Construction of a global map of human gene expression : the process, tools and analysis

This thesis studies human gene expression space using high throughput gene expression data from DNA microarrays. In molecular biology, high throughput techniques allow numerical measurements of expression of tens of thousands of genes simultaneously. In a single study, this data is traditionally obtained from a limited number of sample types with a small number of replicates. For organism-wide analysis, this data has been largely unavailable and the global structure of human transcriptome has remained unknown. This thesis introduces a human transcriptome map of different biological entities and analysis of its general structure. The map is constructed from gene expression data from the two largest public microarray data repositories, GEO and ArrayExpress. The creation of this map contributed to the development of ArrayExpress by identifying and retrofitting the previously unusable and missing data and by improving the access to its data. It also contributed to creation of several new tools for microarray data manipulation and establishment of data exchange between GEO and ArrayExpress. The data integration for the global map required creation of a new large ontology of human cell types, disease states, organism parts and cell lines. The ontology was used in a new text mining and decision tree based method for automatic conversion of human readable free text microarray data annotations into categorised format. The data comparability and minimisation of the systematic measurement errors that are characteristic to each lab- oratory in this large cross-laboratories integrated dataset, was ensured by computation of a range of microarray data quality metrics and exclusion of incomparable data. The structure of a global map of human gene expression was then explored by principal component analysis and hierarchical clustering using heuristics and help from another purpose built sample ontology. A preface and motivation to the construction and analysis of a global map of human gene expression is given by analysis of two microarray datasets of human malignant melanoma. The analysis of these sets incorporate indirect comparison of statistical methods for finding differentially expressed genes and point to the need to study gene expression on a global level.

Computational Methods for Locating and Analyzing Conserved Gene Regulatory DNA Elements

This thesis presents methods for locating and analyzing cis-regulatory DNA elements involved with the regulation of gene expression in multicellular organisms. The regulation of gene expression is carried out by the combined effort of several transcription factor proteins collectively binding the DNA on the cis-regulatory elements. Only sparse knowledge of the 'genetic code' of these elements exists today. An automatic tool for discovery of putative cis-regulatory elements could help their experimental analysis, which would result in a more detailed view of the cis-regulatory element structure and function. We have developed a computational model for the evolutionary conservation of cis-regulatory elements. The elements are modeled as evolutionarily conserved clusters of sequence-specific transcription factor binding sites. We give an efficient dynamic programming algorithm that locates the putative cis-regulatory elements and scores them according to the conservation model. A notable proportion of the high-scoring DNA sequences show transcriptional enhancer activity in transgenic mouse embryos. The conservation model includes four parameters whose optimal values are estimated with simulated annealing. With good parameter values the model discriminates well between the DNA sequences with evolutionarily conserved cis-regulatory elements and the DNA sequences that have evolved neutrally. In further inquiry, the set of highest scoring putative cis-regulatory elements were found to be sensitive to small variations in the parameter values. The statistical significance of the putative cis-regulatory elements is estimated with the Two Component Extreme Value Distribution. The p-values grade the conservation of the cis-regulatory elements above the neutral expectation. The parameter values for the distribution are estimated by simulating the neutral DNA evolution. The conservation of the transcription factor binding sites can be used in the upstream analysis of regulatory interactions. This approach may provide mechanistic insight to the transcription level data from, e.g., microarray experiments. Here we give a method to predict shared transcriptional regulators for a set of co-expressed genes. The EEL (Enhancer Element Locator) software implements the method for locating putative cis-regulatory elements. The software facilitates both interactive use and distributed batch processing. We have used it to analyze the non-coding regions around all human genes with respect to the orthologous regions in various other species including mouse. The data from these genome-wide analyzes is stored in a relational database which is used in the publicly available web services for upstream analysis and visualization of the putative cis-regulatory elements in the human genome.

Ideological notions in public health care rationing : Case studies from Oregon, New Zealand and Finland

The purpose of this dissertation is to analyze and explicate the ideological content, which is often implicit, in the health care rationing discussion. The phrase "ideological content" refers to viewpoints and assumptions expressed in the rationing discussion that may be widespread and accepted, but without clear evidential support. The study method is philosophical text analysis. The study begins by exploring the literature from the 1970s that affects the present-day rationing discussion. Since ideological contents may have different emphases in realm of health care, three representative cases were studied. The first was a case study of the first and best-known rationing experiment in the American state of Oregon, namely, an experimental rationing plan within the public health program Medicaid, which is designed to provide care for the poor and underprivileged. The second was a study of the only national-level public priority setting that has been conducted in New Zealand. The third examined the Finnish Care Guarantee plan introduced in March 2005. The findings show that several problematic and scientifically mostly unproven concepts have remained largely uncontested in the debate about public health care rationing. Some of these notions already originated decades ago in studies that relied on outdated data or research paradigms. The problematic ideological contents have also been taken up from one publication into another, thereby affecting the rationing debate. The study suggests that before any new public health care rationing experiments are undertaken, these ideological factors should be properly examined, especially in order to avoid repetitious research and perhaps erroneous rationing decisions.

