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  • Nieminen, Tarja (Helsingin yliopisto, 2015)
    Social capital has been widely discussed in research. An increasing amount of literature has linked social capital to various health outcomes and well-being. However, both health and social capital are complex phenomena, and there is still inconsistency in the research findings. The general aim of this study was to examine the associations between social capital, health behaviour and health among adult Finnish population. The conceptualization and operationalization of social capital varies according to discipline and level. In this study, social capital is measured at the individual level assuming that an individual s investment in group activity reflects social capital seen as a resource related to social networks and group membership. Individual benefits are accessed through social connections in varied groups and society. Thus the resources do not reside within the individual but rather in the structure of person s social networks. Social capital was measured on three dimensions in this study: 1) social support, 2) social networks and participation and 3) trust and reciprocity. The association between these dimensions and health were examined. Health was investigated as self-rated health, psychological well-being and mortality. This study utilised the data of the Health 2000 Survey conducted in 2000−2001. Of people aged 30 and over, 89% participated in the home interview and 80% in the general health examination. The study material presents the whole population unusually well. The National Institute for Health and Welfare (THL; formerly the National Public Health Institute, KTL) had the overall responsibility for the project. In addition, the project organization involved a wide range of research and funding agencies. This survey contains a rich armoury of questions about health and illnesses, health behaviour, capacity for work, functional capacity and use of health services. Furthermore, it includes a broad selection of questions used in measuring social capital. The results found an accumulation of social capital and general welfare for the same groups: the highest levels of social capital were found among the young, well-educated and married people. However, all socio-demographic subgroups seem to benefit from social capital. Regardless of all socio-demographic characteristics, high levels of social capital were associated with good health, associations which varied among different health-related behaviours, but social participation had a strong statistical association with all components of health and all health behaviours. Regardless of chronic diseases people with high levels of social capital felt healthier than those with low levels. The positive association between social capital and survival was statistically significant among men and suggestive among women. These findings indicate that social capital contributes to health. Health inequalities between population sub-groups are still substantial. Health could be promoted and health inequalities reduced by developing tools for increasing social participation especially in those groups lacking social capital−and who often also suffer from several health problems.
  • Buchholz, Matias (Helsingin yliopisto, 2015)
    The aim of the present work (Roman Law in Greek: Prolegomena to a Linguistic Study of the Composition and Semantics of the Byzantine Vocabulary of Procedural Law) is to study the composition and semantics of Byzantine Greek legal vocabulary, especially that related to procedural law, from the perspective of the Latin influence on Greek. The work is based on a contact-linguistic and semantic analysis of the occurrences of a number of relevant expressions in the primary sources (not only technical terms in the narrowest sense, but also polysemous words). These occurrences have been mainly extracted from the databases TLG (literary sources), PHI (inscriptions) and DDbDP (papyri). The work is not an exhaustive treatment of all relevant words. Instead, by focusing on a selection of examples and on methodological questions, it tries to open a new perspective on Byzantine legal language. The first main chapter (Chapter 4) provides an overview of the ways in which Latin influenced the composition of Byzantine legal vocabulary. Previous research has often focused on lexical borrowings, but, since these are only part of the story, I argue that our understanding of Byzantine legal vocabulary would benefit from an increased attention to semantic borrowings (loan translations/calques and borrowed meanings) and to unchanged Greek words (that is, their continued use vs. their marginalization through Latin influence). I also evaluate the usefulness of different criteria for the distinction between integrated and non-integrated lexical borrowings (Lehnwort vs. Fremdwort). I claim that, i.a., morphological adaptation is not a conclusive criterion, while frequency and distribution over different sub-genres of legal writings are more informative. In addition, I argue that the phenomenon of code-switching, practically neglected in previous studies on Byzantine legal language, was present and would warrant further linguistic research. Chapter 5 is devoted to the semantics of Byzantine legal vocabulary, especially to the ways it differed from that of Latin, and to whether these differences are due to contact-induced change or to language-internal developments. The meanings of individual words often contracted or expanded, and sometimes even shifted. I propose certain systematic effects, e.g., that loanwords are easily affected by a contraction of meaning, and that the lack of contact-induced semantic change is largely restricted to technical terms proper. These developments concerning individual words mean that the semantic structure of Byzantine legal vocabulary as a whole is different from the legal vocabulary of Latin. Even if this has no effects on the legal system itself, it certainly means that we are dealing with another view of that system.
  • Cousminer, Diana (Helsingin yliopisto, 2015)
    Puberty is a highly variable developmental stage marked by the development of secondary sex characteristics and the attainment of reproductive maturity. Variation during childhood developmental phases correlates with altered disease risk in adulthood; variation in pubertal growth and timing, in particular, correlates with adult risk for type 2 diabetes, obesity, adverse cardiovascular heath, and hormone-dependent cancers. While normal variation in age at menarche (AAM) has recently been investigated in large-scale genome-wide association (GWA) studies, the genetic regulation of male puberty remains less understood. Moreover, extreme variation in pubertal timing is a common cause for referral to pediatric specialists, while the underlying genetic factors are largely unknown. This work aimed to identify both common and rare genetic variants influencing pubertal growth and timing in both sexes. Utilizing Finnish population-based samples with frequent height measurements across puberty, we ran GWA of growth during late puberty and uncovered an association for variants near LIN28B, the most robust menarche-associated locus. Investigation of the longitudinal effects of two partly-correlated markers, one tagging a pubertal timing effect and one tagging an effect on adult stature, revealed distinct sex-specific association patterns with height growth from birth until adulthood. Thus, the LIN28B locus tags an important developmental regulator of both growth and maturational development. We then expanded to include European-wide samples within the Early Growth Genetics (EGG) Consortium. Genetic mapping of three pubertal growth traits revealed 9 novel pubertal growth variants in addition to LIN28B, 5 of which also associated with pubertal timing, and one which associated with childhood and adult body mass index (BMI). Longitudinal investigation of these variants showed diverse patterns of association with height growth, some of which contradicted epidemiological correlations between rapid prepubertal growth, advanced puberty, and reduced final adult stature. Given the complex relationships between these traits, tracking individual unique effects across multiple periods of growth may help uncover the pathways linking childhood development with adult health outcomes. Also within the EGG