Complement factor H dysfunction in atypical hemolytic uremic syndrome

Alternative pathway (AP) of complement can be activated on any surface, self or non-self. In atypical hemolytic uremic syndrome (aHUS) the AP regulation on self surfaces is insufficient and leads to complement attack against self-cells resulting usually in end-stage renal disease. Factor H (FH) is one of the key regulators of AP activation on the self surfaces. The domains 19 and 20 (FH19-20) are critical for the ability of FH to discriminate between C3b-opsonized self and non-self surfaces and are a hot-spot for mutations that have been described from aHUS patients. FH19-20 contains binding sites for both the C3d part of C3b and self surface polyanions that are needed for efficient C3b inactivation. To study the dysfunction of FH19-20, crystallographic structures of FH19-20 and FH19-20 in complex with C3d (FH19-20:C3d) were solved and aHUS-associated and structurally interesting point mutations were induced to FH19-20. Functional defects caused by these mutations were studied by analyzing binding of the FH19-20 mutant proteins to C3d, C3b, heparin, and mouse glomerular endothelial cells (mGEnCs). The results revealed two independent binding interfaces between FH19-20 and C3d - the FH19 site and the FH20 site. Superimposition of the FH19-20:C3d complex on the previously published C3b and FH1-4:C3b structures showed that the FH20 site on C3d is partially occluded, but the FH19 site is fully available. Furthermore, binding of FH19-20 via the FH19 site to C3b did not block binding of the functionally important FH1-4 domains and kept the FH20 site free to bind heparin or an additional C3d. Binding assays were used to show that FH20 domain can bind to heparin while FH19-20 is bound to C3b via the FH19 site, and that both the FH19 site and FH20 are necessary for recognition of non-activator surfaces. Simultaneous binding of FH19 site to C3b and FH20 to anionic self structures are the key interactions in self-surface recognition by FH and thereby enhanced avidity of FH explains how AP discriminates between self and non-self. The aHUS-associated mutations on FH19-20 were found to disrupt binding of the FH19 or FH20 site to C3d/C3b, or to disrupt binding of FH20 to heparin or mGEnC. Any of these dysfunctions leads to loss of FH avidity to C3b bearing self surfaces explaining the molecular pathogenesis of the aHUS-cases where mutations are found within FH19-20.