Naiset, luonto ja uskonto : Ekofeministinen lähestymistapa uskontotieteessä

Tutkielmassa tarkastellaan ekofeminismiä ja sen tarjoamia mahdollisuuksia uskonnollisten luontodiskurssien tutkimiselle. Ekofeminismi on saavuttanut Suomessa yllättävän vähäistä kiinnostusta siitäkin huolimatta, että sekä feministisellä tutkimuksella että toisaalta uskontoekologialla on jalansijansa suomalaisessakin uskontotieteessä. Tutkielman tehtävänä onkin osaltaan paikata tätä tyhjiötä ja paitsi esitellä keskeisiä ekofeministisiä teorioita, niin myös näiden pohjalta kehitellä uudenlaista näkökulmaa uskontotieteelliseen, ihmisen ja luonnon suhdetta koskevaan tutkimukseen. Metodologisena viitekehyksenä tutkielmassa on käytetty sekä van Dijkin kriittisen diskurssianalyysin että Chris Weedonin kuvaileman jälkistrukturalistisen teorian perusperiaatteita, vaikkei diskurssianalyysi olekaan tutkielman pääasiallinen tavoite. Vaikka tutkielmassa sitoudutaan avoimesti ekofeministiseen projektiin, on näkökulma myös käytettyyn tutkimuskirjallisuuteen kriittinen: yhtäältä ekofeminististä näkökulmaa esitetään vaihtoehdoksi ns. perinteisille uskonnontutkimuksen teorioille, toisaalta tarkastellaan itseään ekofeminismiä ja sen lähtökohtia itsekriittisesti. Tutkielmassa käytetty uskonnon määritelmä nojaa Clifford Geerzin määritelmään uskonnosta symbolijärjestelmänä, joka osaltaan muokkaa yhteiskunnallista järjestystä sekä yhteiskunnan jäsenten syvimpiä arvoja ja asenteita. Näin nähtynä uskonnolla on tärkeä asema myös luontodiskurssien muodostamisessa ja ylläpitämisessä, eikä sitä näin ollen ole syytä jättää ekofeministisen tarkastelun ulkopuolelle. Ekofeminismi on 1970-luvulla syntynyt feminismin haara, jonka perustana on ajatus, että kaikki alistamisen muodot ovat verkkomaisessa suhteessa toisiinsa ja niiden taustalla toimivat samat mekanismit, oli kyseessä sitten rotuun, luokkaan, sukupuoleen tai lajiin perustuva sortaminen. Sorron taustalla toimivan ideologian ydin on käsitys järjen vallasta luonnon yli, jolloin alistetut ryhmät sekä naisellistetaan että naturalisoidaan. Tämän käsityksen perustan muodostavat länsimaista ajattelua jäsentävät dualismit kuten järki/tunne, mies/nainen, mieli/ruumis, yhteiskunta/luonto. Myös ympäristökriisin katsotaan nousevan näistä dualismeista, joten niiden tarkastelu, esiinkaivaminen ja purkaminen ovat yksi tärkeä osa ekofeminististä projektia. Näin ollen myös tässä tutkielmassa on kiinnitetty erityishuomio dualismeihin käyttäen apuna Val Plumwoodin teoriaa dualistisista mekanismeista ja toisaalta Karen Warrenin teoriaa dualismeihin nojaavasta herruuden logiikasta. Tutkielmassa luodaan myös katsaus länsimaisen, dualismeille pohjaavan luontosuhteen syntyyn niin filosofiassa, tieteessä kuin kristinuskossakin siten, kuin se ekofeminismin parissa yleisesti käsitetään. Tutkielmassa keskitytään kahteen ekofeministiseen pääsuuntaukseen, materiaaliseen ja kulttuuriseen ekofeminismiin. Näistä ensimmäisen taustalla ovat erilaiset sosialistiset ja marxilaiset teoriat: painotus on biologisesti ja sosiaalisesti sukupuolittuneessa työn jakautumisessa sekä naisen asemassa uusintavan työn tekijänä ja välittäjänä kulttuurin ja luonnon välissä. Kulttuurinen ekofeminismi puolestaan näkee ongelmien juuret enempi kulttuurisina, jolloin pääpaino on patriarkaalisen kulttuurin tavassa väheksyä kaikkea feminiiniseksi luokiteltua ja siten sekä naisia että luontoa. Tutkielmassa nämä kaksi näkökulmaa yhdistetään, sillä symbolis-materiaalisen sortokäsityksen mukaisesti huomio tulee kiinnittää yhtä lailla sorron materiaaliseen kuin kulttuuriseenkin puoleen. Tämän yhdistämisen tuloksena muodostuu uudenlainen näkökulma: ekofeministinen holismi. Ekofeministisen holismin teorian juuret ovat paitsi yllä mainituissa ekofeminismin muodoissa, niin myös pyrkimyksessä ylittää ekofeministisen ajattelun sisäiset dualismit. Teoria nojaa yhtäältä ns. ekologiseen hoivaetiikkaan ja toisaalta ajatukseen ekologisesta holismista: kokonaisuus hahmotetaan osiensa kautta, ja pääpaino on erilaisten suhteiden verkkomaisessa ymmärtämisessä. Huomio kiinnitetään yhtä lailla materiaaliseen kuin diskursiiviseenkin todellisuuteen, sillä valtarakenteet muotoutuvat näiden kahden vuorovaikutuksesta. Ekofeministinen holismi tarjoaakin uskonnollisten luontodiskurssien kriittiseen tarkasteluun monipuolisen näkökulman, jonka avulla on mahdollista paljastaa näiden diskurssien taustalla vaikuttavia dualistisia rakenteita samalla, kun huomioidaan myös näiden rakenteiden materiaaliset ja sosiaaliset vaikutukset. Kasaantuvien ekologisten ja sosiaalisten ongelmien edessä tällainen näkökulma puoltaa paikkaansa myös uskontotieteessä. Avainsanat: ekofeministiset teoriat - länsimainen luontosuhde - dualismit - ekologinen holismi - ekologinen hoivaetiikka - uskonnollinen luontodiskurssi