Consortium, GWA meta-analysis of Tanner genital and breast staging data uncovered the first robust male puberty locus on chromosome 16 near MKL2, a locus which also associates with advanced menarche, decreased pubertal growth, and shorter adult stature. Furthermore, part of the genetic architecture underlying the onset of puberty is shared between males and females, evidenced by the high correlation between menarche-advancing alleles and earlier male genital development. However, while BMI-increasing alleles strongly correlate with advanced breast development in girls, our data shows that these variants play a more complex role in male puberty. Finally, we performed targeted sequencing of the pericentromeric region of chromosome 2 previously robustly linked with constitutional delay of growth and puberty (CDGP), an extreme delay in normal pubertal timing, in multiply affected Finnish families. Analysis of shared low-frequency variation in genes and regulatory regions of the best functional candidate genes revealed 6 protein-altering variants in a single gene, DNAH6, in 10 of the families. However, follow-up sequencing in an additional 135 Finnish CDGP cases failed to provide evidence for enrichment of DNAH6 mutations compared to a large, unique set of SISu Finnish population controls. DNAH6 is potentially an appropriate candidate gene that may be involved in the regulation of steroid hormone biosynthesis by the cytoskeleton. This study highlights the difficulties of detecting susceptibility variants under a linkage signal for complex traits. Taken together, these results advance our understanding of the genetics of pubertal timing and development in both sexes. However, more work is needed to understand how each genetic locus functions in the biology of puberty and childhood growth, and further study of the genetic loci highlighted in this work may help pinpoint the mechanisms that link the timing of this important developmental stage with adult health and risk for common diseases. Keywords: puberty, development, growth, genome-wide association studies (GWAS), targeted sequencing, constitutional delay of growth and puberty (CDGP)
  • Nordman, Nina (Helsingin yliopisto, 2015)
    Analytical microsystems are attractive in modern bioanalysis where sample amounts often are low and fast analyses are required. Microsystems also provide the prospect of integrating several functional elements on a single platform. The aim of this work was to develop analytical microsystems for fast analysis of bio- and drug molecules. For this, microchips with separation- and injection channels and monolithically integrated electrospray ionization (ESI) emitter were fabricated of epoxy photoresist SU-8 by photolithography and adhesive bonding. For peptide mass fingerprinting and protein sequencing characteristic tryptic peptides were fast and easily separated and detected by microchip capillary electrophoresis (MCE)-ESI/mass spectrometry (MS). Additionally, protein identification based on tandem MS fragmentation data of a single tryptic peptide was achieved. Finally, this rapid (total analysis time below ten minutes) microchip method permitted analysis of human muscle cell lysates. For online coupling of microchip capillary isoelectric focusing (cIEF) to ESI/MS a bilateral sheath flow interface or a two-dimensional separation unit was integrated on-chip. Rapid focusing of peptides by their isoelectric points (pI) was achieved without pretreatment of the SU-8 surface. After focusing the peptides were electrokinetically mobilized toward ESI/MS. The two-dimensional chip design enabled unique separation selectivity for peptides based on both pI values and intrinsic electrophoretic mobilities by multiplex-cIEF-transient-isotachophoresis. Rapid metabolic profiling was demonstrated from urine after intake of tramadol or paracetamol. Both phase I- and II metabolites were separated and detected by MCE-ESI/MS within 35 s. In addition, Michaelis-Menten kinetics was successfully determined for the CYP450-mediated oxidation of bufuralol to 1-hydroxybufuralol. Sample preconcentration (pretreatment) was integrated on-chip by solid-phase extraction (SPE) and liquid-phase microextraction (LPME). For SPE, a monolith zone was firmly anchored at the injection cross of the MCE-ESI/MS microchip by laser induced photopolymerization. The monolith was selective toward hydrophobic and hydrophilic sample molecules and enrichment factors as high as 23-fold was achieved with a loading time as short as 25 s. In addition, LPME was easily downscaled to low volume applications and offered selectivity in the analysis of phase I metabolites compared to SPE. In contrast to previous research in the same field this work offers bioanalysis with several on-chip integrated steps (preconcentration, injection, separation, and analysis) without considerably increasing the short analysis times characteristic of microchip assays.
  • Stenholm, Noora (2015)
    Involuntary displacements are more common than ever, and the reasons vary from natural disasters, wars and conflicts to environmental degradation and development-induced displacement. Typically, the victims of these phenomena inhabit the Global South, and are further impoverished due to the lack of having a say where and how to live. The lack of social justice and recognition of social development is typical in large-scale involuntary displacements, and also affects to the abilities of people to reconstruct and recover after resettlement. The linkage between forced migration and risk to impoverishment has been widely acknowledged especially in cases that lack participatory measures and proper compensation for the victims. When the impacts are recognized, it is understood that forced resettlement has effects in the economic, social, and physical spheres of life, and can be a major burden for the urban poor. However, involuntary displacement also disrupts the attachments and constructions of sense of place, which have further impacts on social cohesion. The question of community reorganization is crucial in the context where resettlement is simultaneous and combines various heterogeneous groups. The aim of this research is to examine the extent and quality of rehabilitation after involuntary displacement in an urban environment in Sri Lanka. The focus in this research is given to women, as gender is a significant factor in resettlement outcomes, yet it is often ignored in planning and implementation. Gender roles and norms in Sri Lanka are still fixed and conventional, making it an interesting approach to study resettlement and rehabilitation and the daily interactions and perceptions on them. A case study for this research took place in four resettlement sites in the outskirts of Colombo Metro Region, Sri Lanka, which is in the midst of significant urban development plans that aim to relocate tens of thousands of slum dwellers in the need to release prime lands for investments, simultaneously beautifying the city and fighting frequent flooding. The methodological approach applied in this study addresses feminist geography while it looks at rehabilitation measures in the everyday life point of view. It utilized semi-structured interviews of resettled women as a key research method. The case study took place in upgraded underserved settlements that inhabit tsunami-displaced people and development-induced displaced people. Also local experts were interviewed in order to gain a broader understanding of the dynamics and urban policies in the Colombo Metro Region. The case evidences that rehabilitation is a slow process of adaptation, and that physical assets alone cannot improve the livelihoods of slum dwellers. More emphasis should be put into the social relations and community dynamics if participatory measures and development-from-within are to fully deliver. Also full tenure is needed in order to the people to adapt to the mainstream society. For women the question of belonging and reconstructing the sense of place is essential as they spend a lot of their time at home and the immediate environment, and are traditionally in charge of homemaking. Therefore the sense of place and community are essential in the creation of social cohesion and management of the new neighborhood, and along with gender sensitive approaches should not be overlooked if sustainable resettlement is to be pursued as a consequence of ever more crowded cities of the South.
