Viitotut elämät : Kuurojen nuorten aikuisten kokemuksia viittomakielisestä elämästä Suomessa

The goal of the study is to build an image of deafness and of the lives of the deaf from their own per-spectives. The lives of deaf sign language users are analysed through the concept of identity. The start-ing point for the study is the idea that identities are moulded and structured in action and interaction and are, therefore, continuous processes. The terminology and ideas used in the present study are mostly based on Erving Goffman s (1971, 1986) work in which he sees identity as a representation of self. Via our language and our actions we build and present an image of ourselves to others and to ourselves alike. The research aims at answering the following questions concerning the lives of deaf sign language users: how do deaf people build an image of themselves as deaf people, what kind of meanings does deafness acquire in their lives, and what opportunities do they have to be perceived by others as they feel they are, i.e. to present their true self . In order to answer these questions, the narratives provided by eighteen deaf young adults, aged 25 35, in narrative interviews carried out in sign language, have been analysed. The methodology used is that of a data-based, qualitative analysis and narrative analy-sis. The study follows the lines of prior qualitative research carried out in the field of sociology of health and in the study of everyday life. The subjects are divided into three groups according to the linguistic environment dominant in the family: 1) a deaf child in a deaf family, 2) a deaf child in a hearing family using sign language, and 3) a deaf child in a hearing family where sign language was not used. The childhood family has great significance in the way a child constructs his or her identity as a deaf person. The process of construct-ing an identity in the first group can be defined as being automatic or inherited, in the second group the process can be described as being a collective/joint identity-building process, whereas in the third group the process is ambivalent and delayed. The opportunities the deaf have in building their identi-ties as deaf people have been examined through the concept of a collective story reservoir. Research shows that the deaf have, at least partly, a different collective story reservoir that they can rely on from the one the hearing have. Interaction with other deaf people and access to the collective story reservoir is important, because it enables the deaf to form an idea of their own deafness and the life of a deaf person. Three different ways of understanding deafness can be conceptualized from the narratives of the inter-viewed deaf people. In the outdated counter-narrative and the reductive narrative of deafness as an abnormality, the subjects are not capable of seeing themselves as forming part of the narratives or identifying themselves with the ways the deaf are depicted. Yet, the characterizations prevalent in them are the ones that the deaf constantly come across in their day-to-day lives. The narrative through which the subjects depict themselves and their lives can be defined as a pluralistic narrative. The plu-ralistic narrative consists of three elements: the coexistence of the world of the deaf and that of the hearing, the orientation to sign language, and the replacement of local networks with global networks. Although modern Finnish society and its varied social services and subsidy systems enable the realiza-tion of the kind of life described in the pluralistic narrative, the issues of power and inequality still frequently emerge in the narratives in which the deaf young adults described themselves and their lives. Two kinds of power mechanisms can be perceived in the descriptions: belittling and excluding power. These considerably diminish the opportunities of sign language users to create the kind of life that would reflect their personalities while limiting the chances for presenting the self to others.

Retirement Transition and Well-being : A 16-year Longitudinal Study

The ageing of the labour force and falling employment rates have forced policy makers in industrialized countries to find means of increasing the well-being of older workers and of lengthening their work careers. The main objective of this thesis was to study longitudinally how health, functional capacity, subjective well-being, and lifestyle change as people grow older, and what effect retirement has on these factors and on their relationships. The present study is a follow-up questionnaire study of Finnish municipal workers, conducted in 1981 to 1997 at the Finnish Institute of Occupational Health. In 1981, a postal questionnaire was sent to 7344 municipal workers in different parts of Finland. The respondents were born between 1923 and 1937. A total of 6257 persons responded to the first questionnaire. In the end, a total of 3817 persons had responded to all four (1981, 1985, 1992, 1997) questionnaires. (The response rate was 69% of the living participants). Cross-tabulations, comparison of means, logistic regression analyses and general linear models with repeated measures were used to derive the results. The transition from work life to retirement, and the following years as a pensioner were associated with many changes. Involvement in various activities increased during the transition stage but later decreased to the previous level. Physical exercise was an exception: it became increasingly popular over the years. Perceived health improved markedly from the working stage to the retirement transition stage, even though morbidity increased steadily during the follow-up. On the other hand, functional capacity decreased over the follow-up, especially among those who were occupationally active until the retirement stage. Subjective well-being remained stable during the follow-up period. There were, however, great differences based on the type of work, favouring those whose work had been mental in nature. The impact of activity level on maintaining well-being became greater during the follow-up, whereas the effect of physical functioning diminished. Good physical functioning and an active life-style contributed to staying on at work until normal retirement age. Also work-related factors, i.e. possibilities for development and influence at work, responsibility for others, meaningful work, and satisfaction with working time arrangements were positively related to continuing working. The transition from work to retirement had a positive impact on a person s health and functional capacity. The study results support the view that it should be possible to ease one s work pace during the last years of a work career. This might lower the threshold between work and retirement and convince people that there will still be time to enjoy retirement also a few years later.

