Human genetic variation in the Baltic Sea region: Features of population history and natural selection

In this thesis, the genetic variation of human populations from the Baltic Sea region was studied in order to elucidate population history as well as evolutionary adaptation in this region. The study provided novel understanding of how the complex population level processes of migration, genetic drift, and natural selection have shaped genetic variation in North European populations. Results from genome-wide, mitochondrial DNA and Y-chromosomal analyses suggested that the genetic background of the populations of the Baltic Sea region lies predominantly in Continental Europe, which is consistent with earlier studies and archaeological evidence. The late settlement of Fennoscandia after the Ice Age and the subsequent small population size have led to pronounced genetic drift, especially in Finland and Karelia but also in Sweden, evident especially in genome-wide and Y-chromosomal analyses. Consequently, these populations show striking genetic differentiation, as opposed to much more homogeneous pattern of variation in Central European populations. Additionally, the eastern side of the Baltic Sea was observed to have experienced eastern influence in the genome-wide data as well as in mitochondrial DNA and Y-chromosomal variation – consistent with linguistic connections. However, Slavic influence in the Baltic Sea populations appears minor on genetic level. While the genetic diversity of the Finnish population overall was low, genome-wide and Y-chromosomal results showed pronounced regional differences. The genetic distance between Western and Eastern Finland was larger than for many geographically distant population pairs, and provinces also showed genetic differences. This is probably mainly due to the late settlement of Eastern Finland and local isolation, although differences in ancestral migration waves may contribute to this, too. In contrast, mitochondrial DNA and Y-chromosomal analyses of the contemporary Swedish population revealed a much less pronounced population structure and a fusion of the traces of ancient admixture, genetic drift, and recent immigration. Genome-wide datasets also provide a resource for studying the adaptive evolution of human populations. This study revealed tens of loci with strong signs of recent positive selection in Northern Europe. These results provide interesting targets for future research on evolutionary adaptation, and may be important for understanding the background of disease-causing variants in human populations.

Molecular genetics of X-linked cone-rod dystrophy and Åland Island eye disease

Inherited retinal diseases are the most common cause of vision loss among the working population in Western countries. It is estimated that ~1 of the people worldwide suffer from vision loss due to inherited retinal diseases. The severity of these diseases varies from partial vision loss to total blindness, and at the moment no effective cure exists. To date, nearly 200 mapped loci, including 140 cloned genes for inherited retinal diseases have been identified. By a rough estimation 50% of the retinal dystrophy genes still await discovery. In this thesis we aimed to study the genetic background of two inherited retinal diseases, X-linked cone-rod dystrophy and Åland Island eye disease. X-linked cone-rod dystrophy (CORDX) is characterized by progressive loss of visual function in school age or early adulthood. Affected males show reduced visual acuity, photophobia, myopia, color vision defects, central scotomas, and variable changes in fundus. The disease is genetically heterogeneous and two disease loci, CORDX1 and CORDX2, were known prior to the present thesis work. CORDX1, located on Xp21.1-11.4, is caused by mutations in the RPGR gene. CORDX2 is located on Xq27-28 but the causative gene is still unknown. Åland Island eye disease (AIED), originally described in a family living in Åland Islands, is a congenital retinal disease characterized by decreased visual acuity, fundus hypopigmentation, nystagmus, astigmatism, red color vision defect, myopia, and defective night vision. AIED shares similarities with another retinal disease, congenital stationary night blindness (CSNB2). Mutations in the L-type calcium channel α1F-subunit gene, CACNA1F, are known to cause CSNB2, as well as AIED-like disease. The disease locus of the original AIED family maps to the same genetic interval as the CACNA1F gene, but efforts to reveal CACNA1F mutations in patients of the original AIED family have been unsuccessful. The specific aims of this study were to map the disease gene in a large Finnish family with X-linked cone-rod dystrophy and to identify the disease-causing genes in the patients of the Finnish cone-rod dystrophy family and the original AIED family. With the help of linkage and haplotype analyses, we could localize the disease gene of the Finnish cone-rod dystrophy family to the Xp11.4-Xq13.1 region, and thus establish a new genetic X-linked cone-rod dystrophy locus, CORDX3. Mutation analyses of candidate genes revealed three novel CACNA1F gene mutations: IVS28-1 GCGTC>TGG in CORDX3 patients, a 425 bp deletion, comprising exon 30 and flanking intronic regions in AIED patients, and IVS16+2T>C in an additional Finnish patient with a CSNB2-like phenotype. All three novel mutations altered splice sites of the CACNA1F gene, and resulted in defective pre-mRNA splicing suggesting altered or absent channel function as a disease mechanism. The analyses of CACNA1F mRNA also revealed novel alternative wt splice variants, which may enhance channel diversity or regulate the overall expression level of the channel. The results of our studies may be utilized in genetic counseling of the families, and they provide a basis for studies on the pathogenesis of these diseases. In the future, the knowledge of the genetic defects may be used in the identification of specific therapies for the patients.

