Evolution of Bioaffinity Reagents by Phage Display

Antibodies are natural binding proteins produced in vertebrates as a response to invading pathogens and foreign substances. Because of their capability for tight and specific binding, antibodies have found use as binding reagents in research and diagnostics. Properties of cloned recombinant antibodies can be further improved by means of in vitro evolution, combining mutagenesis with subsequent phage display selection. It is also possible to isolate entirely new antibodies from vast naïve or synthetic antibody libraries by phage display. In this study, library techniques and phage display selection were applied in order to optimise binding scaffolds and antigen recognition of antibodies, and to evolve new and improved bioaffinity reagents. Antibody libraries were generated by random and targeted mutagenesis. Expression and stability were mainly optimised by the random methods whereas targeted randomisation of the binding site residues was used for optimising the binding properties. Trinucleotide mutagenesis allowed design of defined randomisation patterns for a synthetic antibody library. Improved clones were selected by phage display. Capture by a specific anti- DHPS antibody was exploited in the selection of improved phage display of DHPS. Efficient selection for stability was established by combining phage display selection with denaturation under reducing conditions. Broad-specific binding of a generic anti-sulfonamide antibody was improved by selection with one of the weakest binding sulfonamides. In addition, p9 based phage display was studied in affinity selection from the synthetic library. A TIM barrel protein DHPS was engineered for efficient phage display by combining cysteinereplacement with random mutagenesis. The resulting clone allows use of phage display in further engineering of DHPS and possibly use as an alternative-binding scaffold. An anti-TSH scFv fragment, cloned from a monoclonal antibody, was engineered for improved stability to better suite an immunoassay. The improved scFv tolerates 8 – 9 °C higher temperature than the parental scFv and should have sufficient stability to be used in an immunoanalyser with incubation at 36 °C. The anti-TSH scFv fragment was compared with the corresponding Fab fragment and the parental monoclonal antibody as a capturing reagent in a rapid 5-min immunoassay for TSH. The scFv fragment provided some benefits over the conventionally used Mab in anayte-binding capacity and assay kinetics. However, the recombinant Fab fragment, which had similar kinetics to the scFv, provided a more sensitive and reliable assay than the scFv. Another cloned scFv fragment was engineered in order to improve broad-specific recognition of sulfonamides. The improved antibody detects different sulfonamides at concentrations below the maximum residue limit (100 μg/kg in EU and USA) and allows simultaneous screening of different sulfonamide drug residues. Finally, a synthetic antibody library was constructed and new antibodies were generated and affinity matured entirely in vitro. These results illuminate the possibilities of phage display and antibody engineering for generation and optimisation of binding reagents in vitro and indicate the potential of recombinant antibodies as affinity reagents in immunoassays.

Analysis of electricity distribution network operation business models and capitalization of control room functions with DMS

Electricity distribution network operation (NO) models are challenged as they are expected to continue to undergo changes during the coming decades in the fairly developed and regulated Nordic electricity market. Network asset managers are to adapt to competitive technoeconomical business models regarding the operation of increasingly intelligent distribution networks. Factors driving the changes for new business models within network operation include: increased investments in distributed automation (DA), regulative frameworks for annual profit limits and quality through outage cost, increasing end-customer demands, climatic changes and increasing use of data system tools, such as Distribution Management System (DMS). The doctoral thesis addresses the questions a) whether there exist conditions and qualifications for competitive markets within electricity distribution network operation and b) if so, identification of limitations and required business mechanisms. This doctoral thesis aims to provide an analytical business framework, primarily for electric utilities, for evaluation and development purposes of dedicated network operation models to meet future market dynamics within network operation. In the thesis, the generic build-up of a business model has been addressed through the use of the strategicbusiness hierarchy levels of mission, vision and strategy for definition of the strategic direction of the business followed by the planning, management and process execution levels of enterprisestrategy execution. Research questions within electricity distribution network operation are addressed at the specified hierarchy levels. The results of the research represent interdisciplinary findings in the areas of electrical engineering and production economics. The main scientific contributions include further development of the extended transaction cost economics (TCE) for government decisions within electricity networks and validation of the usability of the methodology for the electricity distribution industry. Moreover, DMS benefit evaluations in the thesis based on the outage cost calculations propose theoretical maximum benefits of DMS applications equalling roughly 25% of the annual outage costs and 10% of the respective operative costs in the case electric utility. Hence, the annual measurable theoretical benefits from the use of DMS applications are considerable. The theoretical results in the thesis are generally validated by surveys and questionnaires.