Reinhold Niebuhrin syntikäsitys

Reinhold Niebuhrin syntikäsitys rakentuu hänen ihmiskäsitykseensä kuuluvan dikotomian henki-luonto, sekä sitä sisällöllisesti vastaavan käsiteparin vapaus-rajallisuus, varaan. Ihmisen hengen kykyjä ovat transsendenssi yli luonnon, itsetranssendenssi sekä vapaus. Toisaalta ihminen on luontonsa kautta sidottu elollisen luonnon rajallisuuteen, vajavaisuuteen ja kuolevaisuuteen. Ihmisen rajallisuus on hengen kykyjen tavoin Jumalan luomisessa ihmiselle antama ominaisuus, ja siksi hyvä. Ihmisen asema rajallisena ja vapaana, eli ihmisen ristiriita antaa hänelle aiheen synnin tekemiseen. Tämä ihmisen ristiriita ei kuitenkaan ole synnin syy. Ihmisen asema luonnon ja hengen rajapinnassa saa hänet levottomaksi. Levottomuus on ihmisen ristiriidan väistämätön seuralainen ja samalla synnin sisäinen ennakkoehto. Raamatun lankeemuskertomus on Niebuhrin mukaan myytti, joka kuvaa symbolisesti ihmisen lankeamista syntiin. Lankeemusmyyttiä ei pidä tulkita kirjaimellisesti eikä kausaalisesti, sillä tällöin se menettää todellisen merkityksensä. Lankeemusmyytin mukaan ihmisen pahaa edeltää pahan voima, eli paholainen. Koska paholainen lankesi ennen ihmistä, ihmisen synti ei seuraa väistämättä ihmisen tilanteesta vapaana ja rajallisena. Ihmisen synti ei myöskään ole silkkaa perverssiyttä, tietoista pahan tekemistä ja Jumalan vastaista uhmaa. Ihmisen vapaus ja rajallisuus muuttuvat kiusaukseksi vasta, kun ne on tulkittu väärin. Ihmisen tekoa edeltävä pahan voima ehdottaa tätä tulkintaa ihmiselle. Niebuhr kuvaa Kierkegaardilta lainaamillaan ilmauksilla, kuinka 'synti asettaa itsensä' ja 'synti edellyttää itsensä'. Hän puhuu myös 'synnin laadullisesta hypystä'. Syntiä ei koskaan voi johtaa tietystä tilanteesta nousevasta kiusauksesta. Itsensä asettava synti on ihmisen oma synti. Synti edellyttää itsensä tarkoittaa, että kaikkea syntiä edeltää epäuskon synti. Ilman epäuskoa ihmisen levottomuus ei johtaisi syntiin. Niebuhrin metodinen tukeutuminen Kierkegaardiin ei ole johdonmukaista, mistä osittain johtuu, että hänen käsityksensä ihmisen syntiin lankeamisesta on ristiriitainen. Niebuhr sotkee myytti- ja historiapuheen keskenään. Ihmisen tietoisuus ja vapaus ovat edellytys sille, että ihminen ylipäänsä voi tehdä syntiä. Niebuhr torjuu perinteisen kristillisen näkemyksen, jonka mukaan lankeemus merkitsi radikaalia muutosta ihmisen tahdon vapauteen. Ihmisen huomio, ettei hän kykene tekemään valintaa hyvän ja pahan välillä, on Niebuhrin mukaan