Lukeminen ja kirjallisuus modernissa opiskeluympäristössä : Tapaustutkimus kuuden peruskoulun 4.-6. luokan telemaattinen kirjallisuuspiiri Matilda -hankkeesta

Tutkimuksen tavoitteena oli kartoittaa ja kehittää modernia opiskeluympäristöä hyödyntävää kirjallisuuspiiritoimintaa ja sitä kautta edistää oppilaiden mahdollisuuksia osallistua elämyksellistä lukemista painottavaan kirjallisuuspiiriin sekä vahvistaa heidän kiinnostustaan tieto- ja viestintätekniikan käyttöön. Tutkimusaineisto kerättiin lukuvuonna 1997 1998 kyselyin ja haastatteluin sekä observoimalla lähiopetustilanteita ja virtuaaliryhmien sähköpostiviestintää. Lisäksi käytettiin valmiita dokumentteja ja asiakirjoja. Tutkimusjoukkona oli Matildaan osallistuneet 4.-6. luokan oppilaat kuudelta Espoon ala-asteelta sekä neljä tutoria, koordinaattori ja joitakin luokanopettajia Matilda-kouluista. Tutkimusongelmat suuntautuivat pääasiassa matildalaisten kokemuksiin opiskelusta modernissa opiskeluympäristössä, suhteesta tieto- ja viestintätekniikkaan sekä siihen, mitä uutta lukemiseen ja kirjallisuuteen liittyvää he kertoivat oppineensa ja kokeneensa. Koska tutkimuskohteen kaltaisia kokeiluita, joissa yhdistyy kirjallisuuspiiritoiminta ja moderni tieto- ja viestintätekniikka, ei ainakaan Suomessa ole aikaisemmin ollut, päädyttiin tutkimusmetodologian valinnassa kvalitatiiviseen otteeseen. Tutkimusote noudatti tapaustutkimuksen ja kehittämistutkimuksen periaatteita. Vaikka tutkimus oli menetelmältään kvalitatiivinen, aineistoa käsiteltiin myös kvantifioiden, mutta yleistyksiä tehtiin ainoastaan tapauksen suuntaan. Tutkimustulokset osoittivat, että opiskelu oli oppilaille positiivinen kokemus. He pitivät erityisesti etäopiskelun itsenäisestä työskentelystä ja lähiopetuspäivistä. Heidän suhtautumisensa tieto- ja viestintätekniikkaan muuttui positiivisemmaksi ja heidän taitonsa tieto- ja viestintätekniikan käyttäjinä kehittyivät. Oppilaat saivat positiivisia lukukokemuksia, heidän lukualueensa laajeni ja osa heistä kertoi lukutyylinsä muutoksista ja syvenemisestä. Oppilaat kokivat ongelmallisimmaksi hankkeen sekavan tutorointi-systeemin, kiireisen aikataulun sekä tietokoneisiin ja -verkkoon liittyvät ongelmat. kirjallisuuspiiri, kolmilukutaito, lukutaito, kirjallisuus, lukeminen, elämyksellinenlukeminen, kirjallisuudenopetus, moderni opiskeluympäristö, avoin ja joustava opiskeluympäristö, telematiikka, tieto- ja viestintätekniikka reading circle, teaching of literature, tri-literacy, literacy, reading, literature, aestheticreading, modern learning enviroment, open anf flexible learning enviroment, telematics, modern information technology

Pyhä Kolminaisuus vai pilven reunalla istuva partasuu? : Jumalakuva evankelisluterilaisissa ja ortodoksissa 1.–4.-luokan uskonnon oppikirjoissa 1970–80- ja 2000-luvuilla

