Genetic alterations in microsatellite-unstable colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in Finland. Of all CRC tumors, 15% display microsatellite-instability (MSI) caused by defective cellular mismatch repair. Cells displaying MSI accumulate a high number of mutations genome-wide, especially in short repeat areas, microsatellites. When targeting genes essential for cell growth or death, MSI can promote tumorigenesis. In non-coding areas, microsatellite mutations are generally considered as passenger events. Since the discovery of MSI and its linkage to cancer, more that 200 genes have been investigated for a role in MSI tumorigenesis. Although various criteria have been suggested for MSI target gene identification, the challenge has been to distinguish driver mutations from passenger mutations. This study aimed to clarify these key issues in the research field of MSI cancer. Prior to this, background mutation rate in MSI cancer has not been studied in a large-scale. We investigated the background mutation rate in MSI CRC by analyzing the spectrum of microsatellite mutations in non-coding areas. First, semenogelin I was studied for a possible role in MSI carcinogenesis. The intronic T9 repeat of semenogelin I was frequently mutated but no evidence for selection during tumorigenesis was obtained. Second, a sequencing approach was utilized to evaluate the general background mutation rate in MSI CRC. Both intronic and intergenic repeats harbored extremely high mutation rates of ≤ 87% and intergenic repeats were more unstable than the intronic repeats. As mutation rates of presumably neutral microsatellites can be high in MSI CRC in the absence of apparent selection pressure, high mutation frequency alone is not sufficient evidence for identification of driver MSI target genes. Next, an unbiased approach was designed to identify the mutatome of MSI CRC. By combining expression array data and a database search we identified novel genes possibly related to MSI CRC carcinogenesis. One of the genes was studied further. In the functional analysis this gene was observed to cause an abnormal cancer-prone cellular phenotype, possibly through altered responses to DNA damage. In our recent study, smooth muscle myosin heavy chain 11 (MYH11) was identified as a novel MSI CRC gene. Additionally, MYH11 has a well established role in acute myeloid leukemia (AML) through an oncogenic fusion protein CBFB-MYH11. We investigated further the role of MYH11 in AML by sequencing. Three novel missense variants of MYH11 were identified. None of the variants were present in the population-based control material. One of the identified variants, V71A, lies in the N-terminal SH3-like domain of MYH11 of unknown function. The other two variants, K1059E and R1792Q are located in the coil-coiled myosin rod essential for the regulation and filament formation of MYH11. The variant K1059E lies in the close proximity of the K1044N that has been functionally assessed in our earlier work of CRC and has been reported to cause total loss of MYH11 protein regulation. As the functional significance of the three novel variants examined in this work remains unknown, future studies should clarify the further role of MYH11 in AML leukaemogenesis and in other malignancies.

Pilgrimage as a Lifestyle : A Contemporary Greek Nunnery as a Pilgrimage Site

The aim of this research is to present, interpret and analyze the phenomenon of pilgrimage in a contemporary, suburban Greek nunnery, and to elucidate the different functions that the present-day convent has for its pilgrims. The scope of the study is limited to a case nunnery, the convent of the Dormition of the Virgin, which is situated in Northern Greece. The main corpus of data utilized for this work consists of 25 interviews and field diary material, which was collected in the convent mainly during the academic year 2002-2003 and summer 2005 by means of participant observation and unstructured thematic interviewing. It must be noted that most Greek nunneries are not really communities of hermits but institutions that operate in complex interaction with the surrounding society. Thus, the main interest in this study is in the interaction between pilgrims and nuns. Pilgrimage is seen here as a significant and concrete form of interaction, which in fact makes the contemporary nunneries dynamic scenes of religious, social and sometimes even political life. The focus of the analysis is on the pilgrims’ experiences, reflected upon on the levels of the individual, the Church institution, and society in general. This study shows that pilgrimage in a suburban nunnery, such as the convent of the Dormition, can be seen as part of everyday religiosity. Many pilgrims visit the convent regularly and the visitation is a lifestyle the pilgrims have chosen and wish to maintain. Pilgrimage to a contemporary Greek nunnery should not be ennobled, but seen as part of a popular religious sentiment. The visits offer pilgrims various tools for reflecting on their personal life situations and on questions of identity. For them the full round of liturgical worship is a very good reason for going to the convent, and many see it as a way of maintaining their faith and of feeling close to God. Despite cultural developments such as secularization and globalization, pilgrims are quite loyal to the convent they visit. It represents the positive values of ‘Greekness’ and therefore they also trust the nuns’ approach to various matters, both personal and political. The coalition of Orthodoxy and nationalism is also visible in their attitudes towards the convent, which they see as a guardian of Hellenism and as nurturing Greek values both now and in the future.