Men´s health behaviour, health beliefs and need for health counselling : A study amongst 40-year-old males from one Helsinki City region

Tavoitteena oli tutkia 40-vuotiaiden miesten terveyskäyttäytymistä, terveysuskomuksia ja miesten saamaa terveysneuvontaa Helsingissä. 273 miestä vastasi kyselyyn ja osallistui terveystutkimuksiin. Terveydentilan perusteella miehet arvioitiin matalan (n=145) ja korkean (n=128) riskin ryhmiin. Khin neliö-testillä tutkittiin elämäntapa- ja riskitekijöitä koetun terveyden (hyvä, keskinkertainen/huono) luokissa ja verrattiin matalan ja korkean riskin ryhmiä em. tekijöiden osalta. Askeltavalla logistisella regressiomallilla analysoitiin tulosmuuttujia taustatekijöiden, terveyskäyttäytymisen, terveysuskomusten ja kliinisten riskitekijöiden avulla sekä arvioitiin oireiden ja vaivojen suhdetta koettuun terveydentilaan. Korkeassa riskissä olevien terveyttä seurattiin vuosina 2001–2004 analysoimalla mini-intervention vaikutusta terveysriskeihin ja elintapoihin varianssianalyysin avulla (ANOVA) (n=46). Matalasta vastausprosentista johtuen (39.6%), ei-vastanneiden aineistoa kerättiin käyttämällä syvähaastattelua (n=28) sekä puhelinkyselyä (n=40). Lopullinen aineisto koostui 341 miehestä. Tulokset osoittivat, että miehillä oli sydän- ja verisuonitautiriskejä. Kaksi kolmesta osallistuneista oli ylipainoisia tai lihavia, yli kolmanneksella vyötärönympärys oli ≥100 cm, ja yli 40%:llä oli diastolinen verenpaine ≥90 mmHg. Yli puolet tupakoi päivittäin ja 40% käytti alkoholia runsaasti. Ristiriitaisuutta ilmensi se, että huolimatta riskitekijöistä noin puolet miehistä koki terveydentilansa hyväksi. Sairauden tai vamman puute, hyvä suun terveydentila ja normaali vyötärönympärys olivat yhteydessä hyväksi koettuun terveydentilaan. Suora yhteys voitiin havaita omaisten tarjoaman neuvonnan ja vähäisen alkoholin käytön välillä. Masennus ja unettomuus olivat voimakkaasti yhteydessä loppuun palamiseen. Miehillä oli erilaisia fyysisiä ja psyykkisiä oireita, jotka korreloivat voimakkaasti masennuksen kanssa. Pieni määrä miehistä koki saaneensa terveysneuvontaa hoitohenkilökunnalta verrattuna perheenjäseniltä saatuun ohjaukseen. Korkeariskisten miesten (n=46) arvot parantuivat merkitsevästi lyhyellä aikavälillä. Kolesteroliarvoja lukuunottamatta ne palautuivat kolmen vuoden kuluttua alkumittausarvoja kohti. Laadullinen tutkimus osoitti, että “ei-vastanneet“ eivät osallistuneet projektiin, sillä he olivat oireettomia tai kiireisiä. Heillä todettiin samoja terveysriskejä kuin projektiin osallistuneilla. Syvähaastattelussa miehet toivat esille kokemuksiaan huolista, vihan tunteista, peloista ja yksinäisyydestä. Hoidonantajien on tärkeää ymmärtää ristiriidat miesten subjektiivisen ja objektiivisen terveydentilan välillä, mikä auttaa havaitsemaan esteitä terveyskäyttäytymiselle. Yhä enemmän tarvitaan yhteistyötä yksityisen ja julkisen terveydenhuollon välillä varmistamaan terveystottumusten jatkuminen miesten keskuudessa.