Ydinperheen politiikka

The research topic is the formation of nuclear family understanding and the politicization of nuclear family. Thus, the question is how did family historically become understood particularly as nuclear family and why did it become central in terms of politics and social? The research participates in discussions on the concept and phenomena of family. Central theme of analysis is to ask what is family? Family is seen as historically contingent and the discussions on the concept and phenomena are done via historical analysis. Center of attention is nuclear family, thus, a distinction between the concepts of family and nuclear family is made to be able to focus on historically specific phenomena of nuclear family. Family contrary to the concept of nuclear family -- in general is seen to be able to refer to families in all times and all cultures, as well as all types of families in our times and culture. The nuclear family understanding is examined through two separate themes, that of parent-child relationships and marital relations. Two simultaneous processes give nuclear family relations its current form: on the one hand the marital couple as the basis of family is eroding and losing its capacity to hold the family together; on the other, in Finland at least from 1950s on, the normal development of the child has became to be seen ontologically bound to the (biological) mother and (via her to) the father. In the nucleus of the family is the child: the biological, psychological and social processes of normal development are seen ontologically bound to the nuclear family relations. Thus, marriages can collapse, but nuclear family is unbreakable. What is interesting is the historical timing: as nuclear family relations had just been born, the marriage dived to a crisis. The concept and phenomena of nuclear family is analyzed in the context of social and politics (in Finnish these two collapses in the concept of yhteiskunnallinen , which refers both to a society as natural processes as well as to the state in terms of politics). Family is political and social in two senses. First, it is understood as the natural origin of the social and society. Human, by definition, is understood as a social being and the origin of social, in turn, is seen to be in the family. Family is seen as natural to species. Disturbances in family life lead to un-social behaviour. Second, family is also seen as a political actor of rights and obligations: family is obligated to control the life of its members. The state patronage is seen at the same time inevitable family life is way too precious to leave alone -- and problematic as it seems to disturb the natural processes of the family or to erode the autonomy of it. The rigueur of the nuclear family is in the role it seems to hold in the normal development of the child and the future of the society. The disturbances in the families first affect the child, then the society. In terms of possibility to re-think the family the natural and political collide: the nuclear family seems as natural, unchangeable, un- negotiable. Nuclear family is historically ontologised. The biological, psychological and social facts of family seem to be contrary to the idea of negotiation and politics the natural facts of family problematise the politics of family. The research material consists of administrational documents, memoranda, consultation documents, seminar reports, educational writings, guidebooks and newspaper articles in family politics between 1950s and 1990s.

Knowledge through Discussion : An Interpretation of Epistemology in Plato's Meno

According to Meno s paradox we cannot inquire into what we do not know because we do not know what we are inquiring into. There are many ways to interpret the paradox but the central issue about our ability to reach truth is a profound one. In the dialogue Meno, Plato presents the paradox and an outline of a solution which enables us to reach knowledge (epistēmē) through philosophical discussion. During the last century Meno has often been considered transitional between Socratic thinking and Plato s own philosophy, and thus the dialogue has not been adequately interpreted as an integrated whole. Therefore the distinctive epistemology of the dialogue has not gained due notice. In this thesis the dialogue is analysed as an integrated whole and the philosophical interpretation also takes into account its dramatic features. The thesis emphasises the role of language and definitions in acquiring knowledge. Among the results concerning these subjects is a new interpretation of Socrates s defintion of shape (schēma). The theory of anamnēsis all learning is recollection in the Meno is argued to answer the paradox philosophically although Plato s presentation also contains playful and ironic elements. The background of the way Plato presents his case is that he appreciated the fact that no argument can plausibly demonstrate that argumentation is able to reach truth. In the Meno, Plato makes the earliest explicit distinction between knowledge and true belief in the history of Western philosophy. He also gives a definition of knowledge which is the basis of the so called classical definition of knowledge as justified true belief. In the Meno, true beliefs become knowledge when someone ties them down by reasoning about the explanation. The analysis of the epistemology of the dialogue from this perspective gives an interpretation which integrates the central concepts of the epistemology in the dialogue elenchos, anamnēsis and hypothetical inquiry into a unified whole which contains a plausible argument according to which the ignorant can reach knowledge through discussion. The conception that emerges by such an analysis is interesting both from the point of view of current interests and that of the history of philosophy. The method of knowledge acquisition in the Meno can, for example, be seen as a predecessor of modern scientific methods. The Meno is the earliest Greek mathematical text that has survived in its original form. The analysis presented in the thesis of the geometric passages in the dialogue provides new results both concerning Socrates s geometry lesson with the slave and the example presenting the hypothetical method. Concerning the latter, a new interpretation is presented. Keywords: anamnēsis, epistēmē, knowledge, Meno s paradox, Plato

