Towards a Critique of the Concept of the Right to Self-Determination in Africa : A Conceptual Examination and the Cases of Western Sahara, Southern Sudan and Eritrea

This thesis examines the right to self-determination which is a norm used for numerous purposes by multiple actors in the field of international relations, with relatively little clarity or agreement on the actual and potential meaning of the right. In international practice, however, the main focus in applying the right has been in the context of decolonization as set by the United Nations in its early decades. Thus, in Africa the right to self-determination has traditionally implied that the colonial territories, and particularly the populations within these territories, were to constitute the people who were entitled to the right. That is, self-determination by decolonization provided a framework for the construction of independent nation-states in Africa whilst other dimensions of the right remained largely or totally neglected. With the objective of assessing the scope, content, developments and interpretations of the right to self-determination in Africa, particularly with regard to the relevance of the right today, the thesis proceeds on two fundamental hypotheses. The first is that Mervyn Frost s theory of settled norms, among which he lists the right to self-determination, assumes too much. Even if the right to self-determination is a human right belonging to all peoples stipulated, inter alia, in the first Article of the 1966 International Human Rights Covenants, it is a highly politicized and context-bound right instead of being settled and observed in a way that its denial would need special justification. Still, the suggested inconsistency or non-compliance with the norm of self-determination is not intended to prove the uselessness or inappropriateness of the norm, but, on the contrary, to invite and encourage debate on the potential use and coverage of the right to self-determination. The second hypothesis is that within the concept of self-determination there are two normative dimensions. One is to do with the idea and practice of statehood, the nation and collectivity that may decide to conduct itself as an independent state. The other one is to do with self-determination as a human right, as a normative condition, to be enjoyed by people and peoples within states that supersedes state authority. These external and internal dimensions need to be seen as complementary and co-terminous, not as mutually exclusive alternatives. The thesis proceeds on the assumption that the internal dimension of the right, with human rights and democracy at its core, has not been considered as important as the external. In turn, this unbalanced and selective interpretation has managed to put the true normative purpose of the right making the world better and bringing more just polity models into a somewhat peculiar light. The right to self-determination in the African context is assessed through case studies of Western Sahara, Southern Sudan and Eritrea. The study asks what these cases say about the right to self-determination in Africa and what their lessons learnt could contribute to the understanding and relevance of the right in today s Africa. The study demonstrates that even in the context of decolonization, the application of the right to self-determination has been far from the consistent approach supposedly followed by the international community: in many respects similar colonial histories have easily led to rather different destinies. While Eritrea secured internationally recognized right to self-determination in the form of retroactive independence in 1993, international recognition of distinct Western Sahara and Southern Sudan entities is contingent on complex and problematic conditions being satisfied. Overall, it is a considerable challenge for international legality to meet empirical political reality in a meaningful way, so that the universal values attached to the norm of self-determination are not overlooked or compromised but rather reinforced in the process of implementing the right. Consequently, this thesis seeks a more comprehensive understanding of the right to self-determination with particular reference to post-colonial Africa and with an emphasis on the internal, human rights and democracy dimensions of the norm. It is considered that the right to self-determination cannot be perceived only as an inter-state issue as it is also very much an intra-state issue, including the possibility of different sub-state arrangements exercised under the right, for example, in the form of autonomy. At the same time, the option of independent statehood achieved through secession remains a mode of exercising and part of the right to self-determination. But in whatever form or way applied, the right to self-determination, as a normative instrument, should constitute and work as a norm that comprehensively brings more added value in terms of the objectives of human rights and democracy. From a normative perspective, a peoples right should not be allowed to transform and convert itself into a right of states. Finally, in light of the case studies of Western Sahara, Southern Sudan and Eritrea, the thesis suggests that our understanding of the right to self-determination should now reach beyond the post-colonial context in Africa. It appears that both the questions and answers to the most pertinent issues of self-determination in the cases studied must be increasingly sought within the postcolonial African state rather than solely in colonial history. In this vein, the right to self-determination can be seen not only as a tool for creating states but also as a way to transform the state itself from within. Any such genuinely post-colonial approach may imply a judicious reconsideration, adaptation or up-dating of the right and our understanding of it in order to render it meaningful in Africa today.

