349 resultados para ihmisen suolistobakteeristo
Resumo:
The parenthood experience of a mother with a disabled child and the meaning of the social environment and parent-professional partnerships The importance of parental guidance when a family has a child with a disability or autism has been pointed out by several studies. The present research was based on the premise that by supporting the mother we can help the whole family to cope better and the professionals in day care or at school are able to support parents. The starting point was the subjective experience, which is also the central focus of the phenomenological method. The purpose of this study was firstly to describe the experience of the mother and the dialogue between mother and educational professionals. Secondly it was the task of this research to discover what kind of support and information the mother obtains from her social environment. At the background of this study there was the ecological theory of Bronfenbrenner, the ecocultural approach by Gallimore and the interactive examination of family that take into consideration the whole environment and personal situation. The research data was collected by interviewing the mothers, the day care personnel and the teachers at school. In this research there were a total of 32 interviews and 24 informants: 10 mothers who have a child with a disability and/or autism, 8 professionals in day care and 6 teachers at school. This study was longitudinal because the same mothers were interviewed twice, first in 1998 and then after five years in 2003. It was thus possible to get information on whether their life situation had changed and the nature of those changes. The data of this study was analysed by the method of phenomenological psychology that was applied for this study. The findings indicated that all mothers had experienced many complicated emotional feelings such as: anger, mourning, fear and sadness as well as love and bonding. It can be said that several human feelings existed at the same time. Mothers experienced that the support of the social environment, for example, relatives, families in the same situation and persons taking care of the child had significant meaning for their coping. However the life situation among the mothers varied. Mostly mothers received valuable support for their parenthood and they have adopted a strong emotion for manage ring. Mothers with an autistic child were more stressed than mothers with a mentally retarded child. A few mothers had numerous problems with taking care of their child and they did not get enough help. Same mothers were very exhausted too and the situation was quite the same after five years, when their child was teenager. All mothers said that after starting school the support for the family had significally diminished. Mothers said that dialogue with teacher got on without problems, but there were meetings seldom, so it wasn´t possible to get enough support for their parenthood. Keywords: parenthood, motherhood, disability, early special education, family-centred.
Resumo:
Tutkimuksessa analysoidaan teoriatasolla web-avusteisen tiedontuottamisyhteistyön kokeilutoiminnassa esiin tulleita ongelmia ja kootaan niiden viitoittamana teoriaperustaa tulevaisuuden työskentelytavalle, tietämyksen web-avusteiselle ryhmäprosessoinnille. Keskiössä on ihminen kognitiivisena tiedonkäsittelijänä ja elinikäisenä oppijana. Organisaatiossa vallitsevat toimintastrategiat, ryhmätyöskentelyn organisointi ja ryhmässä toteutuvat käytännöt muodostavat yksilön toimintaa ohjaavan sosiaalisen toimintaympäristön, joka säätelee yhteistyöprosessin onnistumista. Yhteistyötä tarkastellaan sosiaalisen tiedonkäsittelyn ryhmäilmiönä, jossa käsite yhteistyökyky kyseenalaistuu. Tuotetussa teoriaperustassa ihminen nähdään monitasoisten oppimishaasteiden ristitulessa. Koulutuksessa vallitseva absoluuttinen tietokäsitys on pystyttävä muuttamaan konstruktivistiseksi tietokäsitykseksi: yhteistä tietämystä ryhmänä tuotettaessa yksilöiden tietämys on rakennusaineena. Koulussa saatu sosiaalisen tiedonkäsittelyn malli, itsekeskeisen tiedonkäsittelyn malli, ei sovellu tietämyksen ryhmäprosessointiin. Malliin liittyviä oppeja on poisopittava samalla kun ryhmäjäsenenä on suunniteltava ja yhdessä opeteltava ryhmäkeskeisiä ja web-avusteisia tiedonkäsittelymalleja. Näin yhteistyöprosessissa toteutuu rinnakkain asiaoppimista ja toimintaoppimista. Näitä molempia on tarpeen tukea kehitettäessä uudenlaisia web-avusteisia työskentelymenetelmiä. Osassa I esitellään tutkimuksen kokemusperäisiä virikkeitä. Suhteellisen tietokäsityksen mukaisesti tämä tutkimus on kiinteästi kytkeytynyt tutkijan elinikäiseen oppimiseen ja tutkimus kuvataan tutkijan yksilöllisen tietämyksen prosessointina. Tutkimusaiheen löytymiseen johtaneet käytännön havainnot aloittavat sen takia raportoinnin. Erityisesti koulun sosiaalisen tiedonkäsittelyn organisointi on tarkastelun kohteena. Osassa II hahmotetaan tutkimusnäkökulmaa. Tutkimuskysymykset ovat lähinnä viitoittamassa tietämyksen etsintää. Tutkimusmenetelmä, kokeilutoiminnan analysointi, on saanut vahvasti vaikutteita toimintatutkimuksesta. Tutkimusasetelman perustana on toimintaan kytkeytyvä ihmiskäsitys. Kirjallisuuden avulla etsitään mahdollisia kytkeytymiä ihmisen käyttäytymisen ja sosiaalisen toiminnan organisoinnin välillä. Osa III kuvailee tutkimusaihetta koskevan ymmärryksen prosessointia. Esiymmärrys yhteistyöstä ja yhteistyökäsitteen määrittely mahdollistavat kokeilutoimintaan ryhtymisen. Uusi viestintämahdollisuus (www) nähdään yhteisessä tiedonkäsittelyssä apuvälineenä. Käytännön kokeilujaksot tarjoavat aineksia kognitiivisen tiedonkäsittelyn syvällisten periaatteiden löytymiselle. Inhimillinen toiminta ja sosiaalinen tiedonkäsittely