Terveyskaupan erikoisliikkeen menestystarina: strategia ja houkuttelevuus yritysostajan perspektiivistä

Tutkielman tavoitteena on tiivistetysti edesauttaa Lappeenrannan Lifeterveyskaupan yritysmyyntiprosessia kuvailemalla kohdeyrityksen strategiaa, menestystekijöitä ja houkuttelevuutta yritysostajan näkökulma huomioiden siten, että niiden hahmottaminen ja omaksuminen helpottuu yritysostajalle. Tutkielman sisältöä voidaan hyödyntää yritysmyyntiprosessissa sellaisenaan tai tarpeen mukaan muunneltuna. Tutkielma on kvalitatiivinen tapaustutkimus, joka sisältää piirteitä käsite- ja toiminta-analyyttisestä sekä osin nomoteettisesta tutkimusotteesta. Aineisto kerättiin puolistrukturoiduilla teemahaastatteluilla. Kohdeyrityksen strategia on asiakaslähtöinen. Perusstrategia kohdeyrityksessä on riippuvainen kilpailijakontekstista, mutta useimmissa tapauksissa kilpailuetu perustuu differointiin. Suurena terveyskaupan erikoisliikkeenä voidaan hyödyntää myös suuruuden ekonomiaa. Yrityksen toiminta on alalle fokusoitua. Life-terveyskauppaketjuun kuuluminen ja erinomainen liiketilan sijainti ovat olleet tärkeitä tekijöitä menestyksessä. Runsas mainonta, suuri neuvotteluvoima toimittajiin nähden, tuoteportfolion hallinta, osaava henkilöstö ja hyvät sopimusehdot ovat edesauttaneet menestystä. Venäjä-potentiaali Lappeenrannassa on suuri. Markkina-asema on talousaseman ohella erinomainen ja hyödyksi sekä yritykselle että yritysostajalle.

Lääkevaihdon ja viitehintajärjestelmän vaikutukset patenttisuojattujen lääkevalmisteiden kohtuullisen tukkuhinnan vahvistamismenettelyyn

Pro gradu-tutkielman ensisijaisena tavoitteena oli selvittää, millaisia muutoksia lääkevaihto ja lääkkeiden viitehintajärjestelmä ovat aiheuttaneet patenttisuojattujen lääkevalmisteiden kohtuullisen tukkuhinnan vahvista-mismenettelyyn. Tätä menettelyä koskevat säännökset sisältyvät sairausvakuutuslain 6. lukuun, joten tutkimuksessa pyrittiin selvittämään kyseisen luvun soveltamista ja siinä mahdollisesti tapahtuneita muutoksia. Lääkevaihto otettiin Suomessa käyttöön 1.4.2003 ja viitehintajärjestelmä 1.4.2009. Lääkevalmisteiden hinnat ovat laskeneet niiden myötä merkittävästi. Tutkimusaineiston muodostivat 241 lääkkeiden hintalautakunnan sairausvakuutuskorvattavuutta ja kohtuullista tukkuhintaa koskevaa päätöstä vuosilta 2000-2010. Lisäksi käytössä oli muita päätöksiin liittyviä dokumentteja. Tutkimusaineisto lääkevaihdon käyttöönottoa edeltäneeltä ajalta jäi niukaksi. Tutkimuksen keskeiset havainnot liittyvätkin nimenomaan viitehintajärjestelmän käyttöönottoon. Nämä havainnot kuvaavat sitä, millaiset muutokset kohtuullisen tukkuhinnan vahvistamisessa ovat johtaneet patenttisuojattujen lääkevalmisteiden hintojen laskuun.