Modern computed tomography techniques in stroke management

Technological development of fast multi-sectional, helical computed tomography (CT) scanners has allowed computed tomography perfusion (CTp) and angiography (CTA) in evaluating acute ischemic stroke. This study focuses on new multidetector computed tomography techniques, namely whole-brain and first-pass CT perfusion plus CTA of carotid arteries. Whole-brain CTp data is acquired during slow infusion of contrast material to achieve constant contrast concentration in the cerebral vasculature. From these data quantitative maps are constructed of perfused cerebral blood volume (pCBV). The probability curve of cerebral infarction as a function of normalized pCBV was determined in patients with acute ischemic stroke. Normalized pCBV, expressed as a percentage of contralateral normal brain pCBV, was determined in the infarction core and in regions just inside and outside the boundary between infarcted and noninfarcted brain. Corresponding probabilities of infarction were 0.99, 0.96, and 0.11, R² was 0.73, and differences in perfusion between core and inner and outer bands were highly significant. Thus a probability of infarction curve can help predict the likelihood of infarction as a function of percentage normalized pCBV. First-pass CT perfusion is based on continuous cine imaging over a selected brain area during a bolus injection of contrast. During its first passage, contrast material compartmentalizes in the intravascular space, resulting in transient tissue enhancement. Functional maps such as cerebral blood flow (CBF), and volume (CBV), and mean transit time (MTT) are then constructed. We compared the effects of three different iodine concentrations (300, 350, or 400 mg/mL) on peak enhancement of normal brain tissue and artery and vein, stratified by region-of-interest (ROI) location, in 102 patients within 3 hours of stroke onset. A monotonic increasing peak opacification was evident at all ROI locations, suggesting that CTp evaluation of patients with acute stroke is best performed with the highest available concentration of contrast agent. In another study we investigated whether lesion volumes on CBV, CBF, and MTT maps within 3 hours of stroke onset predict final infarct volume, and whether all these parameters are needed for triage to intravenous recombinant tissue plasminogen activator (IV-rtPA). The effect of IV-rtPA on the affected brain by measuring salvaged tissue volume in patients receiving IV-rtPA and in controls was investigated also. CBV lesion volume did not necessarily represent dead tissue. MTT lesion volume alone can serve to identify the upper size limit of the abnormally perfused brain, and those with IV-rtPA salvaged more brain than did controls. Carotid CTA was compared with carotid DSA in grading of stenosis in patients with stroke symptoms. In CTA, the grade of stenosis was determined by means of axial source and maximum intensity projection (MIP) images as well as a semiautomatic vessel analysis. CTA provides an adequate, less invasive alternative to conventional DSA, although tending to underestimate clinically relevant grades of stenosis.

The Finnish Competition State and Entrepreneurial Policies in the Helsinki Region