Photobiological studies of Baltic Sea phytoplankton

Phytoplankton ecology and productivity is one of the main branches of contemporary oceanographic research. Research groups in this branch have increasingly started to utilise bio-optical applications. My main research objective was to critically investigate the advantages and deficiencies of the fast repetition rate (FRR) fluorometry for studies of productivity of phytoplankton, and the responses of phytoplankton towards varying environmental stress. Second, I aimed to clarify the applicability of the FRR system to the optical environment of the Baltic Sea. The FRR system offers a highly dynamic tool for studies of phytoplankton photophysiology and productivity both in the field and in a controlled environment. The FRR metrics obtain high-frequency in situ determinations of the light-acclimative and photosynthetic parameters of intact phytoplankton communities. The measurement protocol is relatively easy to use without phases requiring analytical determinations. The most notable application of the FRR system lies in its potential for making primary productivity (PP) estimations. However, the realisation of this scheme is not straightforward. The FRR-PP, based on the photosynthetic electron flow (PEF) rate, are linearly related to the photosynthetic gas exchange (fixation of 14C) PP only in environments where the photosynthesis is light-limited. If the light limitation is not present, as is usually the case in the near-surface layers of the water column, the two PP approaches will deviate. The prompt response of the PEF rate to the short-term variability in the natural light field makes the field comparisons between the PEF-PP and the 14C-PP difficult to interpret, because this variability is averaged out in the 14C-incubations. Furthermore, the FRR based PP models are tuned to closely follow the vertical pattern of the underwater irradiance. Due to the photoacclimational plasticity of phytoplankton, this easily leads to overestimates of water column PP, if precautionary measures are not taken. Natural phytoplankton is subject to broad-waveband light. Active non-spectral bio-optical instruments, like the FRR fluorometer, emit light in a relatively narrow waveband, which by its nature does not represent the in situ light field. Thus, the spectrally-dependent parameters provided by the FRR system need to be spectrally scaled to the natural light field of the Baltic Sea. In general, the requirement of spectral scaling in the water bodies under terrestrial impact concerns all light-adaptive parameters provided by any active non-spectral bio-optical technique. The FRR system can be adopted to studies of all phytoplankton that possess efficient light harvesting in the waveband matching the bluish FRR excitation. Although these taxa cover the large bulk of all the phytoplankton taxa, one exception with a pronounced ecological significance is found in the Baltic Sea. The FRR system cannot be used to monitor the photophysiology of the cyanobacterial taxa harvesting light in the yellow-red waveband. These taxa include the ecologically-significant bloom-forming cyanobacterial taxa in the Baltic Sea.

Linkittäminen, tekijänoikeus ja verkkojulkaiseminen

Artikkelissa tutkitaan soveltuuko tekijänoikeus linkittämisen sääntelyyn. Selvitys tehdään linkittäjän näkökulmasta.

