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(2014)Tutkielmassa esitellään keskeisimpiä robusteja menetelmiä logistiselle regressiomallille. Menetelmien toimivuutta ja käyttökelpoisuutta selvitetään kokeellisesti empiirisen aineiston sekä simulointimallin avulla. Eri menetelmien välisiä eroja on pyritty selvittämään kokeellisten tarkasteluiden yhteydessä.
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(2013)Den schweiziska läkaren Guido Piderman fick genom flera sammanträffanden följa med Internationella Röda korskommitténs (ICRC) delegat på ett besök till finska fångläger. Han reagerade starkt på de sovjetiska krigsfångarnas situation och bestämde sig under hösten 1942 att publicerade en pamflett och starta en kampanj för dessa fångar. Pidermans kampanj väckte starkt motstånd både hos ICRC samt finska och schweiziska myndigheter och det är dessa reaktioner som analyseras i denna forskning. Det empiriska materialet är insamlat i ICRC:s arkiv i Geneve och en stor del av materialet har inte varit tillgängligt i Finland tidigare. Genom att utforska Pidermanaffären ur ett mikrohistoriskt perspektiv framkommer nya aspekter av ICRC:s krigstida arbete. I denna forskning uppfattas ICRC som en normentreprenör i enlighet med Finnermores och Sikkinks idéer. Pidermans pamflett försatte ICRC i en krisartad situation som kom att ha sin mest intensiva fas i november och december 1942. Forskningen rör sig från det marginella till det allmänna, och börjar med att beskriva Pidermanaffären på nära håll (mikronivå) för att sedan övergå till att analysera vilka delområden i ICRC:s arbete som den påverkar. Forskningens mål är att förstå varför Pidermans kampanj, ett initiativ i marginalen, kom att väcka reaktioner hos så många parter. Pidermanaffären visar att ICRC:s överlevnadsstrategi under kriget – att ty sig till neutralitetsprincipen – inte längre fungerade på önskat vis då organisationen inte längre förmådde leva upp till rollen som normentreprenör. Frågan om de sovjetiska krigsfångarna är känslig och ICRC:s dåliga relationer till Sovjetunionen paralyserar organisationen.
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(2022)Goal: The aim of this master thesis are two. First, the aim is to describe, analyse, and interpret how instruction striving to strengthen the students' spelling skills is planned and realized in the lower school grades, in which the students are still at the beginning of their writing development process. Second, the aim is to investigate what assessment and feedback the students are offered regarding their spelling. Purposefully, the study has been limited to the students in grades 1 – 4 in primary school and to the Swedish and literature teaching subject. The study took place in schools in Finland with Swedish as language of instruction. The Core Curriculum of Basic Education (first published 2014, in English 2016) mentions correct spelling mostly incidentally, even if spelling skills may affect students' experience of themselves, their school success, and have an influence on their future study and professional opportunities. Therefore, it is important to explore how the primary school teachers have chosen to work to strengthen the students' spelling skills. Method: The empirical study is based on interviews with seven teachers, who teach in grades 1–4. The study was carried out from a realistic perspective to study as neutrally and objectively as possible the teaching that strives to strengthen the students' spelling skills. To support the interviews, an interview guide was created. The interview guide is based on a literature review based on previous research. In the analysis, I strove to find similarities, differences and repeated topics. Based on the collected material and the analysis process, eight topics emerged. Finally, I discuss the results in relation to previous research. Results: The interviewed teachers felt that the students develop their correct spelling as a natural part of all text work, both in the Swedish and literature subject and in cross-curricular teaching. The teachers believed that the students' writing motivation is more important than correct spelling. Obviously, the students are offered limited or no assessment and feedback on their spelling, with the exception of spelling tests. The results showed that in the interviewed teachers’ classrooms, spelling test is the only method by which the correct spelling is taught. The texts the teachers choose for the spelling tests usually contain a topic related to correct spelling, such as double designation or a certain sound. The teachers in this study found the use of spelling test problematic, since the students and their guardians have the major responsibility for practicing before the spelling test. Thus, the teachers felt that this created unequal conditions for the students.
