Cellular Membranes as a Playground for Semliki Forest Virus Replication Complex

All positive-strand RNA viruses utilize cellular membranes for the assembly of their replication complexes, which results in extensive membrane modification in infected host cells. These alterations act as structural and functional scaffolds for RNA replication, providing protection for the viral double-stranded RNA against host defences. It is known that different positive-strand RNA viruses alter different cellular membranes. However, the origin of the targeted membranes, the mechanisms that direct replication proteins to specific membranes and the steps in the formation of the membrane bound replication complex are not completely understood. Alphaviruses (including Semliki Forest virus, SFV), members of family Togaviridae, replicate their RNA in association with membranes derived from the endosomal and lysosomal compartment, inducing membrane invaginations called spherules. Spherule structures have been shown to be the specific sites for RNA synthesis. Four replication proteins, nsP1-nsP4, are translated as a polyprotein (P1234) which is processed autocatalytically and gives rise to a membrane-bound replication complex. Membrane binding is mediated via nsP1 which possesses an amphipathic α-helix (binding peptide) in the central region of the protein. The aim of this thesis was to characterize the association of the SFV replication complex with cellular membranes and the modification of the membranes during virus infection. Therefore, it was necessary to set up the system for determining which viral components are needed for inducing the spherules. In addition, the targeting of the replication complex, the formation site of the spherules and their intracellular trafficking were studied in detail. The results of current work demonstrate that mutations in the binding peptide region of nsP1 are lethal for virus replication and change the localization of the polyprotein precursor P123. The replication complex is first targeted to the plasma membrane where membrane invaginations, spherules, are induced. Using a specific regulated endocytosis event the spherules are internalized from the plasma membrane in neutral carrier vesicles and transported via an actin-and microtubule-dependent manner to the pericentriolar area. Homotypic fusions and fusions with pre-existing acidic organelles lead to the maturation of previously described cytopathic vacuoles with hundreds of spherules on their limiting membranes. This work provides new insights into the membrane binding mechanism of SFV replication complex and its role in the virus life cycle. Development of plasmid-driven system for studying the formation of the replication complex described in this thesis allows various applications to address different steps in SFV life cycle and virus-host interactions in the future. This trans-replication system could be applied for many different viruses. In addition, the current work brings up new aspects of membranes and cellular components involved in SFV replication leading to further understanding in the formation and dynamics of the membrane-associated replication complex.

Mechanisms for alphavirus nonstructural polyprotein processing

Replication and transcription of the RNA genome of alphaviruses relies on a set of virus-encoded nonstructural proteins. They are synthesized as a long polyprotein precursor, P1234, which is cleaved at three processing sites to yield nonstructural proteins nsP1, nsP2, nsP3 and nsP4. All the four proteins function as constitutive components of the membrane-associated viral replicase. Proteolytic processing of P1234 polyprotein is precisely orchestrated and coordinates the replicase assembly and maturation. The specificity of the replicase is also controlled by proteolytic cleavages. The early replicase is composed of P123 polyprotein intermediate and nsP4. It copies the positive sense RNA genome to complementary minus-strand. Production of new plus-strands requires complete processing of the replicase. The papain-like protease residing in nsP2 is responsible for all three cleavages in P1234. This study addressed the mechanisms of proteolytic processing of the replicase polyprotein in two alphaviruses Semliki Forest virus (SFV) and Sindbis virus (SIN) representing different branches of the genus. The survey highlighted the functional relation of the alphavirus nsP2 protease to the papain-like enzymes. A new structural motif the Cys-His catalytic dyad accompanied with an aromatic residue following the catalytic His was described for nsP2 and a subset of other thiol proteases. Such an architecture of the catalytic center was named the glycine specificity motif since it was implicated in recognition of a specific Gly residue in the substrate. In particular, the presence of the motif in nsP2 makes the appearance of this amino acid at the second position upstream of the scissile bond a necessary condition for the cleavage. On top of that, there were four distinct mechanisms identified, which provide affinity for the protease and specifically direct the enzyme to different sites in the P1234 polyprotein. Three factors RNA, the central domain of nsP3 and the N-terminus of nsP2 were demonstrated to be external modulators of the nsP2 protease. Here I suggest that the basal nsP2 protease specificity is inherited from the ancestral papain-like enzyme and employs the recognition of the upstream amino acid signature in the immediate vicinity of the scissile bond. This mechanism is responsible for the efficient processing of the SFV nsP3/nsP4 junction. I propose that the same mechanism is involved in the cleavage of the nsP1/nsP2 junction of both viruses as well. However, in this case it rather serves to position the substrate, whereas the efficiency of the processing is ensured by the capability of nsP2 to cut its own N-terminus in cis. Both types of cleavages are demonstrated here to be inhibited by RNA, which is interpreted as impairing the basal papain-like recognition of the substrate. In contrast, processing of the SIN nsP3/nsP4 junction was found to be activated by RNA and additionally potentiated by the presence of the central region of nsP3 in the protease. The processing of the nsP2/nsP3 junction in both viruses occurred via another mechanism, requiring the exactly processed N-terminus of nsP2 in the protease and insensitive to RNA addition. Therefore, the three processing events in the replicase polyprotein maturation are performed via three distinct mechanisms in each of two studied alphaviruses. Distinct sets of conditions required for each cleavage ensure sequential maturation of P1234 polyprotein: nsP4 is released first, then the nsP1/nsP2 site is cut in cis, and liberation of the nsP2 N-terminus activates the cleavage of the nsP2/nsP3 junction at last. The first processing event occurs differently in SFV and SIN, whereas the subsequent cleavages are found to be similar in the two viruses and therefore, their mechanisms are suggested to be conserved in the genus. The RNA modulation of the alphavirus nonstructural protease activity, discovered here, implies bidirectional functional interplay between the alphavirus RNA metabolism and protease regulation. The nsP2 protease emerges as a signal transmitting moiety, which senses the replication stage and responds with proteolytic cleavages. A detailed hypothetical model of the alphavirus replicase core was inferred from the data obtained in the study. Similar principles in replicase organization and protease functioning are expected to be employed by other RNA viruses.