Matkailurakentaminen ja sen diskursiivinen rakentuminen Kilpisjärvellä

This master s thesis examines tourism related housing and related discourses in the village of Kilpisjärvi, Finland. I study the tourism development in Kilpisjärvi and the debate related to this process. My methodology is based on discourse and content analysis. The purpose of this study is to examine and classify the discourses of tourism related housing and what are the lessons learned from the recent development of Kilpisjärvi. Kilpisjärvi is the northernmost village in western Finnish Lapland, located in the middle of the highest mountain area of Finland. The area has been reindeer herding area of Saami people for centuries, but it has lacked permanent settlement until the beginning of 20th century. The first tourist accommodation was built in 1930s, followed by the road in 1940s and the hotel in 1950s. Traditionally the area has attracted skiers and hikers. The area is also known for its extraordinary nature and rare plant life. Tourism development was slow in Kilpisjärvi until the turn of millennium when rapid growth in tourism related housing was triggered by extensive land use planning. Small wilderness village of Kilpisjärvi has grown to a tourism centre with over 800 beds in commercial enterprises, more than hundred second-homes, and two large caravan areas. This development has raised conflicts among villagers. The empirical part of this study is based on the interviews of 17 permanent dwellers of Kilpisjärvi and three Norwegian cottage owners. Six discourses can be distinguished: 1) Nature and landscape, 2) Economy, 3) Place, 4)Reindeer herding, 5) Governance and 6) Possibilities to influence decision-making. The first discourse stressed that tourism development and building should adapt to nature and landscape, while economic discourse stressed the economical importance of tourism to Kilpisjärvi and the municipality of Enontekiö. The third discourse noted the change of Kilpisjärvi as a place due to the boom of tourism development. The discourse of reindeer herding was clearly distinguished from others, seeing tourism development merely negative. Governance was seen as an important tool in regulating development, but many saw that the municipal administration has failed to take into account other aspects of tourism development than economical factors. Many villagers saw their influence in decision-making weak, while landowners and municipal decision-makers were seen as oligarchy in land-use planning regardless of formal participatory planning process enforced by law. I conclude that it is important to take into account the diversity of local discourses in tourism development and land use issues. Transparent and genuine participatory planning process would promote sustainable development, prevent conflicts and allow decisions and development which would satisfy larger number of local dwellers than presently.

The EU and Institutional Twinning in Morocco - An inquiry into the motives of cooperation through discourse ethics

This study examines Institutional Twinning in Morocco as a case of EU cooperation through the pragmatic, ethical and moral logics of reason in Jürgen Habermas’s discourse ethics. As a former accession tool, Twinning was introduced in 2004 for legal approximation in the context of the European Neighborhood Policy. Twinning is a unique instrument in development cooperation from a legal perspective. With its long historical and cultural ties to Europe, Morocco presents an interesting case study of this new form of cooperation. We will analyse motives behind the Twinning projects on illegal immigration, environment legislation and customs reform. As Twinning is a new policy instrument within the ENP context, there is relatively little preceding research, which, in itself, constitutes a reason to inquire into the subject. While introducing useful categories, the approaches discussing “normative power Europe” do not offer methodological tools precise enough to analyse the motives of the Twinning cooperation from a broad ethical standpoint. Helene Sjursen as well as Esther Barbé and Elisabeth Johansson-Nogués have elaborated on Jürgen Habermas’ discourse ethics in determining the extent of altruism in the ENP in general. Situating the analysis in the process-oriented framework of Critical Theory, discourse ethics provides the methodological framework for our research. The case studies reveal that the context in which they operate affects the pragmatic, ethical and moral aspirations of the actors. The utilitarian notion of profit maximization is quite pronounced both in terms of the number of Twinning projects in the economic sphere and the pragmatic logics of reason instrumental to security and trade-related issues. The historical background as well internal processes, however, contribute to defining areas of mutual interest to the actors as well as the motives Morocco and the EU sometimes described as the external projection of internal values. Through its different aspects, Twinning cooperation portrays the functioning of the pragmatic, ethical and moral logics of reason in international relations.