  • Ito, Sanae (Helsingin yliopisto, 2015)
    Assurbanipal, the last great king of the Assyrian Empire (934-609 BC), ruled from 668 BC until at least 630 BC. He had to spend four years suppressing a revolt by ama - umu-ukīn, his older brother and the king of Babylon (667-648 BC), but his reign was much longer than his predecessors and he controlled almost all the area of the Ancient Near East. One of the essential bodies of research material on his reign is his correspondence, which has never before been studied in detail because much of it has been published in cuneiform copies only. His extant correspondence consists of 359 letters: 72 letters from him (the so-called royal letters) and 287 letters to him. Royal letters are particularly rare in the Assyrian correspondence and Assurbanipal s royal letters outnumber those of his predecessors, hence this dissertation focuses on them. The letters deal with political, military, and diplomatic matters through the king s point of view and in his words. The aim of this research has been to find out what image of himself Assurbanipal tried to convey in his letters and how he utilized the image in order to further Assyrian policies. The dissertation uses philological method and also takes advantage of the electronic database of the Neo-Assyrian Text Corpus Project (Helsinki), which contains the majority of texts of the Neo-Assyrian period in transliteration. Most of Assurbanipal s royal letters were written during the revolt and its aftermath, and sent to Babylonia, Elam, and the Sealand, which were deeply involved in the revolt. Since the most common recipients of the missives were citizens, Assurbanipal clearly considered it particularly important to address the population at large when the revolt shook the foundation of the empire. As the royal letters originate in the state archives in the capital of Assyria, Nineveh, most of them are archival copies or drafts. Two languages and two scripts (Neo-Assyrian, Neo-Babylonian) were used in them, but the drafts would have first been drawn up in Neo-Assyrian, and later translated into Neo-Babylonian, perhaps first in Assyrian script and only later in Babylonian script. Assurbanipal had dialogue with both adversaries and adherents, emphasized the favours he had done, and described himself as a benevolent and merciful king who was capable of establishing justice, peace, and equality in the realm. He involved Nippur and Uruk in Assyrian military activities against rebels and settled a sibling rivalry between the governor of Ur and his predecessor. He continued a conciliatory policy towards Babylon even during the revolt in order to resolve the conflict peacefully. He tried to incorporate foreign countries into Assyrian control by treaties and sometimes exerted direct pressure on them with thinly veiled threats. Some countries came under Assyrian rule at their own initiative in order to acquire military and political gains from Assyria. Throughout the royal letters, he stressed his devotion to the gods and their support for his rule. Especially A ur, supreme god of Assyria, was an important figure in the letters.
  • Wester, Cecilia (2015)
    Syftet med denna studie är att öka förståelsen av de försörjningssvårigheter som drabbar de äldre kvinnor i Finland som kan antas höra till de allra fattigaste, det vill säga kvinnliga folkpensionärer som fyllt 65 år. I studien analyseras de bidragande faktorerna till att kvinnliga folkpensionärer själva upplever sig ha försörjningssvårigheter. För att närma mig en förståelse av de kvinnliga folkpensionärernas försörjningssvårigheter har jag använt mig av ett kritiskt feministiskt livsloppsperspektiv. Från ett livsloppsperspektiv behöver de kvinnliga folkpensionärernas ekonomiska villkor i det åldrande livsskedet förstås i en växelverkan med deras levnadsvillkor i tidigare livsskeden. Studiens centrala forskningsfrågor är Hurudana upplevda försörjningssvårigheter har kvinnliga folkpensionärer? Vilka skillnader föreligger mellan kvinnliga folkpensionärer? Vilka socioekonomiska och hälsorelaterade faktorer i det nuvarande livsskedet och vilka livsloppsrelaterade erfarenheter är centrala för att förstå kvinnliga folkpensionärers upplevda försörjningssvårigheter? Är dessa centrala faktorer könsspecifika? Materialet består av enkätdata (n=1470) som samlats in år 2011 i samband med Folkpensionsanstaltens och Svenska social- och kommunalhögskolans forskningsprojekt ”Folkpensionärers sociala och ekonomiska trygghet”. Den empiriska analysen har genomförts med hjälp av frekvenstabeller och sambandsanalyser. I analysen framkom att över 70 % av alla respondenter upplevde sig ha åtminstone mindre försörjningssvårigheter. Det finns dock skillnader beträffande försörjningssvårigheter och karakteristika bland de kvinnliga folkpensionärerna. I analysen framkom också att dålig hälsa, försörjningssvårigheter i barndomen och en försämrad levnadsstandard i och med pensioneringen är faktorer som har samband med upplevda försörjningssvårigheter i nuläget både bland kvinnliga och manliga folkpensionärer. Däremot var låg inkomst, ensamboende och arbetslivsanknytning i samband med upplevda försörjningssvårigheter enbart bland kvinnliga folkpensionärer. Att vara äldre kvinna och lyfta full folkpension innebär enligt resultaten dock inte nödvändigtvis att ha svårigheter att klara den egna försörjningen. Jag tolkar de kvinnliga folkpensionärernas försörjningssvårigheter med utgångspunkt i Evy Gunnarssons modell enligt vilken äldre kvinnors försörjningssvårigheter måste förstås i relation till hur väl de lyckas trygga sin inkomst via en eller en kombination av de tre huvudsakliga inkomstkällorna arbete, familj och stat.
