Kategoria-analyysin päivitys

Kirjallisuusarvostelu

Imaging Neuroinflammation in Progressive Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system CNS), where inflammation and neurodegeneration lead to irreversible neuronal damage. In MS, a dysfunctional immune system causes auto‐reactive lymphocytes to migrate into CNS where they initiate an inflammatory cascade leading to focal demyelination, axonal degeneration and neuronal loss. One of the hallmarks of neuronal injury and neuroinflammation is the activation of microglia. Activated microglia are found not only in the focal inflammatory lesions, but also diffusely in the normal‐appearing white matter (NAWM), especially in progressive MS. The purine base, adenosine is a ubiquitous neuromodulator in the CNS and also participates in the regulation of inflammation. The effect of adenosine mediated via adenosine A2A receptors has been linked to microglial activation, whereas modulating A2A receptors may exert neuroprotective effects. In the majority of patients, MS presents with a relapsing disease course, later advancing to a progressive phase characterised by a worsening, irreversible disability. Disease modifying treatments can reduce the severity and progression in relapsing MS, but no efficient treatment exists for progressive MS. The aim of this research was to investigate the prevalence of adenosine A2A receptors and activated microglia in progressive MS by using in vivo positron emission tomography (PET) imaging and [11C]TMSX and [11C](R)‐PK11195 radioligands. Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed to evaluate structural brain damage. Non‐invasive input function methods were also developed for the analyses of [11C]TMSX PET data. Finally, histopathological correlates of [11C](R)‐PK11195 radioligand binding related to chronic MS lesions were investigated in post‐mortem samples of progressive MS brain using autoradiography and immunohistochemistry. [11C]TMSX binding to A2A receptors was increased in NAWM of secondary progressive MS (SPMS) patients when compared to healthy controls, and this correlated to more severe atrophy in MRI and white matter disintegration (reduced fractional anisotropy, FA) in DTI. The non‐invasive input function methods appeared as feasible options for brain [11C]TMSX images obviating arterial blood sampling. [11C](R)‐PK11195 uptake was increased in the NAWM of SPMS patients when compared to patients with relapsing MS and healthy controls. Higher [11C](R)‐PK11195 binding in NAWM and total perilesional area of T1 hypointense lesions was associated with more severe clinical disability, increased brain atrophy, higher lesion load and reduced FA in NAWM in the MS patients. In autoradiography, increased perilesional [11C](R)‐PK11195 uptake was associated with increased microglial activation identified using immunohistochemistry. In conclusion, brain [11C]TMSX PET imaging holds promise in the evaluation of diffuse neuroinflammation in progressive MS. Being a marker of microglial activation, [11C](R)‐ PK11195 PET imaging could possibly be used as a surrogate biomarker in the evaluation of the neuroinflammatory burden and clinical disease severity in progressive MS.

Roadmap for Service Charging Development

Corporate support functions are increasingly being concentrated into service centers. Service Management principles guide companies in the transition. Service Financial Management is an integral part in supporting the strategic positioning of the service center. The main goal of this thesis is to create a step-by-step plan to improve and automate the service charging processes for the finance service function of the case company. Automating the service transaction data collection for reporting is expected to improve efficiency, reliability and transparency. Interviews with finance service managers are held to define current processes and areas for improvement. These create the basis for the creation of a development roadmap that takes place in two phases. The first phase is to create an environment where automation is possible, and the second phase is the automation of each finance service. Benchmarking interviews are held with the service centers in three other companies to discover best practices. The service charging processes between the studied companies are found incompatible, and suggestions for process automation cannot be inferred. Some implications of Service Financial Management decisions to the strategy of the service center are identified. The bundling of services and charging them inside or outside of the goal-setting frame of the business unit can be used to support the strategic choice and customer acceptance of the service center.