saavat teoriatason analysoinnissa oppimiseen perustuvia tulkintoja. Osassa IV esitellään tutkimuksen tavoitteena ollutta teoriaperustaa tietämyksen web-avusteiselle ryhmäprosessoinnille. Teoriatiivistelmässä keskiöön nousee ihmisen kognitiivinen tiedonkäsittely sekä konstruktivistisen asiaoppimisen että selviytymispainotteisen toimintaoppimisen muodossa. Sosiaalinen toimintaympäristö nähdään osallisena kognitiivisessa tiedonkäsittelyssä ja selityksenä sille, että yhteinen tiedonkäsittely ei onnistu pelkästään tietoverkkoympäristössä vaan tarvitaan myös sosiaalisia tapaamisia. Kokeilutoiminnan opetuksia tuodaan esille yhteistyöprosessin keskeisten tapahtumien tarkastelussa. Tuotettua teoriaperustaa koetellaan tieteen kentällä vertailemalla sitä muiden tutkijoiden julkaisemiin käsityksiin. Tietoverkkoteknologian suhdetta inhimilliseen tiedonkäsittelyyn verrataan muualla saatuihin ja julkaistuihin käsityksiin. Avainsanat: tietointensiivinen yhteistyö, tiedontuottamisyhteistyö, yhteistyöprosessi, yhteistyökyky, yhteistyökyvyttömyys, virtuaalinen yhteistyöorganisaatio, yksilöllinen tietämys, yhteisen ymmärryksen etsintä, yhteinen tietämys, kognitiivinen tiedonkäsittely, asiaoppiminen, toimintaoppiminen, sosiaalinen tiedonkäsittely, sosiaalinen toimintaympäristö, automatisoitunut toimintamalli, yksilökeskeinen toimintamalli, itsekeskeinen toimintamalli, ryhmäkeskeinen toimintamalli, sosiaalisen tiedonkäsittelyn toimintastrategia, työympäristössä oppiminen.
Resumo:
Tutkimus käsittelee verkko-opetusinnovaation leviämistä perusasteen ja lukion maantieteeseen vuosina 1998–2004. Työssä sovellettiin opetusinnovaation leviämismallia ja innovaatioiden diffuusioteoriaa. Aineisto hankittiin seitsemänä vuotena kyselylomakkeilla maantieteen verkko-opetuksen edelläkävijäopettajilta, jotka palauttivat 326 lomaketta. Tutkimuksen pääongelmat olivat 1) Millaisia edellytyksiä edelläkävijäopettajilla on käyttää verkko-opetusta koulun maantieteessä? 2) Mitä sovelluksia ja millä tavoin edelläkävijäopettajat käyttävät maantieteen verkko-opetuksessa? 3) Millaisia käyttökokemuksia edelläkävijäopettajat ovat saaneet maantieteen verkko-opetuksesta? Tutkimuksessa havaittiin, että tietokoneiden riittämätön määrä ja puuttuminen aineluokasta vaikeuttivat maantieteen verkko-opetusta. Työssä kehitettiin opettajien digitaalisten mediataitojen kuutiomalli, johon kuuluvat tekniset taidot, informaation prosessointitaidot ja viestintätaidot. Opettajissa erotettiin kolme verkko-opetuksen käyttäjätyyppiä: informaatiohakuiset kevytkäyttäjät, viestintähakuiset peruskäyttäjät ja yhteistyöhakuiset tehokäyttäjät. Verkko-opetukseen liittyi intensiivisiä myönteisiä ja kielteisiä kokemuksia. Se toi iloa ja motivaatiota opiskeluun. Sitä pidettiin rikastuttavana lisänä, joka haluttiin integroida opetukseen hallitusti. Edelläkävijäopettajat ottivat käyttöön tietoverkoissa olevaa informaatiota ja sovelsivat työvälineohjelmia. He pääsivät alkuun todellisuutta jäljittelevien virtuaalimaailmojen: satelliittikuvien toistaman maapallon, digitaalikarttojen ja simulaatioiden käytössä. Opettajat kokeilivat verkon sosiaalisia tiloja reaaliaikaisen viestinnän, keskusteluryhmien ja ryhmätyöohjelmien avulla. Mielikuvitukseen perustuvat virtuaalimaailmat jäivät vähälle sillä opettajat eivät juuri pelanneet viihdepelejä. He omaksuivat virtuaalimaailmoista satunnaisia palasia käytettävissä olevan laite- ja ohjelmavarustuksen mukaan. Virtuaalimaailmojen valtaus eteni tutkimuksen aikana digitaalisen informaation hyödyntämisestä viestintäsovelluksiin ja aloittelevaan yhteistyöhön. Näin opettajat laajensivat virtuaalireviiriään tietoverkkojen dynaamisiksi toimijoiksi ja pääsivät uusin keinoin tyydyttämään ihmisen universaalia tarvetta yhteyteen muiden kanssa. Samalla opettajat valtautuivat informaation kuluttajista sen tuottajiksi, objekteista subjekteiksi. Verkko-opetus avaa koulun maantieteelle huomattavia mahdollisuuksia. Mobiililaitteiden avulla informaatiota voidaan kerätä ja tallentaa maasto-olosuhteissa, ohjelmilla sitä voidaan muuntaa muodosta toiseen. Internetin autenttiset ja ajantasaiset materiaalit tuovat opiskeluun konkretiaa ja kiinnostavuutta, mallit, simulaatiot ja paikkatieto havainnollistavat ilmiöitä. Viestintä- ja yhteistyövälineet sekä sosiaaliset informaatiotilat vahvistavat yhteistyötä. Avainsanat: verkko-opetus, internet, virtuaalimaailmat, maantiede, innovaatiot
Resumo:
The aim of this philosophical and theoretical study is to outline a conceptual framework, which could be used to describe the qualitative characteristics of household activities from a holistic point of view. The philosophical part of the study deals with ontological and epistemological approaches. Ontological questions of existence are based on the holistic notion of man. The epistemological approach to household activities is based on the Aristotelian concept of knowledge, according to which actions are viewed as being praxis and poiesis in type. The concept of rationality is essential. As a result of the study, concepts describing the qualitative contents of the concept of mastery of everyday life are presented. Mastery of everyday life describes an individual's understanding of how to act in a household and promote the common good. The qualitative dimensions are the aims of actions, knowledge that guides actions and interaction. From the standpoint of these dimensions, the development of mastery of everyday life means an increase in the individual's sense of responsibility, so that s/he is gradually able to deal responsibility with the whole household, the immediate environment and the surrounding community and society. The quality of interaction develops so that the significance of communicative interaction becomes central. There are three levels in the mastery of everyday life, which differ from one other in respect to the development of reflective thought and the scope of understanding. The whole conceptual framework will contribute to the study of both household activities and the teaching of home economics. Key words: holistic notion of man, rationality, interaction.