Dental Service Utilization, Dental Health Production and Equity in Dental Care: the Finnish Experience

This thesis is grounded on four articles. Article I generally examines the factors affecting dental service utilization. Article II studies the factors associated with sector-specific utilization among young adults entitled to age-based subsidized dental care. Article III explores the determinants of dental ill-health as measured by the occurrence of caries and the relationship between dental ill-health and dental care use. Article IV measures and explains income-related inequality in utilization. Data employed were from the 1996 Finnish Health Care Survey (I, II, IV) and the 1997 follow-up study included in the longitudinal study of the Northern Finland 1966 Birth Cohort (III). Utilization is considered as a multi-stage decision-making process and measured as the number of visits to the dentist. Modified count data models and concentration and horizontal equity indices were applied. Dentist s recall appeared very efficient at stimulating individuals to seek care. Dental pain, recall, and the low number of missing teeth positively affected utilization. Public subvention for dental care did not seem to statistically increase utilization. Among young adults, a perception of insufficient public service availability and recall were positively associated with the choice of a private dentist, whereas income and dentist density were positively associated with the number of visits to private dentists. Among cohort females, factors increasing caries were body mass index and intake of alcohol, sugar, and soft drinks and those reducing caries were birth weight and adolescent school achievement. Among cohort males, caries was positively related to the metropolitan residence and negatively related to healthy diet and education. Smoking increased caries, whereas regular teeth brushing, regular dental attendance and dental care use decreased caries. We found equity in young adults utilization but pro-rich inequity in the total number of visits to all dentists and in the probability of visiting a dentist for the whole sample. We observed inequity in the total number of visits to the dentist and in the probability of visiting a dentist, being pro-poor for public care but pro-rich for private care. The findings suggest that to enhance equal access to and use of dental care across population and income groups, attention should focus on supply factors and incentives to encourage people to contact dentists more often. Lowering co-payments and service fees and improving public availability would likely increase service use in both sectors. To attain favorable oral health, appropriate policies aimed at improving dental health education and reducing the detrimental effects of common risk factors on dental health should be strengthened. Providing equal access with respect to need for all people ought to take account of the segmentation of the service system, with its two parallel delivery systems and different supplier incentives to patients and dentists.

Essays on Illegal Activities, Institutions and Economic Growth

In public economics, two extremist views on the functions of a government compete: one emphasizes government working for the public interest to provide value for the citizens, while another regards government mainly as a workhorse for private interests. Moreover, as the sole legitimate authority, the government has the right to define the rules and laws as well as to enforce them. With respect to regulation, two extremes arise: from too little regulation to too much of it. If the government does not function or ceases to exist, the state falls into anarchy or chaos (Somalia). If it regulates too much, it will completely suffocate private activities, which might be considered extralegal (the former Soviet Union). In this thesis I scrutinize the government s interventionist policies and evaluate the question of how to best promote economic well-being. The first two essays assume that the government s policies promote illegal activity. The first paper evaluates the interaction between the government and the mafia, and pays attention to the law enforcement of underground production. We show that the revenue-maximizing government will always monitor the shadow economy, as monitoring contributes to the government s revenue. In general, both legal and illegal firms are hurt by the entry of the mafia. It is, however, plausible that legal firms might benefit by the entry of the mafia if it competes with the government. The second paper tackles the issue of the measurement of the size of the shadow economy. To formulate policies it is essential to know what drives illegal economic activity; is it the tax burden, excess regulation, corruption or a weak legal environment? In this paper we propose an additional explanation for tax evasion and shadow production, namely cultural factors as manifested by religion as determinants of tax morality. According to our findings, Catholic and Protestant countries do not differ in their tax morale. The third paper contributes to the literature discussing the role of the government in promoting economic and productivity growth. Our main result is that, given the complex relationship between economic growth and economic freedom, marketization has not necessarily been beneficial in terms of growth. The last paper builds on traditional growth literature and revisits the debate on convergence clubs arising from demographic transition. We provide new evidence against the idea that countries within a club would converge over time. Instead, we propose that since the demographic transition is a dynamic process, one can expect countries to enter the last regime of stable, modern growth in stages.