Aseellinen voima Yhdysvaltojen strategisena instrumenttina 2000-luvulla

Tutkimuksen kohteena on Yhdysvaltojen aseellinen voimankäyttö 2000-luvulla. Tavoitteena on ymmärtää miten Yhdysvaltojen aseellisen voimankäytön merkitys kansallisten etujen tavoittelussa on muuttunut George W. Bushin ja Barack Obaman presidenttikausien aikana. Muutos liittyy myös laajempaan sodankuvan muutokseen länsimaissa kylmän sodan jälkeisellä ajanjaksolla. Tutkimuksen teoreettinen viitekehys rakentuu modernin konstruktivismin ja tieteellisen realismin varaan. Analyysissa tarkastellaan sekä Yhdysvaltojen aseellisen voimankäytön tilanteita ja tapoja että virallisia puheita ja lausuntoja, joissa Yhdysvallat on toimiaan perustellut. Teoreettisen viitekehyksen mukaisesti Yhdysvaltojen presidenttien puheiden katsotaan liittyvän yhdysvaltalaisiin käsityksiin aseellisesta voimankäytöstä ja samalla yhdessä aseellisen voimankäytön kanssa muokkaavan edelleen näitä käsityksiä. Ajallisesti tutkimus rajattiin presidenttien George W. Bush ja Barack Obama hallintokausille aikavälille 20.01.2001‒4.3.2014. Aseelliseen voimaan ja sen käyttöön liittyviä käsityksiä etsittiin presidenttien puheista ja empiirisen analyysin kohteiksi valittiin tilanteet, joissa Yhdysvallat oli käyttänyt aseellista voimaa tai aseellisen voiman käyttämättä jättäminen oli aiheuttanut keskustelua. Aseellisen voimankäytön merkityksen muuttuminen kansallisten intressien tavoittelussa ilmenee tarkastelulla ajanjaksolla monella tavalla. Tarkastelujakson alussa Yhdysvalloilla oli yleisen, 1990-luvun kuluessa vakiintuneen käsityksen mukaan ennen kaikkea teknologisen etumatkansa vuoksi maailman tehokkaimmat asevoimat, mutta käsitykset sodasta eivät muodostaneet koherenttia kokonaisuutta. Vuoden 2001 jälkeen terrorisminvastaisesta sodasta muodostui tärkein Yhdysvaltojen johtaja-asemaa ja aseellisen voiman käyttöä kansainvälisessä järjestelmässä selittävä viitekehys. Sotilaalliset takaiskut ja liittolaisten painostaminen kuitenkin kuluttivat voimavaroja ja heikensivät sodan oikeutusta kansainvälisessä järjestelmän piirissä. Obama pyrki esiintymään vaihtoehtona Bushin politiikalle erityisesti suhtautumisellaan aseellisen voiman käyttöön ja terrorismin muodostamaan uhkaan. Yhdysvaltojen toiminta perustuu kansainväliseen turvallisuusyhteistyöhön ja kynnys aseellisen voiman käyttöön on kasvanut. Vaikka konkreettinen voimankäyttö on vähentynyt Obaman kausilla, monet sotaan ja aseelliseen voimaan liittyvät käsitykset ovat kuitenkin pysyneet miltei muuttumattomina verrattuna Bushin kausiin. Yhdysvaltojen tapa käyttää voimaa Obaman kausilla osoittaa että käsitykset aseellisesta voimasta perustuvat edelleen vahvasti teknologian tuottamaan suorituskykyyn. Mikäli Yhdysvallat käyttää aseellista voimaansa lähitulevaisuudessa, perustuvat toimintaa ohjaavat periaatteet yhteistyöhön alueellisten toimijoiden kanssa ja teknologiakeskeiseen sodankäyntiin.

Moniääninen tutkimus rintamanaisista

Kirjallisuusarvostelu

Toimittajien suorituskykymittariston suunnittelu ja toteutus

Tämän diplomityön tarkoituksena oli kehittää teollisuusyrityksen toimittajahallintaa suorituskykymittauksen avulla. Työssä suunnitellaan ja toteutetaan toimittajien suorituskykymittaristo teoriatiedon avulla. Projektin lopputuloksena case-yrityksellä on käytössään kokonaisvaltainen toimittajien suorituskykymittaristo ja kehittyneet toimittajahallinnan prosessit. Työn teoriaosuudessa syvennytään erilaisiin suorituskykymittariston kehittämisen viitekehyksiin. Lisäksi teoriaosuudessa käsitellään hyvän suorituskykymittariston vaatimuksia ja suositeltuja mittauksen seuranta-alueita. Työn empiriaosuudessa rakennetaan suorituskykymittaristo vaihe vaiheelta perustuen tapaustutkimukseen. Kehitettyä suorituskykymittaristoa testattiin simulaatiovaiheen aikana case-yrityksen kolmella tehtaalla. Käyttäjäpalautteen perusteella mittaristo täytti teoriaosuudessa löydetyt tärkeimmät vaatimukset suorituskykymittaristolle. Mittaristo on helppokäyttöinen, visuaalinen ja sen raportoinnista saa arvokasta informaatiota toimittajien arviointiin. Diplomityön konkreettisia hyötyjä case-yritykselle ovat olleet laatupoikkeamien kehittynyt havaitseminen ja toimittajan hintakilpailukyvyn parantunut arviointi. Kaikkein merkittävin hyöty case-yritykselle on kuitenkin ollut systemaattinen toimittaja-arviointiprosessi, minkä suorituskykymittaristo mahdollistaa.

