Musta teksti valkean päällä : pohjatekstit merkityksenantajina Toni Morrisonin romaanissa Beloved

English summary: The significance of intertexts in Toni Morrison's novel Beloved

Nuoren Apollon syöksykierre : sivistyneistö ja kansallisen ideologian murroksia

Päivi Molarius

”Käsitteitä tarpeen mukaan". Kirjallisuustieteelliset käsitteet lukion kirjallisuudenopetuksessa

Tavoitteeni tässä tutkimuksessa oli selvittää, miten kirjallisuustieteellisiä proosa-anayysin käsitteitä opetetaan opetussuunnitelman mukaisissa lukion äidinkielen ja kirjallisuuden oppikirjoissa ja miten hyvin kokelaat hallitsivat kertoja-käsitteen tekstitaidon ylioppilaskokeessa keväällä 2007. Samalla pohdin, minkälainen kirjallisuustieteellinen käsitteistö palvelisi tekstianalyysin opetusta koulussa, koska Lukion opetussuunnitelman perusteet 2003 ja äidinkielen ylioppilaskoe edellyttävät äidinkielen ja kirjallisuuden opetukselta ja oppilailta käsitteiden käyttöä. Tutkimusaineistonani olivat kaikki kuusi käytössä olevaa lukion äidinkielen ja kirjallisuuden oppikirjaa ja 440 kpl kevään 2007 äidinkielen tekstitaidon ylioppilaskokeen vastaustekstiä. Oppikirjoja tarkastelin soveltamalla niiden arviointiin Lev S. Vygotskin ajatuksia arkikäsitteiden ja tieteellisten käsitteiden opettamisesta ja Hans Aeblin esittämiä teoreettisia malleja käsitteiden opettamisesta ja oppimisesta. Tutkimukseni osoittaa, että opetussuunnitelmassa mainittujen proosa-analyysin käsitteiden kertoja, näkökulma, motiivi, aihe ja teema opetus on epätäsmällistä. Oppikirjoissa ei ole otettu huomioon sitä, että käsitteenoppiminen on monivaiheinen prosessi. Myöskään problematiikkaa, joka aiheutuu kyseisten käsitteiden määrittelyn kirjavuudesta ja käytöstä sekä arkikielen käsitteinä että tieteellisinä käsitteinä, ei oppikirjoissa käsitellä. Sama näkyy ylioppilaskoeaineistossa: oppilaat eivät hallitse käsitettä kertoja tieteellisenä käsitteenä. Tietoisuus kirjallisuustieteellisten käsitteiden määrittelyn problematiikasta ja arkikäsitteiden ja tieteellisten käsitteiden ontologisista kategorioista on onnistuneen käsitteenoppimisen edellytys. Kirjallisuustieteelliset käsitteet ovat metakäsitteitä, jotka edellyttävät oppilaiden metakäsitteellisen tietoisuuden ja motivaation hyödyntämistä opetuksessa, jossa olisi sovellettava monipuolisesti eri oppimiskäsitysten parhaita puolia hyödyntäviä lähestymistapoja, erilaisia pedagogisia diskursseja. Koulujen kirjallisuudenopetusta suunniteltaessa ja kirjallisuustieteellisiä käsitteitä opetettaessa on otettava huomioon niin kirjallisuustieteen kuin kasvatustieteen näkökulma. Opetussuunnitelman ja ylioppilaskokeen asettama vaatimus käsitteiden käytöstä on kohtuuton, mikäli ei sovita, miten käsitteet määritellään ja mitä käsitteitä kokelaiden oletetaan ylioppilaskokeessa hallitsevan. Kirjallisuustieteellisten käsitteiden puutteellisen opetuksen oppikirjoissa ja niiden epämääräisen käytön ylioppilaskokeen tehtävänannoissa ja arvioinnissa voi kärjistyneimmillään nähdä oppilaan oikeusturvakysymyksenä

Hjärtats vanor, tankens välvilja och handens gärning : dygd som vårdetiskt grundbegrepp