Keskiluokkainen kulutuseetos 1920–1950-luvuilla syntyneiden suomalaisten kulutuskerronnassa

Tutkielmassa tarkastellaan suomalaista kulutuskulttuuria ja sen muuttumista kulutuskerronnan kautta. Aineisto koostuu 39 iäkkään, 1920–1950-luvuilla syntyneen, suomalaisen kuluttajaelämäkerroista, jotka kerättiin kirjoituskilpailulla. Tutkielmassa analysoidaan informanttien kulutukseen ja rahankäyttöön liittämiä hyveitä sekä sitä, millaisista kulutuseetoksista hyveet kertovat. Elämäkertojen erittelyyn ja tulkintaan on sovellettu lähiluentaa. Analyysin avulla on rakennettu tulkinta keskiluokkaisesta kulutuseetoksesta. Tutkimuksen teoreettinen viitekehys pohjautuu kulutuksen normatiivisia merkityksiä, kulutuseetoksia ja keskiluokkaisuutta käsitteleviin tutkimuksiin. Tulkintaa ohjaa lisäksi ymmärrys tutkittavan sukupolven elämänkulusta suomalaisen kulutusyhteiskunnan kehityksen näkökulmasta. Tutkittavan sukupolven elämän aikana kotitalous on kehittynyt agraarisen yhteiskunnan omavaraisesta tuotantoyksiköstä vauraan yhteiskunnan kulutukseen ja sosiaaliseen uusintamiseen keskittyväksi instituutioksi. Palkkatyöläisyys, vapaa-aika ja kulutusmahdollisuudet ovat lisääntyneet, ja yhteiskuntaa leimaa keskiluokkaistuminen. Elämäkerroista löytyvät säästäväisyyden ja vaatimattomuuden hyveet kertovat talonpoikaisen kulutueetoksen olevan edelleen keskeinen kulutuseetos, mutta niukkuuden hyveellistämisen lisäksi kulutuskerronnasta löytyy myös modernimpia tapoja suhtautua kulutukseen. Tulkitsen kuluttajaelämäkerroista löytyvien järkevyyden, tavallisuuden ja työnteon hyveiden kertovan keskiluokkaisuudesta. Hyveellinen kuluttaminen on keskiluokkaisessa kulutuseetoksessa talonpoikaista kulutuseetosta sallivampaa. Se määrittyy niukan kuluttamisen sijaan kohtuullisen ja tavallisen kuluttamisen hyveellistämiseksi. Keskiluokkaisessa kulutuseetoksessa on hyväksyttävää nauttia kohtuudella ja järkevästi omalla työllä ansaitusta vaurastumisesta. Talonpoikaisesta kulutuseetoksesta poiketen keskiluokkainen kulutuseetos hyväksyy kulutuksesta saatavan nautinnon. Sanonta ”ensin työ, sitten huvi” kuvaa keskiluokkaisen kulutuseetoksen tapaa suhtautua vaurastumisen mukanaan tuomaan kulutuskulttuuriin ja sen nautintoihin.

HALLINNONTASOJEN VÄLINEN DIALOGI JA ERITYISOPETUKSEN MUUTOS BYROKRAATTISENA INSTITUUTIONA : - Kymppikuntien loppuraportin ja Erityisopetuksen strategian sisällönanalyyttinen vertailu

The rise of Special education numbers in Finland has caused a situation where Finland s ten largest LEA s so called kymppikunnat (ten communes) have expressed their growing concern of organizing the special education in the current institutional settings. The LEA s started the conversation of redefining special education system in 2004. Their aim was to target the governments attention to the problematics of special education. By the request of the Ministry of Education the LEA s prepared a final report concerning the central questions in the Finnish special education system. On the basis of the LEA s survey it became even clearer that the legislation, funding system and curriculum are tightly linked together. The following LEA s took part into the writing process Espoo, Helsinki, Jyväskylä, Kuopio, Lahti, Lappeenranta, Tampere, Turku and Vantaa. The report was hand over to the Ministry of Education at 18.8.2006. After the delivery the Ministry organized special education development group meetings 17 times in the year 2007. The result of the LEA s report and the development meetings was a new Special Education Strategy 2007. I am observing the dialogue between administrational levels in governmental institutions change process. The research is a content analysis where I compare the Erityistä tukea tarvitsevan oppilaan opetuksen järjestämisen uudistaminen osana yhtenäistä perusopetusta- kohti laatua ja joustavuutta (The renewal of the organization of teaching for student with special educational needs as part of unified education for all - towards quality and flexibility) document to Erityisopetuksen strategia (Special education strategy) document. My aim was to find out how much of their own interests have the LEA s been able to integrate into the official governmental documentation. The data has been organized and analyzed quantitatively with Macros created as additional parts in Microsoft Excel software. The document material has also been arranged manually on sentence based categorization into an Excel matrix. The results have been theoretically viewed from the special education reform dialogue perspective, and from the angle of the change process of a bureaucratic institution. My target has been to provide a new viewpoint to the change of special education system as a bureaucratic institution. The education system has traditionally been understood as a machine bureaucracy. By the review provided in my pro gradu analysis it seems however that the administrational system in special education is more of a postmodern network bureaucracy than machine bureaucracy. The system appears to be constructed by overlapping, crossing and complex networks where things are been decided. These kinds of networks are called "governance networks . It seems that the governmental administrational - and politic levels, the third sector actors and other society s operators are mixed in decision making.