merkittävin osoitus ihmisen vapaudesta. Ihmisen tietoisuus synnistään ei koskaan ole täydellistä. Ihminen ei tee syntiä täysin tietoisesti ja harkitusti. Toisaalta ihmisen osittainen tietämättömyys synnistään on synnin seuraus. Voidakseen jatkaa synnin tekemistä, eli voidakseen pitäytyä kohtuuttomassa itserakkaudessaan, ihmisen on petettävä ensin itseään, sitten toisia ihmisiä. Niebuhr määrittelee hyvin pidättyväisesti näkemyksensä perisynnistä. Perisynti on ennen kaikkea ihmisen taipumus synnin tekemiseen. Synti on peräisin ihmisen tahdon viasta. Toisaalta Niebuhrin mukaan ihminen tekee väistämättä syntiä. Niebuhr on muutamissa yhteyksissä varovaisesti sillä kannalla, että ihmisen luonto on synnin seurauksena turmeltunut. Toisissa yhteyksissä hän torjuu tällaisen näkemyksen. Niebuhrin näkemys synnin väistämättömyydestä sekä näkemys ihmisen tahdon viasta jäävät jossain määrin irrallisiksi osiksi hänen ihmiskäsityksessään. Ihmisen synti on ylpeyttä ja aistillisuutta. Ihmisellä on taipumus kieltää joko rajallisuutensa tai vapautensa. Kieltäessään rajallisuutensa hän lankeaa ylpeyteen. Kieltäessään vapautensa hän lankeaa aistillisuuteen. Ylpeyden muotoja on neljä: vallanylpeys, tiedonylpeys, moraalinen ylpeys ja hengellinen ylpeys. Aistillisuudessa on kolme vaihetta. Aistillisuus on itserakkautta, yritystä paeta itseä toiseen ihmiseen tai luontoon sekä kolmanneksi pakoa tyhjyyteen ja tiedostamattomuuteen. Synti ja syyllisyys liittyvät väistämättä seksiin. Seksi on aistillisuuden elävin ilmaus ja samalla ihmisen luovuuden kliimaksi. Niebuhr pitää ihmisyhteisöjä yksilöiden ohella rajallisessa mielessä synnin subjekteina. Yhteisöillä on yksilöiden tavoin henki ja luonto, sekä itsetranssendenssin elimiä. Niebuhr pitää yhteisöjä yksilöitä moraalisesti pahempina. Yhteisöt aiheuttavat yksilöitä enemmän objektiivista pahaa. Niebuhr kritisoi syntikäsityksensä pohjalta liberalismiksi kutsumaansa ajattelua. Liberalismin perustana on Niebuhrin mukaan kehityksen idea, joka on perusteetonta optimistista uskoa täydellistyvään maailmaan ja uskoa historiaan itsensä lunastavana prosessina. Niebuhrin mukaan kaikki vallankäyttö elämässä johtaa sortoon ja epäoikeudenmukaisuuteen. Sen vuoksi yhteisöjä on hallittava voimien balanssilla sekä hallituksella. Nämä tekijät on mahdollista ottaa pätevästi huomioon vain demokratiassa. Niebuhr näkee kirkon silkkana ihmisyhteisönä, jolle on kuitenkin suotu evankeliumi. Hän korostaa kirkon syntisyyttä, muttei ollenkaan sen pyhyyttä.