Pk-yrityksen polku systemaattiseen tuote- ja elinkaaritiedon hallintaan

Tutkimus on tehty Tekesin DTP-ohjelman Sinfonet-tutkimusprojektin puitteissa aikavälillä 2009-2011. Työssä on laadittu kokonaisvaltainen tuote- ja elinkaaritiedon hallinnan (eng. Product Lifecycle Management, PLM) tiekartta ja kehityssuunnitelma pienelle engineering-yritykselle. Työ käsittelee asiakkaan erikoisvaatimusten mukaan räätälöitävän tuotteen tuote- ja elinkaaritiedon hallinnan systematisointia pk-yrityksessä. Vaikka PLM-tiekartta on laadittu yksittäiselle yritykselle, sitä voidaan tietyin edellytyksin soveltaa myös toisten pk-yritysten tai engineeringyritysten PLM:n kehittämiseen. Teoriassa tarkastellaan ensinnäkin kohdeyritykseen liittyviä erityispiirteitä, pyritään ymmärtämään engineering–yrityksen ja pk-yrityksen erikoispiirteitä sekä niiden vaikutusta PLM:n kehittämiseen. Toiseksi esitellään PLM:n viittä keskeistä osaaluetta, yksi- ja viisiulotteisten PLM-kypsyysmallien käyttöä yrityksen nykytilan arvioimiseksi sekä rakennetaan engineering-yrityksen kokonaisvaltainen PLM-malli ja kahdeksan askeleen PLM-kehityspolku. PLM-malli jäsentää tiedonhallintaa prosessien kautta ja se koostuu viidestä osaalueesta: strategia identifioi asiakastarpeet sekä määrittelee kuinka tuotteiden ja prosessien avulla asiakastarpeet tyydytetään; prosessit ovat yrityksen toiminnan ydin, joissa tuotemallit ja tuote- ja tietorakenteet kehitetään sekä tuoteyksilöt toimitetaan asiakkaalle; rakenteet pohjautuvat strategiassa valittuun tuote- ja tiedonhallinnan strategiaan ja niiden tehtävänä on tukea ja tehostaa toimintaprosesseja; kulttuuri ja ihmiset muodostavat aineettoman pääoman, jonka vaikutuksesta prosessit toimivat ja tuotteet pystytään toimittamaan asiakkaalle; informaatioteknologia on työkalu, jota käytetään prosesseissa ja tietorakenteiden ylläpidossa, pääosin dokumentoidun tiedon luomiseen, hankitaan, varastoimiseen, jakamiseen ja soveltamiseen. Tapaustutkimuksessa kuvataan kohdeyrityksen nykytilaa PLM:n viidellä keskeisellä osa-alueella, tehdään PLM kypsyysarvio kahdella menetelmällä, määritellään yrityksen tavoitetila ja laaditaan yritykselle ensin alustava PLM roadmap ja lopulta kokonaisvaltaiseen PLM-malliin perustuva PLM roadmap ja PLM:n jatkokehityssuunnitelma.

Teholähteet led-valaistuksessa ja sopivan valinta kotitalouskäyttöön

Led-valaisun kehitys on mahdollistanut sen käytön kodin yleisvalaistuksessa. Työssä tutkitaan eri led-valaisuun soveltuvia teholähteitä, joista valitaan teknisiltä ominaisuuksiltaan sopivin kodin yleiskäyttöön. Tutkittavia teholähteitä ovat lineaariset ja hakkuriteholähteet. Teholähteiden ominaisuuksista tarkastellaan hyötysuhteita ja tehokertoimia, joista molempien perusteella sopivin teholähdetyyppi valitaan.