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Rodun ja kasvatusajan vaikutus liharotuisten nautojen teurasominaisuuksiin sekä lihan syöntilaatuun (2020)Tässä tutkimuksessa selvitettiin liharotuisten nautojen rodun ja kasvatusajan yhteyttä ruhon teurasominaisuuksiin sekä lihan syöntilaatuun. Lisäksi tässä tutkimuksessa selvitettiin ultraäänellä mitattujen ominaisuuksien fenotyyppistä korrelaatiota eläimen teurasominaisuuksiin sekä lihan syöntilaatuun. Tutkimuksen aineistona oli Rotukarjan hyvinvoinnin ja taloudellisten toimintaedellytysten parantaminen -hankkeen (2010–2013) ruokintakokeen tulokset. Lopullinen aineisto sisälsi 158 sonnin tiedot, jotka edustivat viittä yleistä Suomessa kasvatettavaa liharotua. Rodut olivat aberdeen angus, charolais, hereford, limousin ja simmental. Teurasominaisuuksista mitattiin teuraspainoa, teurasprosenttia, lihakkuutta ja rasvaisuutta. Lihan syöntilaadun tutkimus sisälsi tiedon lihan marmoroitumisasteesta, pH-arvosta, leikkuuvasteesta, valumasta ja väriominaisuuksista, vaaleudesta (L), punaisuudesta (a) ja keltaisuudesta (b) sekä arvion aistinvaraisesta syöntilaadusta. Aistinvarainen syöntilaatu sisälsi mureuden, mehukkuuden, maun sekä näiden yhteispisteet. Tilastollisina menetelminä käytettiin type 2-testauksen sisältävää ANOVA-mallia sekä ls-keskiarvoja, Tukeyn parittaisvertailua ja regressioanalyysiä. Tutkimuksen tulosten perusteella voidaan todeta, että rodulla on merkitsevä vaikutus useaan tutkittuun ominaisuuteen. Taloudellisesti näistä merkittävämpiä ovat teurasprosentti, lihakkuus ja rasvaisuus. Lyhyt kasvatusaika on taloudellisesti kannattavampi kuin pitkä kasvatusaika, kun huomioidaan ominaisuuksiin vaikuttavat panostetut resurssit. Lyhyellä kasvatusajalla kasvatettujen sonnien teuraspaino, teurasprosentti ja lihakkuus olivat suhteessa korkeammat kuin pitkän kasvatusajan ryhmän eläimillä. Ultraäänellä mitatulla ulkofileen paksuudella on suotuisa yhteys teurasprosenttiin. Ultraäänellä mitatulla marmoroitumisasteella on suotuisa yhteys lihan marmoroitumisasteeseen, punaisuuteen, mureuteen (aistinvarainen ja leikkuuvaste), mehukkuuteen ja aistinvaraisen arvioinnin yhteispisteisiin.
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(2019)Tämä Pro Gradu -tutkielma käsittelee rohingyojen historiaa sekä vähemmistöoikeuksien kehittymistä rinnakkain. Työn tarkoituksena on vastata kolmeen kysymykseen. Selvitän, miksi rohingyoja on syrjitty järjestelmällisesti. Lisäksi tutkin, onko vähemmistöoikeuksien kehittymisellä ollut jonkinlaista merkitystä rohingyojen historiassa ja nykypäivässä. Tämän jälkeen selvitän, kohtaako rohingyojen historia vähemmistöoikeuksien historian ja mikä muodostaa ja synnyttää vähemmistöoikeuksia sekä miten vähemmistöoikeuksien olemassaolo saa oikeutuksensa. Kysymyksenasettelu ja rakenne määrittelevät tutkielman metodin. Lähestymistapa on oikeushistoriallinen. Tutkin ja selitän rohingya-kansan historiaa ja muutosta peilaten sitä vähemmistöoikeuksien kehitykseen. Lähdeaineistona ovat lähinnä englanninkieliset akateemiset artikkelit sekä vähemmistöoikeuksia käsittelevät kansainväliset teokset. Nykypäivää lähestyttäessä olen turvautunut sanomalehtiartikkeleihin tutkimuksen puuttuessa. Rohingyojen systemaattinen syrjintä on monen asian summa, mutta merkittävimpinä tekijöinä taustalta löytyy brittien siirtomaapolitiikka ja sen laukaisema uskonnollisen nationalismin nousu, buddhalaisuuden vahva asema ja sen kytkeytyminen politiikkaan, Myanmarin autokraattinen hallinto ja sen syrjivä politiikka, ratkaisemattomat konfliktit Rakhinen alueella sekä taloudelliset intressit Rakhinessa. Lisäksi syrjintää on vauhdittanut faktatiedon, tutkimuksen ja kriittisen median puute sekä sosiaalisen median, erityisesti Facebookin, nousu. Vähemmistöoikeuksien kehityksellä ei vaikuta olleen merkittävää vaikutusta rohingyojen kohteluun. Kansainvälinen vähemmistöoikeusnormisto on ottanut askelia vähemmistöjen suojelun osalta ja instrumentit ovat kehittyneet, mutta rohingyoihin tämä kehitys ei näytä juuri ulottuneen. Tutkielmassani on kyseessä law in books, law in action -teoria, joka sopii rohingyojen tilanteeseen hyvin; vaikka jokin oikeudellinen doktriini on kirjattu oikeudelliseen instrumenttiin, se ei välttämättä toteudu tosielämässä. Vähemmistöoikeuksilla vaikuttaa olevan merkitystä vain, jos ne muuttuvat käytökseksi, ne tunnetaan ja niihin luotetaan. Vähemmistöoikeuksien vaikuttavuuden arvioinnissa tulee ottaa huomioon käytännön ja säännöksen suhde, mahdollisuus vedota oikeusnormeihin, valtion yleinen demokratiakehitys, toimijoiden monet intressit ja niiden suhde oikeuksiin sekä rikkomustapauksissa vastuuseensaattamisjärjestelmät ja niiden toimivuus.