Top quark mass measurement in the lepton plus jets channel using a modified matrix element method

We report a measurement of the top quark mass, m_t, obtained from ppbar collisions at sqrt(s) = 1.96 TeV at the Fermilab Tevatron using the CDF II detector. We analyze a sample corresponding to an integrated luminosity of 1.9 fb^-1. We select events with an electron or muon, large missing transverse energy, and exactly four high-energy jets in the central region of the detector, at least one of which is tagged as coming from a b quark. We calculate a signal likelihood using a matrix element integration method, with effective propagators to take into account assumptions on event kinematics. Our event likelihood is a function of m_t and a parameter JES that determines /in situ/ the calibration of the jet energies. We use a neural network discriminant to distinguish signal from background events. We also apply a cut on the peak value of each event likelihood curve to reduce the contribution of background and badly reconstructed events. Using the 318 events that pass all selection criteria, we find m_t = 172.7 +/- 1.8 (stat. + JES) +/- 1.2 (syst.) GeV/c^2.

Transverse momentum and pseudorapidity distributions of charged hadrons in pp collisions at sqrt(s) = 0.9 and 2.36 TeV

Measurements of inclusive charged-hadron transverse-momentum and pseudorapidity distributions are presented for proton-proton collisions at sqrt(s) = 0.9 and 2.36 TeV. The data were collected with the CMS detector during the LHC commissioning in December 2009. For non-single-diffractive interactions, the average charged-hadron transverse momentum is measured to be 0.46 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 0.9 TeV and 0.50 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 2.36 TeV, for pseudorapidities between -2.4 and +2.4. At these energies, the measured pseudorapidity densities in the central region, dN(charged)/d(eta) for |eta|

Governance Matters : China's Developing Western Region with a Focus on Qinghai Province