Resumo:
The objective of the dissertation was to determine the concept of sustainable development according to current understanding and to analyze the structuration of sustainable daily life and how it varies between different groups. The present dissertation is both a literature-based theoretical study and data-based empirical research. The theoretical framework of the study was a greated model of the Structuration of Sustainability in Everyday Life. The model is based on a synthesis of Giddens Theory of Structuration (1984), Spaargaren JA van Vliet's Theory of Consumption as Social Practices (2000) and principles of sustainable development. According to the model created, sustainable everyday life is generated in a context of internal and external factors compromising the interests of ecosystems, society and business. The literature used in the thesis included international and national statements on sustainable development and research into sustainability and the transition to sustainable societies. The data were collected at Helsinki Metropolia University of Applied Sciences. The discretionary sample consisted of students of social services (n = 210) and were collected using the semantic differential technique. The data were analyzed using quantitative and qualitative methods. The results showed that the value placed on ecological, economic and social sustainability increased with age. Activity in non governmental organizations was associated with the acceptance of sustainable development as a whole and especially with global responsibility. Women's everyday life promoted sustainability more than men´s. People living in Helsinki had more sustainable ways of living than those living in the surrounding municipalities because of greater recycling and the low importance given to ownership. Prefering vegetarian food turned out to be a real opportunity for a more sustainable way of living because there were few barriers identified. Contradictory human behavior occurred when advanced sustainable consumer were ready to risk their health. The importance of communality was high and it was considered an aspect of health. The most significant obstacles to sustainable development in daily life were high costs, lack of knowledge and busyness. Similar attitudes towards sustainable development translate into different people´s behavior, which indicates complexities of the behaviour change in the context of sustainable development. The role of non governmental organizations is significant in increasing global responsibility. Education presents an opportunity to increase sustainability, but there are challenges to face from system thinking and in understanding entities in a state of transition towards sustainable everyday life. The responsibility of policy makers is paramount because high costs create a barrier to a sustainable way of living. The implementation of the concept of sustainable development should be focused on the planetary ethics which cover humans, animals, plants and ecosystems. Keywords: Sustainable development, sustainable thinking, behaviour change
Resumo:
The aim of the thesis was to compare the correspondence of the outcome a computer assisted program appearance compared to the original image. The aspect of the study was directed to embroidery with household machines. The study was made from the usability point of view with Brother's PE-design 6.0 embroidery design programs two automatic techniques; multicoloured fragment design and multicoloured stitch surface design. The study's subject is very current because of the fast development of machine embroidery. The theory is based on history of household sewing machines, embroidery sewing machines, stitch types in household sewing machines, embroidery design programs as well as PE-design 6.0 embroidery design program's six automatic techniques. Additionally designing of embroidery designs were included: original image, digitizing, punching, applicable sewing threads as well as the connection between embroidery designs and materials used on embroidery. Correspondences of sewn appearances were examined with sewing experimental methods. 18 research samples of five original image were sewn with both techniques. Experiments were divided into four testing stages in design program. Every testing stage was followed by experimental sewing with Brother Super Galaxie 3100D embroidery machine. Experiments were reported into process files and forms made for the techniques. Research samples were analysed on images syntactic bases with sensory perception assessment. Original images and correspondence of the embroidery appearances were analysed with a form made of it. The form was divided into colour and shape assessment in five stage-similarity-scale. Based on this correspondence analysis it can be said that with both automatic techniques the best correspondence of colour and shape was achieved by changing the standard settings and using the makers own thread chart and edited original image. According to the testing made it is impossible to inform where the image editing possibilities of the images are sufficient or does the optimum correspondence need a separate program. When aiming at correspondence between appearances of two images the computer is unable to trace by itself the appearance of the original image. Processing a computer program assisted embroidery image human perception and personal decision making are unavoidable.