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(2018)Objectives. The aim of the present study is to identify factors influencing primary school teachers' perceptions of their own competence in teaching programming. Programming was included in the Finnish curriculum in 2016 and has consequently not yet been studied in depth. Thus, the factors influencing teachers' competence in this study were initially selected through discourse with teachers and from studies examining the problems in teaching ICT. In this study emotions affecting teaching (enthusiasm, fear/anxiety), previous experiences, other teachers and school administration are treated as factors potentially influencing teachers' competence. Methods. Teachers' evaluations of their attitudes and emotions towards teaching programming as well as background information were obtained using a web-based questionnaire with 7-point Likert and open-ended complementary items. A total of 253 participants completed the questionnaire. The data was analyzed using a mixed methods design which comprised i) conducting a multiple linear regression analysis and ii) qualitative examination of common themes found in open-ended questions. Conclusions. Seven significant predictors to teaching competence were found in multiple regression modelling. Regression analysis determined that the most influential variables to competence were enthusiasm, teacher's awareness of what teaching programming requires of her/him and previous experiences as trainings or trying programming with students. The open-ended questions revealed that teachers emphasized the importance of being able to try new teaching subjects and the need to be explained what is expected of them regarding new procedures as including programming in the curriculum. Importantly, teachers were largely unaware of what teaching programming required of them. Finally, the results indicate that offering possibilities to try programming at school and explaining teachers what it means to teach programming in practice increases teachers' competence.
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(2017)Tutkielman tavoitteena on kehittää menetelmiä eli algoritmeja roikkuvan sateen tunnistamiseksi säätutkamittauksista. Roikkuvan sateen määritellään olevan ‘meteorologisista kohteista peräisin olevia sateen havaintoja, jotka eivät vastaa maan pinnalle asti päätyvää sadetta pystysuoran ilmapilarin kohdalla’. Määritelmä kattaa sekä pilvet että haihtuvan sateen. Algoritmikehitystä varten tutkielmassa käytetään havaintoja kymmenestä käsin valitusta tapauksesta vuosien 2011-2013 ajalta Suomesta. Tapauksiin tiedetään liittyvän roikkuvaa sadetta. Havaintolähteinä käytetään säätutkia, automaattisia säähavaintoasemia ja tiesääasemia. Tutkielmassa kehitettäviä algoritmeja on kolme: 1) tutkaheijastavuustekijän pystysuuntaista profiilia tarkasteleva algoritmi, 2) säätutkan ja sademittareiden havaintoja yhdistävä algoritmi ja 3) ehtofunktioalgoritmi, joka tarkastelee yksittäisen havainnon korkeutta ja tutkaheijastavuustekijän voimakkuutta. Algoritmit luokittelevat säätutkan havaintoja yhteen korkeintaan viidestä eri luokituksesta. Mahdollisten luokitusten määrä riippuu algoritmista. Algoritmien toimintaa tarkasteltiin vertaamalla eri algoritmien antamia luokituksia toisiinsa. Vertailun perusteella algoritmien todettiin olevan melko hyvin yksimielisiä tutkielman puitteissa. Yksimielisyys heikkeni, kun etäisyys säätutkasta oli riittävän suuri (yli 120 km). Vertailussa havaittiin myös, että tietyissä tilanteissa kaikki algoritmit eivät pysty luokittelemaan havaintoa sateeksi tai roikkuvaksi sateeksi. Tämän ristiriitaisuuden todettiin johtuvan algoritmien luokittelusäännöissä käytetyistä ehdoista. Tutkielman tulokset ovat kuitenkin rohkaisevia ja algoritmeja suositellaan otettavaksi käyttöön vähintään puolioperatiivisesti. Lisäksi tutkielmassa annetaan ehdotuksia jatkotutkimusta varten.