The main aim of the study is to elucidate the meaning and dimensions of the concept of „virtue‟, and to find the place of virtue in a caritative caring ethics, i.e. a caring ethics based on human love and mercy. The intention is to create a theory model which utilizes the possibilities of virtue in developing the caritative caring ethics as a whole. The caritative caring ethics has a universal potential – it is primarily not a professional ethics, but it may form a frame of reference and basis for formulating ethical codes, and for ethical discussions within different caring contexts. The hermeneutic approach of the study is inspired by Gadamer‟s philosophical hermeneutics combined with the view of hermeneutics as a hypothetical-deductive process. The study is guided by Eriksson‟s model of definition of concepts. The concept of „virtue‟ is studied focusing on its ethical dimensions. These ethical dimensions of virtue are seen as anchored to an inner ethos, whereas ethos stands for the ontological goodness, a basic notion of the Good that permeates the entity of the human being, and forms the base of the culture where he lives and acts. The overarching research questions are: 1. What is virtue? 2. What is „virtue‟ as a basic concept in caring science? 3. What place does virtue have in caritative caring ethics? The answer of the first question is mainly searched for by an ontological determination comprising partly an etymologic and semantic analysis of „virtue‟, and partly a determination of the essence of virtue. The answer to the second and third questions are mainly searched for using a contextual determination, where the purposive context and pragmatic features of virtue are studied in relation to caring ethics. The ontological and contextual determinations are brought together through hermeneutical interpretation, forming a new whole, which constitutes the results of the study. The results of the study are depicted in a theory model, in which the movement of virtue from ethos to deed is moulded as caritative caring ethics. The material of the study consists of dictionaries, texts written by Aristotle and St. Thomas Aquinas, articles, dissertations, and books, as well as parts of a pilot survey answered by 33 nurses. The results of the study show that the essence of virtue is primarily functional, not ethical. The ethical emerges when virtue is contextualized in a human communion. Virtue makes something fulfil its function well; makes the human being good, and gives him morals and morality. The human being needs prudence, love, and humility to acquire and develop the moral virtues. Virtue is a power, related to a value, which considering a caritative caring ethics consists of the caritas motif. Human love is shown through deeds, making the human being do what he is expected to do. Virtue, as an active power of becoming, affirms and clarifies the human being‟s ability to develop in the direction of the Good. Virtue becomes essential and unifying when morality appears in the human mind as auctoritas, an inner, prompting power based on divinity or a transcendental ethos. Together ethos and virtue create opportunities for an inner ethics based on voluntariness and joy in being and doing the true, the good, and the beautiful.

Identification and characterisation of a novel adhesin of Streptococcus suis and its use as a target of adhesion inhibition and bacterial detection

Streptococcus suis is an important pig pathogen but it is also zoonotic, i.e. capable of causing diseases in humans. Human S. suis infections are quite uncommon but potentially life-threatening and the pathogen is an emerging public health concern. This Gram-positive bacterium possesses a galabiose-specific (Galalpha1−4Gal) adhesion activity, which has been studied for over 20 years. P-fimbriated Escherichia coli−bacteria also possess a similar adhesin activity targeting the same disaccharide. The galabiose-specific adhesin of S. suis was identified by an affinity proteomics method. No function of the protein identified was formerly known and it was designated streptococcal adhesin P (SadP). The peptide sequence of SadP contains an LPXTG-motif and the protein was proven to be cell wall−anchored. SadP may be multimeric since in SDS-PAGE gel it formed a protein ladder starting from about 200 kDa. The identification was confirmed by producing knockout strains lacking functional adhesin, which had lost their ability to bind to galabiose. The adhesin gene was cloned in a bacterial expression host and properties of the recombinant adhesin were studied. The galabiose-binding properties of the recombinant protein were found to be consistent with previous results obtained studying whole bacterial cells. A live-bacteria application of surface plasmon resonance was set up, and various carbohydrate inhibitors of the galabiose-specific adhesins were studied with this assay. The potencies of the inhibitors were highly dependent on multivalency. Compared with P-fimbriated E. coli, lower concentrations of galabiose derivatives were needed to inhibit the adhesion of S. suis. Multivalent inhibitors of S. suis adhesion were found to be effective at low nanomolar concentrations. To specifically detect galabiose adhesin−expressing S. suis bacteria, a technique utilising magnetic glycoparticles and an ATP bioluminescence bacterial detection system was also developed. The identification and characterisation of the SadP adhesin give valuable information on the adhesion mechanisms of S. suis, and the results of this study may be helpful for the development of novel inhibitors and specific detection methods of this pathogen.