Resumo:
Purpose This study focused on craft from a standpoint of phenomenological philosophy and craft was interpreted through Maurice Merleau-Ponty’s phenomenology of the body. The main focus was the physical phase of the craft process, wherein a product is made from material. The aim was to interpret corporality in craft. There is no former research focusing on lived body in craft science. Physical, bodily making is inalienable in craft, but it is not articulated. Recent discussion has focused on craft as ”whole”, which emphasizes designing part in the process, and craft becomes conceptualized with the theories of art and design. The axiomatic yet silenced basis of craft, corporality, deserves to become examined as well. That is why this study answers the questions: how craft manifests in the light of phenomenology of the body and what is corporality in craft? Methods In this study I cultivated a phenomenological attitude and turned my exploring eye on craft ”in itself”. In addition I restrained myself from mere making and placed myself looking at the occurrence of craft to describe it verbally. I read up Maurice Merleau-Ponty’s phenomenology of the body on his principal work (2002) and former interpretations of it. Interpreting and understanding textual data were based on Gadamer’s hermeneutics, and the four-pronged composition of the study followed Koski’s (1995) version of the Gadamerian process of textual interpretation. Conclusions In the construction of bodily phenomenology craft was to be contemplated as a mutual relationship between the maker and the world materializing in bodily making. At the moment of making a human being becomes one with his craft, and the connection between the maker, material and the equipment appears as communication. Operational dimension was distinctive in the intentionality of craft, which operates in many ways, also in craft products. The synesthesia and synergy of craft were emphasized and craft as bodily practice came to life through them. The moment of making appeared as situation generating time and space, where throwing oneself into making may give the maker an experience of upraise beyond the dualism of mind and body. The conception of the implicit nature of craft knowledge was strengthened. In the light of interpretation it was possible to conceptualize craft as a performance and making ”in itself” as a work of art. In that case craft appeared as bodily expression, which as an experience approaches art without being it after all. The concept of aesthetic was settled into making as well. Bodily and phenomenological viewpoint on craft gave material to critically contemplate the concept of “whole craft” (kokonainen käsityö) and provided different kind of understanding of craft as making.
Resumo:
This study highlights the formation of an artifact designed to mediate exploratory collaboration. The data for this study was collected during a Finnish adaptation of the thinking together approach. The aim of the approach is to teach pulps how to engage in educationally beneficial form of joint discussion, namely exploratory talk. At the heart of the approach lies a set of conversational ground rules aimed to promote the use of exploratory talk. The theoretical framework of the study is based on a sociocultural perspective on learning. A central argument in the framework is that physical and psychological tools play a crucial role in human action and learning. With the help of tools humans can escape the direct stimulus of the outside world and learn to control ourselves by using tools. During the implementation of the approach, the classroom community negotiates a set of six rules, which this study conceptualizes as an artifact that mediates exploratory collaboration. Prior research done about the thinking together approach has not extensively researched the formation of the rules, which give ample reason to conduct this study. The specific research questions asked were: What kind of negotiation trajectories did the ground rules form during the intervention? What meanings were negotiated for the ground rules during the intervention The methodological framework of the study is based on discourse analysis, which has been specified by adapting the social construction of intertextuality to analyze the meanings negotiated for the created rules. The study has town units of analysis: thematic episode and negotiation trajectory. A thematic episode is a stretch of talk-in-interaction where the participants talk about a certain ground rule or a theme relating to it. A negotiation trajectory is a chronological representation of the negotiation process of a certain ground rule during the intervention and is constructed of thematic episodes. Thematic episodes were analyzed with the adapted intertextuality analysis. A contrastive analysis was done on the trajectories. Lastly, the meanings negotiated for the created rules were compared to the guidelines provided by the approach. The main result of the study is the observation, that the meanings of the created rules were more aligned with the ground rules of cumulative talk, rather than exploratory talk. Although meanings relating also to exploratory talk were negotiated, they clearly were not the dominant form. In addition, the study observed that the trajectories of the rules were non identical. Despite connecting dimensions (symmetry, composition, continuity and explicitness) none of the trajectories shared exactly the same features as the others.
