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Currency undervaluation is a well-known and commonly used method for stimulating economic growth. Although the exact effects of exchange rate arrangements on international trade are highly debated, the fact that strong interlinkages between the two exist is unquestionable. This thesis departs from the generally accepted truth that an undervalued currency functions in practice as a subsidy to exports and tariff on imports. By using the method of legal dogmatics, the thesis analyzes how currency undervaluation can be assessed under international law, focusing on the examination of whether invoking the provisions of the IMF Articles of Agreement or WTO agreements to challenge currency undervaluation could be successful. In order to understand the issues behind this question, the first part of this thesis provides a short overview of the history of international regulation of currencies and the rise and fall of the Bretton Woods system. Parting from the principle of monetary sovereignty and its implications, the thesis provides a cursory glance at the development of international obligations regarding currencies and exchange rates. The second part deals shortly with the relevant provisions of the IMF’s Articles of Agreement and the shortcomings related thereto. Article IV(1)(iii) of the IMF Articles of Agreement places an obligation on member states to avoid manipulating exchange rates in order to gain an unfair competitive advantage over other members. Despite in theory providing an answer to the problem of currency undervaluation, this provision is in practice essentially inoperative, due to the subjective element included in it. Even in the unlikely case that the IMF were to reach the decision that one of its members was in breach of this Article, it has no effective dispute settlement system it could avail itself of if the said member state did not comply with the IMF’s recommendations to remove the breach. With the IMF being unable to effectively deal with the issue, the attention of politicians and academics alike has turned to the WTO, which provides an extremely effective dispute settlement mechanism. Due to its tariff-cum-subsidy effects, currency undervaluation makes it possible for WTO members to circumvent their obligations under the WTO agreements by nullifying, or at least diminishing, the effects of tariff concessions and eluding the prohibition on granting export subsidies. This thesis aims to provide an in-depth analysis of the WTO provisions that are most probable to be invoked with the aim of curbing currency undervaluation: Article XV of the General Agreement on Tariffs and Trade and the WTO provisions on subsidies. As an integral part of this examination, the thesis first discusses the relationship between the International Monetary Fund and the World Trade Organization in currency-related matters and the division of jurisdiction between the two institutions. The main finding in this regard is that although the interpretation of these provisions could in theory be stretched in order to cover currency undervaluation, the WTO cannot at present provide a sustainable answer to the issue of currency undervaluation. This thesis argues that the problems in adjudicating currency manipulation essentially arise from historical developments and the failure to adapt the instruments of international law to a new economic reality. This, together with the fear of overlapping jurisdictions between international institutions, has led to a loophole in international economic law. Initially the division of authority between the WTO and the IMF was clear: exchange rate issues under the par value system were a matter to be dealt with exclusively within the IMF. After the breakdown of the par value system, misuse of monetary policies became easier and more frequent, but nothing was done to reinforce the authority of the IMF. This has led to a situation where the IMF has the jurisdiction to deal with exchange rate issues, but lacks an effective enforcement mechanism to ensure that its rulings are followed. The WTO on the other hand has at its disposal an extremely effective dispute resolution mechanism but lacks jurisdiction regarding currency issues.

Background: Epithelial ovarian cancer is the most common type of ovarian cancer and is the most lethal gynecologic cancer due to its late diagnosis. Compared to ovarian cancer, endometrial carcinoma, as the most common gynecologic malignancy, is referred to as the “curable cancer”, as it can be detected early. As aberrant promoter methylation patterns are a common change in human cancer, detection of promoter methylation status may help in early diagnosis. In this study, we used a custom-designed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay as a rapid and easy method, to simultaneously detect the methylation status of multiple genes in ovarian and endometrial cancer samples. Aims: To design and test an MS-MLPA assay for analyzing promoter methylation of four genes associated with ovarian and endometrial cancers. The selected genes were HNF1 homeobox B (HNF1β), Ten-eleven translocation 1(TET1), L1 cell adhesion molecule (L1CAM), and AT-rich interactive domain 1A (ARID1A). These genes are known to have expression changes by DNA methylation. Methods: The promoter DNA methylation patterns of these four genes were analyzed in 15 cancer cell lines and 5 normal cell lines and DNAs using bisulfite sequencing. Six synthetic probe pairs were designed and optimized by applying them to cancer and normal cell lines and normal DNAs and comparing the results with those of bisulfite sequencing. Finally, the MS-MLPA assay was performed on patient specimens according to the MRC-HOLLAND MS-MLPA general protocol and methylation frequencies were calculated from MS-MLPA data. Results and conclusion: The MS-MLPA assay gave accurate methylation results with the 170 samples assayed. The HNF1B, L1CAM, and TET1 Genes were observed methylated in tumor samples whereas they were not methylated in the normal samples or showed very little methylation, suggested to be favorable diagnostic markers. MS-MLPA robustly and sensitively detects the promoter DNA methylation status.