Stalinismin lyhyt kurssi : Suomalaiset Moskovan Lenin-koulussa 1926-1938

This study of the Finns at the International Lenin School (ILS) reflects history of the Soviet Union during Stalin's era, history of the Communist International (Comintern) as well as history of Finnish communism. The life span of the ILS (1926-1938) matches up with creating and establishing the power structures of Stalinism. Both the ILS and Finnish Communism in the USSR became casualties of the Great Terror (1937-1938). After the WW2, however, the Soviet education was appreciated inside the Communist Party of Finland (CPF). If Finland would have become People's Democracy, the former ILS students would have composed the inner circle of the new "democratic" government. The Finnish teachers of the ILS were leaders of the CPF that was headquartered in Moscow. At the ILS studied in total 141 Finnish communists. The purpose of the ILS was to educate the communist parties' leading stratum of functionaries. They were supposed to internalize current values, methods and discipline of the Bolsheviks. This study evaluates the effects of the total school experience on the Finns that often ended in another total institution in Finland: prison. The curricula of the ILS consisted of theory of Marxism-Leninism, party history, political economics and themes of campaigns of Stalinism. The ILS year included participation in Bolshevik party life and practical work. During summer excursions (praktikas) the students could acquaint themselves with building of socialism in the Soviet Republics. At the ILS, intention to ideological moulding was not hidden. The students were supposed to adopt the Stalinist identity of the professional revolutionaries of the era. The ILS was saturated with ideology and propaganda. This study analyzes especially uses of history as vehicle of ideological standardisation and as instrument of power. Stalin contributed personally to shortcomings of history writing of the communist party. Later he supervised writing of the inclusive handbook of communism, "History of the All-Union Communist Party. Short Course". Special attention will be paid to the effects of Stalin's intervention at the ILS and inside the CPF. The life of the Finns at the ILS and outside the school is described at grass roots. The dividing line between personal and political is analyzed by charting emotional, intimate and bodily experiences of the Finns of the ILS. The fates of the ILS Finns after the studying or teaching period in Moscow are explored in detail. The protagonist among the teachers is Yrjö Sirola that was called "father of the CPF cadres". The Finnish ILS teachers and the formed students that had remained in the USSR were most severely hit by the Great Terror. The Soviet education had most importance in Finland of post WW2 period. The training at the ILS, however, did not contribute to revolution in Finland. The main heading of the study, "A Short Course of Stalinism", crystallises interpretation of the ILS as seat of learning of ideological unity of Stalinism. On the other hand, the title includes a statement of incompleteness of the Stalinist education if the schooling at the ILS had remained in one year.

Essays on Misplanning Wealth and Health: A Behavioural Approach

The dissertation consists of three essays on misplanning wealth and health accumulation. The conventional economics assumes that individual's intertemporal preferences are exponential (exponential preferences, EP). Recent findings in behavioural economics have shown that, actually, people do discount near future relatively heavier than distant future. This implies hyperbolic intertemporal preferences (HP). Essays I and II concentrate especially on the effects of a delayed completion of tasks, a feature of behaviour that HP enables. Essay III uses current Finnish data to analyse the evolvement of the quality adjusted life years (QALYs) and inconsistencies in measuring that. Essay I studies the existence effects of a lucrative retirement savings program (SP) on the retirement savings of different individual types having HP. If the individual does not know that he will have HP also in the future, i.e. he is the naïve, for certain conditions, he delays the enrolment on SP until he abandons it. Very interesting finding is that the naïve retires then poorer in the presence than in the absence of SP. For the same conditions, the individual who knows that he will have HP also in the future, i.e. he is the sophisticated, gains from the existence of SP, and retires with greater retirement savings in the presence than in the absence of SP. Finally, capabilities to learn from past behaviour and about intertemporal preferences improve possibilities to gain from the existence but an adequate time to learn must be then guaranteed. Essay II studies delayed doctor's visits, theirs effects on the costs of a public health care system and government's attempts to control patient behaviour and fund the system. The controlling devices are a consultation fee and a deductible for that. The deductible is effective only for a patient whose diagnosis reveals a disease that would not get cured without the doctor's visit. The naives delay their visits the longest while EP-patients are the quickest visitors. To control the naives, the government should implement a low fee and a high deductible, while for the sophisticates the opposite is true. Finally, if all the types exist in an economy then using an incorrect conventional assumption that all individuals have EP leads to worse situation and requires higher tax rates than assuming incorrectly but unconventionally that only the naives exists. Essay III studies the development of QALYs in Finland 1995/96-2004. The essay concentrates on developing a consistent measure, i.e. independent of discounting, for measuring the age and gender specific QALY-changes and their incidences. For the given time interval, use of a relative change out of an attainable change seems to be almost intact to discounting and reveals that the greatest gains are for older age groups.