This study is about governance in contemporary China. The focus is on Qinghai Province, one of the twelve provincial-level units included in the western region development strategy launched in 2000 by the government of China. Qinghai, the subject of the case study, is not a very well-known province. Hence, this study is significant, because it provides new knowledge about the province of Qinghai, its governance and diverse challenges, and deepens one s overall knowledge regarding China. Qinghai province is one of the slowest developing regions of China. My research problem is to analyze to what extent provincial development correlates with the quality of governance. The central concept of this research is good governance. This dissertation employs a grounded theory approach while the theoretical framework of this study is built on the Three World s approach of analyzing the three main themes, namely, the environment, economic development, and cultural diversity, and to support the empirical work. Philosophical issues in the humanities and contemporary theories of governance are brought in to provide deeper understanding of governance, and to understand to what extent and how characteristics of good governance (derived from the Western canon) are combined with Chinese tradition. A qualitative research method is chosen to provide a deeper understanding of the contemporary challenges of Qinghai (and China) and to provide some insight into the role and impact of governance on provincial development. It also focuses on the Tibetan ethnic group in order to develop as full an understanding as possible about the province. The challenges faced by Qinghai concern in particular its environment, economic development, and cultural diversity, all of which are closely interrelated. The findings demonstrate that Qinghai Province is not a powerful actor, because it has weak communications with the central government and weak collaboration with its stakeholders and civil society. How Qinghai s provincial government conducts provincial development remains a key question in terms of shaping the province s future. The question is how is Qinghai s government best able to govern in a way that is beneficial for the people. This study demonstrates that this is a significant question that challenges governance everywhere, and particularly in China given the absence of democracy. This study provides the ingredients for reflection as to how provincial government can be motivated to choose to govern in a sustainable way, instead of leaning on growth factors with too little consideration about the impact on the environment and the people.

Novel Multiple Sclerosis Predisposing Genetic Variants Outside the HLA Region

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Both environmental factors and several predisposing genes are required to generate MS. Despite intensive research these risk factors are still largely unknown, the pathogenesis of MS demyelination is poorly understood, and no curative treatment exists. Both prevalence and familial occurrence of MS are exceptionally high in a Finnish population subisolate, Southern Ostrobothnia, presumably due to enrichment of predisposing genetic variants within this region. Previous linkage scan on MS pedigrees from Southern Ostrobothnia detected three main MS loci on chromosomes 5p, 6p (HLA) and 17q. Linkage studies in other populations have also provided independent evidence for the location of MS susceptibility genes in these regions. Further, these loci are syntenic to the experimental autoimmune encephalomyelitis (EAE) susceptibility loci of rodents. In this thesis work an effort was made to localize MS predisposing alleles of the linked loci outside the HLA region by studying familial MS cases from the Southern Ostrobothnia isolate. Analysis of the 5p locus revealed one region, flanking the complement component 7 (C7) gene. The identified relatively rare haplotype seems to have a fairly large effect on genetic susceptibility of MS (frequency MS 12%, controls 4%; p=0.000003, OR=2.73). Evidence for association with alleles of the region and MS was seen also in more heterogeneous populations. Convincingly, plasma C7 protein levels and complement activity correlated with the risk haplotype identified. The finding stimulated us to study other complement cascade genes in MS. No evidence for association could be observed with the complement component coding genes outside 5p. A scan of the 17q locus provided evidence for association with variants of the protein kinase C alpha (PRKCA) gene (p=0.0001). Modest evidence for association with PRKCA was observed also in Canadian MS families. Finally we used a candidate gene based approach to identify potential MS loci. Mutations of DAP12 and TREM2 cause a recessively inherited CNS white matter disease PLOSL. Interestingly, DAP12 and TREM2 are located in MS regions on 6p and 19q, and we tested them as potential candidate genes in the Finnish MS sample. No evidence for association with MS was observed. This thesis provides an example of how extended families from special populations can be utilized in fine-mapping of the linked loci. A first relatively rare MS variant was identified utilizing the strength of a Finnish population subisolate. This variant seems to have an effect on activity of the complement system, which has previously been suggested to have an important role in the pathogenesis of MS.

The Role of Genes on Chromosome Locus 4q12 in Human Central Nervous System Tumors