  • Kareinen, Ilona (Helsingin yliopisto, 2015)
    Atherosclerosis is an inflammatory disease characterized by the accumulation of cholesterol in the arterial intima and consequently the formation of atherosclerotic plaques. Formation of these plaques is initiated by the appearance of macrophage foam cell in the arterial intima. Foam cells are formed as excessive cholesterol accumulates in the cytosol of macrophages and finally the net influx exceeds the efflux of cholesterol. Excessive accumulation of chemically modified cholesterol in foam cells finally leads to apoptosis and contributes to the formation of the lipid core in atherosclerotic plaques. The efflux of cholesterol from foam cells is essential for preventing the progression of atherosclerosis. The only unidirectional transporters ABCA1 and ABCG1, expressed on macrophages, transport intracellular cholesterol actively to distinct subpopulations of HDL. ApoA-I, the most important structural and functional component of nascent preβ-migrating HDL particles, receives cholesterol from ABCA1. Lipid-free HDL and apoA-I are sensitive to proteolytic modification leading to loss of function of these molecules. Functional apoA-I is essential for removal of cellular cholesterol and for cholesterol homeostasis. Cholesterol efflux initiates reverse cholesterol transport (RCT) which is the pathway for removal of cholesterol from the periphery for its final excretion into feces. The tiny fraction of total body-RCT that originates from the cholesterol-loaded macrophage foam cells located in the intima, is considered the only RCT component directly involved in atherosclerosis. Mast cells are bone marrow-derived inflammatory cells that are able to activate and secrete various mast cell mediators. Mast cells infiltrate the inflamed arterial intima where they can be activated through several stimuli present in the atherosclerotic intima. Mast cells release several inflammatory compounds of which histamine is probably the best known for its notorious effects in anaphylaxis. In addition to histamine and other vasoactive compounds, such as serotonin and bradykinin, mast cells release upon activation their unique serine proteases, tryptase and chymase. Chymase involvement in the progression of atherosclerosis has been suggested in a number of studies. Chymase is an enzyme capable of degrading LDL and HDL components leading to increased uptake of the modified LDL by macrophage foam cells or resulting in diminished cholesterol efflux, respectively. The purpose of this study was to evaluate whether mast cell-dependent HDL and apoA-I proteolysis would occur in vivo and whether such modification would alter the cholesterol efflux capacities of these cholesterol acceptors and finally affect the macrophage-specific RCT (mRCT). In the present study it was demonstrated for the first time that mast cell activation in vivo resulted in HDL proteolysis. Systemic mast cell activation led to the degradation of lipoprotein particles present in HDL and the entire preβ-HDL and α-HDL subpopulations were reduced in mouse serum following systemic mast cell activation. Systemic activation of mast cells in mice blunted the ability of serum and intraperitoneal fluid to promote cholesterol efflux from macrophage foam cells in vitro. Rat cardiac mast cell activation ex vivo led to the production of truncated apoA-I. ApoA-I was cleaved at the carboxyl-terminal region at Phe229 and Tyr192 or only at Tyr192 depending on the mast cell stimulus. Local peritoneal mast cell activation led to decreased ability of intraperitoneally injected apoA-I to promote macrophage cholesterol efflux in vitro. Furthermore treatment with intact lipid-free apoA-I but not chymase-treated apoA-I increased the overall mRCT from the peritoneal cavity to the intestinal contents within 3 hours. Importantly such an increase was fully blocked by the mast cell-specific degranulating compound 48/80 in mast cell-competent mice but not in mast cell-deficient mice. Interestingly local mast cell activation in the skin was able to promote mRCT from skin to feces. This was due to increased vascular permeability and influx of plasma HDL particles to skin consequently leading to increased mRCT. This stimulatory effect could be reproduced by the sole administration of the mast cell mediators, histamine, serotonin, and bradykinin. Importantly histamine treatment in apoA-I deficient mice was unable to promote mRCT. In conclusion, mast cell chymase is able to proteolyze HDL and lipid-free apoA-I reducing their abilities to promote cellular cholesterol efflux. Proteolysis of lipid-free apoA-I by rat cardiac mast cell chymase can occur within minutes and results in the formation of carboxyl-terminally truncated apoA-I. ApoA-I proteolysis in vivo results in reduced mRCT. Local mast cell activation in the skin results in increased mRCT due to increased availability of cholesterol acceptors in the vicinity of macrophage foam cells. These two seemingly opposite results underline the pleiotropic role of mast cells in the development of atherosclerosis
  • Pääkkönen, Antti Juha Sakari (2015)
    Tutkielma tarkastelee toimeksiantoihin perustuvia markkinoita peliteoreettisesta näkökulmasta. Tämän kaltaiset markkinat muodostavat merkittävän osan nykyisestä arvopaperikaupasta. Toimeksiannot mahdollistavat vapaamman roolin markkinoiden osanottajille. Myydessään tai ostaessaan osanottajat voivat suostua tarjolla oleviin markkinahintoihin tai he voivat määritellä rajahinnan eli haluamansa rajan mihin hintaan he toivovat kaupan toteutuvan. Tutkielman ensimmäinen kappale esittelee lyhyesti markkinoita ja niihin liittyviä käsitteitä. Asiaa valaistaan myös lyhyen esimerkin kautta. Tämän jälkeen tutkielma siirtyy tarkastelemaan tarvit-tavia esitietoja joita tulemme tarvitsemaan jatkossa. Kertaamme lyhyesti peliteoreettisia käsitteitä sekä Markovin ketjuihin liittyvää teoriaa, jossa päätarkoituksena on todistaa, että positiivisesti palautuvalla, pelkistymättömällä ja aperiodisella Markovin ketjulla on olemassa yksikäsitteinen tasapainojakauma. Tätä tietoa tulemme tarvitsemaan kun siirrymme tarkastelemaan markkinamallimme kehitystä pitkällä aikavälillä. Kolmas kappale sisältää tutkielman keskeisimmän asian, markkinamallin. Mallin ovat kehittäneet Thierry Foucault, Ohad Kadan sekä Eugene Kandel. Reaalimaailman markkinoita hieman yksinkertaistaen malli kuvaa kahdenlaisia markkinoiden osanottajia, kärsimättömiä ja kärsivällisiä, ja heidän toimintaansa. Osanottajat saapuvat markkinoille Poisson-jakautuneesti ja voivat suostua tarjolla oleviin markkinahintoihin asettamalla markkinatoimeksiannon tai he voivat asettaa rajatoimeksiannon, jolloin he määrittelevät haluamansa rajahinnan. Mallin perusteiden jälkeen siirrymme tarkastelemaan osanottajien toimeksiantostrategioita sekä toimeksiantojen keskimääräisiä toteutumisaikoja. Näiden välillä on molemminpuolinen riippuvuussuhde ja jotta pääsisimme selville markkinoiden dynamiikasta, tutkimme seuraavaksi tasapainotilaa. Tässä osa- nottajien toimeksiantostrategiat lasketaan siten, että toimeksiantojen keskimääräiset odotusajat lasketaan olettaen, että jokainen osanottaja noudattaa tasapainon mukaista toimeksi-antostrategiaa. Tämän jälkeen pääsemme tarkastelemaan miten mallin parametrit ohjailevat markkinoiden kehitystä. Tutkimme mitkä seikat vaikuttavat kaupankäynnin nopeuteen, miten hyvin markkinat kykenevät palautumaan usean perättäisen markkinatoimeksiannon aiheuttamasta myynti- ja ostohintojen erotuksen eli spreadin kasvamisesta, kuinka tehokkaasti markkinat toimivat, miten osanottajien saapumistiheys vaikuttaa markkinoihin sekä miten markkinat kehittyvät pitkällä aikavälillä. Tämän jälkeen selvennämme kuvaamme markkinoista esimerkin avulla. Lopuksi tutkielman liitteistä löytyy lyhyt aiheeseen liittyvä sanasto sekä Matlab/Octave ohjelma- listaus, jonka avulla on mahdollista mallintaa markkinamalliamme ja jota käyttäen kolmannen kappaleen esimerkit on luotu.