Food webs in the era of molecular revolution – Like resolving the Gordian knot with a tricorder

Living nature consists of countless organisms, which are classified into millions of species. These species interact in many ways; for example predators when foraging on their prey, insect larvae consuming plants, and pathogenic bacteria drifting into humans. In addition, abiotic nature has a great initiative impact on life through many factors (including sunlight, ambient temperature, and water. In my thesis, I have studied interactions among different life forms in multifaceted ways. The webs of these interactions are commonly referred to as food webs, describing feeding relationships between species or energy transfer from one trophic level to another. These ecological interactions – whether they occur between species, between individuals, or between microorganisms within an individual – are among the greatest forces affecting natural communities. Relationships are tightly related to biological diversity, that is, species richness and abundances. A species is called a node in food web vocabulary, and its interactions to other species are called links. Generally, Artic food webs are considered to be loosely linked, simple structures. This conception roots into early modern food webs, where insects and other arthropods, for example, were clumped under one node. However, it has been shown that arthropods form the greatest part of diversity and biomass both in the tropics and in Arctic areas. Earlier challenges of revealing the role of insects and microorganisms in interactions webs have become possible with the help of recent advances in molecular techniques. In the first chapter, I studied the prey diversity of a common bat, Myotis daubentonii, in southwestern Finland. My results proved M. daubentonii being a versatile predator whose diet mainly consists of aquatic insects, such as chironomid midges. In the second chapter, I expanded the view to changes in seasonal and individual-based variation in the diet of M. daubentonii including the relationship between available and observed prey. I found out that chironomids remain the major prey group even though their abundance decreases in proportion to other insect groups. Diet varied a lot between individuals, although the differences were not statistically significant. The third chapter took the study to a large network in Greenland. I showed that Artic food webs are very complex when arthropods are taken into account. In the fourth chapter, I examined the bacterial flora of M. daubentonii and surveyed the zoonotic potential of these bacteria. I found Bartonella bacteria, of which one was described as a new species named after the locality of discovery. I have shown in my thesis that Myotis daubentonii as a predator links many insect species as well as terrestrial and aquatic environments. Moreover, I have exposed that Arctic food webs are complex structures comprising of many densely linked species. Finally, I demonstrated that the bacterial flora of bats includes several previously unknown species, some of which could possibly turn in to zoonosis. To summarize, molecular methods have untied several knots in biological research. I hope that this kind of increasing knowledge of the surrounding nature makes us further value all the life forms on earth.

Influencing Perceived Agency: A Study into User Experiences in Digital Interactive Storytelling

User experience is a crucial element in interactive storytelling, and as such it is important to recognize the different aspects of a positive user experience in an interactive story. Towards that goal, in the first half of this thesis, we will go through the different elements that make up the user experience, with a strong focus on agency. Agency can be understood as the user’s ability to affect the story or the world in which the story is told with interesting and satisfying choices. The freedoms granted by agency are not completely compatible with traditional storytelling, and as such we will also go through some of the issues of agency-centric design philosophies and explore alternate schools of thought. The core purpose of this thesis is to determine the most important aspects of agency with regards to a positive user experience and attempt to find ways for authors to improve the overall quality of user experience in interactive stories. The latter half of this thesis deals with the research conducted on this matter. This research was carried out by analyzing data from an online survey coupled with data gathered by the interactive storytelling system specifically made for this research (Regicide). The most important aspects of this research deal with influencing perceived agency and facilitating an illusion of agency in different ways, and comparing user experiences in these different test environments. The most important findings based on this research include the importance of context-controlled and focused agency and settings in which the agency takes place and the importance of ensuring user-competency within an interactive storytelling system. Another essential conclusion to this research boils down to communication between the user and the system; the goal of influencing perceived agency should primarily be to ensure that the user is aware of all the theoretical agency they possess.