A quantitative view on fuzzy numbers

Since its introduction, fuzzy set theory has become a useful tool in the mathematical modelling of problems in Operations Research and many other fields. The number of applications is growing continuously. In this thesis we investigate a special type of fuzzy set, namely fuzzy numbers. Fuzzy numbers (which will be considered in the thesis as possibility distributions) have been widely used in quantitative analysis in recent decades. In this work two measures of interactivity are defined for fuzzy numbers, the possibilistic correlation and correlation ratio. We focus on both the theoretical and practical applications of these new indices. The approach is based on the level-sets of the fuzzy numbers and on the concept of the joint distribution of marginal possibility distributions. The measures possess similar properties to the corresponding probabilistic correlation and correlation ratio. The connections to real life decision making problems are emphasized focusing on the financial applications. We extend the definitions of possibilistic mean value, variance, covariance and correlation to quasi fuzzy numbers and prove necessary and sufficient conditions for the finiteness of possibilistic mean value and variance. The connection between the concepts of probabilistic and possibilistic correlation is investigated using an exponential distribution. The use of fuzzy numbers in practical applications is demonstrated by the Fuzzy Pay-Off method. This model for real option valuation is based on findings from earlier real option valuation models. We illustrate the use of number of different types of fuzzy numbers and mean value concepts with the method and provide a real life application.

Convergence in Industry Evolution

The objective of the thesis is to enhance understanding of the evolution of convergence. Previous research has shown that the technological interfaces between distinct industries are one of the major sources of new radical cross-industry innovations. Despite the fact that convergence in industry evolution has attracted a substantial managerial interest, the conceptual confusion within the field of convergence exists. Firstly, this study clarifies the convergence phenomenon and its impact to industry evolution. Secondly, the study creates novel patent analysis methods to analyze technological convergence and provide tools for anticipating the early stages of convergence. Overall the study combines the industry evolution perspective and the convergence view of industrial evolution. The theoretical background for the study consists of the industry life cycle theories, technology evolution, and technological trajectories. The study links several important concepts in analyzing industry evolution, technological discontinuities, path-dependency, technological interfaces as a source of industry transformation, and the evolutionary stagesof convergence. Based on reviewing the literature a generic understanding of industry transformation and industrial dynamics was generated. In the convergence studies, the theoretical basis is in the discussion of different convergence types and their impacts on industry evolution, and in anticipating and monitoring the stages of convergence. The study is divided in two parts. The first part gives a general overview, and the second part comprises eight research publications. Our case study is based historically on two very distinct industries of the paper and electronics companies as a test environment to evaluate the importance of emerging business sectors and technological convergence as a source of industry transformation. Both qualitative and quantitative research methodology are utilized. The results of this study reveal that technological convergence and complementary innovations from different fields have significant effect to the emerging new business sector formation. The patent-based indicators in the analysis of technological convergence can be utilized on analyzing technology competition, capability and competence development, knowledge accumulation, knowledge spill-overs, and technology-based industry transformation. The patent-based indicators can provide insights to the future competitive environment. Results and conclusions from empirical part seem not be in conflict with real observations in the industry.

ABOVEGROUND AND BELOWGROUND BIOMASS AND CARBON ESTIMATES FOR CLONAL EUCALYPTUS TREES IN SOUTHEAST BRAZIL

Eucalyptus plantations represent a short term and cost efficient alternative for sequestrating carbon dioxide from the atmosphere. Despite the known potential of forest plantations of fast growing species to store carbon in the biomass, there are relatively few studies including precise estimates of the amount of carbon in these plantations. In this study it was determined the carbon content in the stems, branches, leaves and roots of a clonal Eucalyptus grandis plantation in the Southeast of Brazil. We developed allometric equations to estimate the total amount of carbon and total biomass, and produced an estimate of the carbon stock in the stand level. Altogether, 23 sample trees were selected for aboveground biomass assessment. The roots of 9 of the 23 sampled trees were partially excavated to assess the belowground biomass at a singletree level. Two models with DBH, H and DBH2H were tested. The average relative share of carbon content in the stem, branch, leaf and root compartments was 44.6%, 43.0%, 46.1% and 37.8%, respectively, which is smaller than the generic value commonly used (50%). The best-fit allometric equations to estimate the total amount of carbon and total biomass had DBH2H as independent variable. The root-to-shoot ratio was relatively stable (C.V. = 27.5%) probably because the sub-sample was composed of clones. Total stand carbon stock in the Eucalyptus plantation was estimated to be 73.38 MgC ha-1, which is within the carbon stock range for Eucalyptus plantations.