Human central nervous system (CNS) tumors are a heterogeneous group of tumors occurring in brain, brainstem and spinal cord. Malignant gliomas (astrocytic and oligodendroglial tumors), which arise from the neuroepithelial cells are the most common CNS neoplasms in human. Malignant gliomas are highly aggressive and invasive tumors, and have a very poor prognosis. The development and progression of gliomas involve a stepwise accumulation of genetic alterations that generally affect either signal transduction pathways activated by receptor tyrosine kinases (RTKs), or cell cycle arrest pathways. Constitutive activation or deregulated signaling by RTKs is caused by gene amplification, overexpression or mutations. The aberrant RTK signaling results in turn in the activation of several downstream pathways, which ultimately lead to malignant transformation and tumor proliferation. Many genetic abnormalities implicated in nervous system tumors involve the genes located at the chromosomal region 4q12. This locus harbors the receptor tyrosine kinases KIT, PDGFRA and VEGFR2, and other genes (REST, LNX1) with neural function. Gene amplification and protein expression of KIT, PDGFRA, and VEGFR2 was studied using clinical tumor material. REST and LNX1, as well as NUMBL, the interaction partner of LNX1, were studied for their gene mutations and amplifications. In our studies, amplification of LNX1 was associated with KIT and PDGFRA amplification in glioblastomas, and coamplification of KIT, PDGFRA and VEGFR2 was detected in medulloblastomas and CNS primitive neuroectodermal tumors. PDGFRA amplification was also correlated with poor overall survival. Coamplification of KIT, PDGFRA and VEGFR2 was observed in a subset of human astrocytic and oligodendroglial tumors. We suggest that genes at 4q12 could be a part of a larger amplified region, which is deregulated in gliomas, and could be used as a prognostic marker of tumorigenic process. The signaling pathways activated due to gene amplifications, activating gene mutations, and overexpressed proteins may be useful as therapeutic targets for glioma treatment. This study also includes the characterization of KIT overexpressing astrocytes, analyzed by various in vitro functional assays. Our results show that overexpression of KIT in mouse astrocytes promotes cell proliferation and anchorage-independent growth, as well as phenotypic changes in the cells. Furthermore, the increased proliferation is partly inhibited by imatinib, a small molecule inhibitor of KIT. These results suggest that KIT may play a role in astrocyte growth regulation, and might have an oncogenic role in brain tumorigenesis. Elucidation of the altered signaling pathways due to specific gene amplifications, activating gene mutations, and overexpressed proteins may be useful as therapeutic targets for glioma treatment.

Community forestry and environmental literacy in northern Thailand : Towards collaborative natural resource management and conservation

Conservation and sustainable management of tropical forests needs a holistic approach: in addition to ecological concerns, socio-economic issues including cultural aspects must be taken into consideration. An ability to adapt practices is a key to successful collaborative natural resource management. Achieving this requires local participation and understanding of local conceptions of the environment. This study examined these issues in the context of northern Thailand. Northern uplands are the home of much of the remaining natural forest in Thailand and several ethnic minority groups commonly referred to as hill tribes. The overall purpose of this study was to grasp a regional view of an ethnically diverse forested area and to elicit prospects to develop community forestry for conservation purposes and for securing people s livelihood. Conservation was a central goal of management as the forests in the area were largely designated as protected. The aim was to study local perceptions, objectives, values and practices of forest management, under the umbrella of the concept environmental literacy, as well as the effects of forest policy on community management goals and activities. Environmental literacy refers to holistic understanding of the environment. It was used as a tool to examine people s views, interests, knowledge and motivation associated to forests. The material for this study was gathered in six villages in Chiang Mai Province. Three minority groups were included in the study, the Karen, Hmong and Lawa, and also the Thai. Household and focus group interviews were conducted in the villages. In addition, officials at district, regional and national levels, workers of non-governmental organisations, and academics were interviewed, and some data were gathered from the students of a local school. The results showed that motivation for protecting the forests existed among each ethnic group studied. This was a result of culture and traditions evolved in the forest environment but also of a need to adapt to a changed situation and environment and to outside pressures. The consequences of deforestation were widely agreed on in the villages, and the impact of socio-economic changes on the forests and livelihood was also recognised. The forest was regarded as a source of livelihood providing land, products and services essential to the people inhabiting rural uplands. Traditions, fire control, cooperation, reforestation, separation of protected and utilisable areas, and rules were viewed as central for conservation. For the villagers, however, conservation meant sustainable use, whereas the government has tended to prefer strict restrictions on forest resource use. Thus, conflicts had arisen. Between communities, cooperation was more dominant than conflict. The results indicated that the heterogeneity of forest dwellers, although it has to be recognised, should not be overemphasised: ethnic diversity can be considered as no major obstacle for successful community forestry. Collaborative management is particularly important in protected areas in order to meet the conservation goals while providing opportunities for livelihood. Forest management needs more positive incentives and increased dialogue.