A concept of god is a wholeness that an individual experiences as God. The Christian concept of god is based on triune God: Father, Son, and the Holy Spirit. The concept of god is examined in different kinds of contexts particularly between the 1940's and the 1970's. Many researches of school books have widely been made in Finland, but, however, only a few from the point of view of the concept of god. Considering this, the concept of god in the school books of Evangelical Lutheran and Orthodox religion from first to fourth grade in 1970–80 and 2000 is examined in this survey. Additionally, the concept of god in curricula between years 1970 and 2004 is studied. The perspective on the concept of god is the change in the course of time and denominational emphasis. As a first hypothesis, God the Father is represented in books in 21st century as a kind and loving figure. As a second hypothesis, the Trinity and the Holy Spirit get more space in Orthodox books comparing with the Lutheran books. Twelve school books of Evangelical Lutheran and Orthodox religion from first to fourth grade were used as a research material. The books were from four different series between the years 1978 and 2005. Teacher's guidebooks and student's exercise books were left outside of this survey. The research material was analyzed by using abductive content analysis and methodological triangulation. This study included both qualitative and quantitative aspects. The classification system which defined the classifying of concept of god from the research material was consisted of the basis of research material, former reseach, and subtext of used theories. The number of mentions in concept of god was higher in books from the 21st century. In Lutheran books, the change was seen as a growth of the category of God the Father. In Orthodox books, the trend was opposite: the category of Jesus the Son had grown. Differing from the presupposition, the features of loving God in new books had less emphasis than in older books in both churces. The mentions of the Holy Spirit and Trinity were marginal. In the Orthodox books, the categories were bigger, as it was presupposed. It could be seen, that the books confirmed the legalistic period of the concept of god on 3rd and 4th grades. The mentions of concept of god in curriculas have diminished and generalized. The diminution was seen most radically in the curriculum from the year 1994. The results tell something about social changes and views of innovation in curricula. In books the change was not perceived that bright. The idea of the concept of god getting shrank and decreased during the time can be refused.

Latent TGF-β binding proteins -3 and -4 : transcriptional control and extracellular matrix targeting

Extracellular matrix (ECM) is a complex network of various proteins and proteoglycans which provides tissues with structural strength and resilience. By harvesting signaling molecules like growth factors ECM has the capacity to control cellular functions including proliferation, differentiation and cell survival. Latent transforming growth factor β (TGF-β) binding proteins (LTBPs) associate fibrillar structures of the ECM and mediate the efficient secretion and ECM deposition of latent TGF-β. The current work was conducted to determine the regulatory regions of LTBP-3 and -4 genes to gain insight into their tissue-specific expression which also has impact on TGF-β biology. Furthermore, the current research aimed at defining the ECM targeting of the N-terminal variants of LTBP-4 (LTBP-4S and -4L), which is required to understand their functions in tissues and to gain insight into conditions in which TGF-β is activated. To characterize the regulatory regions of LTBP-3 and -4 genes in silico and functional promoter analysis techniques were employed. It was found that the expression of LTBP-4S and -4L are under control of two independent promoters. This finding was in accordance with the observed expression patterns of LTBP-4S and -4L in human tissues. All promoter regions characterized in this study were TATAless, GC-rich and highly conserved between human and mouse species. Putative binding sites for Sp1 and GATA family of transcription factors were recognized in all of these regulatory regions. It is possible that these transcription factors control the basal expression of LTBP-3 and -4 genes. Smad binding element was found within the LTBP-3 and -4S promoter regions, but it was not present in LTBP-4L promoter. Although this element important for TGF-β signaling was present in LTBP-4S promoter, TGF-β did not induce its transcriptional activity. LTBP-3 promoter activity and mRNA expression instead were stimulated by TGF-β1 in osteosarcoma cells. It was found that the stimulatory effect of TGF-β was mediated by Smad and Erk MAPK signaling pathways. The current work explored the ECM targeting of LTBP-4S and identified binding partners of this protein. It was found that the N-terminal end of LTBP-4S possesses fibronectin (FN) binding sites which are critical for its ECM targeting. FN deficient fibroblasts incorporated LTBP-4S into their ECM only after addition of exogenous FN. Furthermore, LTBP-4S was found to have heparin binding regions, of which the C-terminal binding site mediated fibroblast adhesion. Soluble heparin prevented the ECM association of LTBP-4S in fibroblast cultures. In the current work it was observed that there are significant differences in the secretion, processing and ECM targeting of LTBP-4S and -4L. Interestingly, it was observed that most of the secreted LTBP-4L was associated with latent TGF-β1, whereas LTBP-4S was mainly secreted as a free form from CHO cells. This thesis provides information on transcriptional regulation of LTBP-3 and -4 genes, which is required for the deeper understanding of their tissue-specific functions. Further, the current work elucidates the structural variability of LTBPs, which appears to have impact on secretion and ECM targeting of TGF-β. These findings may advance understanding the abnormal activation of TGF-β which is associated with connective tissue disorders and cancer.