The thesis examines the intensification and characteristics of a policy that emphasises economic competitiveness in Finland during the 1990s and early 2000s. This accentuation of economic objectives is studied at the level of national policy-making as well as at the regional level through the policies and strategies of cities and three universities in the Helsinki region. By combining the analysis of state policies, urban strategies and university activities, the study illustrates the pervasiveness of the objective of economic competitiveness and growth across these levels and sheds light on the features and contradictions of these policies on a broad scale. The thesis is composed of five research articles and a summary article. At the level of national policies, the central focus of the thesis is on the growing role of science and technology policy as a state means to promote structural economic change and its transformation towards a broader, yet ambivalent concept of innovation policy. This shift brings forward a tension between an increasing emphasis on economic aspects – innovations and competitiveness – as well as the expanding scope of issues across a wide range of policy sectors that are being subsumed under this market- and economy oriented framework. Related to science and technology policy, attention is paid to adjustments in university policy in which there has been increasing pressure for efficiency, rationalisation and commercialisation of academic activities. Furthermore, political efforts to build an information society through the application of information and communication technologies are analysed with particular attention to the balance between economic and social objectives. Finally, changes in state regional policy priorities and the tendency towards competitiveness are addressed. At the regional level, the focus of the thesis is on the policies of the cities in Finland’s capital region as well as strategies of three universities operating in the region, namely the University of Helsinki, Helsinki University of technology and Helsinki School of Economics. As regards the urban level, the main focus is on the changes and characteristics of the urban economic development policy of the City of Helsinki. With respect to the universities, the thesis examines their attempts to commercialise research and thus bring academic research closer to economic interests, and pays particular attention to the contradictions of commercialisation. Related to the universities, the activities of three intermediary organisations that the universities have established in order to increase cooperation with industry are analysed. These organisations are the Helsinki Science Park, Otaniemi International Innovation Centre and LTT Research Ltd. The summary article provides a synthesis of the material presented in the five original articles and relates the results of the articles to a broader discussion concerning the emergence of competition states and entrepreneurial cities and regions. The main points of reference are Bob Jessop’s and Neil Brenner’s theses on state and urban-regional restructuring. The empirical results and considerations from Finland and the Helsinki region are used to comment on, specify and criticise specific parts of the two theses.

Trust and Safe Choices: Coping with health-related risks in food consumption in St. Petersburg

This dissertation considers the problem of trust in the context of food consumption. The research perspectives refer to institutional conditions for consumer trust, personal practices of food consumption, and strategies consumers employ for controlling the safety of their food. The main concern of the study is to investigate consumer trust as an adequate response to food risks, i.e. a strategy helping the consumer to make safe choices in an uncertain food situation. "Risky" perspective serves as a frame of reference for understanding and explaining trust relations. The original aim of the study was to reveal the meanings applied to the concepts of trust, safety and risks in the perspective of market choices, the assessments of food risks and the ways of handling them. Supplementary research tasks presumed descriptions of institutional conditions for consumer trust, including descriptions of the food market, and the presentation of food consumption patterns in St. Petersburg. The main empirical material is based on qualitative interviews with consumers and interviews and group discussions with professional experts (market actors, representatives of inspection bodies and consumer organizations). Secondary material is used for describing institutional conditions for consumer trust and the market situation. The results suggest that the idea of consumer trust is associated with the reputation of suppliers, stable quality and taste of their products, and reliable food information. Being a subjectively constructed state connected to the act of acceptance, consumer trust results in positive buying decisions and stable preferences in the food market. The consumers' strategies that aim at safe food choices refer to repetitive interactions with reliable market actors that free them from constant consideration in the marketplace. Trust in food is highly mediated by trust in institutions involved in the food system. The analysis reveals a clear pattern of disbelief in the efficiency of institutional food control. The study analyses this as a reflection of "total distrust" that appears to be a dominant mood in many contexts of modern Russia. However, the interviewees emphasize the state's decisive role in suppressing risks in the food market. Also, the findings are discussed with reference to the consumers' possibilities of personal control over food risks. Three main responses to a risky food situation are identified: the reflexive approach, the traditional approach, and the fatalistic approach.

Measurement of $d\sigma/dy$ of Drell-Yan $e^+e^-$ pairs in the $Z$ Mass Region from $p\bar{p}$ Collisions at $\sqrt{s}=1.96$ TeV

We report on a CDF measurement of the total cross section and rapidity distribution, $d\sigma/dy$, for $q\bar{q}\to \gamma^{*}/Z\to e^{+}e^{-}$ events in the $Z$ boson mass region ($66M_{ee}