Struggles over resources and representations in territorial conflicts in the Northern Autonomous Atlantic Region (RAAN), Nicaragua

Territoriality is a central issue in indigenous peoples struggles. The territorial struggles involve struggles over the control of natural resources and over political participation and representation, but also over the perception of territorial rights and the symbolic representation of the territory. These struggles are carried through both in material and symbolic ways through recurring to different discourses and representations that provide legitimation for the territorial claims of the group. The study is located in the Northern Autonomous Atlantic Region of Nicaragua. The study concerns the territorial strategies, conceptions and practices of the indigenous people and other actors. Territorial conflicts exist between the autonomous region and the central government of Nicaragua, between mestizo settlers and indigenous people, between different indigenous groups, and between these and development agents such as conservation projects. The study focuses on how territorial discourses and representations are used to legitimate territorial control. Environmental, historical and cartographical discourses are the most important discourses recurred to. The influence of discourses and representations on the territorial practices and policies of the different actors, the links between the local struggles and global processes, and the broader structural factors impacting on the territorial struggles are also analysed. Among the structural factors are the problems related to land tenure and management and the use of natural resources, the advance of the agricultural frontier, the institutional weaknesses of the central and regional governments and the legislative processes. The territorial discourses are both recurred to in a strategic way and also grounded in local ideals and practices. The discourses have produced real effects for example in legislation, land tenure systems, political representation and environmental practices. Although the use of discourses and representations are an important power tool in territorial struggles, territorial control cannot be effectively accomplished merely through representing territorial claims in a legitimate way or through reforming legislation, as the conflicts are also largely a result of structural factors affecting the region. The fieldwork was carried out during a total of twelve months between 2000 and 2002. The research methods used were semi-structured interviews, participant observation and participatory research methods. A broad range of literary sources were also used to collect data. The study is located within the field of critical political geography with a discursive political ecology approach. It can be called a critical realist approach to the discursive analysis of indigenous territoriality.

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.

Role of γ1 Laminin and Its KDI Peptide in the Central Nervous System

Since the 1980 s, laminin-1 has been linked to regeneration of the central nervous system (CNS) and promotion of neuronal migration and axon guidance during CNS development. In this thesis, we clarify the role of γ1 laminin and its KDI tripeptide in development of human embryonic spinal cord, in regeneration of adult rat spinal cord injury (SCI), in kainic acid-induced neuronal death, and in the spinal cord tissue of amyotrophic lateral sclerosis (ALS). We demonstrated that γ1 laminin together with α1, β1, and β3 laminins localize at the floor plate region in human embryonic spinal cord. This localization of γ1 laminin is in spatial and temporal correlation with development of the spinal cord and indicates that γ1 laminin may participate in commissural axon guidance during the embryonic development of the human CNS. With in vitro studies using the Matrigel culture system, we demonstrated that the KDI tripeptide of γ1 laminin provides a chemotrophic guidance cue for neurites of the human embryonic dorsal spinal cord, verifying the functional ability of γ1 laminin to guide commissural axons. Results from our experimental SCI model demonstrate that the KDI tripeptide enhanced functional recovery and promoted neurite outgrowth across the mechanically injured area in the adult rat spinal cord. Furthermore, our findings indicate that the KDI tripeptide as a non-competitive inhibitor of the ionotropic glutamate receptors can provide when administered in adequate concentrations an effective method to protect neurons against glutamate-induced excitotoxic cell death. Human postmortem samples were used to study motor neuron disease, ALS (IV), and the study revealed that in human ALS spinal cord, γ1 laminin was selectively over-expressed by reactive astrocytes, and that this over-expression may correlate with disease severity. The multiple ways by which γ1 laminin and its KDI tripeptide provide neurotrophic protection and enhance neuronal viability suggest that the over-expression of γ1 laminin may be a glial attempt to provide protection for neurons against ALS pathology. The KDI tripeptide is effective therapeutically thus far in animal models only. However, because KDI containing γ1 laminin exists naturally in the human CNS, KDI therapies are unlikely to be toxic or allergenic. Results from our animal models are encouraging, with no toxic side-effects detected even at high concentrations, but the ultimate confirmation can be achieved only after clinical trials. More research is still needed until the KDI tripeptide is refined into a clinically applicable method to treat various neurological disorders.