Mass spectrometry and n-in-one analytics in early drug discovery: Combinatorial chemistry libraries, lipophilicity and absorption screening

This thesis describes current and past n-in-one methods and presents three early experimental studies using mass spectrometry and the triple quadrupole instrument on the application of n-in-one in drug discovery. N-in-one strategy pools and mix samples in drug discovery prior to measurement or analysis. This allows the most promising compounds to be rapidly identified and then analysed. Nowadays properties of drugs are characterised earlier and in parallel with pharmacological efficacy. Studies presented here use in vitro methods as caco-2 cells and immobilized artificial membrane chromatography for drug absorption and lipophilicity measurements. The high sensitivity and selectivity of liquid chromatography mass spectrometry are especially important for new analytical methods using n-in-one. In the first study, the fragmentation patterns of ten nitrophenoxy benzoate compounds, serial homology, were characterised and the presence of the compounds was determined in a combinatorial library. The influence of one or two nitro substituents and the alkyl chain length of methyl to pentyl on collision-induced fragmentation was studied, and interesting structurefragmentation relationships were detected. Two nitro group compounds increased fragmentation compared to one nitro group, whereas less fragmentation was noted in molecules with a longer alkyl chain. The most abundant product ions were nitrophenoxy ions, which were also tested in the precursor ion screening of the combinatorial library. In the second study, the immobilized artificial membrane chromatographic method was transferred from ultraviolet detection to mass spectrometric analysis and a new method was developed. Mass spectra were scanned and the chromatographic retention of compounds was analysed using extract ion chromatograms. When changing detectors and buffers and including n-in-one in the method, the results showed good correlation. Finally, the results demonstrated that mass spectrometric detection with gradient elution can provide a rapid and convenient n-in-one method for ranking the lipophilic properties of several structurally diverse compounds simultaneously. In the final study, a new method was developed for caco-2 samples. Compounds were separated by liquid chromatography and quantified by selected reaction monitoring using mass spectrometry. This method was used for caco-2 samples, where absorption of ten chemically and physiologically different compounds was screened using both single and nin- one approaches. These three studies used mass spectrometry for compound identification, method transfer and quantitation in the area of mixture analysis. Different mass spectrometric scanning modes for the triple quadrupole instrument were used in each method. Early drug discovery with n-in-one is area where mass spectrometric analysis, its possibilities and proper use, is especially important.

Internet- ja postikysely osallistavan suunnittelun menetelmänä Puijon metsäsuunnitteluprosessissa

Osallistavan suunnittelun määrä Suomessa on viime vuosina kasvanut huomattavasti. Asukaskyselyt ovat yksi tapa osallistaa asukkaita, ja ne sopivat erityisesti suuren yleisön osallistamiseen. Internetissä toteutetut asukaskyselyt nopeuttaisivat ja helpottaisivat asukaskyselyiden tekemistä mm. siksi, että tieto voidaan tallentaa suoraan sähköiseen muotoon. Internetin käyttö asukaskyselyiden tekemisessä on kuitenkin uusi menetelmä, josta on vasta vähän tutkimustietoa. Ongelmallista Internet-kyselyissä on se, että kasvaneista käyttäjämääristä huolimatta kaikilla ei edelleenkään ole mahdollisuutta käyttää Internetiä. Lisäksi Internet-kyselyn otos on yleensä valikoitunut ja otoskoon määritteleminen on hankalaa. Tutkielma toteutettiin osana Kuopion kaupungin Puijon alueen vuorovaikutteista suunnitteluprosessia. Tutkielman tavoitteena oli vertailla Internet-kyselyä postikyselyyn, jotta saataisiin selville, onko Internet-kysely kelvollinen osallistamismenetelmä. Lisäksi tavoitteena oli profiloida vastaajia mielipiteiden ja taustamuuttujien perusteella. Tutkielman aineistona oli Kuopiossa tammikuussa 2009 toteutetun, Puijon aluetta koskevan asukaskyselyn tulokset. Aineiston analysointiin käytettiin faktorianalyysia, klusterianalyysia, erotteluanalyysia ja korrespondenssianalyysia. Katoa tutkittiin ?2-testillä ja laskemalla ristitulosuhteet. Sekä Internet- että postikyselyn vastaajista muodostuivat Tyytymättömien, Tyytyväisten ja Luonnonsuojelijoiden vastaajaryhmät, joilla olivat melko samanlaiset mielipiteet ja taustamuuttujat molemmissa aineistoissa. Tyytymättömät olivat tyytymättömiä Puijon alueen nykytilaan eivätkä arvostaneet Puijoa. Myös Luonnonsuojelijat olivat tyytymättömiä Puijon alueen ja metsien nykyiseen hoitoon, mutta eivät kannattaneet metsänhoitoa. Tyytyväisten mielestä Puijon alueella kaikki on nyt kunnossa. Lisäksi postikyselyn aineistosta muodostui Kehittäjät-ryhmä ja Internet-kyselyn vastaajista Virkistäytyjät-ryhmä. Internet-kyselyssä 46–60-vuotiaat ja korkeakoulutetut olivat yliedustettuina, mutta kummallakaan kyselyllä ei saatu edustavaa otosta kuopiolaisista. Katoa oli paljon. Edes keskustelua herättänyt aihe ei riittänyt aktivoimaan kuopiolaisia vastaamaan kyselyyn ja tutkielmassa käytettyjen tutkimusmenetelmien kannalta kyselylomake oli puutteellinen. Tämän tutkielman tuloksista saatiin lopulta lähinnä suuntaviivoja Puijon suunnitelmaehdotuksille. Kunnissa tarvitaan uusia työkaluja osallistamiseen, ja tähän tarpeeseen Internet-kysely olisi kustannustehokas vastaus. Sen vuoksi Internet-kyselyä kannattaa edelleen tutkia ja kehittää. Internet-kyselyllä olisi mahdollista saada edustavampi otos, jos vastaajat valittaisiin satunnaisotannalla ja he saisivat salasanan kyselyyn. Myös kaikille avoimella kyselyllä voitaisiin kartoittaa mielipiteitä, kunhan tuloksia tulkittaisiin kriittisesti.