Pala kakusta : tulonjaon oikeudenmukaisuus modernissa poliittisessa filosofiassa

Pro gradu -tutkielmani käsittelee tulonjaon oikeudenmukaisuuteen liittyviä kysymyksiä viime vuosikymmenien poliittisessa filosofiassa. Työni tutkimuskohteena ovat erilaiset distribuutiomallit ja redistribuution oikeutus. Lähtökohtanani työssäni toimi John Rawlsin aloittama keskustelu distributiivisesta oikeudenmukaisuudesta. Rawlsin teos A Theory of Justice (1971) toimi modernin tulonjaon oikeudenmukaisuus-keskustelun lähtölaukauksena. Rawlsin näkemyksien pääkommentaattoreina työssäni toimivat G.A Cohen, Robert Nozick, Michael Walzer, Thomas Nagel, Liam Murphy ja Thomas Pogge. Tutkimukseni tarkoituksena on tutkia yhteiskunnallisen tulonjaon oikeudenmukaisuutta. Käsittelen kysymyksiä siitä kuinka yhteiskunnalliset hyvät tulisi jakaa ja millaisia tulisi olla niiden rakenteellisten ratkaisujen, jotka mahdollistavat oikeudenmukai- sen yhteiskunnan. Toinen tärkeä kysymys työssäni on, kuinka voimme oikeuttaa jo kertaalleen jaetun uudelleenjakamisen eli redistribuution, ilman että kajoamme yksilöiden perusoikeuksiin. Tutkin työssäni distribuutioon ja redistribuutioon liittyvien näkemysten suhdetta niihin arvoihin, joita länsimaiset liberalismiin ja demokratiaan sitoutuneet yhteiskunnat korostavat, kuten ihmisten perusoikeudet, riittävä toimeentulo ja vapaus. Millaisilla tulonjakoon liittyvillä keinolla voimme päästä lähemmäksi kyseisten arvoja toteutumista yhteiskunnissamme? Tällöin kuvaan astuu myös kysymys lähtökohtien ja lopputuloksen oikeudenmukaisuuden merkityksestä. Voimmeko muutella toteutettua distribuutiota redistribuution avulla, jos emme saa aikaan niitä tuloksia, joita olimme toivoneet? Työni lopussa kysyn: jos toteamme, että meidän tulisi pyrkiä kohti oikeudenmukaisempaa tulonjakoa kansallisvaltioiden sisällä, niin miten tämän tulisi vaikuttaa näkemyksiimme kansainvälisestä tulonjaosta? Tutkimuksessani selvisi, että on vaikea löytää moraalisia perusteita sille, miksi yhteiskunnissamme ei tulisi pyrkiä kohti tasa- arvoisempaa tulonjakoa. Markkinoiden vapautta ja absoluuttisia omistusoikeuksia korostavilla näkemyksillä ei ole moraalisesti kestäviä perusteita, minkä vuoksi niihin vetoaminen ei ole riittävä syy olla puuttumatta tulonjakoon oikeudenmukaisuuden näkökulmasta. Länsimaisissa yhteiskunnissa arvopohjanamme ovat ihmis- ja kansalaisoikeudet. Samoin on linjattu, että yhteis- kuntaan kuuluu alueita, jotka eivät toimi markkinapohjaisesti. Yhteiskunnan puuttuminen tulonjakoon ei itsessään loukkaa kenenkään perusoikeuksia Redistribuutio on osa samaa prosessia kuin distribuutio. Mitään distribuutiota on vaikea pitää abso- luuttisena, eikä mikään distribuutio pysy muuttumattomana. Näin ollen redistribuutio jatkaa samaa oikeudenmukaisen jaon pyrkimystä, mikä ilmeni aikaisemmassa jaossa. Asioiden uudelleenjakaminen hyvästä syystä ei ole itsessään moraalisesti kestämätöntä. Verotusta on vaikea pitää moraalisena ongelmana, sillä verotus linkittyy yhteiskunnissamme samaan rakenteeseen kuin omistusoikeudet. Näin ollen samalla kun yhteiskunta takaa omistusoikeudet, se varaa myös oikeuden puuttua tulonjakoon.

Tyttöjen kesken : Monikulttuurisuus ja sukupuolten tasa-arvo nuorisotyössä.

Among Girls Youth Work, Multiculturalism and Gender Equality Finland s increasingly multicultural society concerns younger generations in a very particular manner. Starting already in pre-school kindergartens, children from different cultural backgrounds share their everyday existence. The focus of this study is Finland s increasingly multicultural society that has challenged youth work professionals in particular and made them rethink questions related to content, basic values and goals of youth work. These reconsiderations include the following essential questions: which of these pedagogic principles are defined as Finnish, and under what kinds of circumstances would the youth workers be ready to negotiate about them. These questions, which are related to multiculturalism, are then linked to the girls position, status and gender equality. The research examines how gender equality is articulated in relation to multiculturalism and vice versa, in what contexts youth work-related questions are negoatiated in, and how these negotiations then relate to gender issues. The present study combines theoretical concepts and debates from both post-colonial and youth research, and has benefited greatly from previous research which has examined the everyday lives of young people with multicultural backgrounds and conceptualised the different meanings of age, ethnicity, culture and gender. Neither multiculturalism nor gender equality is, however, taken as a given concept in this study; rather the research focuses on how youth workers understand and define these concepts and how they are used. The emphasis has been on monitoring the varying consequences of different understandings and definitions in terms of everyday work and practices. The goal of this study has been to find typical ways of conceptualising multiculturalism, gender equality and the role of girls in the context of youth work. The focus of the research is not just the youth workers different views but also the notions of the girls themselves. These are then further analysed by examining the ways the girls negotiate their agency. Examples of how the girls agency is defined and the different forms of agency that are offered to the girls within the context of leisure time activities and youth work have been sought. The kind of agency the girls then assume is also examined. The data in this research is comprised of interviews with young people with multicultural backgrounds (n=39), youth workers (n=42) and of ethnographic fieldwork (2003 2005). The fieldwork concentrated on following different types of youth work activities that were targeted at girls with migrant backgrounds. These were organized both by selected municipalities and NGOs. The research shows that various questions related to multicultural issues have enhanced the visibility of gender equality in the field of youth work. The identification of gender-based inequality is especially closely linked to the position of girls from migrant backgrounds. These girls are a source of particular worry and the aim of the many activity groups for migrant girls is to educate them so that they can become equal Finnish citizens . The youth work itself is seen as gender-neutral and equality based. Equality in this context is defined as a purely quantitative concept, and the solution to any possible inequalities is thus the exact same treatment for everyone . The girls themselves seem mainly confused by the role that is offered to them. They would need a voice and the possibility to have an impact on the planning of youth work activities. They want to have their views heard. The role of the victim assigned to them is very confining and makes it difficult to act. At the same time the research shows how gender-sensitive youth work is seen to mean youth work with girls. Gender-sensitive work with boys is not really done or is done very little, even if many of the interviewees are of the opinion that the true materialization of gender equality would require boys to be taken into account too. The principle of gender equality should be shared by the entire youth work profession. Keywords Youth work, equality, multiculturalism, gender sensitivity, agency, girls, young people, sexuality