Essays in Philosophical Moral Psychology

The dissertation consists of four essays and a comprehensive introduction that discusses the topics, methods, and most prominent theories of philosophical moral psychology. I distinguish three main questions: What are the essential features of moral thinking? What are the psychological conditions of moral responsibility? And finally, what are the consequences of empirical facts about human nature to normative ethics? Each of the three last articles focuses on one of these issues. The first essay and part of the introduction are dedicated to methodological questions, in particular the relationship between empirical (social) psychology and philosophy. I reject recent attempts to understand the nature of morality on the basis of empirical research. One characteristic feature of moral thinking is its practical clout: if we regard an action as morally wrong, we either refrain from doing it even against our desires and interests, or else feel shame or guilt. Moral views seem to have a conceptual connection to motivation and emotions – roughly speaking, we can’t conceive of someone genuinely disapproving an action, but nonetheless doing it without any inner motivational conflict or regret. This conceptual thesis in moral psychology is called (judgment) internalism. It implies, among other things, that psychopaths cannot make moral judgments to the extent that they are incapable of corresponding motivation and emotion, even if they might say largely the words we would expect. Is internalism true? Recently, there has been an explosion of interest in so-called experimental philosophy, which is a methodological view according to which claims about conceptual truths that appeal to our intuitions should be tested by way of surveys presented to ordinary language users. One experimental result is that the majority of people are willing to grant that psychopaths make moral judgments, which challenges internalism. In the first article, ‘The Rise and Fall of Experimental Philosophy’, I argue that these results pose no real threat to internalism, since experimental philosophy is based on a too simple conception of the relationship between language use and concepts. Only the reactions of competent users in pragmatically neutral and otherwise conducive circumstances yield evidence about conceptual truths, and such robust intuitions remain inaccessible to surveys for reasons of principle. The epistemology of folk concepts must still be based on Socratic dialogue and critical reflection, whose character and authority I discuss at the end of the paper. The internal connection between moral judgment and motivation led many metaethicists in the past century to believe along Humean lines that judgment itself consists in a pro-attitude rather than a belief. This expressivist view, as it is called these days, has far-reaching consequences in metaethics. In the second essay I argue that perhaps the most sophisticated form of contemporary expressivism, Allan Gibbard’s norm-expressivism, according to which moral judgments are decisions or contingency plans, is implausible from the perspective of the theory of action. In certain circumstances it is possible to think that something is morally required of one without deciding to do so. Morality is not a matter of the will. Instead, I sketch on the basis of Robert Brandom’s inferentialist semantics a weak form of judgment internalism, according to which the content of moral judgment is determined by a commitment to a particular kind of practical reasoning. The last two essays in the dissertation emphasize the role of mutual recognition in the development and maintenance of responsible and autonomous moral agency. I defend a compatibilist view of autonomy, according to which agents who are unable to recognize right and wrong or act accordingly are not responsible for their actions – it is not fair to praise or blame them, since they lacked the relevant capacity to do otherwise. Conversely, autonomy demands an ability to recognize reasons and act on them. But as a long tradition in German moral philosophy whose best-known contemporary representative is Axel Honneth has it, both being aware of reasons and acting on them requires also the right sort of higher-order attitudes toward the self. Without self-respect and self-confidence we remain at the mercy of external pressures, even if we have the necessary normative competence. These attitudes toward the self, in turn, are formed through mutual recognition – we value ourselves when those who we value value us. Thus, standing in the right sort of relations of recognition is indirectly necessary for autonomy and moral responsibility. Recognition and valuing are concretely manifest in actions and institutions, whose practices make possible participation on an equal footing. Seeing this opens the way for a kind of normative social criticism that is grounded in the value of freedom and automomy, but is not limited to defending negative rights. It thus offers a new way to bridge the gap between liberalism and communitarianism.

Yhteisöllisyys juutalaisessa kansallisuusajattelussa ja Israelin valtion itsenäisyysjulistuksessa

The Idea of Community in the Jewish National Thinking and in the Proclamation of Independence The aim of this study is to clarify the idea of community in the Jewish national thinking and in the Proclamation of Independence of the State of Israel in 1948. The method is the community analysis. The values of the culture are studied by two- and threefold dimensions on the arena. On the field of that arena one can find the society of order, the society of pressure, the societies made by mosaics and the societies that are breaking apart. The community way of behaving means, that the individuals voluntarily follow common values. The earliest Jewish ideals elevated the concept of unity among the people. The reality in the society was different especially in Roman times when the religious and national thinking was fragmented into four different main views. During the Diaspora the religious tradition mostly warned against pursuing a Jewish state, but many forms of Anti-Judaism and the new national thinking in the nineteenth century created the Zionist movement. The religious Jewish people did not rely on the earthy nationalism and when some of them later chose Zionism, they stressed the religious aspects in governing the state. The cultural Zionists preferred a slower and more low key spiritual way of change. The Revisionists saw no alternatives but to use military force. Many in the majority, the Labour movement, hoped that the progress brought to the region by Zionism would change the minds of opponents. The general appearance of the proclamation is optimistic. It characterizes national and political unity gathering people who think differently and who come from different factions of the Jewish political and cultural orientation. These people can be placed on different corners in the community analysis. The proclamation concentrates on state and administrative points of view. It aims at a state for the Jews, and the Jewishness of the state is more clearly seen in later legislation. The hope for co-operation from all sides was clearly articulated. The central aim was the security of the Jews. The proclamation has a community quotation because it aimed to build up a net of cooperation. The vision of building a nation of their own is balanced by the collaboration with the Arabs and the international community. In the same roclamation the individual civil rights are side by side with the Prophets thoughts about peace and justice. The Proclamation describes a society of a good order which aims at uniting the people. In the midst of grave difficulties a noble proclamation of national and international co-operation was created. It was not taken for granted that the ideals would be realized. The care of the national homeland could become egocentric nationalism and the attention to the Prophets heritage could turn to emphasizing strict religious rules or to isolation from others. The emphasis of civil rights could turn to assimilation or in other words to other kinds of values in their own country.