Resumo:
Tutkimuksen päätarkoitus oli hahmottaa verkko-opetuksen arvoja ja arviointia luokanopettajan näkökulmasta. Teoreettisena viitekehyksenä oli mediakasvatus ja didaktiikan käsitys opetus opiskelu oppimisprosessista. Didaktisena perustana käytettiin Kansasen ym. (2000) opettajan pedagogista ajattelua, Lahdeksen (1997) didaktiikan kehämallia sekä Uljensin (1997) opetus opiskelu oppimisprosessia. Lähtökohtana oli luokanopettajan arvioinnin kautta pohtia opetuksen, opiskelun ja oppimisen sekä tieto- ja viestintätekniikan yhtymistä koulukontekstissa. Tutkimuksen pääongelmat olivat: 1) Minkälainen oli luokanopettajan käsitys verkko-opetuksen toteuttamisesta? 2) Miten luokanopettaja arvioi verkko-opetusta? Myös ensimmäistä pääongelmaa lähestyttiin arvojen ja arvioinnin näkökulmasta. Menetelmänä käytettiin teemahaastattelua. Teemahaastattelun teemoja jäsennettiin Gallinin (2001) sosiokulttuurisen verkko-opetuksen arviointimallin sekä Tellan ja Mononen-Aaltosen (2001) mediakasvatuksen monitasomallin avulla. Aineistonkeruussa kahdeksan helsinkiläistä luokanopettajaa vastasivat lyhyeen kyselyyn, jonka jälkeen heitä haastateltiin välittömästi. Laadullisen aineiston analyysissä teemoiteltiin aineisto, ja tämän rinnalla rakennettiin aineistolähtöistä analyysiä. Näiden vuorovaikutuksesta syntyivät tutkimuksen johtopäätökset. Keskeisinä tuloksina tutkimuksessa nähtiin luokanopettajan verkko-opetukseen liittyvien arvojen kaksi eri näkökulmaa: (A) opetus opiskelu oppimismenetelmien ja -tulosten arvonäkökulma sekä (B) ns. kasvatuksellinen ja koulukulttuurin arvonäkökulma. Arvonäkökulmien pohjalta hahmotettiin johtopäätöksissä erilaisia tasoja luokanopettajan opetuksen, opiskelun ja oppimisen arvioinnista, kun tieto- ja viestintätekniikka on mukana prosessissa. Kaksi tasoa tarkennettiin verkko-opetuksen arvioinnin fokuksiksi, jotka olivat (1) teknologinen ja (2) tavoitteinen fokus. Teknologisessa arvioinnin fokuksessa (1) arviointia hallitsee huoli oppilaasta ihmisenä. Arviointi liittyy joko siihen, että oppilaan on opittava perustaidot tieto- ja viestintätekniikassa ja ymmärrettävä Internetin mahdollisuudet, tai siihen, että opettaja pyrkii suojelemaan lapsia Internetin uhkilta ja liialliselta altistumiselta esimerkiksi digitaalisille peleille. Verkko-opetuksen tavoitteinen arvioinnin fokus (2) nojaa siihen, minkälaisia tavoitteita luokanopettaja yleisesti asettaa opetukselleen, vaikka tieto- ja viestintätekniikka ei liittyisikään prosessiin. Fokuksen taustalla on myös mediakasvatuksen näkökulma tieto- ja viestintätekniikan opetuskäyttöön, jolloin keskeistä on, että opetuksen suunnittelu ja arviointi ei lähde teknologiasta käsin vaan didaktiikasta ja peda-gogisista arvoista. Verkko-opetuksen arvioinnin fokusten voidaan nähdä täydentävän toisiaan. Fokusten varioinnissa voidaan puhua luokanopettajan kohdalla todellisesta mediataidosta, joka ulottuu yli ammatillisen pätevyyden aina opettajan henkilökohtaiseen kehittymisen kaareen. Avainsanat: Verkko-opetus, arvot, arviointi, opetus-opiskelu-oppimisprosessi, opettajan pedagoginen ajattelu, tieto- ja viestintätekniikan opetuskäyttö Keywords: Network-Based Education (NBE), values, evaluation, teaching-studying-learning process, teacher's pedagogical thinking, educational use of information and communication technologies (ICT)
Resumo:
Tutkimuksessa etsittiin vastauksia kysymykseen, miten saariston tekstiilikäsityöläinen tavoittelee ekologista kestävyyttä työssään. Mitä ekologisuus hänelle merkitsee ja miten se ilmenee hänen töissään? Kertojana on sekä tuote että tekijä. Tutkimus on fenomenologisesti orientoitunut ja vastauksia tutkimuskysymyksiin haettiin teorian ja aineiston vuoropuhelulla . Analyysimenetelmänä käytettiin sisällön analyysia. Analysoitava aineisto on hankittu haastattelemalla yhdeksää käsityöläistä, jotka asuvat Lounais-Suomen, Ahvenanmaan ja Tukholman alueen saaristoissa. Tutkimuksen teoreettisissa lähtökohdissa on tarkasteltu kestävän kehityksen ja saariston käsityön suhdetta. Kulttuuriseen, sosiaaliseen, taloudelliseen ja tuotannolliseen kestävyyteen panostamalla pyritään ekologiseen kestävyyteen. Käsityöläisen arvot, taidot ja tiedot vaikuttavat kehityksen eri osa-alueilla. Käsityöläisen toimintaympäristönä oli saaristo, sen luonto ja ihmisen aikaansaama kulttuuri. Tutkimuksessa selvitettiin sitä, miten saaristo ja saaristolaisuus vaikuttivat käsityöläisen tapaan toimia ja kertoa tekemistään tuotteista. Ekologisuus saaristolaiskäsityössä