Oncolytic Adenoviruses with Radiation Therapy for Treatment of Prostate Cancer

Prostate cancer is the most common cancer in males. Although many patients with localized disease can be cured with surgery and radiotherapy, advanced disease and especially castration resistant metastatic disease remains incurable, with a median life expectancy of less than 18 months. Oncolytic adenoviruses (Ads) are a new promising treatment against cancer due to their innate capacity to kill cancer cells. Viral replication in tumor cells leads to oncolysis and production of a multiplicity of new virions that are capable of further destroying cancerous tissue. Oncolytic Ads can be modified for tumor targeted infection and replication and be armed with therapeutic transgenes to maximize the oncolytic effect. Worldwide, clinical trials with oncolytic Ads have demonstrated good safety while the antitumor efficacy remains to be improved. Importantly, the best responses have been reported when oncolytic adenoviruses have been combined with standard cancer treatments, such as chemotherapy and radiation. Further, a challenge in many virotherapy approaches has been the monitoring of virus replication in vivo. Reporter genes have been extensively used as transgenes to evaluate the biodistribution of the virus and activity of specific promoters. However, these techniques are often limited to preclinical evaluation and not amenable to human use. The aim of the thesis was to find and develop new oncolytic Ads with maximum efficacy against metastatic, castration resistant prostate cancer and study them in vitro and in vivo combined to different forms of radiation therapy. Using combination therapy, we were aiming for better antitumor efficacy with reduced side effects. Capsid modified Ads for enhanced transduction were studied. Serotype 3 targeted chimera, Ad5/3, was found to have enhanced infectivity for prostate cancer and was used for developing new viruses for the study. Correlation between Ad-encoded marker peptide secretion and simultaneous viral replication was evaluated and the effects of radiotherapy on viral replication were studied in detail. We found that the repair of double strand breaks caused by ionizing radiation was inhibited by adenoviral proteins and led to autophagic cell death. Both subcutaneous models and intrapulmonary tumor models mimicking metastatic, aggressive disease were used in vivo. Virus efficacy was evaluated by intratumoral injections. Also, intravenous administration was evaluated to study the effectiveness in metastatic disease. Oncolytic adenovirus treatment led to significant tumor growth control and increased the survival rate of the mice. These results were further improved when oncolytic Ads were combined with radiation therapy. Oncolytic Ads expressing human sodium/iodide transporter (hNIS) as a transgene were evaluated for their oncolytic potency and for the functionality of hNIS in vitro and in vivo. Monitoring of viral replication was also assessed using different imaging modalities relative to clinical use. SPECT imaging of tumor-bearing mice was evaluated and combined with simultaneous CT-scanning to obtain important anatomical information on biodistribution, also in a three-dimensional form. It was shown that hNIS-expressing adenoviruses could harbour a bi-functional transgene allowing for localization and imaging of viral replication. Targeted radiotherapy was applied by systemic radioiodide administration and resulted in iodide accumulation into Ad-infected tumor. The combination treatment showed significantly enhanced antitumor efficacy in mice bearing prostate cancer tumors. In summary, the results presented above aim to provide new treatment modalities for castration resistant prostate cancer. Molecular insights were provided for better understanding of the benefits of combined radiation therapy and oncolytic adenoviruses, which will hopefully facilitate the translation of the approach into clinical use for humans.