The Vexing Case of Igor Shafarevich, a Russian Political Thinker

The Russian mathematician, academician and former dissident Igor Shafarevich (b. 1923) is commonly mentioned in Western scholarly studies on perestroika and post-perestroika-era Russian politics as one of the most notable anti-Semites and extreme nationalists of the country. This notoriety owes to Shafarevich’s old samizdat article Russophobia, which was published in 1988. The scandal surrounding Russophobia came to a head when the president of The National Academy of Sciences in the United States asked Shafarevich, its honorary member, to resign. Nothing like this had ever happened in the academy’s history. The present dissertation discusses Shafarevich’s political activities, his texts and ideas as well as their reception. Particular attention is given to Russophobia, whose detailed examination proves very clearly that its reputation as an anti-Semitic text is groundless. The reasons for Russophobia’s hasty but fierce condemnation were many, but only one was that when the Soviet system began to tumble, it was commonly assumed that a vigorous rise in anti-Semitism and extreme nationalism in the Soviet Union/Russia would be just a matter of time. Many observers were highly sensitised to detecting its signs and symptoms. The dissertation also shows that most of those to write the first criticisms of Russophobia and to liken Shafarevich to the ideologues of Nazi Germany were the same people he had criticised in Russophobia for their deterministic view of history and irrational manner of connecting things for the purpose of fanning the flames of distrust between Russia’s Jews and Russians. In retrospect, it is fairly evident that Shafarevich actually managed to effectively “neutralise” the message of many of those obsessed with the Jews among his Russian contemporaries and contributed to the fact that anti-Jewish sentiments have been a great deal less popular in post-communist Russia than so many had feared and expected. The thesis also thoroughly discusses Shafarevich’s other texts and activities before Russophobia’s appearance and after it. In the 1970s, Shafarevich was one of the best-known dissidents in the Soviet Union. He worked together with academician Andrei Sakharov in a dissidents’ unofficial human rights committee and co-operated closely with Aleksandr Solzhenitsyn before Solzhenitsyn’s exile. Then, during the chaotic years of perestroika, Shafarevich defended the basic rights of ordinary citizens and warned that the hype concerning democracy could become counterproductive if the most palpable result of the reforms was the disappearance of citizens’ basic security and elementary social justice. One of the conclusions of the thesis is that even if the world around Shafarevich has changed considerably, his views have remained essentially the same since the late 1960s and early 1970s.

The Restless Love of Thinking : The Concept Liebe in Hegel's Philosophy

The German philosopher G.W.F.Hegel (1770–1831) is best known for his idealistic system philosophy, his concept of spirit [Geist] and for his dictum that the existing and the rational overlap. This thesis offers a new perspective: it examines the working of the concept ‘love’ in Hegel’s philosophy by looking at the contexts and function he puts it to, from his earliest writings to the very last lectures he gave. The starting point of the inquiry is that he applied the concept Liebe to different contexts for different purposes, but each time to provide an answer to a specific philosophical problem. His formulation, reformulation and use of ‘love’ give possible solutions to problems the solving of which was crucial to the development of his thought as a whole. The study is divided into three parts, each analysing the different problems and solutions to which Hegel applied the concept of love. The first part, "Love, morality and ethical life", examines these interconnected themes in Hegel’s early work. The main questions he addressed during this period concerned how to unite Kant’s philosophy and the Greek ideal of the good life. In this context, the concept ‘love’ did three things. First, it served to formulate his grounding idea of the relation between unity and difference, or the manifold. Secondly, it was the key to his attempt to base an ideal folk religion on Christianity interpreted as a religion of love. Finally, it provided the means to criticise Kant’s moral philosophy. The question of the moral value of love helped Hegel to break away from Kant’s thought and develop his own theory about love and ethical life. The second part of the study, "Love and the political realm", considers the way 'Liebe' functions in connection with questions concerning the community and political life in Hegel’s work. In addition to questioning the universal applicability of the concept of recognition as a key to his theory of social relations, the chapters focus on gender politics and the way he conceptualised the gender category ‘woman’ through the concept ‘love’. Another line of inquiry is the way the figure of Antigone was used to conceptualise the differentiated spheres of action for men and women, and the part ‘love’ played in Hegel’s description of Antigone’s motives. Thirdly, Hegel’s analogy of the family and the state and the way ‘love’ functions in an attempt to promote understanding of the relation between citizens and the state are examined. The third and final part of the study, "Love as absolute spirit", focuses on ‘love’ within Hegel’s systemic thought and the way he continued to characterise Geist through the language of Liebe up until and including his very last works. It is shown how Liebe functions in his hierarchical organisation of the domains of art, religion and philosophy, and how both art and religion end up in similar structural positions with regard to philosophy. One recurrent theme in the third part is Hegel’s complex relation to Romantic thought. Another line of investigation is how he reconstructed Christianity as a religion of love in his mature work. In striking contrast to his early thought, in his last works Hegel introduced a new concept of love that incorporated negativity, and that could also function as the root of political action.