Juutalaisvastaisuus suomalaisissa aikakauslehdissä ja kirjallisuudessa 1918-1944

Anti-Semitism existed in Finland during the whole period covered by this study. The immoral acts associated with Jews in the articles were mostly regarded as universal habits, qualities and/or modes of action, that is, unconnected with any particular Finnish Jew. Researchers have tried to explain anti-Semitism in several ways. The theory of Jews as outsiders has been a popular explanation as well as xenophobia, chimerical anti-Semitism and the socio-economic models. The main sources of this study have been over 400 Finnish periodicals and magazines, literature and text books published between 1918 and 1944. This vast number of magazines includes those of the army and the civil guard, religion, humour and the papers of the Finnish extreme right. One can see a distinct foreign and especially German influence in the subjects and phraseology of Finnish anti-Semitic writings between 1918 and 1944. Several known Finnish anti-Semitic writers had some kind of link with Germany. Some Finnish organisations and societies were openly anti-Semitic during this period. There had been cycles in the activity of anti-Semitic writing in Finland, obvious peaks appearing in 1918 1919, 1929 1931, 1933 1938 and 1942 1944. The reason for the 1918 1919 activity was the civil rights which were granted to the Jews in Finland, and the Russian Bolshevik revolution. The worldwide depression from 1929 to 1932 seem to be the reason for new anti-Semitic writing activity. The rise of National Socialism in Germany and the influence this phenomenon had in Finland was the reason for the peak during 1933 1938. During the continuation war 1942 1944 National Socialist Germany was fighting side-by-side with Finland and their anti-Semitic propaganda found easier access to Finland. Of the 433 magazines, journals and newspapers which were used in this study, 71 or 16.4 per cent had at least one article that can be identified as anti-Semitic; especially the magazines of national socialists and other extreme right parties were making anti-Semitic annotations. There were about 50 people known to have written anti-Semitic articles. At least half of these known writers had studied at the university, including as many as 10 priests. Over and above these, there was an even larger number of people who wrote under a pseudonym. The material used suggested that anti-Semitism was not very popular in Finland between 1918 and 1944. Anti-Semitic articles appeared mostly in the magazines of the extreme right, but their circulation was not very large. A proof of the slight influence of these extreme right anti-Semitic ideas is that, beside the tightening of policy towards Jewish immigrants in 1938 and the handing over of eight of these refugees to Germany in 1942, the official policy of Finland never became anti-Semitic. As was stated before, despite the cycles in the number of writings, there does not appear to have been any noticeable change in public opinion. One must also remember that most Finns had not at that period actually met a Jew. The material used suggests that between 1918 and 1944 the so-called Jewish question was seemingly unimportant for most Finns and their attitude to Jews and Jewishness can be described as neutral.

Itsenäisen Suomen puolesta : Sotilaskomitea 1915-1918

For Independent Finland. The Military Committee 1915–1918 In the course of the First World War, several organizations were founded with the purpose of making Finland independent or, at least, restoring her autonomous status. The Military Committee was the most significant active independence organization in Finland in the First World War, in addition to the activist student movement, i.e., the Jaeger Movement. The Military Committee was an organization founded in 1915 by officers who had attended the Hamina Cadet School, with the goal of creating a national army for a liberation war against the Russian troops. It was believed that the liberation war should succeed only with the help of the German Army. With the situation in society continually tensing up in the autumn 1917, the Military Committee also had to figure on the possibility of a Civil War. The activities of the Military Committee started in the early part of 1915 when they were still small-scale, but they gained significant momentum after the Russian Revolution in March 1917. In January 1918, the Military Committee formed the general staff for the White Army, the Senate’s troops. The independence-related activities of the Hamina cadets in the years of the First World War were more extensive and multifaceted than has been believed heretofore. The work of the Military Committee was divided into preparations for a liberation war in Finland, on one hand, and in Stockholm and Berlin, on the other hand. In Finland, the Military Committee took part in intelligence gathering for Germany and in supporting the recruiting Jaegers, and later in founding the civil guard organization, in solving the law and order authorities issue, and finally in selecting the Commander-in-Chief for the Senate’s troops. The member of the Military Committee, especially Captain Hannes Ignatius of the Cavalry contributed greatly to the drafting of the independence activists’ national action plan in Stockholm in May 1917. This plan preceded the formation of the civil guard organization. The Military Committee’s role in founding the civil guards was initially minor, but in the fall of 1917, the Military Committee started to finance the activities of the civil guards, named several former officers as commanders of the civil guards and finally overtook the entire civil guard movement. In Stockholm and Berlin, the representatives of the Military Committee were in active contact with both the high command of the German Army and with the representatives of the Swedish Army. Colonel Nikolai Mexmontan, who was a representative of the Military Committee, collaborated with Swedish officers and Jaeger officers in Stockholm in coming up with comprehensive and detailed plans for starting the Liberation War. Under Mexmontan’s leadership, there were serious negotiations to enter into a confederation with Germany. Lieutenant Colonel Wilhelm Thesleff, on the other hand, became the commander of the Jaeger Battalion 27. The influence and importance of the Military Committee came to the forefront in independent and conflict-torn Finland. The Military Committee became a Senate committee on the 7th of January 1918, with its chairman, for all practical purposes, as the Commander-in-Chief in an eventual war. Lieutenant General Claes Charpentier was the chairman of the Military Committee from mid-December 1917 onwards, but on the 15th of January 1918 he had to resign in favour of Lieutenant General Gustaf Mannerheim. Soon after that, Mannerheim got an order from the chairman of the Senate P. E. Svinhufvud to organize and assume the leadership of the law and order authorities. The chairman of the Military Committee became the Commander-in-Chief of the Senate troops in January 1918, and the Military Committee became the Commander-in-Chief’s general staff. The Military Committee had turned from a clandestine organization into the first general staff of the independent Finnish Army.