Antizyme Inhibitor 2 : A Novel Regulator of Cellular Polyamine Homeostasis

Polyamines are organic polycations that participate in various physiological functions, including cell proliferation, differentiation and apoptosis. Cellular polyamines originate from endogenous biosynthesis and exogenous sources. Their subcellular pool is under strict control, achieved by regulating their uptake and metabolism. Polyamine-induced proteins called antizymes (AZ) act as key regulators of intracellular polyamine concentration. They regulate both the transport of polyamines and the activity and degradation of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. AZs themselves are negatively regulated by antizyme inhibitor (AZIN). AZIN functions as a positive regulator of cellular polyamine homeostasis, which by binding to AZs reactivates ODC and induces the uptake of polyamines. In various pathological conditions, including cancer, polyamine levels are misregulated. Polyamine homeostasis has therefore become an attractive target for therapeutic interventions and it is thus crucial to characterize the molecular basis underlying the homeostatic regulation. A novel human AZIN-resembling protein was previously identified in our group. The purpose of this study was to elucidate the function and distribution of this protein, termed as an antizyme inhibitor 2 (AZIN2). According to my results, AZIN2 functions as a novel regulator of polyamine homeostasis. It shows no enzymatic activity, but instead it binds AZs and negates their activity, which subsequently leads to reactivation of ODC and inhibition of its degradation. Expression of AZIN2 is restricted to terminally differentiated cells, such as mast cells (MC) and neurosecretory cells. In these actively secreting cell types, AZIN2 localizes to subcellular vesicles or granules where its function is important for the vesicle-mediated secretion. In MCs, AZIN2 localizes to the serotonin-containing subset of MC granules, and its expression is coupled to MC activation. The functional role of polyamines as potential mediators of MC activity was also investigated, and it was observed that the secretion of serotonin is selectively dependent on activation of ODC. In neurosecretory cells, AZIN2-positive vesicles localize mainly to the trans-Golgi network (TGN). Depletion of AZIN2 or cellular polyamines causes selective fragmentation of the TGN and retards secretion of proteins. Since addition of exogenous polyamines reverses these effects, the data indicate that AZIN2 and its downstream effectors, polyamines, are functionally implicated in the regulation of secretory vesicle transport. My studies therefore reveal a novel function for polyamines as modulators of both constitutive and regulated secretion. Based on the results, I propose that the role of AZIN2 is to act as a local in situ activator of polyamine biosynthesis.