St. Petersburg Court Chant and the Tradition of Eastern Slavic Church Singing

The present study examines the repertory of liturgical chant known as St. Petersburg Court Chant which emerged within the Imperial Court of St. Petersburg, Russia, and appeared in print in a number of revisions during the course of the 19th century, eventually to spread throughout the Russian Empire and even abroad. The study seeks answers to questions on the essence and composition of Court Chant, its history and liturgical background, and most importantly, its musical relationship to other repertories of Eastern Slavic chant. The research questions emerge from previous literary accounts of Court Chant (summarized in the Introduction), which have tended to be inaccurate and generally not based on critical research. The study is divided into eight main chapters. Chapter 1 provides a survey of the history of Eastern Slavic chant and the Imperial Court Chapel of St. Petersburg until 1917, with special emphasis on the history of singing traditional chant in polyphony, the status of the Court Chapel as a government authority, and its endeavours in publishing church music. Chapter 2 deals with the liturgical background of Eastern chant, the chant genres, and main repertories of Eastern Slavic chant. Chapter 3 concentrates on chant sources: it introduces the musical notations utilised, after which a typology of chant books is presented. The discussion continues with a survey of the sources of Court Chant and their content, the specimens selected for closer analysis, the comparative materials from other repertories, and ends with a commentary on some chant sources that have been excluded. The comparative sources include a specimen from around the beginning of the 12th century, a few manuscripts from the 17th century, and printed and manuscript chant books from the early 18th to early 20th century, covering the geographical area that delimits to the western Ukraine, Astrakhan, Nizhny Novgorod, and the Solovetsky Monastery. Chapter 4 presents the approach and methods used in the subsequent analytical comparisons. After a survey of the pitch organization of Eastern Slavic chant, the customary harmonization strategy of traditional chant polyphony is examined, according to which a method for meaningful analysis of the harmony is proposed. The method is based on the observation that the harmonic framework of chant polyphony derives from the standard pitch collection of monodic chant known as the Church Gamut, specific pitches of which form eight harmonic regions that behave like the usual tonalities of major and harmonic minor. Because of the considerable quantity of comparative chant forms, computer-assisted statistical methods are applied to the analysis of chant melodies. The primary chant forms and their respective comparative forms have been pre-processed into reduced chant prototypes and divided into redactions. The analyses are carried out by measuring the formal dissimilarities of the primary chant forms of the Court Chant repertory against each comparative form, and also by measuring the reciprocal dissimilarities of all chant versions in a redaction, the results of which are subjected to agglomerative hierarchical clustering in order to find out how the chant forms relate to each other. The dissimilarities are determined by applying a metric dissimilarity function that is based on the Levenshtein Distance. Chapter 5 provides the melodic and harmonic analyses of generic chants (chants used for multiple texts of different lengths), i.e., chants for stichera samoglasny and troparia, Chapter 6 of pseudo-generic chants (chants that are used for multiple texts but with certain restrictions), i.e., chants for heirmoi, prokeimena, and three other hymns, and Chapter 7 of non-generic chants, covering nine chants that in the Court repertory are not shared by multiple texts. The results are summarized and evaluated in Chapter 8. Accordingly, it can be established that, contrary to previous conceptions, melodically, Court Chant is in effect a full part of the wider Eastern Slavic chant tradition. Even if it is somewhat detached from the chant versions of the Synodal square-note chant books and the local tradition of Moscow, it is particularly close to chant forms of East Ukraine and some vernacular repertories from Russia. Respectively, the harmonization strategies of Court Chant do not show significant individuality in comparison with those of the available polyphonic comparative sources, the main difference being the part-writing, which generally conforms to western common practice standard, whereas the deviations from this tend to be more significant in other analysed repertories of polyphonic chant. Thus, insofar as the subsequent prevalence of Court Chant is not based on its forceful dissemination by authorities (as suggested in previous literature but for which little tangible evidence could be found in Chapter 1), in the present author’s interpretation, Court Chant attained its dominance principally because musically it was considered sufficiently traditional, and as a chant body supported by the government, was conveniently available in print in serviceable harmonizations.