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(2022)Koronaviruspandemia aiheutti merkittäviä muutoksia ihmisten arkielämään ja herätti uudenlaisia oikeudellisia kysymyksiä pandemianhoitoon liittyen. Erityisesti perus- ja ihmisoikeuksien asettamat rajoitukset pandemianhoidollisille toimenpiteille ovat nousseet esiin oikeustieteellisessä keskustelussa. Rokottamisjärjestystä ja rokotevalmisteiden kohdentamista koskevat näkökulmat herättivät erityisesti vuonna 2021 laajaa yhteiskunnallista keskustelua. Keskustelussa nousivat esiin huolet rokotteiden turvallisuudesta, rokottamisjärjestyksen oikeudenmukaisuudesta sekä rokotevalmisteiden kohdentamiseen liittyvät yhdenvertaisuusnäkökulmat. Tutkielmassa tarkastellaan koronavirusrokotteiden rokottamisjärjestykseen ja rokotevalmisteiden kohdentamiseen liittyvää kysymyksenasettelua oikeudellisessa kontekstissa. Oikeustilaa selvitetään soveltuvan lainsäädännön, lakia alemman asteisen sääntelyn ja erityisesti oikeusasiamiehen ratkaisukäytännön pohjalta. Tutkielman kantavina teemoina ovat priorisoinnin, potilaan itsemääräämisoikeuden ja yhdenvertaisuuden käsitteet, joita tutkielmassa tarkastellaan liikkuen yleisemmältä tasolta kohti yksityiskohtaisempaa tarkastelua oikeusasiamiehen ratkaisukäytännön valossa. Rokottamisjärjestyksestä ja rokotevalmisteiden kohdentamisesta päätettäessä on kyseessä terveydenhuollon rajallisten resurssien priorisoinnista. Vastakkain priorisoinnissa voi nähdä olevan yhtäältä yksilön oikeuksia painottava näkökulma, jossa painottuvat potilaan itsemääräämisoikeutta ja yhdenvertaisuutta puoltavat näkökannat. Tällöin priorisoinnissa tulee ottaa mahdollisimman laajasti huomioon potilaan oikeus päättää hoidossaan käytettävistä rokotevalmisteista sekä potilaiden kohtelu yhdenvertaisella tavalla niin, ettei ketään aseteta perusteettomasti toisia huonompaan asemaan. Toisaalta taas kansanterveydellisestä näkökulmasta painottuvat tartuntatautisääntelyn tarkoitus mm. tartuntatautien ehkäisyssä sekä rajallisten resurssien tilanteessa perus- ja ihmisoikeuksina turvattu pääsy riittävään terveydenhuoltoon. Väestön tasolla tarkasteltaessa priorisoinnissa painottuvat tällöin rokotusten toteuttaminen mahdollisimman nopeasti niin, että suuri osa väestöstä saadaan rokotettua nopeasti. Tartuntatautiepidemiasta johtuvissa poikkeuksellisissa olosuhteissa lainsäätäjän ja viranomaisten tulisi kiinnittää erityistä huomiota lainvalmistelussa ja viranomaistiedottamisessa oikeudellisen valmistelun merkitykseen ja perusteellisuuteen perus- ja ihmisoikeuksien turvaamiseksi poikkeusolosuhteissa.
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(University of HelsinkiHelsingin yliopistoHelsingfors universitet, 1996)Näiden syventävien opintojen alkusysäyksenä toimi kesällä 1992 amerikancockerspanielipennuilla ensimmäisten rokotusten jälkeen havaitut selittämättömät kouristukset. Myöhemmin pinseriharrastajien taholta otettiin yhteyttä pinsereillä yleisenä esiintyvien rokotuskomplikaatioiden vuoksi. Tämän työn tavoitteena oli selvittää amerikancockerspanielien ja pinsereiden rokotuskomplikaatioiden syitä, sekä tehdä yhteenveto Eläinlääkintä- ja elintarvikelaitokseen tehdyistä rokotusreaktioilmoituksista.