Detection and molecular epidemiology of tick-borne encephalitis virus infections

Pdf-file, link above

Warranty Prediction Using Weibull Simulation

The main objective of this master’s thesis is to examine if Weibull analysis is suitable method for warranty forecasting in the Case Company. The Case Company has used Reliasoft’s Weibull++ software, which is basing on the Weibull method, but the Company has noticed that the analysis has not given right results. This study was conducted making Weibull simulations in different profit centers of the Case Company and then comparing actual cost and forecasted cost. Simula-tions were made using different time frames and two methods for determining future deliveries. The first sub objective is to examine, which parameters of simulations will give the best result to each profit center. The second sub objective of this study is to create a simple control model for following forecasted costs and actual realized costs. The third sub objective is to document all Qlikview-parameters of profit centers. This study is a constructive research, and solutions for company’s problems are figured out in this master’s thesis. In the theory parts were introduced quality issues, for example; what is quality, quality costing and cost of poor quality. Quality is one of the major aspects in the Case Company, so understand-ing the link between quality and warranty forecasting is important. Warranty management was also introduced and other different tools for warranty forecasting. The Weibull method and its mathematical properties and reliability engineering were introduced. The main results of this master’s thesis are that the Weibull analysis forecasted too high costs, when calculating provision. Although, some forecasted values of profit centers were lower than actual values, the method works better for planning purposes. One of the reasons is that quality improving or alternatively quality decreasing is not showing in the results of the analysis in the short run. The other reason for too high values is that the products of the Case Company are com-plex and analyses were made in the profit center-level. The Weibull method was developed for standard products, but products of the Case Company consists of many complex components. According to the theory, this method was developed for homogeneous-data. So the most im-portant notification is that the analysis should be made in the product level, not the profit center level, when the data is more homogeneous.

Narrative transportation in global brand content

People understand life and events around them through narratives. Narratives are a new way for marketers to convey messages to consumers about their brands and products. Brand narratives are an effective way to reach out to people due to their influential nature. Narratives have a power to change beliefs and attitudes, making them relevant and interesting for any marketer. The power of narratives has to do with narrative transportation, which narratives can trigger in people. A transported person is more likely to perceive brand or product in a more positive light. The creators of the narrative are able to influence the content of the narrative through message factors that work as antecedents for narrative transportation. This study explored narrative transportation qualities of well established advertisements. The study uses qualitative content analysis to analyze and identify narrative transportation antecedents among Cannes Lion grand prix winners in the film category between years 2005 to 2015 (15 in total). The narrative transportation antecedents are identifiable characters, imaginable plot and verisimilitude, which were used in the analysis of the data. The study analyzes the winners to make judgment on whether they can trigger narrative transportation or not. It was found that the Cannes Lion grand prix winner advertisement mostly had identifiable narratives in them. In most of the advertisement (ten out of fifteen) at least two out of three antecedents were found, thus most of them are able to trigger narrative transportation. The study also found that most narratives in the advertisement were able to be linked to the main brand narrative of the advertiser. In four of the advertisements the link to the brand narrative was not able to be established. The study concludes by discussing certain factors and aspects of the advertisements that were identified to further enhance the narrative transportation qualities of the advertisement.

Mobiili oppimateriaali ja QR-koodit käsityön opetuksessa ja konekohtaisessa perehdytyksessä

Tämän tutkimuksen tarkoituksena on selvittää, miten Turun yliopiston Rauman yksikön opiskelijat kokevat QR- koodien avulla esitettävien perehdytysvideoiden hyödyntävän aineenhallintaansa ja työturvallisuustaitoja työstökoneiden kanssa työskenneltäessä. Lisäksi tutkitaan, kokiko jokin tietty opiskelijaryhmä videoiden parantavan aineenhallintaansa työstökoneiden käytössä paremmin. Tutkimuksen teoriaosassa käsitellään käsityötä oppiaineena, oppimisympäristöä, verkko-opetusta sekä työturvallisuutta. Teoriaosan lopussa käydään läpi taidon opettamisen perinteisiä teorioita. Teoriaosan perusteella on muodostettu kyselylomake, joka perustuu verkko-oppimateriaalin laatukriteereihin. Laatukriteerit ovat vaikuttaneet perehdytysvideoiden tekemiseen sekä QR-koodien sijoitteluun. Tutkimuksessa tehtiin kysely Turun yliopiston opettajankoulutuslaitoksen Rauman yksikön opiskelijoille. Kysely oli täytettävissä Webropol -sivustolla. Linkki kyselyyn oli sijoitettuna työstökoneiden läheisyyteen, samasta paperista löytyi myös linkki perehdytysvideoon. Linkit aukesivat mobiililaitteen QR-koodeja lukevan sovelluksen avulla. Tutkimus on strategialtaan kvantitatiivinen Survey-tutkimus. Kyselyyn vastasi 39 opiskelijaa ja kyselystä saatu aineisto analysoitiin SPSS ohjelmalla. Tutkimustulokset saatiin vertailemalla keskeisiä tunnuslukuja sekä korrelaatiotestejä ja varianssianalyysejä hyödyntämällä. Tutkimuksen tulosten perusteella perehdytysvideot hyödyttävät tehokkaiten opiskelijoita, joiden aikaisemmat taidot ovat heikot. Aikaisempien taitojen ja perehdytysvideosta saadun hyödyn välillä huomattiin selkeä korrelaatio. Perehdytysvideoiden saavutettavuudella ja käytettävyydellä ei nähty keskinäistä korrelaatiota. Tulosten perusteella huomattiin, että luokanopettajaopiskelijat arvioivat omat taitonsa työstökoneiden käytössä heikommaksi, jolloin he myös hyötyivät perehdytysvideoista enemmän.