  • Lahtinen, Aki (2015)
    Fuusioreaktiossa kaksi kevyttä ydintä yhtyy yhdeksi raskaammaksi ytimeksi ja samalla vapautuu energiaa. Fuusioreaktio tarvitsee tapahtuakseen hyvin korkean lämpötilan, minkä seurauksena aine on olomuodoltaan plasmaa. Esimerkiksi fuusioreaktoreissa käytettäväksi suunniteltu vedyn isotooppien deuteriumin ja tritiumin välinen reaktio vaatii tapahtuakseen plasman kuumentamista yli 100 miljoonan kelvinin lämpötiloihin. Tutkituin fuusioreaktorimalli on tokamak, jossa kuumaa plasmaa hallitaan toruksen muotoisessa kammiossa voimakkaiden magneettikenttien avulla. Plasmaa koossapitävästä magneettikentästä huolimatta plasmasta karkaa hiukkasia, jotka lopulta osuvat kammion pinnoille. Yksi tapa kammion pintoihin kohdistuvan lämpö- ja hiukkasvuon pienentämiseksi on suihkuttaa kammioon epäpuhtausatomeja tai -molekyylejä jäähdyttämään reunaplasmaa. Typpi on osoittautunut kiinnostavaksi vaihtoehdoksi tähän tehtävään. Typen kulkeutuminen ja kertyminen reaktorikammion sisällä vaatii kuitenkin vielä lisätutkimuksia. Typen harvinainen isotooppi 15N tarjoaa mahdollisuuden tutkia näitä kysymyksiä. Tyypillisesti tämä tehdään merkkiainekokeiden avulla, jolloin reaktorikammioon suihkutetaan valittua merkkiainetta tunnetuissa olosuhteissa ja kokeen jälkeen selvitetään merkkiaineen jakauma reaktorikammion pinnoilla. Tässä työssä keskityttiin seinätiiliin, jotka on irrotettu ASDEX Upgrade -fuusioreaktorista (AUG) vuosien 2010-2011 koekampanjan jälkeen. Kyseisen koekampanjan lopussa suoritettiin 15N-merkkiainekoe. Työssä tutkittiin tiilistä porattujen näytteiden 15N-pitoisuuksia lentoaika-rekyylianalyysilla (Time Of Flight Elastic Recoil Detection Analysis, TOF-ERDA), ydinreaktioanalyysilla (Nuclear Reaction Analysis, NRA) ja sekundääri-ionimassaspektrometrialla (Secondary Ion Mass Spectrometry, SIMS). Vertailun vuoksi tutkittiin myös 15N:llä implantoituja testinäytteitä. Tutkielman alkuosassa esitellään lyhyesti tokamak-fuusioreaktorin toimintaa, plasman vuorovaikutusta reaktorin seinämän kanssa, typen käyttöä fuusioreaktoreissa, merkkiainekokeita sekä käytetyt mittausmenetelmät. Tutkielma loppuosa keskittyy suoritettuihin mittauksiin, niiden analyysiin ja tuloksiin sekä johtopäätöksiin. Tulosten perusteella mittausmenetelmien välillä on merkittäviä eroja AUG-näytteiden kohdalla, kun taas implantoiduille näytteille erot menetelmien välillä ovat pienet. Erot johtuvat todennäköisesti AUG-näytteiden epätasaisesta pintarakenteesta, minkä seurauksena typen jakauma näytteiden pintakerroksissa vaihtelee. TOF-ERDA:lla tutkittiin näytteistä mahdollisimman sileää pintaa luotettavan analyysin onnistumiseksi. NRA-mittauksissa protonisuihku kohdistui näytteen keskelle suuremmalle pinta-alalle. Suureen alueeseen sisältyy myös karkeampia kohtia, joihin merkkiaineen kertyminen on sileää pintaa suurempaa. Tämän seurauksena NRA:lla saadaan selvästi suurempia tuloksia 15N:n pintatiheydelle kuin TOF-ERDA:lla. Kvadrupolimassaspektrometrissa ilmenneiden ongelmien vuoksi SIMS-mittauksia suoritettiin vain yksi, minkä vuoksi optimaalisten asetusten löytäminen 15N:n mittaamiseen SIMS:llä vaatii vielä lisätutkimuksia.
  • Forsell, Marianne (2015)
    Tämä pro gradu -tutkielma käsittelee pallogeometriaa. Pallogeometria on yksi epäeuklidisista geometrioista, sillä se ei noudata jokaista viittä Eukleideen postulaattia, joihin tasogeometria tuloksineen perustuu. Työn alkupuolella käsitellään tarkemmin paralleelipostulaattia, joka on erottava tekijä euklidisen ja epäeuklidisen geometrian välillä. Pallogeometrian osuus aloitetaan pallon määritelmällä, josta siirrytään isoympyrän määritelmään. Isoympyrän käsite on hyvin oleellinen tässä tutkielmassa esitettyjen lauseiden ja tulosten kannalta. Tutkielmassa esitellään lisäksi pallokolmion, napakolmion ja pallokulman määritelmät. Pallokolmion sivut muodostuvat isoympyrän kaarista ja pallokulmankin käsite liittyy hyvin läheisesti isoympyrään. Pallokulman suuruus voidaan nimittäin laskea isoympyrän kaaren pituutena. Tutkielmassa esitellään myös kolmioepäyhtälö pallokolmioille sekä hieman yllättäväkin tulos siitä, että pallokolmion kulmien summa ei ole vakio. Se on suurempi kuin tasokolmion kulmien summa, mutta pienempi kuin 540 asetta. Tämän tutkielman lopussa käsitellään pallokolmioiden yhdenmuotoisuuslauseita. Tasokolmion yhdenmuotoisuuslauseet ovat yleistettävissä pallokolmioille, mutta pallokolmioille on olemassa myös yhdenmuotoisuuslause, joka ei päde tasogeometrian kolmioille. Kyseinen lause esitellään ja todistetaan tässä tutkielmassa. Lisäksi tutkitaan peilauksen aiheuttamaa eroavaisuutta tasogeometrian ja pallogeometrian yhdenmuotoisuudessa. Tutkielman viimeisenä aiheena esitellään pallokolmion pinta-alan määritelmä sekä tarkastellaan isoympyröiden ja pallon halkaisijan rajoittamaa pallokappaletta – lunea.
  • Konttori, Johanna (2015)
    The aim of this study is to add a new perspective to the large body of scholarly work dealing with the debates on the use of headscarves and full veils in contemporary France. The study examines the discursive construction of national identity by members of the political and social elite as they discuss the use of headscarves in state schools, and the use of full veils in the public sphere more generally. The new perspective that the study presents is threefold. First, the study examines both headscarf and full veil debates, which have so far been mainly studied separately. Second, the data consists of the little-studied transcripts of the hearings organized by the two parliamentary commissions (the Debré and Gerin Commissions) that looked into the headscarf and full veil issues in 2003 and 2009, respectively. Third, even though it has been widely noted in the existing research literature that the headscarf and full veil debates were linked to national identity, it has not been common to draw theoretical insights from nationalism studies, as is done here. The analytical focus is on Muslims and Islam, headscarves and full veils, and their relation to the Republic, its identity and values (notably laïcité). Using analytical tools derived from the discourse-historical approach, the study shows the great variety of different perceptions of Islam and Muslims, but also laïcité, in the data. Even though headscarves and especially full veils are mostly regarded as problematic and even threatening to the Republic, this does not necessarily result in negative perceptions of Muslims and Islam. Finally, the study ponders the usefulness of binary categories. It is concluded that neither the Us vs Them categorization often linked to the construction of national identities nor the claim of Muslims as Others in France entirely fit the data. Instead, it is suggested that the concepts of stranger and national capital enable a more nuanced examination of the place of Muslims and Islam in France.