On the impact of rigorous approaches on the quality of development

Software systems are expanding and becoming increasingly present in everyday activities. The constantly evolving society demands that they deliver more functionality, are easy to use and work as expected. All these challenges increase the size and complexity of a system. People may not be aware of a presence of a software system, until it malfunctions or even fails to perform. The concept of being able to depend on the software is particularly significant when it comes to the critical systems. At this point quality of a system is regarded as an essential issue, since any deficiencies may lead to considerable money loss or life endangerment. Traditional development methods may not ensure a sufficiently high level of quality. Formal methods, on the other hand, allow us to achieve a high level of rigour and can be applied to develop a complete system or only a critical part of it. Such techniques, applied during system development starting at early design stages, increase the likelihood of obtaining a system that works as required. However, formal methods are sometimes considered difficult to utilise in traditional developments. Therefore, it is important to make them more accessible and reduce the gap between the formal and traditional development methods. This thesis explores the usability of rigorous approaches by giving an insight into formal designs with the use of graphical notation. The understandability of formal modelling is increased due to a compact representation of the development and related design decisions. The central objective of the thesis is to investigate the impact that rigorous approaches have on quality of developments. This means that it is necessary to establish certain techniques for evaluation of rigorous developments. Since we are studying various development settings and methods, specific measurement plans and a set of metrics need to be created for each setting. Our goal is to provide methods for collecting data and record evidence of the applicability of rigorous approaches. This would support the organisations in making decisions about integration of formal methods into their development processes. It is important to control the software development, especially in its initial stages. Therefore, we focus on the specification and modelling phases, as well as related artefacts, e.g. models. These have significant influence on the quality of a final system. Since application of formal methods may increase the complexity of a system, it may impact its maintainability, and thus quality. Our goal is to leverage quality of a system via metrics and measurements, as well as generic refinement patterns, which are applied to a model and a specification. We argue that they can facilitate the process of creating software systems, by e.g. controlling complexity and providing the modelling guidelines. Moreover, we find them as additional mechanisms for quality control and improvement, also for rigorous approaches. The main contribution of this thesis is to provide the metrics and measurements that help in assessing the impact of rigorous approaches on developments. We establish the techniques for the evaluation of certain aspects of quality, which are based on structural, syntactical and process related characteristics of an early-stage development artefacts, i.e. specifications and models. The presented approaches are applied to various case studies. The results of the investigation are juxtaposed with the perception of domain experts. It is our aspiration to promote measurements as an indispensable part of quality control process and a strategy towards the quality improvement.

Military crisis management in the next decade (2020-2030) : inducing consent or relying on compliance?