ilmeni monin tavoin. Kulttuurinen ja sosiaalinen kestävyys toteutuivat taloudellista ja tuotannollista kestävyyttä paremmin. Koulutuksen koettiin olevan paras keino saavuttaa välitavoitteita kestävässä kehityksessä. Käsityöläisyys nähtiin osana saaristolaiskulttuuria ja verkostoituminen harvaan asutulla seudulla koettiin tärkeäksi. Tutkimuksessa pohdittiin, onko ekologisuus materiaalin alkuperään, työtapaan vai tuotteen käyttöikään ja hävitykseen liittyvä asia. Ekologisuus yhdistettiin usein käsityön materiaaliin ja sen tuotantotapoihin. Arvot konkretisoituvat käsityöläisen puhuessa perheestään ja kasvamisesta käsityöläisyyteen. Ekologiseen käsityöhön panostaminen on myös osa käsityöläisen kasvuprosessia. Ekologiseen kestävyyteen pyrkiminen käsityössä herätti myös ristiriitaisia tunteita. Käsityöläisyys on elinkeino markkinoilla, joilla globaali kauppa määrittelee säännöt. Merkitseekö ekologiseen kestävyyteen pyrkiminen kurkottamista kohti totuutta? Avainsanat: ekologinen kestävyys, kestävä kehitys, arvot, käsityöläisyys, käsityö, saaristo saaristolaisuus
Resumo:
Advanced stage head and neck cancers (HNC) with distant metastasis, as well as prostate cancers (PC), are devastating diseases currently lacking efficient treatment options. One promising developmental approach in cancer treatment is the use of oncolytic adenoviruses, especially in combination therapy with conventional cancer therapies. The safety of the approach has been tested in many clinical trials. However, antitumor efficacy needs to be improved in order to establish oncolytic viruses as a viable treatment alternative. To be able to test in vivo the effects on anti-tumor efficiency of a multimodal combination therapy of oncolytic adenoviruses with the standard therapeutic combination of radiotherapy, chemotherapy and Cetuximab monoclonal antibody (mAb), a xenograft HNC tumor model was developed. This model mimics the typical clinical situation as it is initially sensitive to cetuximab, but resistance develops eventually. Surprisingly, but in agreement with recent findings for chemotherapy and radiotherapy, a higher proportion of cells positive for HNC cancer stem cell markers were found in the tumors refractory to cetuximab. In vitro as well as in vivo results found in this study support the multimodal combination therapy of oncolytic adenoviruses with chemotherapy, radiotherapy and monoclonal antibody therapy to achieve increased anti-tumor efficiency and even complete tumor eradication with lower treatment doses required. In this study, it was found that capsid modified oncolytic viruses have increased gene transfer to cancer cells as well as an increased antitumor effect. In order to elucidate the mechanism of how oncolytic viruses promote radiosensitization of tumor cells in vivo, replicative deficient viruses expressing several promising radiosensitizing viral proteins were tested. The results of this study indicated that oncolytic adenoviruses promote radiosensitization by delaying the repair of DNA double strand breaks in tumor cells. Based on the promising data of the first study, two tumor double-targeted oncolytic adenoviruses armed with the fusion suicide gene FCU1 or with a fully human mAb specific for human Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) were produced. FCU1 encodes a bifunctional fusion protein that efficiently catalyzes the direct conversion of 5-FC, a relatively nontoxic antifungal agent, into the toxic metabolites 5-fluorouracil and 5-fluorouridine monophosphate, bypassing the natural resistance of certain human tumor cells to 5-fluorouracil. Anti-CTLA4 mAb promotes direct killing of tumor cells via apoptosis and most importantly immune system activation against the tumors. These armed oncolytic viruses present increased anti-tumor efficacy both in vitro and in vivo. Furthermore, by taking advantage of the unique tumor targeted gene transfer of oncolytic adenoviruses, functional high tumor titers but low systemic concentrations of the armed proteins were generated. In addition, supernatants of tumor cells infected with Ad5/3-24aCTLA4, which contain anti-CTLA4 mAb, were able to effectively immunomodulate peripheral blood mononuclear cells (PBMC) of cancer patients with advanced tumors. -- In conclusion, the results presented in this thesis suggest that genetically engineered oncolytic adenoviruses have great potential in the treatment of advanced and metastatic HNC and PC.