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(2010)Actin stress fibers are dynamic structures in the cytoskeleton, which respond to mechanical stimuli and affect cell motility, adhesion and invasion of cancer cells. In nonmuscle cells, stress fibers have been subcategorized to three distinct stress fiber types: dorsal and ventral stress fibers and transverse arcs. These stress fibers are dissimilar in their subcellular localization, connection to substratum as well as in their dynamics and assembly mechanisms. Still uncharacterized is how they differ in their function and molecular composition. Here, I have studied involvement of nonmuscle alpha-actinin-1 and -4 in regulating distinct stress fibers as well as their localization and function in human U2OS osteosarcoma cells. Except for the correlation of upregulation of alpha-actinin-4 in invasive cancer types very little is known about whether these two actinins are redundant or have specific roles. The availability of highly specific alpha-actinin-1 antibody generated in the lab, revealed localization of alpha-actinin-1 along all three categories of stress fibers while alphaactinin-4 was detected at cell edge, distal ends of stress fibers as well as perinuclear regions. Strikingly, by utilizing RNAi-mediated gene silencing of alpha-actinin-1 resulted in specific loss of dorsal stress fibers and relocalization of alpha-actinin-4 to remaining transverse arcs and ventral stress fibers. Unexpectedly, aberrant migration was not detected in cells lacking alpha-actinin-1 even though focal adhesions were significantly smaller and fewer. Whereas, silencing of alpha-actinin-4 noticeably affected overall cell migration. In summary, as part of my master thesis study I have been able to demonstrate distinct localization and functional patterns for both alpha-actinin-1 and -4. I have identified alpha-actinin-1 to be a selective dorsal stress fiber crosslinking protein as well as to be required for focal adhesion maturation, while alpha-actinin-4 was demonstrated to be fundamental for cell migration.
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(2021)Epithelial cells line the surfaces of organs and tissues in a continuous and tightly packed manner, thereby functioning as a protective barrier between the tissue and the external environment known as the epithelium. During development, the epithelium undergoes a series of morphogenetic events which alters the shape and size of epithelial cells, enabling them to perform tissue specific functions in mature tissue. During morphogenesis, cells sense the mechanical forces and establish polarity through cell proliferation and rearrangement according to morphogenetic signalling pathways. This manoeuvre is achieved by the underlying actin cytoskeleton network which enables cells to resist the tension and stresses of morphogenesis via alteration of filament dynamics and network architecture. In vivo, numerous actin-regulatory proteins generate various polymerized forms of straight, branched, or contractile actin-myosin filaments, regulating dynamic actin filament turnover. The robust actin cytoskeleton provides the cell with protrusive and contractile forces that enable cells to migrate, maintain, and change its shape and form during morphogenetic events. Actin filament depolymerization is accomplished by ADF/cofilin (Drosophila homolog twinstar) binding to actin monomers (G-actin) and actin filaments. However, ADF/cofilin alone is not very efficient in promoting disassembly of actin monomers, especially in subcellular regions where ADF/cofilin is highly concentrated. AIP1 (Drosophila homolog flare) then enhances actin depolymerization via preferential binding to ADF/Cofilin rich regions in vitro. The aim of my thesis was to study the localization and roles of AIP1 and cofilin in follicular epithelium during Drosophila oogenesis. My results showed that Actin-Interacting-Protein-1 (AIP1) was expressed throughout oogenesis. AIP1 expression was increased in cell type-specific manner and AIP1 showed spatiotemporal localization in follicular epithelium during oogenesis. Silencing of AIP1 led to accumulation of ectopic F-actin aggregates, localization of which may reflect the cellular sites of dynamic actin reorganization in the follicular epithelium. My results also indicate that AIP1 may be indirectly responsible for maintaining epithelial integrity as its silencing resulted in formation of epithelial gaps throughout follicular epithelium. Also delays in border cell migration were observed. Considering the above, understanding how AIP1 functions in Drosophila morphogenetic events would therefore pave the way for a greater understanding of how this protein works in other organisms. The knowledge gained may also be used to extend the current understanding of the role of actin binding proteins in diseased states.
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(2020)The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.
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(2017)When goods are sold internationally, it is common that the seller receives the purchase price against documents. In many cases, the buyer does not have a chance to examine the goods before the seller obtains payment. Therefore, the buyer must rely on the accuracy of the information contained in the documents. The objective of the thesis is to discuss the risks that are related to the purchase price being paid against the documents. Furthermore, the thesis analyses what additional roles documents play in the contract of sale and contracts supplementing it. The main focus is on the bill of lading, which is a sea transportation document issued by the carrier, because it enables, for example, the goods to be sold during transit. A documentary credit is a commonly used method of payment. In order for the seller to obtain the purchase price, the seller must deliver conforming documents to the bank. This creates a documentary risk, meaning that there is a risk that documents provided by the seller might not be in accordance with the terms of the letter of credit. If this happens the bank must refuse payment. From the buyer’s perspective, there is a risk that the documents do not communicate accurately the status of the goods on loading. The description of the goods in the bill of lading is subject to the carrier’s obligation to check the quantity, quality, and condition of the goods. In practice, the carrier’s obligation to check is limited in particular when goods are containerised. Therefore, the information cannot be entirely reliable. Moreover, the carrier is not able to assess whether the goods are in accordance with the contract of sale because he is not an expert surveyor and not aware of the terms of the sale contract. According to the Finnish Maritime Code, the carrier is liable for inaccurate information in some situations which enhances the transferability of the document. The research illustrates that the system seeks to ensure that the documents are accurate. However, is not without gaps and thus, there is a risk that the seller obtains the payment even when the goods are not in accordance with the agreement between the seller and the buyer. Moreover, the system has not been constructed in a way which would easily detect the seller’s fraud. This is because the banks that examine the documents supplied by the seller adopt a formalistic approach which does not seek to assess the actual condition of the goods, rather it is based on the assumption that their description is sufficient. The bill of lading is also a tool needed in the delivery of the goods. Goods might arrive before the documents which certainly increases the likeliness of the carrier delivering the goods to the wrong party without complying with the rules on delivery as stipulated in the Finnish Maritime Code. The industry has developed arrangements to mitigate the risks related to delivery without a bill of lading which shows that the document is not able to meet the needs of today’s trade.