Receptors and endocytosis of coxsackievirus A9

Coxsackievirus A9 (CV-A9) belongs to human enteroviruses within family Picornaviridae, which are the main cause of aseptic meningitis. In addition, CV-A9 causes a wide range of other clinical manifestations of acute disease including respiratory infections, myocarditis, encephalitis and severe generalized infections in newborns. In this study, the functions of integrins αVβ6 and αVβ3 in the attachment and cellular entry of CV-A9 were analyzed. Further, virus and cell surface interactions and endocytosis of CV-A9 were studied in specific cell lines. Also, a method for production of GFP-expressing CV-A9 particles by long PCR-mediated mutagenesis and in vivo transcription was developed. The results indicated that RGD-motif (arginine-glycine-asparagine) that resides in the viral capsid is important for CV-A9 infection particularly in cell lines expressing integrin αVβ6 and that this integrin serves as a high affinity attachment receptor for the virus. CV-A9 is also capable of infecting certain cell lines independently of αV-integrins by binding to the cell surface HSPA5 protein. Regardless of the attachment stage, the internalization of the virus occurs via the same entry pathway and is dependent on β2M, dynamin, and Arf6 but independent of clathrin and caveolin-1. Furthermore, the virus internalization occurs within Arf6-containing vesicles suggesting that Arf6 is central mediator of CV-A9 endocytosis. While in this study the results of CV-A9 endocytosis were based on microscopical visualization within individual fixed cells, a rapid method for generation of a virus for real-time imaging was also described.

VAP-1 as drug target in inflammation : structural features determining ligand interactions

Vascular adhesion protein-1 (VAP-1), which belongs to the copper amine oxidases (CAOs), is a validated drug target in inflammatory diseases. Inhibition of VAP-1 blocks the leukocyte trafficking to sites of inflammation and alleviates inflammatory reactions. In this study, a novel set of potent pyridazinone inhibitors is presented together with their X-ray structure complexes with VAP-1. The crystal structure of serum VAP-1 (sVAP-1) revealed an imidazole binding site in the active site channel and, analogously, the pyridazinone inhibitors were designed to bind into the channel. This is the first time human VAP-1 has been crystallized with a reversible inhibitor and the structures reveal detailed information of the binding mode on the atomic level. Similarly to some earlier studied inhibitors of human VAP-1, the designed pyridazinone inhibitors bind rodent VAP-1 with a lower affinity than human VAP-1. Therefore, we made homology models of rodent VAP-1 and compared human and rodent enzymes to determine differences that might affect the inhibitor binding. The comparison of the crystal structures of the human VAP-1 and the mouse VAP-1 homology model revealed key differences important for the species specific binding properties. In general, the channel in mouse VAP-1 is more narrow and polar than the channel in human VAP-1, which is wider and more hydrophobic. The differences are located in the channel leading to the active site, as well as, in the entrance to the active site channel. The information obtained from these studies is of great importance for the development and design of drugs blocking the activity of human VAP-1, as rodents are often used for in vivo testing of candidate drugs. In order to gain more insight into the selective binding properties of the different CAOs in one species a comprehensive evolutionary study of mammalian CAOs was performed. We found that CAOs can be classified into sub-families according to the residues X1 and X2 of the Thr/Ser-X1-X2-Asn-Tyr-Asp active site motif. In the phylogenetic tree, CAOs group into diamine oxidase, retina specific amine oxidase and VAP-1/serum amine oxidase clades based on the residue in the position X2. We also found that VAP-1 and SAO can be further differentiated based on the residue in the position X1. This is the first large-scale comparison of CAO sequences, which explains some of the reasons for the unique substrate specificities within the CAO family.