  • Järvinen, Anna (2015)
    Tutkimuksen tavoitteena oli löytää migreenille ja epilepsialle altistavia geneettisiä variantteja eksomisekvensoinnin avulla kromosomista 14q12-q23. Aineistona toimi kumpaakin sairautta ilmentävä suomalainen suku. Migreenidiagnoosit asetettiin kyselylomakkeen pohjalta, johon vastasi 111 henkilöä. Lomakkeen avulla karakterisoitiin tarkemmin suvun fenotyyppi migreenin suhteen. Aineistosta 61,3 % kärsi migreenistä ja 13,5 % epilepsiasta. Epilepsia assosioitui selkeästi aurattomaan migreeniin: epileptikoista 73,3 % sairasti auratonta migreeniä ja aurallista vain 20 %. Samanaikainen epilepsia lisäsi migreenioireiden vakavuutta. Epilepsiasta kärsivien migreeni alkoi keskimäärin nuorempana, oli oirekuvaltaan vaikeampaa ja kohtausten lukumäärä oli suurempi kuin vertailuryhmällä, joka kärsi pelkästä migreenistä. Eksomisekvensointia varten valittiin 8 henkilöä, joilta etsittiin harvinaisia variantteja, jotka segregoivat sairauden mukana ja aiheuttavat toiminnallisesti kiinnostavan muutoksen. 13 varianttia pääsi lopulliseen tarkasteluun. Näistä kaksi sijaitsi SYNE2-geenissä, joka osallistuu neurogeneesin säätelyyn. Jompikumpi varianteista esiintyi viidellä eksomisekvensoidulla henkilöllä, kaikilla heterotsygoottisina. Ne eivät kuitenkaan esiintyneet aineistossa siten, että niitä voitaisiin pitää migreenille ja epilepsialle altistavina variantteina. Lisäksi määritettiin kandidaattigeeneiksi SYNE2 ja NPAS3, joista seulottiin ei-eksonisia variantteja ilman vakuuttavia löydöksiä.
  • Palmujoki, Katri (Uusfilologinen yhdistys, 2015)
    Kyseessä on Mallorcalla vuonna 1541 painetun ensimmäisen espanjankielisen lapsenpäästöopin ja lastenhoiden käsikirjan editio ja kommentaari. Varsinaisen tekstiedition ohella, jossa on selvitetty tekstiin liittyviä epäselviä ja vaikeasti ymmärrettäviä kohtia, on laadittu laaja kommentaari, jossa analysoidaan kirjan tekijän Damián Carbónin kieltä kaikilla sen osa-alueilla: fonologia ja grafiat, morfosyntaksi ja leksikko. 1500-luvun ensimmäinen puolisko oli espanjan kielen kehityksen kannalta murrosaikaa, jona uudet ja vanhan kielen rakenteet elivät rinnakkain, toisten jäädessä sivuun ja toisten vakiintuessa. Päämääränä on ollut luonnehtia Carbónin kieltä tämän myllerrysten kauden puitteissa, sekä sijoittaa se sille kuuluvalle paikalle espanjan kielen periodisaatiossa. Katalaaninkielisellä Mallorcan saarella espanja oli jo vakiintunut yläluokan kieleksi; Carbónin tekstistä on havaittavissa suhteellisen vähän katalaanin vaikutusta. Tutkimuksen aluksi heräsi kysymys siitä, keille kirja oli tarkoitettu. Sen oli alunperin tilannut nimeltä mainitsematon mallorcalainen arvohenkilö, jonka vaimolla oli ollut useita keskenmenoja. Ottaen huomioon naisten alhainen lukutaitoprosentti ja se seikka, että tavallinen kansa ei vielä 1500-luvulla puhunut espanjaa, että kirja on pikemminkin osoitettu välskäreille ja että se on samalla ollut sivistyneelle yleisölle ja yläluokalle suunnattu teos.
  • Mönttinen, Heli (2015)
    The right-hand-shaped polymerases comprising the DNA/RNA polymerase superfamily represent at least six different protein families containing replicases, transcriptases and repair proteins from all three domains of life as well as from their viruses. All of these polymerases have at least three subdomains: fingers, palm and thumb, which form together a structure resembling a right-hand. The catalytic site is located in the palm subdomain, in which polymerization process is catalysed by two Mg2+ ions. There can also be additional ions such as the non-catalytic ion in the RNA-dependent RNA polymerase of phage φ6, which is located approximately 6 Ångströms from the catalytic site. The phylogeny and common regions of the right-hand-shaped polymerases have been previously studied mainly using amino acid sequence alignments. However, the sequence similarity between polymerases belonging into different protein families is low and therefore, the structure alignment provides a potential alternative because protein structures can retain similarity longer in evolution than amino acid sequences. In this thesis, the common structural features between and within the families of the right-hand-shaped polymerases are described, and based on the structural cores the phylogenetic trees are deduced. In addition, the phylogenetic relationships between the right-hand-shaped polymerases and other structurally related proteins are described. As results, it is shown that a phylogenetic tree following the established boundaries of protein families is possible to construct based on structural core sharing no sequence identity. This tree, illustrating long distance phylogenetic relationships suggests that the known right-hand-shaped polymerase families are not the closest relatives to each other. The phylogenies within polymerase families suggest that the relationships among the polymerases do not always follow the evolution of the corresponding organism, which implies horizontal gene transfer between cells, and cells and viruses. The phylogeny of RNA virus RNA polymerases seem to be dependent on the priming mechanism and it does not follow the virion architecture or the Baltimore classification. In addition, the viral RNA-dependent RNA polymerases seem to share a third ion binding site in the proximity of catalytic site.