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.

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.

Elite Bargaining and the Evolution of Centre-Periphery Relations in Post-Soviet Russia : A Comparative Analysis

This work is concerned with presenting a modified theoretical approach to the study of centre-periphery relations in the Russian Federation. In the widely accepted scientific discourse, the Russian federal system under the Yeltsin Administration (1991-2000) was asymmetrical; largely owing to the varying amount of structural autonomy distributed among the federation s 89 constituent units. While providing an improved understanding as to which political and socio-economic structures contributed to federal asymmetry, it is felt that associated large N-studies have underemphasised the role played by actor agency in re-shaping Russian federal institutions. It is the main task of this thesis to reintroduce /re-emphasise the importance of actor agency as a major contributing element of institutional change in the Russian federal system. By focusing on the strategic agency of regional elites simultaneously within regional and federal contexts, the thesis adopts the position that political, ethnic and socio-economic structural factors alone cannot fully determine the extent to which regional leaders were successful in their pursuit of economic and political pay-offs from the institutionally weakened federal centre. Furthermore, this work hypothesises that under conditions of federal institutional uncertainty, it is the ability of regional leaders to simultaneously interpret various mutable structural conditions then translate them into plausible strategies which accounts for the regions ability to extract variable amounts of economic and political pay-offs from the Russian federal system. The thesis finds that while the hypothesis is accurate in its theoretical assumptions, several key conclusions provide paths for further inquiry posed by the initial research question. First, without reliable information or stable institutions to guide their actions, both regional and federal elites were forced into ad-hoc decision-making in order to maintain their core strategic focus: political survival. Second, instead of attributing asymmetry to either actor agency or structural factors exclusively, the empirical data shows that both agency and structures interact symbiotically in the strategic formulation process, thus accounting for the sub-optimal nature of several of the actions taken in the adopted cases. Third, as actor agency and structural factors mutate over time, so, too do the perceived payoffs from elite competition. In the case of the Russian federal system, the stronger the federal centre became, the less likely it was that regional leaders could extract the high degree of economic and political pay-offs that they clamoured for earlier in the Yeltsin period. Finally, traditional approaches to the study of federal systems which focus on institutions as measures of federalism are not fully applicable in the Russian case precisely because the institutions themselves were a secondary point of contention between competing elites. Institutional equilibriums between the regions and Moscow were struck only when highly personalised elite preferences were satisfied. Therefore the Russian federal system is the product of short-term, institutional solutions suited to elite survival strategies developed under conditions of economic, political and social uncertainty.

Pentitol phosphate dehydrogenases: Discovery, characterization and use in D-arabitol and xylitol production by metabolically engineered Bacillus subtilis

The ultimate goal of this study has been to construct metabolically engineered microbial strains capable of fermenting glucose into pentitols D-arabitol and, especially, xylitol. The path that was chosen to achieve this goal required discovery, isolation and sequencing of at least two pentitol phosphate dehydrogenases of different specificity, followed by cloning and expression of their genes and characterization of recombinant arabitol and xylitol phosphate dehydrogenases. An enzyme of a previously unknown specificity, D-arabitol phosphate dehydrogenase (APDH), was discovered in Enterococcus avium. The enzyme was purified to homogenity from E. avium strain ATCC 33665. SDS/PAGE revealed that the enzyme has a molecular mass of 41 ± 2 kDa, whereas a molecular mass of 160 ± 5 kDa was observed under non-denaturing conditions implying that the APDH may exist as a tetramer with identical subunits. Purified APDH was found to have narrow substrate specificity, converting only D-arabitol 1-phosphate and D-arabitol 5-phosphate into D-xylulose 5-phosphate and D-ribulose 5-phosphate, respectively, in the oxidative reaction. Both NAD+ and NADP+ were accepted as co-factors. Based on the partial protein sequences, the gene encoding APDH was cloned. Homology comparisons place APDH within the medium chain dehydrogenase family. Unlike most members of this family, APDH requires Mn2+ but no Zn2+ for enzymatic activity. The DNA sequence surrounding the gene suggests that it belongs to an operon that also contains several components of phosphotransferase system (PTS). The apparent role of the enzyme is to participate in arabitol catabolism via the arabitol phosphate route similar to the ribitol and xylitol catabolic routes described previously. Xylitol phosphate dehydrogenase (XPDH) was isolated from Lactobacillus rhamnosus strain ATCC 15820. The enzyme was partially sequenced. Amino acid sequences were used to isolate the gene encoding the enzyme. The homology comparisons of the deduced amino acid sequence of L. rhamnosus XPDH revealed several similar enzymes in genomes of various species of Gram-positive bacteria. Two enzymes of Clostridium difficile and an enzyme of Bacillus halodurans were cloned and their substrate specificities together with the substrate specificity of L. rhamnosus XPDH were compared. It was found that one of the XPDH enzymes of C. difficile and the XPDH of L. rhamnosus had the highest selectivity towards D-xylulose 5-phosphate. A known transketolase-deficient and D-ribose-producing mutant of Bacillus subtilis (ATCC 31094) was further modified by disrupting its rpi (D-ribose phosphate isomerase) gene to create D-ribulose- and D-xylulose-producing strain. Expression of APDH of E. avium and XPDH of L. rhamnosus and C. difficile in D-ribulose- and D-xylulose-producing strain of B. subtilis resulted in strains capable of converting D-glucose into D-arabitol and xylitol, respectively. The D-arabitol yield on D-glucose was 38 % (w/w). Xylitol production was accompanied by co-production of ribitol limiting xylitol yield to 23 %.