Runsasrasvaisen- ja vähärasvaisendieetin sekä kalorirajoituksen ja resveratrolin vaikutus SIRT1–proteiinin määrään hiirten sydämissä ja maksoissa

Lihavuus on kasvava ongelma länsimaissa. Siihen liittyy useita metabolisia muutoksia, jotka johtavat erilaisiin kohde-elinvaurioihin. Vaurioiden mekanismien tunnistaminen on tärkeää, jotta niiden ehkäisyyn voidaan kehittää uusia elintapa- ja lääkehoitoja. Tämän tutkimuksen tarkoituksena oli selvittää ravinnon rasvamäärän, resveratrolin ja kalorirajoituksen vaikutuksia hiirten sydämissä ja maksoissa sekä määrittää näiden vaikutus SIRT1 – proteiinin määrään kyseisissä kudoksissa. Tutkimuksessa vertailtiin Western Blot – menetelmän avulla SIRT1:n pitoisuutta hiirten sydämissä ja maksoissa. SIRT1:n lokalisaatio osoitettiin immunohistokemiallisen värjäyksen avulla. Sydänlihassolujen hypertrofiaa arvioitiin mikroskoopin avulla HE – värjätyistä leikkeistä. Resveratrolin vaikutus sydänlihassolujen hypertrofian asteeseen jäi vähäiseksi. Kalorirajoitus lisäsi SIRT1:n määrää sekä sydämessä että maksassa ja esti sydänlihassolujen hypertrofian. Tutkimus tarjoaa hyvän pohjan selvittää laajemmin resveratrolin vaikutusta SIRT1:n aktivaatioon ja sitä kohde-elinvaurioiden estoon.

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

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

Governance theory as a framework for empirical research : a case study on local environmental policy-making in Helsinki, Finland

Governance has been one of the most popular buzzwords in recent political science. As with any term shared by numerous fields of research, as well as everyday language, governance is encumbered by a jungle of definitions and applications. This work elaborates on the concept of network governance. Network governance refers to complex policy-making situations, where a variety of public and private actors collaborate in order to produce and define policy. Governance is processes of autonomous, self-organizing networks of organizations exchanging information and deliberating. Network governance is a theoretical concept that corresponds to an empirical phenomenon. Often, this phenomenon is used to descirbe a historical development: governance is often used to describe changes in political processes of Western societies since the 1980s. In this work, empirical governance networks are used as an organizing framework, and the concepts of autonomy, self-organization and network structure are developed as tools for empirical analysis of any complex decision-making process. This work develops this framework and explores the governance networks in the case of environmental policy-making in the City of Helsinki, Finland. The crafting of a local ecological sustainability programme required support and knowledge from all sectors of administration, a number of entrepreneurs and companies and the inhabitants of Helsinki. The policy process relied explicitly on networking, with public and private actors collaborating to design policy instruments. Communication between individual organizations led to the development of network structures and patterns. This research analyses these patterns and their effects on policy choice, by applying the methods of social network analysis. A variety of social network analysis methods are used to uncover different features of the networked process. Links between individual network positions, network subgroup structures and macro-level network patterns are compared to the types of organizations involved and final policy instruments chosen. By using governance concepts to depict a policy process, the work aims to assess whether they contribute to models of policy-making. The conclusion is that the governance literature sheds light on events that would otherwise go unnoticed, or whose conceptualization would remain atheoretical. The framework of network governance should be in the toolkit of the policy analyst.