Resumo:
Glaucoma is a group of progressive optic neuropathies causing irreversible blindness if not diagnosed and treated in the early state of progression. Disease is often, but not always, associated with increased intraocular pressure (IOP), which is also the most important risk factor for glaucoma. Ophthlamic timolol preparations have been used for decades to lower increased intraocular pressure (IOP). Timolol is locally well tolerated but may cause e.g. cardiovascular and pulmonary adverse effects due to systemic absorption. It has been reported that approximately 80% of a topically administered eye drop is systemically absorbed. However, only limited information is available on timolol metabolism in the liver or especially in the human eye. The aim of this work was to investigate metabolism of timolol in human liver and human ocular tissues. The expression of drug metabolizing cytochrome P450 (CYP) enzymes in the human ciliary epithelial cells was studied. The metabolism of timolol and the interaction potential of timolol with other commercially available medicines were investigated in vitro using different liver preparations. The absorption of timolol to the aqueous humor from two commercially available products: 0.1% eye gel and 0.5% eye drops and the presence of timolol metabolites in the aqueous humor were investigated in a clinical trial. Timolol was confirmed to be metabolized mainly by CYP2D6 as previously suggested. Potent CYP2D6 inhibitors especially fluoxetine, paroxetine and quinidine inhibited the metabolism of timolol. The inhibition may be of clinical significance in patients using ophthalmic timolol products. CYP1A1 and CYP1B1 mRNAs were expressed in the human ciliary epithelial cells. CYP1B1 was also expressed at protein level and the expression was strongly induced by a known potent CYP1B1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The CYP1B1 induction is suggested to be mediated by aryl hydrocarbon receptor (AHR). Low levels of CYP2D6 mRNA splice variants were expressed in the human ciliary epithelial cells and very low levels of timolol metabolites were detected in the human aqueous humor. It seems that negligible amount of CYP2D6 protein is expressed in the human ocular tissues. Timolol 0.1% eye gel leads to aqueous humor concentration high enough to achieve therapeutic effect. Inter-individual variation in concentrations is low and intraocular as well as systemic safety can be increased when using this product with lower timolol concentration instead of timolol 0.5% eye drops.
Resumo:
Cathepsin D (CTSD) is a lysosomal protease, the deficiency of which is fatal and associated with neurodegeneration. CTSD knock-out mice, which die at the age of four weeks, show intestinal necrosis, loss of lymphoid cells and moderate pathological changes in the brain. An active-site mutation in the CTSD gene underlies a neurodegenerative disease in newborn sheep, characterized by brain atrophy without any changes to visceral tissues. The CTSD deficiences belong to the group of neuronal ceroid-lipofuscinoses (NCLs), severe neurodegenerative lysosomal storage disorders. The aim of this thesis was to examine the molecular and cellular mechanisms behind neurodegeneration in CTSD deficiency. We found the developmental expression pattern of CTSD to resemble that of synaptophysin and the increasing expression of CTSD to coincide with the active period of myelination in the rat brain, suggesting a role for CTSD in early rat brain development. An active-site mutation underlying the congenital ovine NCL not only affected enzymatic activity, but also changed the stability, processing and transport of the mutant protein, possibly contributing to the disease pathogenesis. We also provide CTSD deficiency as a first molecular explanation for human congenital NCL, a lysosomal storage disorder, characterized by neuronal loss and demyelination in the central nervous system. Finally, we show the first evidence for synaptic abnormalities and thalamocortical changes in CTSD-deficient mice at the molecular and ultrastructural levels. Keywords: cathepsin D, congenital, cortex, lysosomal storage disorder, lysosome, mutation, neurodegeneration, neuronal ceroid-lipofuscinosis, overexpression, synapse, thalamus
Resumo:
Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamine (DA), noradrenaline (NA) and adrenaline, which are vital neurotransmitters and hormones that play important roles in the regulation of physiological processes. COMT enzyme has a functional Val158Met polymorphism in humans, which affects the subjects COMT activity. Increasing evidence suggests that this functional polymorphism may play a role in the etiology of various diseases from schizophrenia to cancers. The aim of this project was to provide novel biochemical information on the physiological and especially pathophysiological roles of COMT enzyme as well as the effects of COMT inhibition in the brain and in the cardiovascular and renal system. To assess the roles of COMT and COMT inhibition in pathophysiology, we used four different study designs. The possible beneficial effects of COMT inhibition were studied in double-transgenic rats (dTGRs) harbouring human angiotensinogen and renin genes. Due to angiotensin II (Ang II) overexpression, these animals exhibit severe hypetension, cardiovascular and renal end-organ damage and mortality of approximately 25-40% at the age of 7-weeks. The dTGRs and their Sprague-Dawley controls tissue samples were assessed with light microscopy, immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and high-pressure liquid chromatography (HPLC) to evaluate the tissue damages and the possible protective effects pharmacological intervention with COMT inhibitors. In a second study, the consequence of genetic and pharmacological COMT blockade in blood pressure regulation during normal and high-sodium was elucidated using COMT-deficient mice. The