A systematic-ecological approach to Baltic Sea ice studies of algae and protists

The seasonal occurrence of sea ice that annually covers almost half the Baltic Sea area provides a unique habitat for halo- and cold temperature-tolerant extremophiles. Baltic Sea ice biology has more than 100 years of tradition that began with the floristic observation of species by the early pioneers using light microscopic techniques that were the only thing available at the time. Since the discovery of life within sea ice, more technologies have become available for taxonomy. Electron microscopy and genetic evidence have been used to identify sea ice biota revealing increased numbers of taxa. Meanwhile ecologists have used light microscopic cell enumeration in addition to the chemical and physical properties of sea ice in attempts to explain the food web structure of sea ice and its functions. Thus, during the Baltic winter, the sea ice hosts more abundant and diverse microbial communities than the water column beneath it. These communities are typically dominated by autotrophic diatoms together with a diverse assortment of dinoflagellates, auto- and heterotrophic flagellates, ciliates, metazoan rotifers and bacteria, which are mostly responsible for the recycling of nutrients. This thesis comprises ecological and systematic studies. In addition to the results of the previous studies carried out on landfast ice, the data presented here provide new insight into the spatial distribution of pelagial sea ice, which has remained largely unexplored. The studies reveal spatial heterogeneity in the pelagial sea ice of the Gulf of Bothnia. There were mismatches in chlorophyll-a concentrations and in photosynthetic efficiencies of the communities studied. The temporal succession was followed and experimental studies performed investigating the community responses towards increased or decreased light in landfast ice in the Gulf of Finland. The systematic studies carried out with established dinoflagellate cultures revealed a new resting cyst belonging to common sea ice dinoflagellate, Scrippsiella hangoei (Schiller) Larsen 1995. The cyst can be used to explain the overwintering of this species during prolonged periods of darkness. The dissimilarities and similarities in the material isolated from the sea ice called for description of a new subspecies Heterocapsa arctica ssp. frigida. The cells obtained in the cultured material were unlike those of the previously described species, necessitating description of ssp. frigida. As a result of its own unique habitus, the subspecies had been noted by Finnish taxonomists during the past three decades and thus its annual occurrence and geographical distribution in the Baltic Sea. This illustrates how combining ecology and systematics increases our understanding of organisms.