Valittujen makrolidien ominaisuudet ja niiden vaikutukset fermentoinnin jälkeiseen jatkokäsittelyyn

Työn kirjallisessa osuudessa tarkasteltiin makrolideja yleisellä tasolla keskittyen kahden makrolidin ominaisuuksiin molekyylitasolla. Näiden tautomerisoitumista käsitellään tuoden esiin sekä yhdisteiden rakenteelliset yhteneväisyydet ja eroavaisuudet että niiden vaikutukset yhdisteiden vaikutusmekanismiin ja metaboliaan. Kirjallisessa osuudessa perehdyttiin myös makrolidien biosynteesiin ja tuotantoprosessiin keskittyen downstream-prosessointiin ja erityisesti biosynteesistä peräisin oleviin epäpuhtauksiin. Lisäksi kirjallisessa osuudessa käsiteltiin argentaatiokromatografian perusteita. Kokeellisessa osuudessa yhdelle makrolidille kehitettiin argentaatiokromatografiaan perustuva puhdistusmenetelmä. Perinteisillä kromatografisilla menetelmillä yhdistettä ei voida puhdistaa kaikista sen epäpuhtauksista. Makrolidin puhtaus argentaatiokromatografian jälkeen oli 98,6 %. Lisäksi kehitettiin uusi kiteytysmenetlmä, jossa yhdiste kiteytettiin anhydridina tavanomaisen monohydraattimuodon sijasta. Makrolidin analysointiin kehitettiin HPLC-menetelmä, joka validoitiin ICH:n ohjeiden mukaisesti. Yhditeen tautomeerimuodot ja siinä esiintyvät epäpuhtaudet tutkittiin käyttäen LC/MS-analyysia. Yhden epäpuhtauden rakenne varmistettiin eristämisen jälkeen NMR:n avulla. Saatavilla olevien tietojen mukaan yhdisteen tulkittuja NMRspektrejä ei ole julkaistu. Lisäksi aiemmin tuntematon epäpuhtaus identifioitiin perustuen retentioaikaan ja MS-analyysiin.

Alppihiihdon alkutaival : Pujottelu- ja tunturihiihto Suomessa 1920-luvulta 1960-luvulle

The object of study in this thesis is Finnish skiing culture and Alpine skiing in particular from the point of view of ethnology. The objective is to clarify how, when, why and by what routes Alpine skiing found its way to Finland. What other phenomena did it bring forth? The objective is essentially linked to the diffusion of modern sports culture to Finland. The introduction of Alpine skiing to Finland took place at a time when skiing culture was changing: flat terrain skiing was abandoned in favour of cross-country skiing in the early decades of the 20th century, and new techniques and equipment made skiing a much more versatile sport. The time span of the study starts from the late 19th century and ends in the mid-20th century. The spatial focus is in Finland. People and communities formed through their actions are core elements in the study of sports and physical activity. Organizations tend to raise themselves into influential actors in the field of physical culture even if active individuals work in their background. Original archive documents and publications of sports organizations are central source material for this thesis, complemented by newspapers and sports magazines as well as photographs and films on early Alpine skiing in Finland. Ever since their beginning in the late 19th century skiing races in Finland had mostly taken place on flat terrain or sea ice. Skiing in broken cross-country terrain made its breakthrough in the 1920 s, at a time when modern skiing techniques were introduced in instruction manuals. In the late 1920 s the Finnish Women s Physical Education Association (SNLL) developed unconventional forms of pedagogical skiing instruction. They abandoned traditional Finnish flat terrain skiing and boldly looked for influences abroad, which caused friction between the leaders of the women s sports movement and the (male) leaders of the central skiing organization. SNLL was instrumental in launching winter tourism in Finnish Lapland in 1933. The Finnish Tourism Society, the State Railways and sports organizations worked in close co-operation to instigate a boom in tourism, which culminated in the inauguration of a tourist hotel at Pallastunturi hill in the winter of 1938. Following a Swedish model, fell-skiing was developed as a domestic counterpart to Alpine skiing as practiced in Central Europe. The first Finnish skiing resorts were built at sites of major cross-country skiing races. Inspired by the slope at Bad Grankulla health spa, the first slalom skiing races and fell-skiing, slalom enthusiasts began to look for purpose-built sites to practice turn technique. At first they would train in natural slopes but in the late 1930 s new slopes were cleared for slalom races and recreational skiing. The building of slopes and ski lifts and the emergence of organized slalom racing competitions gradually separated Alpine skiing from the old fell-skiing. After the Second World War fell-skiing was transformed into ski trekking on marked courses. At the same time Alpine skiing also parted ways with cross-country skiing to become a sport of its own. In the 1940 s and 1950 s Finnish Alpine skiing was almost exclusively a competitive sport. The specificity of Alpine skiing was enhanced by rapid development of equipment: the new skis, bindings and shoes could only be used going downhill.