  • Hokkanen, Ann-Helena (Helsingin yliopisto, 2015)
    Disbudding entails destroying calves horn buds, and in dairy farming is most often done with a hot-iron. Disbudding is routinely carried out because hornless cattle are considered to be safer for themselves and for humans. Hot-iron disbudding is very painful and causes severe pain-related distress and behavioural changes in calves. Options for treating disbudding-related pain during the procedure, and for 24 hours subsequently, are well known, but continued pain and its management are not much studied in calves after disbudding. Pain can cause restlessness and thus affect calves lying time. Pain in humans and rats also changes sleeping behaviour. Pain connected with disbudding often remains untreated. Reasons for this are unclear. Therefore, more knowledge and research are needed on the recognition of calves pain after hot-iron disbudding, on the duration of pain and on options to treat it in an effective, safe and practical way. Research is also needed on producer knowledge and attitudes towards pain in calves and their decision-making in connection with pain alleviation. The objectives of the work reported in this thesis were all connected with gaining an improved understanding of producer perceptions about pain caused to young calves by hot-iron disbudding, and with options available to increase the use of pain alleviation for this common and painful procedure. Initially we asked dairy producers for their perceptions towards disbudding pain in calves. Then, in order to be able to study the duration of pain after disbudding in the future, we attempted to develop a new device to measure calves lying and sleeping time: a small, neck-based, wireless accelerometer system. Because new methods and various options for pain alleviation are needed, we investigated if sublingual detomidine provided sufficient sedation in calves to allow administration of local anaesthetics prior to disbudding. Because the use of pain alleviation is often a choice faced by producers, we wanted to study Finnish dairy producers interests and motivation regarding pain alleviation in connection with disbudding. We studied Finnish dairy producers perceptions on disbudding-related pain and the need for pain alleviation, and how such perceptions affect the actual practice of pain alleviation. Finnish dairy producers estimated disbudding pain to be severe and producer estimation of pain severity caused by disbudding was correlated with their sensitivity to pain caused by different cattle diseases in general. We were able to develop an accurate device for measuring calves lying and sleeping time. Detomidine oromucosal gel was an effective sedative for calves before infiltration of local anaesthetics and disbudding. Finnish dairy producers who estimated the disbudding-related pain and need for pain alleviation to be high had a veterinarian medicate calves before disbudding more often than producers who ranked disbudding pain and need for pain alleviation lower. Because more studies on duration and alleviation of disbudding pain are needed, our new device for measuring lying and sleeping time in calves could make these studies easier in the future. A non-invasive and user-friendly oromucosal sedation method for calves could enhance the use of local anaesthetics before disbudding by making sedation easier. Our findings among dairy producers support the idea that persons who have knowledge of pain and who think pain alleviation is beneficial and important are also more prone to administer pain alleviation. Education of producers on disbudding-related pain could increase the use of pain alleviation in the future. It could also increase pain alleviation for other cattle diseases because producer perceptions on disbudding-related pain are likely to be connected with pain in cattle in general.
  • Honkasalo, Mikko (Helsingin yliopisto, 2015)
    Diabetes is a common chronic disease with growing prevalence in Finland like worldwide. It shortens the life expectancy and the quality of life. Despite the development in medication and devices there has been only modest improvement in the outcome, especially among type 1 diabetic patients. The aim of this study was to compare the outcome of overall diabetes care in municipalities with different primary health care models of organising the follow-up of type 1 diabetes and type 2 diabetes with special treatment problems. The study also aimed at estimating the feasibility of various indicators of the standard of diabetes care. The outcome, use and costs of health services connected with diabetes and its complications were compared in two suburban communities, Kouvola and Nurmijärvi. In Kouvola the follow-up of all patients had been based on family doctors already over 15 years whereas in Nurmijärvi the follow-up of T1D patients and the complicated T2D patients had been centralized to 1-2 doctors for the same time. The diabetic populations of these municipalities resembled each other. In the centralized system T1D became cheaper for the municipality. Differences in the quality parameters were minor. Both these results were obviously due to more consultations of the specialist level in Kouvola. However, T1D patients were significantly more satisfied with the centralized follow-up model. In conclusion, the centralized follow-up of the most demanding diabetes in PHC is cost-effective and results in high patient satisfaction. The centralized model is better in the follow-up of T1D but in T2D there were no differences between these two models.
  • Selonen, Salla (Helsingin yliopisto, 2015)
    Despite the known toxicity of lead (Pb) and the ban on waterfowl hunting, Pb pellets are still used at shotgun shooting ranges around the world. After firing a shotgun, pellets spread across wide areas, ending up in nearby ecosystems, which typically are forests in Finland. Still, little is known about the effects of Pb in these ecosystems and hardly anything about changes in ecosystem structure and function after range abandonment. Thus, ecosystem-level research was conducted in a shotgun shooting range area to evaluate the fate and effects of Pb in a boreal forest ecosystem and the possible recovery of the system after range abandonment. Bioaccumulation, the leaching and vertical distribution of Pb in the soil, soil nutrients and their leaching as well as structure and activity of decomposer community were studied at two contaminated sites (active [NC] and abandoned [OC] shooting ranges) and a control site, each locating in the same pine forest stand. Furthermore, tree growth, nutritional status and litter production were measured. Total Pb pellet burdens at the contaminated sites were similar, reaching up to 4 kg m-2, and shooting activity had lasted for 20 years at both sites, but occurred 20 years earlier at OC. Total Pb concentrations at the shooting ranges were extremely high, and Pb accumulated in the biota. The vertical distribution of Pb in the organic soil horizon differed between the shooting range sites, with total Pb concentrations at NC being higher in the upper F layer than in the lower H layer, but vice versa at OC. Soil fungi and all studied faunal groups (enchytraeid worms, microarthropods and nematodes) except protozoans were affected negatively by Pb. Lead decreased phosphate (PO43-) and increased nitrate (NO3-) concentrations. pH was also increased by Pb, which can further affect the biota directly or indirectly by changing Pb availability and toxicity. In the entire organic soil horizon, the negative effects of Pb were less pronounced at OC than at NC. In addition, pine needle litter decomposed faster at OC than at NC, and tree (Pinus sylvestris) radial growth was suppressed at NC after shooting activity started and increased at OC after shooting activity ceased. However, in the H layer the effects were stronger at OC, enchytraeid worms being completely absent. Furthermore, leaching of Pb through the organic soil horizon was twice as high at OC as at NC. A decrease in total Pb concentrations and toxicity in the topmost soil layer and enhanced litter decomposition rate at the abandoned shooting range indicate an on-going recovery process. In boreal forest soils that are characterized by low decomposition rates and little soil mixing due to the scarcity of earthworms, a less contaminated soil layer is gradually formed when shooting activities cease. This topmost soil layer can provide habitat for the decomposer biota and promote the recovery of soil functions. However, at the same time the dissolution of Pb from pellets deeper in the soil increases toxicity of the humus and the leaching of Pb, increasing risks to the ecosystem and groundwater quality. These findings suggest that communities and functions in Pb-contaminated boreal forest ecosystems depend on contamination history. However, despite Pb-induced changes in the decomposer communities, only slight changes in ecosystem processes were detected. This indicates high resistance of boreal forest ecosystems to this type of stress.