Macroseismology as a Component of Seismicity Assessments in an Intraplate Region: Studies of Northern Europe with Emphasis on Finland

This work focuses on the role of macroseismology in the assessment of seismicity and probabilistic seismic hazard in Northern Europe. The main type of data under consideration is a set of macroseismic observations available for a given earthquake. The macroseismic questionnaires used to collect earthquake observations from local residents since the late 1800s constitute a special part of the seismological heritage in the region. Information of the earthquakes felt on the coasts of the Gulf of Bothnia between 31 March and 2 April 1883 and on 28 July 1888 was retrieved from the contemporary Finnish and Swedish newspapers, while the earthquake of 4 November 1898 GMT is an example of an early systematic macroseismic survey in the region. A data set of more than 1200 macroseismic questionnaires is available for the earthquake in Central Finland on 16 November 1931. Basic macroseismic investigations including preparation of new intensity data point (IDP) maps were conducted for these earthquakes. Previously disregarded usable observations were found in the press. The improved collection of IDPs of the 1888 earthquake shows that this event was a rare occurrence in the area. In contrast to earlier notions it was felt on both sides of the Gulf of Bothnia. The data on the earthquake of 4 November 1898 GMT were augmented with historical background information discovered in various archives and libraries. This earthquake was of some concern to the authorities, because extra fire inspections were conducted in three towns at least, i.e. Tornio, Haparanda and Piteå, located in the centre of the area of perceptibility. This event posed the indirect hazard of fire, although its magnitude around 4.6 was minor on the global scale. The distribution of slightly damaging intensities was larger than previously outlined. This may have resulted from the amplification of the ground shaking in the soft soil of the coast and river valleys where most of the population was found. The large data set of the 1931 earthquake provided an opportunity to apply statistical methods and assess methodologies that can be used when dealing with macroseismic intensity. It was evaluated using correspondence analysis. Different approaches such as gridding were tested to estimate the macroseismic field from the intensity values distributed irregularly in space. In general, the characteristics of intensity warrant careful consideration. A more pervasive perception of intensity as an ordinal quantity affected by uncertainties is advocated. A parametric earthquake catalogue comprising entries from both the macroseismic and instrumental era was used for probabilistic seismic hazard assessment. The parametric-historic methodology was applied to estimate seismic hazard at a given site in Finland and to prepare a seismic hazard map for Northern Europe. The interpretation of these results is an important issue, because the recurrence times of damaging earthquakes may well exceed thousands of years in an intraplate setting such as Northern Europe. This application may therefore be seen as an example of short-term hazard assessment.

Seismic Tomography and Earthquake Mechanism Beneath the Central Fennoscandian Shield

The aim of this thesis was to study the seismic tomography structure of the earth s crust together with earthquake distribution and mechanism beneath the central Fennoscandian Shield, mainly in southern and central Finland. The earthquake foci and some fault plane solutions are correlated with 3-D images of the velocity tomography. The results are discussed in relation to the stress field of the Shield and with other geophysical, e.g. geomagnetic, gravimetric, tectonic, and anisotropy studies of the Shield. The earthquake data of the Fennoscandian Shield has been extracted from the Nordic earthquake parameter data base which was founded at the time of inception of the earthquake catalogue for northern Europe. Eight earlier earthquake source mechanisms are included in a pilot study on creating a novel technique for calculating an earthquake fault plane solution. Altogether, eleven source mechanisms of shallow, weak earthquakes are related in the 3-D tomography model to trace stresses of the crust in southern and central Finland. The earthquakes in the eastern part of the Fennoscandian Shield represent low-active, intraplate seismicity. Earthquake mechanisms with NW-SE oriented horizontal compression confirm that the dominant stress field originates from the ridge-push force in the North Atlantic Ocean. Earthquakes accumulate in coastal areas, in intersections of tectonic lineaments, in main fault zones or are bordered by fault lines. The majority of Fennoscandian earthquakes concentrate on the south-western Shield in southern Norway and Sweden. Onwards, epicentres spread via the ridge of the Shield along the west-coast of the Gulf of Bothnia northwards along the Tornio River - Finnmark fault system to the Barents Sea, and branch out north-eastwards via the Kuusamo region to the White Sea Kola Peninsula faults. The local seismic tomographic method was applied to find the terrane distribution within the central parts of the Shield the Svecofennian Orogen. From 300 local explosions a total of 19765 crustal Pg- and Sg-wave arrival times were inverted to create independent 3-D Vp and Vs tomographic models, from which the Vp/Vs ratio was calculated. The 3-D structure of the crust is presented as a P-wave and for the first time as an S-wave velocity model, and also as a Vp/Vs-ratio model of the SVEKALAPKO area that covers 700x800 km2 in southern and central Finland. Also, some P-wave Moho-reflection data was interpolated to image the relief of the crust-mantle boundary (i.e. Moho). In the tomography model, the seismic velocities vary smoothly. The lateral variations are larger for Vp (dVp =0.7 km/s) than for Vs (dVs =0.4 km/s). The Vp/Vs ratio varies spatially more distinctly than P- and S-wave velocities, usually from 1.70 to 1.74 in the upper crust and from 1.72 to 1.78 in the lower crust. Schist belts and their continuations at depth are associated with lower velocities and lower Vp/Vs ratios than in the granitoid areas. The tomography modelling suggests that the Svecofennian Orogen was accreted from crustal blocks ranging in size from 100x100 km2 to 200x200 km2 in cross-sectional area. The intervening sedimentary belts have ca. 0.2 km/s lower P- and S-wave velocities and ca. 0.04 lower Vp/Vs ratios. Thus, the tomographic model supports the concept that the thick Svecofennian crust was accreted from several crustal terranes, some hidden, and that the crust was later modified by intra- and underplating. In conclusion, as a novel approach the earthquake focal mechanism and focal depth distribution is discussed in relation to the 3-D tomography model. The schist belts and the transformation zones between the high- and low-velocity anomaly blocks are characterized by deeper earthquakes than the granitoid areas where shallow events dominate. Although only a few focal mechanisms were solved for southern Finland, there is a trend towards strike-slip and oblique strike-slip movements inside schist areas. The normal dip-slip type earthquakes are typical in the seismically active Kuusamo district in the NE edge of the SVEKALAPKO area, where the Archean crust is ca. 15-20 km thinner than the Proterozoic Svecofennian crust. Two near vertical dip-slip mechanism earthquakes occurred in the NE-SW junction between the Central Finland Granitoid Complex and the Vyborg rapakivi batholith, where high Vp/Vs-ratio deep-set intrusion splits the southern Finland schist belt into two parts in the tomography model.