Luomu – ja Reilun kaupan kuluttajien käsityksiä eettisestä ruoan kuluttamisesta

Työn tavoitteena oli kuvata ja analysoida eettisen ruoan kuluttamisen käsitettä luomu – ja Reilun kaupan kuluttajien näkökulmasta. Mielenkiintona oli selvittää, mitä eettisessä ruoan kuluttamisessa koetaan merkitykselliseksi ja mitä ovat eettiset ruokavalinnat. Lisäksi haluttiin selvittää, millä tapaa eettisinä juuri luomu – ja Reilun kaupan tuotteet näyttyivät. Aihetta lähestyttiin tutkielman kirjallisuusosiossa etiikan teorioiden kautta sekä luomalla katsaus eettisen kuluttamisen eri osa-alueisiin eli eettisiin ulottuvuuksiin. Tämä jälkeen keskityttiin eettiseen ruoan kuluttamiseen ja luomu ja Reilun kaupan tuotteiden eettisyyteen vertailevasta näkökulmasta. Kirjallisuuskatsauksen perusteella hahmoteltiin teoreettinen viitekehys, jossa kuvattiin eettisen ruoan kuluttamisen sisältöä ja merkitystä, sekä niiden yhteyttä ruokavalintoihin. Empiirinen aineisto kerättiin keväällä 2010 teemahaastatteluina, joissa haastateltiin 12 luomu- ja Reilun kaupan kuluttajaa. Haastatteluaineisto analysoitiin ja luokiteltiin fenomenografisella menetelmällä. Tutkimuksen tulokset, käsitykset eettisestä ruoan kuluttamisesta esitettiin kuvauskategoriasysteeminä. Eettinen ruoan kuluttaminen näyttäytyi, kuten aikaisemmissa tutkimuksissa, altruistisena välittämisenä niin muista ihmisistä, eläimistä kuin ympäristöstä, mutta voimakkaasti myös kuluttajan ja tämän perheen terveydestä ja turvallisuudesta huolehtimisena. Näistä käsityksistä seuranneet ruokavalinnat olivat lähiruoka, luomu – ja Reilun kaupan tuotteet sekä kasvis- tai kasvispainotteinen ruoka. Näistä korostuneimman eettisenä koettiin lähiruoka. Luomutuotteet puolestaan koettiin pääasiallisesti eettisenä terveyden kannalta ja Reilun kaupan tuotteet muiden ihmisten hyvinvoinnin kannalta. Edellä kuvattujen käsitysten ohella merkittäväksi tulokseksi nousi käsitys eettisestä ruoan kuluttamisesta vapaaehtoisena yksinkertaistamisena, tai ainakin pyrkimyksenä siihen. Yksinkertaistaminen näyttäytyi eriasteisena oman ruoan kulutuksen kohtuullistamisena ja jopa luopumisena omasta mielihyvästä eettisten periaatteiden takia.

Sex steroids in Sjögren's syndrome

Sjögren s syndrome (SS) is a strongly female dominant autoimmune disease. SS targets mainly salivary and lacrimal glands and leads to loss of the secreting acinar cells of these glands. Accordingly, secretion of the affected glands is diminished and the main symptoms of SS, dryness of mouth and eyes, follow. In addition to these sicca symptoms, SS patients suffer from severe fatigue and can have various extraglandular symptoms. To date, the etiology of SS still remains unknown. Female dominance and the late onset of the disease simultaneously with remarkable hormonal changes in the body (menopause, adrenopause) encouraged us to hypothesize that sex steroids, especially androgens, are involved in the onset and progression of SS. We confirmed our hypothesis and showed that patients with SS suffer from androgen depletion both systemically and locally in the target tissue of SS, salivary glands. We especially focused on the local androgen environment in salivary glands and demonstrated that healthy salivary glands contain a complete enzymatic machinery for local synthesis of androgens and estrogens from pro-hormone dehydroepiandrosterone (DHEA). However, in SS salivary glands the enzymes catalyzing the local androgen synthesis are defective and, in a subgroup of patients, practically non-functional. Probably due to this local defect in DHEA processing, therapy with DHEA was found unbeneficial for SS patients in the treatment of fatigue. We also studied the effect of the local androgen depletion on salivary glands. We found that in salivary gland cells and healthy labial salivary glands androgens upregulate integrin subunits α1 and α2, which are important for the communication, differentiation and function of the acinar cells. On the contrary, in SS salivary glands DHEA failed to upregulate these signaling molecules, again probably due to defective processing of DHEA into active androgens. Our finding highlights the importance of the local androgen environment and local DHEA processing for the function and welfare of salivary glands. In conclusion, this study showed that patients with SS are androgen depleted both systemically and locally in salivary glands. SS patients also have a defective local sex steroid synthesizing enzymatic machinery further impairing the local androgen depletion. We also showed that the local androgen defect leads to decreased expression of acinar cell specific integrin molecules, which impairs the signaling between the acinar cells and basement membrane and might thus explain the acinar cell loss seen in SS salivary glands. By showing the importance of the local sex steroid imbalance in SS we have clarified some etiopathogenetic mechanisms of SS, which have thus far remained unknown.