The most outstanding conceptual challenge of modern crisis management is the principle of consent. It is not a problem only at the operational level - it challenges the entire decision-making structures of crisis management operations. In post-cold war times and especially in the 21st century, there has been a transition from peacekeeping with limited size and scope towards large and complex peace operations. This shift has presented peace operations with a dilemma. How to balance between maintaining consent for peace operations, whilst being able to use military force to coerce those attempting to wreck peace processes? To address such a dilemma, this research aims to promote understanding, on what can be achieved by military crisis management operations (peace support operations) in the next decade. The research concentrates on the focal research question: Should military components induce consent or rely on the compliance of conflicting parties in crisis management operations of the next decade (2020 – 2030)? The focus is on military – political strategic level considerations, and especially on the time before political decisions to commit to a crisis management operation. This study does not focus on which actor or organisation should intervene. The framework of this thesis derives from the so called ‘peacebuilding space’, the scope of peace operations and spoiler theory. Feasibility of both peace enforcement and peacekeeping in countering future risk conditions are analysed in this framework. This future-orientated qualitative research uses the Delphi-method with a panel of national and international experts. Citation analysis supports identification of relevant reference material, which consists of contemporary literature, the Delphi-questionnaires and interviews. The research process followed three main stages. In the first stage, plausible future scenarios and risk conditions were identified with the Delphi-panel. In the second stage, operating environments for peace support operations were described and consequent hypotheses formulated. In the third stage, these hypotheses were tested on the Delphi-panel. The Delphi-panel is sufficiently wide and diverse to produce plausible yet different insights. The research design utilised specifically military crisis management and peace operations theories. This produced various and relevant normative considerations. Therefore, one may argue that this research; which is based on accepted contemporary theory, hypotheses derived thereof and utilising an expert panel, contributes to the realm of peace support operations. This research finds that some degree of peace enforcement will be feasible and necessary in at least the following risk conditions: failed governance; potential spillover of ethnic, religious, ideological conflict; vulnerability of strategic chokepoints and infrastructures in ungoverned spaces; as well as in territorial and extra-territorial border disputes. In addition, some form of peace enforcement is probably necessary in risk conditions pertaining to: extremism of marginalised groups; potential disputes over previously uninhabited and resource-rich territories; and interstate rivalry. Furthermore, this research finds that peacekeeping measures will be feasible and necessary in at least risk conditions pertaining to: potential spillover of ethnic, religious, ideological conflict; uncontrolled migration; consequences from environmental catastrophes or changes; territorial and extra-territorial border disputes; and potential disputes over previously uninhabited and resource-rich territories. These findings are all subject to both generic and case specific preconditions that must exist for a peace support operation. Some deductions could be derived from the research findings. Although some risk conditions may appear illogical, understanding the underlying logic of a conflict is fundamental to understanding transition in crisis management. Practitioners of crisis management should possess cognizance of such transition. They must understand how transition should occur from threat to safety, from conflict to stability – and so forth. Understanding transition is imperative for managing the dynamic evolution of preconditions, which begins at the outset of a peace support operation. Furthermore, it is pertinent that spoilers are defined from a peace process point of view. If spoilers are defined otherwise, it changes the nature of an operation towards war, where the logic is breaking the will of an enemy - and surrender. In peace support operations, the logic is different: actions towards spoilers are intended to cause transition towards consent - not defeat. Notwithstanding future developments, history continues to provide strategic education. However, the distinction is that the risk conditions occur in novel futures. Hence, lessons learned from the past should be fitted to the case at hand. This research shows compelling evidence that swaying between intervention optimism and pessimism is not substantiated. Both peace enforcement and peacekeeping are sine qua non for successful military crisis management in the next decade.

Nollapersoonalause suomessa ja virossa. Tutkimus kirjoitetun kielen aineistosta

The present study focuses on the zero person constructions both in Finnish and Estonian. In the zero person construction, there is no overt subject and the verb is in the 3rd person singular form: Fin. Tammikuussa voi hiihtää Etelä-Suomessakin. Est. Jaanuaris saab suusatada ka Lõuna-Soomes ‘In January one can ski even in South-Finland’. The meaning of the zero construction is usually considered generic and open. However, the zero may be interpreted as indexically open so that the reference can be construed from the context. This study demonstrates how the zero may be interpreted as referring to the speaker, the addressee, or anybody. The zero person construction in Finnish has been contrasted to the generic pronoun constructions in Indo-European languages. For example, the zero person is translated in English as you or one; in Swedish and German as man. The grammar and semantics of the Finnish zero person construction have been studied earlier to some extent. However, the differences and similarities between Finnish and Estonian, two closely related languages, have not been thoroughly studied before. The present doctoral thesis sheds light on the zero person construction, its use, functions, and interpretation both in Finnish and Estonian. The approach taken is contrastive. The data comes from magazine articles published in Finnish and translated into Estonian. The data consists of Finnish sentences with the zero person and their Estonian translations. In addition, the data includes literary fiction, and non-translated Estonian corpora texts as well. Estonian and Finnish are closely related and in principle the personal system of the two languages is almost identical, nevertheless, there are interesting differences. The present study shows that the zero person construction is not as common in Estonian as it is in Finnish. In my data, a typical sentence with the zero person in both languages is a generic statement which tells us what can or cannot be done. When making generic statements the two languages are relatively similar, especially when the zero person is used together with a modal verb. The modal verbs (eg. Fin. voida ‘can’, saada ‘may’, täytyä ‘must’; Est. võima ‘may’, saama ‘can’, tulema ’must’) are the most common verbs in both Finnish and Estonian zero person constructions. Significant differences appear when a non-modal verb is used. Overall, non-modal verbs are used less frequently in both languages. Verbs with relatively low agentivity or intentionality, such as perception verb nähdä in Finnish and nägema in Estonian, are used in the zero person clauses in both languages to certain extent. Verbs with more agentive and intentional properties are not used in the Estonian zero person clauses; in Finnish their use is restricted to specific context. The if–then-frame provides a suitable context for the zero person in Finnish, and the Finnish zero person may occur together with any kind of verb in conditional if-clause. Estonian if-clauses are not suitable contexts for zero person. There is usually a da-infinitive, a generic 2nd person singular or a passive form instead of the zero person in Estonian counterparts for Finnish if-clauses with zero person. The aim of this study was to analyze motivations for choosing the zero person in certain contexts. In Estonian, the use of the zero person constructions is more limited than in Finnish, and some of the constraints are grammatical. On the other hand, some of the constraints are motivated by the differences in actual language use. Contrasting the two languages reveals interesting differences and similarities between these two languages and shows how these languages may use similar means differently.