Effect of long-wave UV radiation on mouse melanoma: an in vitro and in vivo study

The skin cancer incidence has increased substantially over the past decades and the role of ultraviolet (UV) radiation in the etiology of skin cancer is well established. Ultraviolet B radiation (280-320 nm) is commonly considered as the more harmful part of the UV-spectrum due to its DNA-damaging potential and well-known carcinogenic effects. Ultraviolet A radiation (320-400 nm) is still regarded as a relatively low health hazard. However, UVA radiation is the predominant component in sunlight, constituting more than 90% of the environmentally relevant solar ultraviolet radiation. In the light of the recent scientific evidence, UVA has been shown to have genotoxic and immunologic effects, and it has been proposed that UVA plays a significant role in the development of skin cancer. Due to the popularity of skin tanning lamps, which emit high intensity UVA radiation and because of the prolonged sun tanning periods with the help of effective UVB blockers, the potential deleterious effects of UVA has emerged as a source of concern for public health. The possibility that UV radiation may affect melanoma metastasis has not been addressed before. UVA radiation can modulate various cellular processes, some of which might affect the metastatic potential of melanoma cells. The aim of the present study was to investigate the possible role of UVA irradiation on the metastatic capacity of mouse melanoma both in vitro and in vivo. The in vitro part of the study dealt with the enhancement of the intercellular interactions occurring either between tumor cells or between tumor cells and endothelial cells after UVA irradiation. The use of the mouse melanoma/endothelium in vitro model showed that a single-dose of UVA to melanoma cells causes an increase in melanoma cell adhesiveness to non-irradiated endothelium after 24-h irradiation. Multiple-dose irradiation of melanoma cells already increased adhesion at a 1-h time-point, which suggests the possible cumulative effect of multiple doses of UVA irradiation. This enhancement of adhesiveness might lead to an increase in binding tumor cells to the endothelial lining of vasculature in various internal organs if occurring also in vivo. A further novel observation is that UVA induced both decline in the expression of E-cadherin adhesion molecule and increase in the expression of the N-cadherin adhesion molecule. In addition, a significant decline in homotypic melanoma-melanoma adhesion (clustering) was observed, which might result in the reduction of E-cadherin expression. The aim of the in vivo animal study was to confirm the physiological significance of previously obtained in vitro results and to determine whether UVA radiation might increase melanoma metastasis in vivo. The use of C57BL/6 mice and syngeneic melanoma cell lines B16-F1 and B16-F10 showed that mice, which were i.v. injected with B16-F1 melanoma cells and thereafter exposed to UVA developed significantly more lung metastases when compared with the non-UVA-exposed group. To study the mechanism behind this phenomenon, the direct effect of UVA-induced lung colonization capacity was examined by the in vitro exposure of B16-F1 cells. Alternatively, the UVA-induced immunosuppression, which might be involved in increased melanoma metastasis, was measured by standard contact hypersensitivity assay (CHS). It appears that the UVA-induced increase of metastasis in vivo might be caused by a combination of UVA-induced systemic immunosuppression, and to the lesser extent, it might be caused by the increased adhesiveness of UVA irradiated melanoma cells. Finally, the UVA effect on gene expression in mouse melanoma was determined by a cDNA array, which revealed UVA-induced changes in the 9 differentially expressed genes that are involved in angiogenesis, cell cycle, stress-response, and cell motility. These results suggest that observed genes might be involved in cellular response to UVA and a physiologically relevant UVA dose have previously unknown cellular implications. The novel results presented in this thesis offer evidence that UVA exposure might increase the metastatic potential of the melanoma cells present in blood circulation. Considering the wellknown UVA-induced deleterious effects on cellular level, this study further supports the notion that UVA radiation might have more potential impact on health than previously suggested. The possibility of the pro-metastatic effects of UVA exposure might not be of very high significance for daily exposures. However, UVA effects might gain physiological significance following extensive sunbathing or solaria tanning periods. Whether similar UVA-induced pro-metastatic effects occur in people sunbathing or using solaria remains to be determined. In the light of the results presented in this thesis, the avoidance of solaria use could be well justified.