Henkilökunnan päihdeongelmat leikkaus- ja teho-osastoilla Suomessa

Anestesiahenkilökunnalla on useissa kansainvälisissä tutkimuksissa todettu esiintyvän enemmän päihteiden väärinkäyttöä kuin muilla erikoisaloilla. Tämän on arveltu johtuvan lääkkeiden helposta saatavuudesta, työn stressaavuudesta tai tahattomasta altistumisesta leikkaussalissa höyrystyneille lääkeaineille. Suomalaisia tutkimuksia aiheesta ei ole julkaistu. Tutkielman tarkoituksena on selvittää sähköpostikyselyiden ja asiantuntijahaastatteluiden avulla henkilökunnan päihdeongelmien yleisyyttä Suomen leikkaus- ja teho-osastoilla. Tavoitteena on myös saada tietoa muun muassa väärinkäytetyistä aineista, ovatko väärinkäyttäjät saaneet hoitoa ongelmaansa ja ovatko he myöhemmin pystyneet palaamaan entiseen työhönsä. Saatujen tulosten mukaan Suomen leikkaus- ja teho-osastojen henkilökunnalla ei näyttäisi esiintyvän sen enempää päihdeongelmia kuin väestössä keskimäärin. Alkoholi on selvästi yleisimmin väärinkäytetty aine, mutta myös opioidien ja bentsodiatsepiinien väärinkäyttöä esiintyy. Huolestuttavaa on, että vaikka suurin osa väärinkäyttäjistä sai hoitoa ongelmaansa, heistä vain kolmasosa pystyi palaamaan entiseen työhönsä ongelmitta. Tutkielmaa käytetään hyväksi Huume- ja päihdetyöryhmän työskentelyssä ja loppuraportissa. Alkuvuodesta 2011 ilmestyvässä loppuraportissa on toimenpide-ehdotuksia, joiden avulla leikkaus- ja teho-osastoilla voidaan ennaltaehkäistä henkilökunnan päihdeongelmia sekä lääkeainevarkauksia.

Prosopis, an Alien among the Sacred Trees of South India

The problematic of invasive species in an alien environment has aroused the attention of scientists all over the world for quite some time. One of the exotic tree species that has provoked special attention in the tropical drylands is Prosopis juliflora. Originating in South America, prosopis (hereafter referred to as prosopis) has been introduced in the hot and semi-arid zones of the world particularly to provide fuelwood, to stabilize sand dunes and to combat desertification. The tree has become an essential source for fuelwood and a provider of several other products and services in areas where it has become established. However, despite the numerous benefits the tree provides to rural people, in several regions prosopis has become a noxious weed with a negative impact on the environment and to the economy of farmers and landowners. In India, prosopis was introduced in Andhra Pradesh in 1877. The tree was then proclaimed as the precious child of the plant world by scientists and local people alike. The purpose of this study was to investigate the overall impact of prosopis on local rural livelihoods in the drylands of South India. Of particular interest was the examination of the different usages of the tree, especially as fuelwood, and people s perceptions of it. Furthermore, the study examined the negative impacts of the uncontrolled invasion of prosopis on croplands, and its occupation of the banks of irrigation canals and other water sources. As another central theme, this study analysed the Hindu classification system for nature and for trees in particular. In India, several tree species are regarded as sacred. This study examined the position of the exotic prosopis among sacred trees, such as the bodhi, banyan and neem trees. The principle method for collecting the field data was by using individual and thematic group interviews. These interviews were semi-structured with open ended questions. Moreover, unstructured interviews as well as general observations provided complementary information. The data were gathered during two fieldwork periods in the states of Andhra Pradesh and Tamil Nadu, in South India. The results confirmed that prosopis both provides benefits and causes hazards to different stakeholders. Farmers and agriculturalists suffer economic losses in areas where prosopis has invaded crop fields and competes with other plants for water and nutrients. On the other hand, for a significant number of poor rural people, prosopis has become an important source of livelihood benefits. This tree, which grows on government wastelands, is commonly a free resource for all and has thus become a major local source of fuelwood. It also provides several other goods and services and cash income that contributes to improve livelihoods in rural communities. Prosopis ranked lowest in the tree classificatioin system of the Hindus of South India. Although it is appreciated for many benefits it provides for poor people, it has remained an outsider compared with the indigenous tree species. On the other hand, the most sacred trees, such as the bodhi or the banyan, are completely excluded from extraction and it is seen as a sacrilege to even cut branches from any of these trees. An unexpected finding was that, in a few cases, prosopis had also been elevated to the status of a sacred tree. Goods and services from prosopis are not utilized in the most beneficial way. Silvicultural management practices are suggested that would provide additional income and employment opportunities. Interventions are recommended to control further invasion of the tree that might cause serious negative effects in the future. For Hindus, the sacred always ranks highest, even above economic gain. The conservation of sacred groves and sacred trees is a tradition that has its roots in ancient history. These socio-religious practices need to be respected and continued. Successful management of tree and forest resources depends on the willingness of the local people to manage their natural resources, and this willingness exists and has always existed in South India. Keywords: South India, drylands, livelihood, fuelwood, invasive, resource, silviculture.