Causes and consequences of variation in nestling immune function

Defence against pathogens is a vital need of all living organisms that has led to the evolution of complex immune mechanisms. However, although immunocompetence the ability to resist pathogens and control infection has in recent decades become a focus for research in evolutionary ecology, the variation in immune function observed in natural populations is relatively little understood. This thesis examines sources of this variation (environmental, genetic and maternal effects) during the nestling stage and its fitness consequences in wild populations of passerines: the blue tit (Cyanistes caeruleus) and the collared flycatcher (Ficedula albicollis). A developing organism may face a dilemma as to whether to allocate limited resources to growth or to immune defences. The optimal level of investment in immunity is shaped inherently by specific requirements of the environment. If the probability of contracting infection is low, maintaining high growth rates even at the expense of immune function may be advantageous for nestlings, as body mass is usually a good predictor of post-fledging survival. In experiments with blue tits and haematophagous hen fleas (Ceratophyllus gallinae) using two methods, methionine supplementation (to manipulate nestlings resource allocation to cellular immune function) and food supplementation (to increase resource availability), I confirmed that there is a trade-off between growth and immunity and that the abundance of ectoparasites is an environmental factor affecting allocation of resources to immune function. A cross-fostering experiment also revealed that environmental heterogeneity in terms of abundance of ectoparasites may contribute to maintaining additive genetic variation in immunity and other traits. Animal model analysis of extensive data collected from the population of collared flycatchers on Gotland (Sweden) allowed examination of the narrow-sense heritability of PHA-response the most commonly used index of cellular immunocompetence in avian studies. PHA-response is not heritable in this population, but is subject to a non-heritable origin (presumably maternal) effect. However, experimental manipulation of yolk androgen levels indicates that the mechanism of the maternal effect in PHA-response is not in ovo deposition of androgens. The relationship between PHA-response and recruitment was studied for over 1300 collared flycatcher nestlings. Multivariate selection analysis shows that it is body mass, not PHA-response, that is under direct selection. PHA-response appears to be related to recruitment because of its positive relationship with body mass. These results imply that either PHA-response fails to capture the immune mechanisms that are relevant for defence against pathogens encountered by fledglings or that the selection pressure from parasites is not as strong as commonly assumed.

Maintaining plant species richness by cattle grazing - mesic semi-natural grasslands as focal habitats

Semi-natural grasslands are the most important agricultural areas for biodiversity. The present study investigates the effects of traditional livestock grazing and mowing on plant species richness, the main emphasis being on cattle grazing in mesic semi-natural grasslands. The two reviews provide a thorough assessment of the multifaceted impacts and importance of grazing and mowing management to plant species richness. It is emphasized that livestock grazing and mowing have partially compensated the suppression of major natural disturbances by humans and mitigated the negative effects of eutrophication. This hypothesis has important consequences for nature conservation: A large proportion of European species originally adapted to natural disturbances may be at present dependent on livestock grazing and / or mowing. Furthermore, grazing and mowing are key management methods to mitigate effects of nutrient-enrichment. The species composition and richness in old (continuously grazed), new (grazing restarting 3-8 years ago) and abandoned (over 10 years) pastures differed consistently across a range of spatial scales, and was intermediate in new pastures compared to old and abandoned pastures. In mesic grasslands most plant species were shown to benefit from cattle grazing. Indicator species of biologically valuable grasslands and rare species were more abundant in grazed than in abandoned grasslands. Steep S-SW-facing slopes are the most suitable sites for many grassland plants and should be prioritized in grassland restoration. The proportion of species trait groups benefiting from grazing was higher in mesic semi-natural grasslands than in dry and wet grasslands. Consequently, species trait responses to grazing and the effectiveness of the natural factors limiting plant growth may be intimately linked High plant species richness of traditionally mowed and grazed areas is explained by numerous factors which operate on different spatial scales. Particularly important for maintaining large scale plant species richness are evolutionary and mitigation factors. Grazing and mowing cause a shift towards the conditions that have occurred during the evolutionary history of European plant species by modifying key ecological factors (nutrients, pH and light). The results of this Dissertation suggest that restoration of semi-natural grasslands by private farmers is potentially a useful method to manage biodiversity in the agricultural landscape. However, the quality of management is commonly improper, particularly due to financial constraints. For enhanced success of restoration, management regulations in the agri-environment scheme need to be defined more explicitly and the scheme should be revised to encourage management of biodiversity.

Dung beetle communities in Madagascar

The traditional aim of community ecology has been to understand the origin and maintenance of species richness in local communities. Why certain species occur in one place but not in another, how ecologically apparently similar species use resources, what is the role of the regional species pool in affecting species composition in local communities, and so forth. Madagascar offers great opportunities to conduct such studies, since it is a very large island that has been isolated for tens of million of years. Madagascar has remarkable faunal and floral diversity and species level endemism reaches 100% in many groups of species. Madagascar is also exceptional for endemism at high taxonomic levels and for the skewed representation of many taxa in comparison with continental faunas. For example, native ungulates that are dominant large herbivorous mammals on the African continent are completely lacking in Madagascar. The largest native Malagasy herbivores, and the main dung producers for Malagasy dung beetles, are the endemic primates, lemurs. Cattle was introduced to Madagascar about 1,000 yrs ago and is today abundant and widespread. I have studied Malagasy dung beetle communities and the distributional patterns of species at several spatial scales and compared the results with comparable communities in other tropical areas. There are substantial differences in dung beetle communities in Madagascar and elsewhere in the tropics in terms of the life histories of the species, species ecological traits, local and regional species diversities, and the sizes of species geographical ranges. These differences are attributed to Madagascar s ancient isolation, large size, heterogeneous environment, skewed representation of the mammalian fauna, and recent though currently great human impact.