blood pressure and the heart rate were measured using direct radiotelemetric blood pressure surveillance. In a third study, the effects of acute and subchronic COMT inhibition during combined levodopa (L-DOPA) + dopa decarboxylase inhibitor treatment in homocysteine formation was evaluated. Finally, we assessed the COMT enzyme expression, activity and cellular localization in the CNS during inflammation-induced neurodegeneration using Western blotting, HPLC and various enzymatic assays. The effects of pharmacological COMT inhibition on neurodegeneration were also studied. The COMT inhibitor entacapone protected against the Ang II-induced perivascular inflammation, renal damage and cardiovascular mortality in dTGRs. COMT inhibitors reduced the albuminuria by 85% and prevented the cardiovascular mortality completely. Entacapone treatment was shown to ameliorate oxidative stress and inflammation. Furthermore, we established that the genetic and pharmacological COMT enzyme blockade protects against the blood pressure-elevating effects of high sodium intake in mice. These effects were mediated via enhanced renal dopaminergic tone and suggest an important role of COMT enzyme, especially in salt-sensitive hypertension. Entacapone also ameliorated the L-DOPA-induced hyperhomocysteinemia in rats. This is important, since decreased homocysteine levels may decrease the risk of cardiovascular diseases in Parkinson´s disease (PD) patients using L-DOPA. The Lipopolysaccharide (LPS)-induced inflammation and subsequent delayed dopaminergic neurodegeneration were accompanied by up-regulation of COMT expression and activity in microglial cells as well as in perivascular cells. Interestingly, similar perivascular up-regulation of COMT expression in inflamed renal tissue was previously noted in dTGRs. These results suggest that inflammation reactions may up-regulate COMT expression. Furthermore, this increased glial and perivascular COMT activity in the central nervous system (CNS) may decrease the bioavailability of L-DOPA and be related to the motor fluctuation noted during L-DOPA therapy in PD patients.
Resumo:
Androgens control a variety of developmental processes that create the male phenotype and are important for maintaining male fertility and normal functions of tissues and organs that are not directly involved in procreation. Androgen receptor (AR) that mediates the biological actions of androgens is a member of the nuclear receptor superfamily of ligand-inducible transcription factors. Although AR was cloned over 15 years ago, the mechanisms by which it regulates gene expression are not well understood. A growing body of in vitro experimental evidence suggests that a complex network of proteins is involved in the androgen-dependent transcriptional regulation. However, the process of AR-dependent transcriptional regulation under physiological conditions is largely elusive. In the present study, a series of experiments were performed, including quantitative chromatin immunoprecipitation (ChIP) assays, to investigate AR-mediated transcription process using living prostate cancer cells. Our results show that the loading of AR and recruitment of coactivators and RNA polymerase II (Pol II) to both the promoter and enhancer of AR target genes are a transient and cyclic event that in addition to hyperacetylation, also involves dynamic changes in methylation, phosphorylation of core histone H3 in androgen-treated LNCaP cells. The dynamics of testosterone (T)-induced loading of AR onto the proximal promoters of the genes clearly differed from that loaded onto the distal enhancers. Significantly, more holo-AR was loaded onto the enhancers than the promoters, but the principal Pol II transcription complex was assembled on the promoters. By contrast, the pure antiandrogen bicalutamide (CDX) complexed to AR elicited occupancy of the PSA promoter, but was unable to load onto the PSA enhancer and was incapable of recruiting Pol II, coactivators and following changes of covalent histone modifications. The partial antagonist cyproterone acetate (CPA) and mifepristone (RU486) were capable of promoting AR loading onto both the PSA promoter and enhancer at a comparable efficiency with androgen in LNCaP cells expressing mutant AR. However, CPA- and RU486-bound AR not only recruited Pol II and coactivator p300 and GRIP1 onto the promoter and enhancer, but also recruited the corepressor NCoR onto the promoter as efficiently as CDX. In addition, we demonstrate that both proteasome and protein kinases are implicated in AR-mediated transcription. Even though proteasome inhibitor MG132 and protein kinase inhibitor DRB (5, 6-Dichlorobenzimidazole riboside) can block ligand-dependent accumulation of PSA mRNA with same efficiency, their use results in different molecular profiles in terms of the formation of AR-mediated transcriptional complex. Collectively, these results indicate that transcriptional activation by AR is a complicated process, which includes transient loading of holo-AR and recruitment of Pol II and coregulators accompanied by a cascade of distinct covalent histone modifications; This process involves both the promoter and enhancer elements, as well as other general components of the cell machineries e.g. proteasome and protein kinase; The pure antiandrogen CDX and the partial antagonist CPA and RU486 exhibit clearly different profiles in terms of their ability to induce the formation of AR-dependent transcriptional complexes and the histone modifications associated with the target genes in human prostate cancer cells. Finally, by using quantitative RT-PCR to compare the expression of sixteen AR co-regulators in prostate cancer cell lines, xenografts, and clinical prostate cancer specimens we suggest that AR co-regulators protein inhibitor of activated STAT1 (PIAS1) and steroid receptor coactivator 1(SRC1) could be involved in the progression of prostate cancer.