Hihnakuljetinjärjestelmien modulointi

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.

Health Related Quality of Life after Childhood Cancer - A Finnish Nationwide survey

The purpose of this Finnish epidemiological nationwide cross-sectional study was to evaluate the Health Related Quality of Life (HRQL) of young people that have survived childhood cancer at least four years after cancer diagnosis. The study aims were (1) to increase knowledge and understanding about the relationship between childhood cancer and its treatment and HRQL of childhood cancer survivors and (2) to identify survivors who need and could benefit from ongoing long-term follow-up, as well as (3) to identify what kind of aftercare the childhood cancer survivors will possibly need. HRQL and fatigue of currently still young survivors of extracranial childhood malignancies were evaluated with self-reports and parent proxy reports. HRQL was measured with age-appropriate generic instruments: PedsQL™, SF-36, 15D, 16D and 17D. Fatigue for children and adolescents aged below 18 years was measured with the PedsQL™ Multidimensional Fatigue Scale Finnish version. PedsQL™ parent-proxy and the PedsQL™ Multidimensional Fatigue Scale Parentproxy instruments were used to assess the perception of the parents on HRQL and fatigue of their children and adolescents. Postal-survey questionnaires were mailed to 852 childhood cancer survivors aged 11-27 years and their randomly selected gender-, age and living-place matched controls, as well as under 18-year-old children´s parents. A total of 474 survivors, 595 controls, 209 survivor’s parent and 253 control’s parent replied. The mean age of survivors at the time of the study was 18.4 years. The mean length of survival was 12.3 years, and the mean age at diagnosis 5.5 years. The most of the Finnish childhood cancer survivors evaluated that their HRQL as good. Survivors rated their HRQL equal or higher than their controls. The only dimension where the survivors scored poorer than the controls was the 15D mobility dimension. Survivors of childhood cancer did not suffer from significant fatigue. There were subgroups of childhood cancer survivors who had poorer level of HRQL, and suffered from fatigue more than the reference group. The demographic factors that associated with poorer HRQL were female gender, greater weight, living alone, need of remedial education, an additional non-cancer diagnosis, survivors with siblings, and self-reported unhappiness. Disease-related factors that associated with poorer HRQL were higher age at the time of diagnosis, the diagnosis of Wilms tumor, neuroblastoma, or osteosarcoma, and treatment with stem cell transplantation. The factors associated with more fatigue in survivors were male gender, older age at evaluation, the need of remedial education at school, lower overall average grade in the latest school marks report, length of survival more than 10 years, lower HRQL-scores, and a sarcoma diagnosis. However, all the used demographic and disease related factors explained only about one third of the variation in the HRQL scores. In open questions, the survivors were most worried about their physical health, but were also worried about their mental health, cancer inheritance, late-effects, and fertility and relapse issues. It seems that there are subgroups of survivors who need and could benefit from ongoing long-term follow-up. In the future, the survivors of childhood cancer need more information about their physical and mental health, as well as on their cancer inheritance, possible late-effects including fertility issues, and on the risk of relapse.