  • Koskela-Niska, Virpi (Helsingin yliopisto, 2015)
    Both ovarian and tubal cancers are rare. Therefore only a few studies explored such postmenopausal hormone therapies (HT) as used in Finland, as a risk factor for these cancers. I compared the incidence of ovarian and tubal cancer in HT users with the incidences of these cancers in the background population in two nationwide cohort studies. To exclude a number of potential confounders I conducted two case-control studies to further elucidate HT use as a risk factor for these cancers. The cohort studies included all women aged 50 or older who had used HT-regimens for 6 months or longer in 1994-2008. These women were identified from the Finnish Medical Reimbursement Register. The ovarian cancer cohort study included 224,015 women using estradiol-progestin therapy (EPT), whereas in the primary fallopian tube carcinoma (PFTC) cohort study included altogether 365,601 women using EPT (n=247,781) or estradiol-only therapy (ET)(n=117,820). These women were followed from the first HT purchase to the diagnosis of ovarian or tubal cancer, death, emigration or to the end of the study period through the national Finnish Cancer Registry. Relative risks of these cancers in HT users were estimated by comparing the incidence of ovarian or tubal cancer in HT users to the age-matched comparable background population and calculating standardized incidence ratios (SIR) and their 95% confidence intervals (CI). In the case-control studies, all 50-year-old or older women with incident ovarian cancer (n=3,958) or PFTC (n= 360) during 1995-2007 were identified from the Cancer Registry. The Population Register provided control women, 3 per each case of ovarian cancer and 10 per each case of PFTC, and parity data. The controls had to be alive and without ovarian/primary fallopian tube cancer and they were matched for age (+/- one month) and place or residence. The controls with an oophorectomy (n=506) or a salpingectomy (n=158) were excluded leaving 11,325 and 3,442 controls, respectively. Odds ratios (OR) with 95% CIs for various HT regimens were estimated by using conditional logistic regression adjusted for parity, ages at deliveries, hysterectomy and sterilization. The use of any type of EPT for less than five years did not modify the overall risk of ovarian cancer. Instead, the use of sequential EPT for five years or longer was associated with an elevation in the overall risk of ovarian cancer (SIR 1.21, 95% CI 1.06-1.37). The risk rises were most marked for serous (1.56; 1.33-1.80) and mixed cancer (1.54; 1.22-1.91) whereas the risk for mucinous cancer was decreased (0.47; 0.22-0.86). The risk increase connected to EPT use did not depend on the progestin type, mode or route of administration of EPT. The use of ET for five years or longer was linked with an increase in the risk for serous ovarian cancer (OR 1.45, 95% CI 1.20-1.75) while the risk of mucinous cancer was decreased (0.35; 0.19-0.67). As a whole the use of ET was accompanied with borderline rise in overall ovarian cancer risk (1.15; 0.99-1.32). In the users of sequential EPT, the risk rise was similar for endometroid (1.88; 1.24-2.86) and serous (1.32; 1.01-1.71) cancers. The use of continuous EPT, tibolone or E+LNG-IUS did not modify the risk of ovarian cancer. The use of ET was not a risk factor for PFTC. However, the use of sequential EPT for five years or longer was accompanied with a risk elevation (SIR 2.15, 95% CI 1.66-2.72), which was further increased if the use of sequential EPT continued for 10 years or longer (3.36; 2.02-5.24). In contrast, the use of continuous EPT did not modify the risk for PFTC. The uses of E+LNG-IUS for five years or longer was associated with increased risks of PFTC (ORs 2.84, 95% CI 1.10-7.38 and 3.37; 2.23-5.08, respectively), but this finding was based on low number of cases and controls. Postmenopausal hormone therapy use modifies the risks of both ovarian and fallopian tube cancers. The risk of serous and endometroid ovarian cancer rises but the risk of mucinous cancer decreases. The use of sequential EPT regimen is characterized with the highest risk elevations. In absolute terms, in 10,000 women using sequential EPT for five years or longer, there would be four extra cases of ovarian cancer and two extra cases of PFTC after follow-up of five years. These data should be incorporated into modern guidelines for the optimal use of HT.
  • Witos, Joanna (Helsingin yliopisto, 2015)
    This doctoral thesis describes the development of novel miniaturized analytical tools applicable to in situ nanoscale studies for a deeper understanding of biomolecular interactions. Capillary electrophoresis (CE), atomic force microscopy (AFM), quartz crystal microbalance (QCM) measurements, and partial filling affinity capillary electrophoresis (PF-ACE) were utilized to study the separation of lipoproteins and their interactions with extracellular matrix (ECM) components. The major focus of the study was on low and high density lipoprotein particles (LDL and HDL), which are the main vehicles of cholesterol transport in human circulation. Lipoproteins are involved in specific interactions with proteoglycans (PGs) and collagens, structural components of ECM of the arterial wall. The interactions lead to the development and progression of atherosclerosis and diabetes. The first step of the work was to clarify, by AFM, the structural and molecular properties of collagens I and III under physiological conditions. Study was made of the effect of decorin on the fibril formation of collagen, which promotes and enhances the binding of collagen with LDL. Moreover, the immobilized collagen I surface was exposed to in situ glycation, and the adsorption pattern of the glycated collagen was elucidated. In addition to AFM, QCM was used to examine characteristics of the interaction between collagens and apolipoprotein B-100 (apoB-100), the major protein of LDL. Values of the dissociation constant were then estimated by evaluating the differences in strength of the binding process. To avoid strong and unwanted adsorption of lipoprotein particles on the inner wall of the capillary, the effect of five different sugars on the separation of lipoproteins was studied by CE in uncoated capillary at physiological pH 7.4. In addition, the effect of the sugars on the size of the lipoproteins was elucidated by asymmetrical flow field-flow fractionation (AsFlFFF) and dynamic light scattering (DLS) measurements. Molecular dynamics (MD) simulations were employed to discover the influence of sugars on the structures of apolipoprotein E (apoE) of HDL and apoB-100 of LDL. In another attempt to eliminate the adsorption of positive analytes and allow their separation, a polycationic coating was developed and covalently bound to the inner wall of the fused silica capillary. The immobilization of the coating was achieved in a three-step procedure during on-line polymerization. The stability study of the coating in wide pH range 3 8 demonstrated the suitability of the coating for the separation of small proteins and -blockers. Finally, PF-ACE technique was used to evaluate in detail the interactions involved in the binding of the most common isoforms of apoE with the major glycosaminoglycan (GAG) chain of PGs, viz., chondroitin-6-sulfate (C6S). As is well known, PF-ACE enables the evaluation of affinity constants only for single-type interactions, and adsorption energy distribution (AED) calculations were introduced to widen its application. AED allowed characterization of the heterogeneity of interactions and permitted evaluation of differences in the binding process strengths. The key contributions of the work are the promising and reliable tools developed for separation and interaction studies of biological processes occurring in the ECM.