Henkilöstöjohtamisen tehostaminen valtionhallinnossa henkilöstötilinpäätös-informaation avulla. Empiirinen tutkimus Suomen valtionhallinnossa tuotettavan henkilöstötilinpäätösinformaation arvosta johtamisessa

Tutkimuksessa selvitetään, edistääkö Suomen valtionhallinnossa tuotettava henkilöstötilinpäätösinformaatio henkilöstöprosesseihin perustuvan henkilöstöstrategian tehokasta toteuttamista. Tutkimuksen uutuusarvo alan kansainvälisen tutkimuksen kentässä perustuu laaja-alaiseen tarkastelunäkökulmaan. Tämän mahdollisti tutkimuskohteena olevasta ilmiöstä käytössä oleva monipuolinen, yhtenäisiin käsitteisiin perustuva ja useita vuosia koskeva henkilöstötilinpäätöksen tunnuslukuaineisto. Aikaisempien tutkimusten usein yksittäisiin tekijöihin perustuvasta analyysistä poiketen, tutkimuksella selvitettiin henkilöstön johtamiseen ja tuloksellisuuteen sidoksissa olevien tekijöiden vaikutuksia laajoina kokonaisuuksina, koskien kaikkia henkilöstön johtamisprosesseja. Tutkimus avaa uusia näköaloja henkilöstöinformaation hyväksikäytölle henkilöstön eri johtamisprosesseissa, jotka liittyvät saumattomasti organisaation toimintaan ja kokonaisjohtamiseen. Käytetty henkilöstön johtamisprosessikeskeinen tarkastelukulma auttaa ymmärtämään henkilöstön osaamisen, motivaation, työhyvinvoinnin, johtamisen ja palkinnan yhteyksiä sekä toisiinsa että organisaation pitkäjänteiseen toimintaan ja tuloksellisuuteen. Tutkimuksen keskeinen tavoite on motivoida johtoa, esimiehiä ja HR -ammattilaisia entistä enemmän hyväksikäyttämään henkilöstöön liittyvää analysoitua tietoa henkilöstöstrategioiden teon ja käytäntöön viennin, johtamisen ja henkilöstösuunnittelun apuvälineenä.

Molecular characterization of sediment bacterial communities affected by fish farming