Hiippakunta diakoniatyön tekijänä ja tukijana : Diakoniatyön kehitys Mikkelin hiippakunnassa 1945-1991

ABSTRACT The diocese as the agent and advocate of diaconial work. The development of diaconial work in the Mikkeli diocese 1945–1991. The roots of Finnish diacony are in the individual devotional life of Pietism. An acting faith had to be evident in acts of love. Following German institutional diacony, diaconial institutions were established in Finland until congregational diacony emerged alongside these institutions in the 1890s. Pastor Otto Aarnisalo acted as a pathfinder in this. He aimed to unite diacony with the Church and the life of the congregation. Diacony had been based on the idea of volunteering to separate it from statutory social work. In 1944 the church law was amended, which made diacony the concern of every member of the congregation. In the years immediately following the Second World War, discussion took place in the Church of Finland about the direction that diacony should take. In the consequential debate, caritative services overcame social diacony. The diocese administration moved to Mikkeli in 1945, when the majority of the Vyborg diocese became part of the USSR in the armistice negotiations. The Mikkeli diocese acted in its diaconial work with the same objectives as the diaconial solutions of the whole church. The acting principle of the diocese diacony became a form of helping which emphasised assistance of the individual. Especially from the 1960s onwards, the country's industrialisation and the reduction of agricultural trade had an effect on the Mikkeli diocese. The diocese administration, specifically Bishop Martti Simojoki and his successor Osmo Alaja, aimed to open up connections to the political left and people working in industry. At least indirectly this helped the diaconial work in industrial localities. In the Mikkeli diocese, a diaconial committee was established in 1971, and its work was overseen by the diocesan chapter of the bishop's office. This enabled the work of the diocese to be organised for the different areas of diacony. Previously, the diaconial work of the Finnish church had primarily been in nursing. The Health Insurance Law of 1972 brought a change to this when the responsibility for health services was transferred to the municipalities. Diacony began to move towards a psychological and spiritual emphasis. Beginning in the 1970s, the diocese started holding diaconial themed days at prescribed intervals. Although these did not result in great realignments, they did help clarify the direction that diacony would take. Large international collections were also carried out, especially in the 1980s. At the same time, socio-ethical activity vitalised and diversified Christian services. The idea that every member of the congregation should practice diacony was a strong factor in the Mikkeli diocese as well. The diocese's vision for diacony was holistic; Christian service was the responsibility of every member of the congregation. During the period of study (1945–1991), the theology of diacony was rather tenuous. Bishop Kalevi Toiviainen, however, brought forth the viewpoint of church doctrine and officially sanctioned theology. Diacony was part of the complete faith of the Church.

The Protection of Traditional Knowledge Associated with Genetic Resources: The Role of Databases and Registers

"The Protection of Traditional Knowledge Associated with Genetic Resources: The Role of Databases and Registers" ABSTRACT Yovana Reyes Tagle The misappropriation of TK has sparked a search for national and international laws to govern the use of indigenous peoples knowledge and protection against its commercial exploitation. There is a widespread perception that biopiracy or illegal access to genetic resources and associated traditional knowledge (TK) continues despite national and regional efforts to address this concern. The purpose of this research is to address the question of how documentation of TK through databases and registers could protect TK, in light of indigenous peoples increasing demands to control their knowledge and benefit from its use. Throughout the international debate over the protection of TK, various options have been brought up and discussed. At its core, the discussion over the legal protection of TK comes down to these issues: 1) The doctrinal question: What is protection of TK? 2) The methodological question: How can protection of TK be achieved? 3) The legal question: What should be protected? And 4) The policy questions: Who has rights and how should they be implemented? What kind of rights should indigenous peoples have over their TK? What are the central concerns the TK databases want to solve? The acceptance of TK databases and registers may bring with it both opportunities and dangers. How can the rights of indigenous peoples over their documented knowledge be assured? Documentation of TK was envisaged as a means to protect TK, but there are concerns about how documented TK can be protected from misappropriation. The methodology used in this research seeks to contribute to the understanding of the protection of TK. The steps taken in this research attempt to describe and to explain a) what has been done to protect TK through databases and registers, b) how this protection is taking place, and c) why the establishment of TK databases can or cannot be useful for the protection of TK. The selected case studies (Peru and Venezuela) seek to illustrate the complexity and multidisciplinary nature of the establishment of TK databases, which entail not only legal but also political, socio-economic and cultural issues. The study offers some conclusions and recommendations that have emerged after reviewing the national experiences, international instruments, work of international organizations, and indigenous peoples perspectives. This thesis concludes that if TK is to be protected from disclosure and unauthorized use, confidential databases are required. Finally, the TK database strategy needs to be strengthened by the legal protection of the TK itself.