilikauden ennustaminen, joka perustuu toteumaan sekä budjetoituihin tietoihin. Budjetin seuranta on järjestetty yrityksen taloudenhallintajärjestelmässä. Luodun budjetointimallin avulla yritys pystyy paremmin suunnittelemaan ja ennustamaan tulevan tilikauden toimintansa. Mallin kehittäminen jo prosessina paransi kohdeyrityksen talousjohtamista. Kustannukset saatiin paremmin esille, jolloin tärkeimpiin eriin ja ongelmiin voidaan puuttua. Mallista saatavan ennusteen avulla yritys pystyy tekemään tarvittavia toimenpiteitä tilikauden aikana. Tulevaisuudessa budjetointimallia tulisi kehittää tukemaan paremmin strategista johtamista sekä huomioimaan paremmin suorituskyvyn seuraamisen näkökulma.
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Hystricognathi represent a monophyletic taxon within Rodentia. Since phylogenetically analyzed morphological systems are essential for revealing evolutionary processes, this study identifies evolutionary character transformations on the stem lineage of Hystricognathi as derived from the author's own work and the literature. Data so far indicate that evolutionary transformations in the rostral head region, the loss of tactile ability in the outer nasal skin and the mobile arrangement of the associated cartilage, were allied with a switch from omnivorous to herbivorous and fiber-rich nutrition. Additional character transformations in the skull assist in digesting such food. Structures associated with reproduction and placentation show a remarkable pro portion of derived character conditions: the chorioallantoic placenta has a ring-shaped organization and growth structure which optimizes the capacity for passive diffusion, a subplacenta occurred as a specialized region responsible for placental invasion and the inverted yolk sac facilitates substance exchange with the main placenta. Finally, precocial newborns evolved as a derived condition within Rodentia. All things considered, a mode of reproduction is indicated, which does not demand excessive additional energy intake by the mother and is in accordance with her low energetic diet. Hystricognathi possess major character transformations that represent prerequisites for their successful radiation at the time when more open ecosystems and grasslands evolved during Earth history. The analysis resulted in the reconstruction of a life-near picture of the hystricognath stem species pattern with high explanatory power in terms of changes in space and time and their interdependence with biodiversity.
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Following the current trend of companies in changing and developing their businesses from transactional approach to relationship and solution oriented approach has set new requirements to internal cooperation of companies too. The relationship between marketing and sales has been identified to be critical to company's success here, but surprisingly little is known about it. The purpose of this study was to deepen understanding of the relationship between sales and marketing in business-to-business sales from operative sales employees' perspectives in solution selling context. The aim was to develop an explorative analytical construction and framework of the interface. The study was conducted as a literature review and an empirical qualitative explorative single case study. The data was collected by conducting six thematic interviews with sales employees of the case company. Observing sales and marketing, written documents and other materials used in sales were used as secondary source of information. The data was analyzed using qualitative case study analysis methods. The findings of the study support previous research findings of the interface between marketing and sales but also bring new propositions as analytical framework to construct the interface. As such, the interface was found to be a multi-dimensional and complex dynamic construction. As results of this study, there was an exploratory framework constructed. The construction consists of three explorative contexts of the interface: internal context, relationship emphasizing context and solution selling context. These contexts are further divided into lower levels as an outcome of the analysis. In addition the identified contexts, there are also conceptual domains identified, which are common to all the contexts. The role of mutual, cross-functional knowledge creation was found to be central in the interface.
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Cyber security is one of the main topics that are discussed around the world today. The threat is real, and it is unlikely to diminish. People, business, governments, and even armed forces are networked in a way or another. Thus, the cyber threat is also facing military networking. On the other hand, the concept of Network Centric Warfare sets high requirements for military tactical data communications and security. A challenging networking environment and cyber threats force us to consider new approaches to build security on the military communication systems. The purpose of this thesis is to develop a cyber security architecture for military networks, and to evaluate the designed architecture. The architecture is described as a technical functionality. As a new approach, the thesis introduces Cognitive Networks (CN) which are a theoretical concept to build more intelligent, dynamic and even secure communication networks. The cognitive networks are capable of observe the networking environment, make decisions for optimal performance and adapt its system parameter according to the decisions. As a result, the thesis presents a five-layer cyber security architecture that consists of security elements controlled by a cognitive process. The proposed architecture includes the infrastructure, services and application layers that are managed and controlled by the cognitive and management layers. The architecture defines the tasks of the security elements at a functional level without introducing any new protocols or algorithms. For evaluating two separated method were used. The first method is based on the SABSA framework that uses a layered approach to analyze overall security of an organization. The second method was a scenario based method in which a risk severity level is calculated. The evaluation results show that the proposed architecture fulfills the security requirements at least at a high level. However, the evaluation of the proposed architecture proved to be very challenging. Thus, the evaluation results must be considered very critically. The thesis proves the cognitive networks are a promising approach, and they provide lots of benefits when designing a cyber security architecture for the tactical military networks. However, many implementation problems exist, and several details must be considered and studied during the future work.
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Communications play a key role in modern smart grids. New functionalities that make the grids ‘smart’ require the communication network to function properly. Data transmission between intelligent electric devices (IEDs) in the rectifier and the customer-end inverters (CEIs) used for power conversion is also required in the smart grid concept of the low-voltage direct current (LVDC) distribution network. Smart grid applications, such as smart metering, demand side management (DSM), and grid protection applied with communications are all installed in the LVDC system. Thus, besides remote connection to the databases of the grid operators, a local communication network in the LVDC network is needed. One solution applied to implement the communication medium in power distribution grids is power line communication (PLC). There are power cables in the distribution grids, and hence, they may be applied as a communication channel for the distribution-level data. This doctoral thesis proposes an IP-based high-frequency (HF) band PLC data transmission concept for the LVDC network. A general method to implement the Ethernet-based PLC concept between the public distribution rectifier and the customerend inverters in the LVDC grid is introduced. Low-voltage cables are studied as the communication channel in the frequency band of 100 kHz–30 MHz. The communication channel characteristics and the noise in the channel are described. All individual components in the channel are presented in detail, and a channel model, comprising models for each channel component is developed and verified by measurements. The channel noise is also studied by measurements. Theoretical signalto- noise ratio (SNR) and channel capacity analyses and practical data transmission tests are carried out to evaluate the applicability of the PLC concept against the requirements set by the smart grid applications in the LVDC system. The main results concerning the applicability of the PLC concept and its limitations are presented, and suggestion for future research proposed.
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Because of the increased availability of different kind of business intelligence technologies and tools it can be easy to fall in illusion that new technologies will automatically solve the problems of data management and reporting of the company. The management is not only about management of technology but also the management of processes and people. This thesis is focusing more into traditional data management and performance management of production processes which both can be seen as a requirement for long lasting development. Also some of the operative BI solutions are considered in the ideal state of reporting system. The objectives of this study are to examine what requirements effective performance management of production processes have for data management and reporting of the company and to see how they are effecting on the efficiency of it. The research is executed as a theoretical literary research about the subjects and as a qualitative case study about reporting development project of Finnsugar Ltd. The case study is examined through theoretical frameworks and by the active participant observation. To get a better picture about the ideal state of reporting system simple investment calculations are performed. According to the results of the research, requirements for effective performance management of production processes are automation in the collection of data, integration of operative databases, usage of efficient data management technologies like ETL (Extract, Transform, Load) processes, data warehouse (DW) and Online Analytical Processing (OLAP) and efficient management of processes, data and roles.
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Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014