Synthesis of neoglycoconjugates and oligosaccharides with potential anti-Helicobacter pylori activity

The significance of carbohydrate-protein interactions in many biological phenomena is now widely acknowledged and carbohydrate based pharmaceuticals are under intensive development. The interactions between monomeric carbohydrate ligands and their receptors are usually of low affinity. To overcome this limitation natural carbohydrate ligands are often organized as multivalent structures. Therefore, artificial carbohydrate pharmaceuticals should be constructed on the same concept, as multivalent carbohydrates or glycoclusters. Infections of specific host tissues by bacteria, viruses, and fungi are among the unfavorable disease processes for which suitably designed carbohydrate inhibitors represent worthy targets. The bacterium Helicobacter pylori colonizes more than half of all people worldwide, causing gastritis, gastric ulcer, and conferring a greater risk of stomach cancer. The present medication therapy for H. pylori includes the use of antibiotics, which is associated with increasing incidence of bacterial resistance to traditional antibiotics. Therefore, the need for an alternative treatment method is urgent. In this study, four novel synthesis procedures of multivalent glycoconjugates were created. Three different scaffolds representing linear (chondroitin oligomer), cyclic (γ-cyclodextrin), and globular (dendrimer) molecules were used. Multivalent conjugates were produced using the human milk type oligosaccharides LNDFH I (Lewis-b hexasaccharide), LNnT (Galβ1-4GlcNAcβ1-3Galβ1-4Glc), and GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc all representing analogues of the tissue binding epitopes for H. pylori. The first synthetic method included the reductive amination of scaffold molecules modified to express primary amine groups, and in the case of dendrimer direct amination to scaffold molecule presenting 64 primary amine groups. The second method described a direct procedure for amidation of glycosylamine modified oligosaccharides to scaffold molecules presenting carboxyl groups. The final two methods that were created both included an oxime-linkage on linkers of different length. All the new synthetic procedures synthesized had the advantage of using unmodified reducing sugars as starting material making it easy to synthesize glycoconjugates of different specificity. In addition, the binding activity of an array of neoglycolipids to H. pylori was studied. Consequently, two new neolacto-based structures, Glcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-Cer and GlcAβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-Cer, with binding activity toward H. pylori were discovered. Interestingly, N-methyl and N-ethyl amide modification of the GlcAβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-Cer glucuronic acid residue resulted in more effective H. pylori binding epitopes than the parent molecule.

Polymorphic low penetrance genes and breast cancer : The role of genes involved in metabolism of xenobiotics, estrogens and reactive oxygen species

Various endogenous and exogenous factors have been reported to increase the risk of breast cancer. Many of those are related to prolonged lifetime exposure to estrogens. Furthermore, a positive family history of breast cancer and certain benign breast diseases are known to increase the risk of breast cancer. The role of lifestyle factors, such as use of alcohol and smoking has been an area of intensive study. Alcohol has been found to increase the risk of breast cancer, whereas the role of smoking has remained obscure. A multitude of enzymes are involved in the metabolism of estrogens and xenobiotics including the carcinogens found in tobacco smoke. Many of the metabolic enzymes exhibit genetic polymorphisms that can lead to inter-individual differences in their abilities to modify hazardous substrates. Therefore, in presence of a given chemical exposure, one subgroup of women may be more susceptible to breast carcinogenesis, since they carry unfavourable forms of the polymorphic genes involved in the metabolism of the chemical. In this work, polymorphic genes encoding for cytochrome P450 (CYP) 1A1 and 1B1, N-acetyl transferase 2 (NAT2), sulfotransferase 1A1 (SULT1A1), manganese superoxide dismutase (MnSOD) and vitamin D receptor (VDR) were investigated in relation to breast cancer susceptibility in a Finnish population. CYP1A1, CYP1B1 and SULT1A1 are involved in the metabolism of both estrogens and xenobiotics, whereas NAT2 is involved only in the latter. MnSOD is an antioxidant enzyme protecting cells from oxidative damage. VDR, in turn, mediates the effects of the active form of vitamin D (1,25(OH)2D3, calcitriol) on maintenance of calcium homeostasis and it has anti-proliferative effects in many cancer cells. A 1.3-fold (95% CIs 1.01-1.73) increased risk of breast cancer was seen among women who carried the NAT2 slow acetylator genotype and a 1.5-fold (95% CI 1.1-2.0) risk was found in women with a MnSOD variant A allele containing genotypes compared to women with the NAT2 rapid acetylator genotype or to those with the MnSOD VV genotype, respectively. Instead, women with the VDR a allele containing genotypes were found to be at a decreased risk for breast cancer (OR 0.73; 95% CI 0.54-0.98) compared to women with the AA genotype. No significant overall associations were found between SULT1A1 or CYP genotypes and breast cancer risk, whereas a combination of the CYP1B1 432Val allele containing genotypes with the NAT2 slow acetylator genotypes posed a 1.5-fold (95% CI 1.03-2.24) increased risk. Moreover, NAT2 slow acetylator genotype was found to be confined to women with an advanced stage of breast cancer (stages III and IV). Further evidence for the association of xenobiotic metabolising genes with breast cancer risk was found when active smoking was taken into account. Women who smoked less than 10 cigarettes/day and carried at least one CYP1B1 432Val variant allele, were at 3.1-fold (95% CI 1.32-7.12) risk of breast cancer compared to women who smoked the same amount but did not carry the variant allele. Furthermore, the risk was significantly increased with increasing number of the CYP1B1 432Val alleles (p for trend 0.005). In addition, women who smoked less than 5 pack-years and carried the NAT2 slow acetylator genotype were at a 2.6-fold (95% CI 1.01-6.48) increased risk of breast cancer compared to women who smoked the same amount but carried the NAT2 rapid acetylator genotype. Furthermore, the combination of the CYP1B1 432Val allele and the NAT2 slow acetylator genotype increased the risk of breast cancer by 2.5-fold (95% CI 1.11-5.45) among ever smokers. Instead, the MnSOD A allele was found to be a risk factor among postmenopausal long-term smokers (>15 years of smoking) (OR 5.1; 95% CI 1.4-18.4) or among postmenopausal women who had smoked more than 10 cigarettes/day (OR 5.5; 95% CI 1.3-23.4) compared to women who had similar smoking habits but carried the MnSOD V/V genotype. Similarly, within subgroups of postmenopausal women who were using oral contraceptives, hormone replacement therapy or alcohol, women carrying the MnSOD A allele genotypes seemed to be at increased risk of breast cancer compared to women with the MnSOD V/V genotype. A positive family history of breast cancer and high parity were shown to be inversely associated with breast cancer risk among women carrying the VDR ApaI a allele or among premenopausal women carrying the SULT1A1*2 allele, respectively.