Structural analyses of (1->3),(1->4)-β-D-glucan of oats and barley

The structures of (1→3),(1→4)-β-D-glucans of oat bran, whole-grain oats and barley and processed foods were analysed. Various methods of hydrolysis of β-glucan, the content of insoluble fibre of whole grains of oats and barley and the solution behaviour of oat and barley β-glucans were studied. The isolated soluble β-glucans of oat bran and whole-grain oats and barley were hydrolysed with lichenase, an enzyme specific for (1→3),(1→4)-β-D-β-glucans. The amounts of oligosaccharides produced from bran were analysed with capillary electrophoresis and those from whole-grains with high-performance anion-exchange chromatography with pulse-amperometric detection. The main products were 3-O-β-cellobiosyl-D-glucose and 3-O-β-cellotriosyl-D-glucose, the oligosaccharides which have a degree of polymerisation denoted by DP3 and DP4. Small differences were detected between soluble and insoluble β-glucans and also between β-glucans of oats and barley. These differences can only be seen in the DP3:DP4 ratio which was higher for barley than for oat and also higher for insoluble than for soluble β-glucan. A greater proportion of barley β-glucan remained insoluble than of oat β-glucan. The molar masses of soluble β-glucans of oats and barley were the same as were those of insoluble β-glucans of oats and barley. To analyse the effects of cooking, baking, fermentation and drying, β-glucan was isolated from porridge, bread and fermentate and also from their starting materials. More β-glucan was released after cooking and less after baking. Drying decreased the extractability for bread and fermentate but increased it for porridge. Different hydrolysis methods of β-glucan were compared. Acid hydrolysis and the modified AOAC method gave similar results. The results of hydrolysis with lichenase gave higher recoveries than the other two. The combination of lichenase hydrolysis and high-performance anion-exchange chromatography with pulse-amperometric detection was found best for the analysis of β-glucan content. The content of insoluble fibre was higher for barley than for oats and the amount of β-glucan in the insoluble fibre fraction was higher for oats than for barley. The flow properties of both water and aqueous cuoxam solutions of oat and barley β-glucans were studied. Shear thinning was stronger for the water solutions of oat β-glucan than for barley β-glucan. In aqueous cuoxam shear thinning was not observed at the same concentration as in water but only with high concentration solutions. Then the viscosity of barley β-glucan was slightly higher than that of oat β-glucan. The oscillatory measurements showed that the crossover point of the G´ and G´´ curves was much lower for barley β-glucan than for oat β-glucan indicating a higher tendency towards solid-like behaviour for barley β-glucan than for oat β-glucan.

Synthesis, Reactivity and Biological Activity of 17β-HSD1 Inhibitors Based on a Thieno[2,3-d]pryrimidin-4(3H)-one Core

Breast cancer is the most common cancer in women in Western countries. In the early stages of development most breast cancers are hormone-dependent, and estrogens, especially estradiol, have a pivotal role in their development and progression. One approach to the treatment of hormone-dependent breast cancers is to block the formation of the active estrogens by inhibiting the action of the steroid metabolising enzymes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of estradiol, the most potent female sex hormone. The 17beta-HSD1 enzyme catalyses the final step and converts estrone into the biologically active estradiol. Blocking 17beta-HSD1 activity with a specific enzyme inhibitor could provide a means to reduce circulating and tumour estradiol levels and thus promote tumour regression. In recent years 17beta-HSD1 has been recognised as an important drug target. Some inhibitors of 17beta-HSD1 have been reported, however, there are no inhibitors on the market nor have clinical trials been announced. The majority of known 17beta-HSD1 inhibitors are based on steroidal structures, while relatively little has been reported on non-steroidal inhibitors. As compared with 17beta-HSD1 inhibitors based on steroidal structures, non-steroidal compounds could have advantages of synthetic accessibility, drug-likeness, selectivity and non-estrogenicity. This study describes the synthesis of large group of novel 17beta-HSD1 inhibitors based on a non-steroidal thieno[2,3-d]pyrimidin-4(3H)-one core. An efficient synthesis route was developed for the lead compound and subsequently employed in the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one based molecule library. The biological activities and binding of these inhibitors to 17beta-HSD1 and, finally, the quantitative structure activity relationship (QSAR) model are also reported. In this study, several potent and selective 17beta-HSD1 inhibitors without estrogenic activity were identified. This establishment of a novel class of inhibitors is a progressive achievement in 17beta-HSD1 inhibitor development. Furthermore, the 3D-QSAR model, constructed on the basis of this study, offers a powerful tool for future 17beta-HSD1 inhibitor development. As part of the fundamental science underpinning this research, the chemical reactivity of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-ones with electrophilic reagents, i.e. Vilsmeier reagent and dimethylformamide dimethylacetal, was investigated. These findings resulted in a revision of the reaction mechanism of Vilsmeier haloformylation and further contributed to understanding the chemical reactivity of this compound class. This study revealed that the reactivity is dependent upon a stereoelectronic effect arising from different ring conformations.