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(2023)Thirty years after the fall of communism, the post-socialist countries find themselves in a state of economic dependency. The main argument of the thesis is that the Visegrad Four (V4) countries (the Czech Republic, Poland, Hungary and Slovakia) operate in an FDI-led growth model, characterized by strong presence of foreign capital (especially in export-oriented manufacturing sector), but a low level of knowledge spill-overs from foreign-owned sectors to those in domestic ownership, which constraints the productivity growth of the domestic-owned enterprises (the so-called dual economy). Integration into the global economy, conducted in the V4 countries mainly through ties with Germany, was initially highly beneficial, however, it is increasingly becoming a constraint on further development, illustrated e. g. by the inability to achieve full convergence to EU-15. The aim of the thesis is to describe how did the FDI-led growth model developed in the V4 countries between 1990 and 2019; what was the political discussion of the growth model; and the differences in these two spheres between the V4 countries. This is studied on two levels: the FDI-led growth model itself (described using a set of macroeconomic indicators); and analysis of the political discussion. The conclusion is that the V4 countries differ both in terms of development of the FDI-led growth model (the biggest outlier is Poland, which is less reliant on foreign investment then rest of the group), and in terms of the political approach to the model (especially Poland and Hungary after 2010 take active steps to limit the impact of the FDI dependency; the Czech Republic and Slovakia are more or less aware of the dependency, but take no interventionist measures). Given the high levels of economic growth in Poland and especially Hungary after 2014, there is most probably a causality between the efforts to limit the dependency and the economic development (although other factors, such as the size of the economy, play a role too). However, it is also argued that unlike certain level of economic nationalism, populism is not a prerequisite for limiting the dependent growth and in the long run can actually be harmful to economic development.
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(2022)Dendritic cells (DCs) are antigen presenting cells found in a resting state throughout the tissues of the body. They play a crucial role in cancer, by enabling the immune system to recognize and kill cancer cells expressing antigens, by presenting them to cytotoxic T-cells. DCs are activated by detection of damage associated molecular patterns or pathogen associated molecular patterns, which leads to maturation of the DCs. Maturation is associated with higher expression of antigen presenting molecules, costimulatory molecules and chemokine receptors. DCs migrate to lymph nodes to present antigens to T-cells to activate the adaptive immune system. Although the maturation profile is well characterized, the signaling and transcription factor network controlling the switch is incompletely understood. β2-integrins are leukocyte specific adhesion molecules, enabling many important cellular functions, such as extravasation of leukocytes into infection sites and cell-to-cell adhesion. DC expressing dysfunctional integrins exhibit a more mature profile with upregulation of DC maturation markers and increased IL-12 and TNF-α cytokine production. This suggests a restrictive role of integrins in DC maturation. The PERK pathway is an unfolded protein response. Its activation leads to phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) to stop protein translation. Previous studies show a decrease in eIF2α phosphorylation upon DC maturation. Here, phosphorylation of eIF2α was hypothesized to be involved in integrin-regulated DC maturation. Inhibition of the eIF2α kinase PERK and phosphatase GADD34 did not induce a significant difference in expression of DC maturation markers (CD80, CD40, CD86, MHC-II and CCR7) or cytokines IL-12 and TNF in BM-DCs. However, DCs with dysfunctional integrins showed lower levels of phosphorylated eIF2α at base levels and exhibited altered phosphorylation after LPS stimulation. An increase in eIF2α phosphorylation could be observed, rather than a decrease observed in DCs with functional integrins. I confirmed increased expression of DC markers MHC-II, CD86 and CD40 in unstimulated BM-DCs with dysfunctional integrins. Additionally, higher levels of CD86 and CD80 were observed in LPS stimulated BM-DCs with dysfunctional integrins. Increased levels of transcription factor NF-κB nuclear translocation and TNF production were observed in LPS stimulated BM-DCs. Additionally, LPS stimulation led to increased expression of the cytokine IL-12. The results of this study therefore indicate that the PERK pathway may not be involved in integrin-regulated DC maturation. Understanding molecular pathways regulating DC maturation aids to understand the biology of these important antigen presenting cells. A complete understanding of the role and regulation of DCs in immunity, including anti-cancer immunity, yields opportunities to optimize DC therapies and to complement current immunotherapies.