”HUVIN JA URHEILUN VUOKSI” Tyttöjunioreiden salibandyharrastuksen taustalla olevia tekijöitä

Tämän tutkimuksen tarkoituksensa oli selvittää, millaisia tekijöitä tyttöjunioreiden salibandyharrastuksen taustalla on. Lisäksi kartoitettiin, kuinka moni kyselyyn vastanneista junioreista oli harkinnut salibandyharrastuksensa lopettamista, ja millaisia tekijöitä lopettamisajatusten taustalla oli. Tavoitteena oli etsiä keinoja, joilla tyttöjuniorit saataisiin pidettyä harrastuksen parissa. Aineisto kerättiin Webropol –kyselyllä B- ja C-ikäisiltä tyttöjunioreilta, jotka pelasivat kaudella 2014-15 Suomen Salibandyliiton alaisissa sarjoissa. Kyselyn linkki lähetettiin seurojen yhteyshenkilöille sähköpostin välityksellä. Kyselyyn vastasi 165 tyttöjunioria. Kyselylomake sisälsi taustatietoja kartoittavia kysymyksiä, 75 salibandyharrastusta koskevaa väittämää, joihin vastattiin viisiportaisella Likert-asteikoilla sekä yhden avoimen kysymyksen. Väittämät rakennettiin pohjautuen aiempaan tutkimustietoon harrastuksen taustalla olevista tekijöistä. Tekijät jaoteltiin viiteen kategoriaan: psyykkiset, sosiaaliset, valmennukselliset, fyysiset ja olosuhdetekijät. Tulokset analysoitiin SPSS-tilastoanalyysiohjelmalla. Juniorit jaettiin kahteen ryhmään sen perusteella olivatko he harkinneet harrastuksen lopettamista kuluneen kauden aikana. Ryhmien vastausten keskiarvoeroja vertailemalla etsittiin lopettamisajatuksiin mahdollisesti yhteydessä olevia tekijöitä. Keskiarvovertailu toteutettiin sekä t-testillä, että epäparametrisella Mann–Whitneyn testillä. Tyttöjuniorit pitivät salibandyä lajina, jonka parissa voi pitää hauskaa ystävien kanssa, kehittyen ja kuntoa kohottaen. Tulosten mukaan kuitenkin neljännes junioreista oli harkinnut lopettavansa ja lopettamisajatukset olivat yleisempiä vanhempien junioreiden keskuudessa. Suurin osa tyttöjunioreista oli tyytyväisiä salibandyharrastukseensa, mutta lopettamista harkinneiden vastausten keskiarvot olivat jokaisessa väittämässä matalampia kuin niillä, jotka eivät olleet harkinneet lopettamista. Lopettamisajatusten taustalla oli useita tekijöitä, eikä mikään yksittäinen tekijä noussut toista selittävämmäksi. Saatujen tulosten pohjalta voidaan todeta, että jokaisella juniorilla on yksilölliset motiivit harrastaa. Seuratoimijoiden olisi tärkeää tiedostaa nämä motiivit ja ottaa ne huomioon toimintaa suunnitellessa ja jokaiselle pelaajalle tulisi luoda mahdollisuus harrastaa omista lähtökohdistaan. Suomen Salibandyliiton ja seurojen tulisi vastata tähän tarpeeseen kehittämällä edelleen monimuotoisia mahdollisuuksia harrastaa.