Fertility in Namibia : Changes in fertility levels in North-Central Namibia 1960-2001, including an assessment of the impact of HIV

The aim of this study was to estimate the development of fertility in North-Central Namibia, former Ovamboland, from 1960 to 2001. Special attention was given to the onset of fertility decline and to the impact of the HIV epidemic on fertility. An additional aim was to introduce parish registers as a source of data for fertility research in Africa. Data used consisted of parish registers from Evangelical Lutheran congregations, the 1991 and 2001 Population and Housing Censuses, the 1992 and 2000 Namibia Demographic and Health Surveys, and the HIV sentinel surveillances of 1992-2004. Both period and cohort fertility were analysed. The P/F ratio method was used when analysing census data. The impact of HIV infection on fertility was estimated indirectly by comparing the fertility histories of women who died at an age of less than 50 years with the fertility of other women. The impact of the HIV epidemic on fertility was assessed both among infected women and in the general population. Fertility in the study population began to decline in 1980. The decline was rapid during the 1980s, levelled off in the early 1990s at the end of war of independence and then continued to decline until the end of the study period. According to parish registers, total fertility was 6.4 in the 1960s and 6.5 in the 1970s, and declined to 5.1 in the 1980s and 4.2 in the 1990s. Adjustment of these total fertility rates to correspond to levels of fertility based on data from the 1991 and 2001 censuses resulted in total fertility declining from 7.6 in 1960-79 to 6.0 in 1980-89, and to 4.9 in 1990-99. The decline was associated with increased age at first marriage, declining marital fertility and increasing premarital fertility. Fertility among adolescents increased, whereas the fertility of women in all other age groups declined. During the 1980s, the war of independence contributed to declining fertility through spousal separation and delayed marriages. Contraception has been employed in the study region since the 1980s, but in the early 1990s, use of contraceptives was still so limited that fertility was higher in North-Central Namibia than in other regions of the country. In the 1990s, fertility decline was largely a result of the increased prevalence of contraception. HIV prevalence among pregnant women increased from 4% in 1992 to 25% in 2001. In 2001, total fertility among HIV-infected women (3.7) was lower than that among other women (4.8), resulting in total fertility of 4.4 among the general population in 2001. The HIV epidemic explained more than a quarter of the decline in total fertility at population level during most of the 1990s. The HIV epidemic also reduced the number of children born by reducing the number of potential mothers. In the future, HIV will have an extensive influence on both the size and age structure of the Namibian population. Although HIV influences demographic development through both fertility and mortality, the effect through changes in fertility will be smaller than the effect through mortality. In the study region, as in some other regions of southern Africa, a new type of demographic transition is under way, one in which population growth stagnates or even reverses because of the combined effects of declining fertility and increasing mortality, both of which are consequences of the HIV pandemic.

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.