Semi-supervised learning of WLAN radio maps

In this thesis a manifold learning method is applied to the problem of WLAN positioning and automatic radio map creation. Due to the nature of WLAN signal strength measurements, a signal map created from raw measurements results in non-linear distance relations between measurement points. These signal strength vectors reside in a high-dimensioned coordinate system. With the help of the so called Isomap-algorithm the dimensionality of this map can be reduced, and thus more easily processed. By embedding position-labeled strategic key points, we can automatically adjust the mapping to match the surveyed environment. The environment is thus learned in a semi-supervised way; gathering training points and embedding them in a two-dimensional manifold gives us a rough mapping of the measured environment. After a calibration phase, where the labeled key points in the training data are used to associate coordinates in the manifold representation with geographical locations, we can perform positioning using the adjusted map. This can be achieved through a traditional supervised learning process, which in our case is a simple nearest neighbors matching of a sampled signal strength vector. We deployed this system in two locations in the Kumpula campus in Helsinki, Finland. Results indicate that positioning based on the learned radio map can achieve good accuracy, especially in hallways or other areas in the environment where the WLAN signal is constrained by obstacles such as walls.

Future chemistry teachers use of knowledge dimensions and high-order cognitive skills in pre-laboratory concept maps

This poster describes a pilot case study, which aim is to study how future chemistry teachers use knowledge dimensions and high-order cognitive skills (HOCS) in their pre-laboratory concept maps to support chemistry laboratory work. The research data consisted of 168 pre-laboratory concept maps that 29 students constructed as a part of their chemistry laboratory studies. Concept maps were analyzed by using a theory based content analysis through Anderson & Krathwohls' learning taxonomy (2001). This study implicates that novice concept mapper students use all knowledge dimensions and applying, analyzing and evaluating HOCS to support the pre-laboratory work.

Wood-inhabiting Basidiomycetes in the Caucasus Region : Systematics and Biogeography

The Caucasus region is a hotspot of biodiversity and is one of the few areas in the Northern Hemisphere which harbor Pleistocene glacial refugia. The region encompasses Armenia, Azerbaijan, Georgia, the southernmost European Russia, NE Turkey, and northern Iran. The study on fungal composition of the Caucasus region and its connection and possible contribution to the present mycota of Europe has largely escaped empirical scrutiny. Using taxonomic surveys, phylogenetic reconstruction methods, haplotype analysis, and similarity tests, this study has aimed to, 1) summarize the knowledge on the occurrence of corticioids and polypores in the Caucasus region, 2) resolve the phylogenetic relationships of selected, resupinate wood-inhabiting basidiomycetes for which the Caucasus region is currently the mere, or one of the noteworthy areas of distribution, and, 3) assess the similarity of Caucasian corticioid fungi to those of Europe and important areas in the Northern Hemisphere, and to examine the significance of the Caucasus region as a glacial refugium for these fungi. This study provides the first catalogue of corticioids and polypores (635 species) occurring in the Caucasus region. The phylogeny and systematics of the Caucasian resupinate taxa in focus has been resolved and the usefulness of some morphological characters has been re-evaluated. In this context, four new genera and two new species were described and five new combinations were proposed, two of which were supplemented with modern descriptions. The species composition of corticioids in the Caucasus region is found to be distinctly more similar to Europe and North America than to East Asia and India. The highest molecular diversity and within population pairwise distance for Peniophorella praetermissa has been detected in the Caucasus and East Asia, with the isolates of the latter area being highly divergent from the European ones. This, and the assignment of root haplotype to the Caucasian isolates in a haplotype network for Phlebia tuberucalta and P. livida, call attention to the role of the Caucasus region in shaping the current mycota of Europe.

The Context and Diffusion of Knowledge in the Finnish Jewellery Industry - The role of the House of Fabergé

Researchers within the fields of economic geography and organizational management have extensively studied learning and the prerequisites and impediments for knowledge transfer. This paper combines two discourses within the two subjects: the-communities-of-practice and the learning region approaches, merging them through the so-called ecology of knowledge-approach, which is used to examine the knowledge transfer from the House of Fabergé to the Finnish jewellery industry. We examine the pre-revolution St Petersburg jewellery cluster and the post-revolution Helsinki, and the transfer of knowledge between these two locations through the components of communities of people, institutions and industry. The paper shows that the industrial dynamics of the Finnish modern-day goldsmith industry was inherently shaped both through the transfer and the non-transfer of knowledge. It also contends that the “knowledge-economy” is not anchored in and exclusive for the high technology sector of the late 20th century.