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(2023)Teacher’s job burnout has been a global concern in recent years, especially during the covid pandemic. To reduce their burnout, job crafting is proposed as a key factor for teachers. Yet previous empirical research has found inconsistency findings between job crafting and burnout. In some studies, job crafting was found to exacerbate instead of reducing the burnout. The current thesis aimed to address this issue from a multi-dimensional perspective. Moreover, basic psychological needs were added as mediators to uncover the mechanism behind the paradoxical relationships between job crafting and burnout among teachers. For those purpose, 726 teachers (Age mean= 39) from China were surveyed online and reported valid responses during 2022. Data were analyzed using Structural Equation Model (SEM) with three dimensions of teacher job (i.e., exhaustion at work; cynicism toward the meaning of work; the sense of inadequacy at work) and four dimensions of job crafting (i.e., increasing social job resources; increasing structural job resources; increasing challenge job demands; decreasing hindering job demands). The present study revealed a suppression effect that obscured the genuine correlation between job crafting (i.e., increasing social job resources, increasing structural job resources) and burnout. Furthermore, the findings contribute to job crafting and burnout relationship by indicating that “decreasing of hindering job demands” may induce burnout cynicism, while “increasing challenge job demands” effectively diminishes burnout (the sense of inadequacy at work). Additionally, the augmentation of “increasing structural job resources” is identified as a catalyst for teacher burnout, manifesting in forms such as heightened work exhaustion and cynicism towards the meaning of work.
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(2022)Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved protein with pleiotropic therapeutic effects in several disease models, including Parkinson’s disease (PD), diabetes and stroke. PD is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and many GWAS-based genes predisposing for PD are involved in oxidative stress. MANF has been shown to alleviate oxidative stress in PD models, however, the role of MANF in the antioxidant defense and mitochondrial respiration is not fully understood. By performing bulk RNA sequencing on wildtype and MANF knockout (MANF-KO) human embryonic stem cells (hESCs), we uncovered several genes involved in antioxidant defense to be up- or downregulated in MANF-KO hESC. Here we report that MANF-KO hESCs do not express the evolutionary conserved antioxidant enzyme catalase. We show that the loss of catalase makes the MANF-KO hESCs more vulnerable to hydrogen peroxide indued oxidative stress, and that MANF-KO hESCs have a reduced maximal respiration and spare respiratory capacity. Additionally, we examined if the loss of catalase in MANF-KO hESCs inhibits the differentiation of the cells to human dopaminergic neurons in vitro. We show that MANF-KO hESCs differentiate to TH+/MAP2+ cells despite a sustained deficiency of catalase, but the MANF-KO DA cultures tend to have a reduced spare respiratory capacity and higher basal glycolytic activity. To elucidate the structure-to-function relationship of MANF we utilize molecular dynamics simulations in combination with spin relaxation data from nuclear magnetic resonance spectroscopy. By examining the two-domain nature of MANF in different intracellular conditions we provide insight of the biological relevance of MANF interactions. Here we show that MANF conformational ensemble is more compact than previously reported. By simulating MANF in the presence of calcium and ATP, in neutral and low pH, we observed competitive binding of ATP and calcium to MANF. This study provides novel evidence of a regulatory role of MANF in the cellular antioxidant defense and explores the biological relevance of ATP and calcium binding to MANF.
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(2016)The purpose of this study is to assess if it is possible to reprogram cardiomyocytes from mouse embryonic fibroblasts by using one transgenic factor, Oct4, and a pool of small molecules added to growth medium. The Oct4 gene was conducted in mouse embryonic fibroblasts by lentiviral vectors. Samples were taken for analysis after 15, 20 and 41 days of growing the fibroblasts with small molecules. Compared to control group, no upregulation of cardiac progenitor or cardiomyocyte specific genes were observed. Concentration of Ctgf decreased in treatment cells compared to control cells, which implies that control cells continued functioning as fibroblasts more than treatment cells. The cell morphology of treatment cells changed in the direction of cardiomyocytes compared to control cells; more cylinder-like and branching compared to spindle-like fibroblasts. A different approach was also attempted, the STAP (Stimulus-Triggered Acquisition of Pluripotency) method, in which fibroblasts are exposed to acid treatment while growing. The pluripotent mRNA expression did not rise in this analysis.