The visual preferences for forest regeneration and field afforestation - four case studies in Finland

The overall aim of this dissertation was to study the public's preferences for forest regeneration fellings and field afforestations, as well as to find out the relations of these preferences to landscape management instructions, to ecological healthiness, and to the contemporary theories for predicting landscape preferences. This dissertation includes four case studies in Finland, each based on the visualization of management options and surveys. Guidelines for improving the visual quality of forest regeneration and field afforestation are given based on the case studies. The results show that forest regeneration can be connected to positive images and memories when the regeneration area is small and some time has passed since the felling. Preferences may not depend only on the management alternative itself but also on the viewing distance, viewing point, and the scene in which the management options are implemented. The current Finnish forest landscape management guidelines as well as the ecological healthiness of the studied options are to a large extent compatible with the public's preferences. However, there are some discrepancies. For example, the landscape management instructions as well as ecological hypotheses suggest that the retention trees need to be left in groups, whereas people usually prefer individually located retention trees to those trees in groups. Information and psycho-evolutionary theories provide some possible explanations for people's preferences for forest regeneration and field afforestation, but the results cannot be consistently explained by these theories. The preferences of the different stakeholder groups were very similar. However, the preference ratings of the groups that make their living from forest - forest owners and forest professionals - slightly differed from those of the others. These results provide support for the assumptions that preferences are largely consistent at least within one nation, but that knowledge and a reference group may also influence preferences.

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.

Microsurgical Aneurysm Model in Rats and Mice: Development of Endovascular Treatment and Optimization of Magnetic Resonance Imaging

The rupture of a cerebral artery aneurysm causes a devastating subarachnoid hemorrhage (SAH), with a mortality of almost 50% during the first month. Each year, 8-11/100 000 people suffer from aneurysmal SAH in Western countries, but the number is twice as high in Finland and Japan. The disease is most common among those of working age, the mean age at rupture being 50-55 years. Unruptured cerebral aneurysms are found in 2-6% of the population, but knowledge about the true risk of rupture is limited. The vast majority of aneurysms should be considered rupture-prone, and treatment for these patients is warranted. Both unruptured and ruptured aneurysms can be treated by either microsurgical clipping or endovascular embolization. In a standard microsurgical procedure, the neck of the aneurysm is closed by a metal clip, sealing off the aneurysm from the circulation. Endovascular embolization is performed by packing the aneurysm from the inside of the vessel lumen with detachable platinum coils. Coiling is associated with slightly lower morbidity and mortality than microsurgery, but the long-term results of microsurgically treated aneurysms are better. Endovascular treatment methods are constantly being developed further in order to achieve better long-term results. New coils and novel embolic agents need to be tested in a variety of animal models before they can be used in humans. In this study, we developed an experimental rat aneurysm model and showed its suitability for testing endovascular devices. We optimized noninvasive MRI sequences at 4.7 Tesla for follow-up of coiled experimental aneurysms and for volumetric measurement of aneurysm neck remnants. We used this model to compare platinum coils with polyglycolic-polylactic acid (PGLA) -coated coils, and showed the benefits of the latter in this model. The experimental aneurysm model and the imaging methods also gave insight into the mechanisms involved in aneurysm formation, and the model can be used in the development of novel imaging techniques. This model is affordable, easily reproducible, reliable, and suitable for MRI follow-up. It is also suitable for endovascular treatment, and it evades spontaneous occlusion.