Fish farming introduces nutrients, microbes and a wide variety of chemicals such as heavy metals, antifoulants and antibiotics to the surrounding environment. Introduction of antibiotics has been linked with the increased incidence of antibiotic resistant pathogenic bacteria in the farm vicinities. In this thesis molecular methods such as quantitative PCR and DNA sequencing were applied to analyze bacterial communities in sediments from fish farms and pristine locations. Altogether four farms and four pristine sites were sampled in the Baltic Sea. Two farm and two pristine locations were sampled over a surveillance period of four years. Furthermore, a new methodology was developed as a part of the study that permits amplifying single microbial genomes and capturing them according to any genetic traits, including antibiotic resistance genes. The study revealed that several resistance genes for tetracycline were found at the sediment underneath the aquaculture farms. The copy number of these genes remained elevated even at a farm that had not used any antibiotics since year 2000, six years before this study started. Similarly, an increase in the amount of mercury resistance gene merA was observed at the aquaculture sediment. The persistence of the resistance genes in absence of any selection pressure from antibiotics or heavy metals suggests that the genes may be introduced to the sediment by the farming process. This is also supported by the diversity pattern of the merA gene between farm and pristine sediments. The bacterial community-level changes in response to fish farming were very complex and no single phylogenetic groups were found that would be typical to fish farm sediments. However, the community structures had some correlation with the exposure to fish farming. Our studies suggest that the established approaches to deal with antibiotic resistance at the aquaculture, such as antibiotic cycling, are fundamentally flawed because they cannot prevent the introduction of the resistance genes and resistant bacteria to the farm area by the farming process. Further studies are required to study the entire fish farming process to identify the sources of the resistance genes and the resistant bacteria. The results also suggest that in order to prevent major microbiological changes in the surrounding aquatic environment, the farms should not be founded in shallow water where currents do not transport sedimenting matter from the farms. Finally, the technique to amplify and select microbial genomes will potentially have a considerable impact in microbial ecology and genomics.

Moral Professionalism in Interaction : Educators' Relational Moral Voices in Urban Schools

The aim of this study was to investigate educators relational moral voices in urban schools and to listen to what they told about moral professionalism and moral practices in challenging urban schools. Their relational moral voices were investigated through the following three questions: 1. What are the educators moral voices in relation to themselves and other people? 2. What are the educators moral voices in relation to their work and society? 3. What kind of interaction process lies between the educators moral voices and the urban school context? The research data of this study were gathered in four urban schools in Jyväskylä and Helsinki. The research schools were chosen for this study according to the criteria of the international Socrates Comenius project called Leading Schools Successfully in Challenging Urban Context: Strategies for Improvement. This study formed part of this project, which investigated successful urban schools as challenging learning environments in nine European countries and explored the principals success in leadership in particular. The data, which included 37 narratively constructed interviews with four principals and key informants selected by the principals, were gathered in interviews conducted in 2006. In other words, the data comprised three interviews with each of four principals, and interviews with two teachers, two parents, and two pupils from each school. In addition, the school deacon from one school was also interviewed. Furthermore, part of the data from one of the research schools included a medium report of the school deacon s work. This study combined the case study method, the narrative approach and the critical incident technique as the methodological framework. In addition, all of these methods served as practical tools for both analyzing and reporting the data. The educators' narrations and the results of the study appear in the original articles (Hanhimäki & Tirri 2008; Hanhimäki 2008b; Hanhimäki & Tirri 2009; Hanhimäki 2008a). The educators moral voices in relation to themselves and other people emerged through the main themes of moral leadership, the development and evaluation process, moral sensitivity, gender, values, and student well-being. The educators moral voices in relation to their work and society emerged through the main themes of multiprofessional cooperation, families and parental involvement, and moral school culture. The idea of moral interaction connected moral professionalism and the methodological combination of this study, which together emphasized social interaction and the creation of understanding and meaning in this interaction. The main point of this study was to state that the educators moral voices emerged in the interaction between the educators themselves and the urban school context. In this interaction, the educators moral professionalism was constructed and shaped in relation to themselves, other people, their work and society. The loudest relational moral voices heard through the main themes were those of caring, cooperation, respect, commitment, and professionalism. When the results were compared to the codes of ethics which guided these educators moral professional work, the ethical principles and values of the codes were clearly visible in their moral practices. The loudest message from the educators narration could be summarized in the words caring, respect and cooperation: at its best, there is just a human being and a human being with caring, respect and cooperation between them. The results of this study emphasize the need for practical approaches such as case studies and the narrative approach in teacher education to encourage educators to become moral professionals capable of meeting the needs of people of varied backgrounds. In addition, opportunities for moral, religious and spiritual education should be noticed and utilized in the plural interaction of urban schools when nurturing pupils and creating a moral school culture. Furthermore, multiprofessional cooperation and parents as the school s primary cooperation partner are needed to carry out the shared duty of moral education in urban schools. Keywords: moral professionalism, educator, relational moral voice, interaction, urban school

Grönlannin mannerjäätikön tulevaisuus: merenpinnan nousu maailmanlaajuisesti ja Itämerellä