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(2018)Oat β-glucans are water soluble non-starch polysaccharides. The health benefits of β-glucan including reduction of post-prandial glycemic response are correlated to its ability of forming viscous solutions. Phytate has also been reported to reduce starch digestion due to its potential of binding starch-digestion-related enzymes such as α-amylase or enzyme co-factors. The previous study showed that a significant amount of phytate was found in both oat β-glucan extract and highly purified β-glucan. The aim of this research was to study the role of residual phytate in the oat β-glucan extracts in starch hydrolysis. Oat β-glucan (OBG) was extracted from oat bran concentrate. OBG with phytate-removal treatment (OBG-PR) was prepared with ion-exchange resin and dialysis. The content of β-glucan, phytate and starch in OBG and OBG-PR were determined with Megazyme kits. The protein and calcium content was also measured. Before adding into the gelatinized wheat starch solution, the β-glucan solutions or phytic acid solution were pre-incubated with porcine pancreatic α-amylase. The starch hydrolysis was induced at physiological pH 6.9 and 37°C. Aliquots were collected at 20 min and 120 min digestion time. Digested starch was calculated based on the released glucoses. Both OBG and OBG-PR inhibited the starch hydrolysis. OBG contained a higher amount of phytate. And it had a stronger inhibitory effect (46%) than that of OBG-PR (34%). Pure phytic acid showed a comparable inhibitory effect on the starch hydrolysis as the OBG intrinsic phytic acid did, when the pure phytic acid was used at the same level as the concentration of intrinsic phytic acid in OBG. The decrease of intrinsic calcium in OBG-PR was found due to the ion-exchange and dialysis process. Consequently, the same amount of calcium was added to OBG-PR. The inhibitory effect of phytic acid on starch hydrolysis was completely reversed by the addition of calcium. Moreover, degradation of β-glucan by lichenase increased starch hydrolysis rate, which confirmed the role of β-glucan viscosity in the reduction of starch hydrolysis. In summary, the residual phytic acid of oat β-glucan, in addition to viscosity, reduced starch hydrolysis, while calcium contributed to promote starch hydrolysis.
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(2023)The lymphatic system is a network of vessels that permeate a substantial part of the whole body. It plays an essential role in fluid homeostasis by the drainage of interstitial fluid from the blood capillaries, after which the fluid, now called lymph, is transported through the vessel network and back to the blood circulation. The lymphatic system also plays an important role in the transportation of immune cells and in activation and maintenance of the immune system. Due to these crucial functions, there is a growing interest in exploiting the lymphatic system in the treatment of many immunological and inflammatory diseases. In many cases, an ideal treatment method would be to induce lymphatic growth (lymphangiogenesis) to boost immunological functions, facilitate resolution of inflammation and reduce the harm from lymphatic vascular abnormalities. However, there is a gap in knowledge in how to induce lymphangiogenesis in a controlled manner, with the major lymphangiogenic growth factor, vascular endothelial factor C (VEGF-C), tending to create disorganized lymphatic networks. The purpose of this thesis is to investigate factors influencing lymphangiogenesis, in an attempt to find ways to control it. Vaahtomeri research group has preliminary results showing a role of planar cell polarity (PCP) in control of dermal lymphatic vessel sprouting (the initial step for the formation of new lymphatic branches) and lymphatic network expansion. The focus of Vaahtomeri research group has been the core PCP protein Van Gogh-like protein 2 (VANGL2), which together with the other core PCP proteins is known to play an important role in the collective cell polarization and morphogenesis in many tissue types. The role of VANGL2 has previously been studied in the lymphatic system, and so far, VANGL2 has been implicated in both lymphatic valve morphogenesis and in flow-induced control of lymphatic endothelial cell (LEC) polarization. However, there still remains a gap in knowledge in what role VANGL2 plays in lymphangiogenesis and the lymphatic network as a whole. In this thesis, I investigated the role of VANGL2 in lymphangiogenesis, firstly by the use of an in vivo lymph node experiment, which offered a robust model to investigate the role of VANGL2 in the mature lymph node lymphatic network. In the experiment, I induced growth of the lymph node lymphatic network by means of an immunization reaction, and then I compared the lymphatic networks of Vangl2-deleted and control mice. Despite some minor differences between the Vangl2-deleted and control lymphatic networks, this experiment did not show a role for VANGL2 in the mature lymph node lymphatic network. Secondly, I investigated the potential mechanistic role of VANGL2 in control of dermal lymphatic vessel sprouting in growth conditions. This experiment showed a specific role for VANGL2 in sprouting of the lymphatic network, thus providing valuable research in understanding how lymphangiogenesis is regulated. Altogether, the results presented in this thesis work as a steppingstone for finding new treatments relating to the safe induction of lymphangiogenesis.
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