Sea level rise is among the most worrying consequences of climate change, and the biggest uncertainty of sea level predictions lies in the future behaviour of the ice sheets of Greenland and Antarctica. In this work, a literature review is made concerning the future of the Greenland ice sheet and the effect of its melting on Baltic Sea level. The relation between sea level and ice sheets is also considered more generally from a theoretical and historical point of view. Lately, surprisingly rapid changes in the amount of ice discharging into the sea have been observed along the coastal areas of the ice sheets, and the mass deficit of Greenland and West Antarctic ice sheets which are considered vulnerable to warming has been increasing from the 1990s. The changes are probably related to atmospheric or oceanic temperature variations which affect the flow speed of ice either via meltwater penetrating to the bottom of the ice sheet or via changes in the flow resistance generated by the floating parts of an ice stream. These phenomena are assumed to increase the mass deficit of the ice sheets in the warming climate; however, there is no comprehensive theory to explain and model them. Thus, it is not yet possible to make reliable predictions of the ice sheet contribution to sea level rise. On the grounds of the historical evidence it appears that sea level can rise rather rapidly, 1 2 metres per century, even during warm climate periods. Sea level rise projections of similar magnitude have been made with so-called semiempirical methods that are based on modelling the link between sea level and global mean temperature. Such a rapid rise would require considerable acceleration of the ice sheet flow. Stronger rise appears rather unlikely, among other things because the mountainous coastline restricts ice discharge from Greenland. The upper limit of sea level rise from Greenland alone has been estimated at half a metre by the end of this century. Due to changes in the Earth s gravity field, the sea level rise caused by melting ice is not spatially uniform. Near the melting ice sheet the sea level rise is considerably smaller than the global average, whereas farther away it is slightly greater than the average. Because of this phenomenon, the effect of the Greenland ice sheet on Baltic Sea level will probably be rather small during this century, 15 cm at most. Melting of the Antarctic ice sheet is clearly more dangerous for the Baltic Sea, but also very uncertain. It is likely that the sea level predictions will become more accurate in the near future as the ice sheet models develop.

Estramustine and its Derivatives in Potentiating Radiotherapy of Prostate Cancer

The purpose of this study was to deepen our knowledge of the combined use of estramustine and radiotherapy in the treatment of prostate cancer. Prostate cancer is a common disease, with a high variability between subjects in its malignant potential. In many cases, the disease is an incidental finding with little or no clinical significance. In other cases, however, prostate cancer may be an aggressive malignant disease, which, if the initial treatment fails, lacks an effective cure and may lead to severe symptoms, metastasis, and death despite all treatment. In many cases, the methods of treatment available at the moment provide cure or significant regression of symptoms, but often at the cost of considerable side effects. Estramustine, a cytostatic drug used for treating advanced cancer of the prostate, has been shown to inhibit prostate cancer progression and also to increase the sensitivity of cancer cells to radiotherapy. The goals of this study were, first, to find out whether it is possible to use either estramustine or an antibody against estramustine binding protein as carrier molecules for bringing therapeutic radioisotopes into prostate cancer cells, and, secondly, to gain more understanding of the mechanisms behind the known radiosensitising effect of estramustine. Estramustine and estramustine binding protein antibody were labelled with iodine-125 to study the biodistribution of these substances in mice. In the first experiment, both of the substances accumulated in the prostate, but radioiodinated estramustine also showed affinity to the liver and the lungs. Since the radiolabelled antibody was found out to accumulate more selectively to the prostate, we studied its biodistribution in nude mice with DU-145 human prostate cancer implants. In this experiment, the prostate and the tumour accumulated more radioactivity than other organs, but we concluded that the difference in the dose of radiation compared to other organs was not sufficient for the radioiodinated antibody to be advocated as a carrier molecule for treating prostate cancer. Mice with similar DU-145 prostate cancer implants were then treated with estramustine and external beam irradiation, with and without neoadjuvant estramustine treatment. The tumours responded to the treatment as expected, showing the radiation potentiating effect of estramustine. In the third experiment, this effect was found without an increase in the amount of apoptosis in the tumour cells, despite previous suggestions to the contrary. In the fourth experiment, we gave a similar treatment to the mice with DU-145 tumours. A reduction in proliferation was found in the groups treated with radiotherapy, and an increased amount of tumour hypoxia and tumour necrosis in the group treated with both neoadjuvant estramustine and radiation. This finding is contradictory to the suggestion that the radiation sensitising effect of estramustine could be attributed to its angiogenic activity.