Tämän tutkimuksen tarkoituksena on tutkia asiakkaiden havaintoja palvelun laatuun ja yrityksen imagoon liittyen. Laatuun ja imagoon liittyvät näkökohdat liittyvät tutkimuksessa Metso konsernin OneMetso konseptiin. Tutkimuksen kohteena olevat asiakasyritykset edustavat sellu- ja paperiteollisuutta sekä voimantuotantoa. Käsitteistöltään tutkimus perustuu laatua ja yrityksen imagoa käsittelevään kirjallisuuteen. Kirjallisuuskatsaus esittelee laatuun ja erityisesti palveluiden laatuun liittyviä erityispiirteitä. Olemassa oleva palveluiden laatua koskeva kirjallisuus perustuu pitkälti yritysten ja yksityishenkilöiden väliseen suhteeseen ja teoreettiselta pohjaltaan SERVQUAL tai Nordic model malleihin. Edellä mainittujen mallien ulottuvuuksia on hyödynnetty myös tässä tutkimuksessa, mutta painotus on yritysten välisessä (B2B) asiayhteydessä. Tämän alan tutkimuksia on tehty viime vuosikymmenenä. Tutkimuksen tulokset perustuvat kyselytutkimukseen joka on tehty Metson sellu- ja paperi sekä voimantuotannon asiakkaille. Kyselyn on tehnyt puhelinhaastatteluihin erikoistunut yritys. Kyselytutkimuksen vastaukset on tässä tutkimuksessa tilastollisesti analysoitu käyttäen ei-parametrista testausmenetelmää. Perustuen vastausten jakaumaan käytetty testausmenetelmä kaikille kysymyksille oli riippumattomien näytteiden Mann-Whitneyn U testi. Tilastollisen testauksen tuloksien perusteella nollahypoteesi hylätään kahdessa asiakkaille esitetyssä kysymyksessä kaikkiaan neljästätoista. Automation ja Power segmenttien asiakkaiden havainnot ovat yhteneviä useimmissa laatuun liittyvistä kysymyksistä. Saadut tulokset tukevat Metson One Metso konseptia. Jatkotutkimuksen aiheena toimisi keskittyminen yrityksen nykyisiin muuttuneisiin segmentteihin syventäen samallamkyselyn laatunäkökohtia.

In the modern era, using personalization when reaching out to potential or current customers is essential for businesses to compete in their area of business. With large customer bases, this personalization becomes more difficult, thus segmenting entire customer bases into smaller groups helps businesses focus better on personalization and targeted business decisions. These groups can be straightforward, like segmenting solely based on age, or more complex, like taking into account geographic, demographic, behavioral, and psychographic differences among the customers. In the latter case, customer segmentation should be performed with Machine Learning, which can help find more hidden patterns within the data. Often, the number of features in the customer data set is so large that some form of dimensionality reduction is needed. That is also the case with this thesis, which includes 12802 unique article tags that are desired to be included in the segmentation. A form of dimensionality reduction called feature hashing is selected for hashing the tags for its ability to be introduced new tags in the future. Using hashed features in customer segmentation is a balancing act. With more hashed features, the evaluation metrics might give better results and the hashed features resemble more closely the unhashed article tag data, but with less hashed features the clustering process is faster, more memory-efficient and the resulting clusters are more interpretable to the business. Three clustering algorithms, K-means, DBSCAN, and BIRCH, are tested with eight feature hashing bin sizes for each, with promising results for K-means and BIRCH.

Sosiolingvistisessa pro-gradu -tutkielmassani tarkastellaan englannin kielen perinteisiä sukupuolittuneiksi koettuja kielenpiirteitä, niihin yhdistettyjä sukupuolistereotypioita ja niiden esiintymistä viimevuosien Hollywood -menestyselokuvissa. Tutkielmani selvittää, tunnistetaanko nämä perinteiset, vuosikymmeniä vallinneet uskomukset sukupuolittuneista kielenpiirteistä edelleen ja tutkii sitä, mihin sukupuoleen nämä kielen piirteet yhdistetään. Lisäksi tutkielma tarkastelee näiden kielellisten sukupuolistereotypioiden leviämistä Suomeen ja tämän leviämisen mahdollista yhteyttä Hollywood -menestyselokuvassa esiintyvään dialogiin. Tutkielman tulokset pohjautuvat verkossa toteutettuun kyselytutkimukseen. Tutkielmani teoriatausta perustuu ensisijaisesti kielitieteilijä Robin Lakoffin teoksessaan Language and a Woman’s Place (1975) esittämiin väittämiin spesifeistä kielipiirteistä, jotka voidaan katsoa perinteisiksi englannin kielen kielellisiksi sukupuolistereotypioiksi. Tutkielma pyrkii valottamaan massakulttuurissa käytetyn englannin kielen vaikutusta sukupuolittuneiden kielistereotypioiden muodostumiseen ja vahvistumiseen. Analyysin kohteeksi ovat valikoituneet Hollywood-menestyselokuvat elokuva-alalla vallitsevan sukupuoliepätasa-arvon sekä Hollywoodin mittavan vaikutusvallan vuoksi. Lisäksi Hollywood-elokuvien dialogia ei ole aiemmissa tutkimuksissa tarkasteltu näiden stereotyyppisten perinteisten kielipiirteiden näkökulmasta. Kyselytutkimuksessa pyydettiin osallistujia arvioimaan kymmentä vuorosanasitaattia, jotka oli valikoitu vuosina 2017–2018 tuotetuista Hollywood –menestyselokuvista ja jotka sisälsivät Lakoffin nimeämiä, sukupuolittuneiksi koettuja kielenpiirteitä. Kyselyn avulla tutkittiin, mitkä kielelliset piirteet vaikuttavat mielipiteen muodostumiseen puhujan sukupuolesta, kun vuorosanasitaattien puhujaa eikä kontekstia tiedetä. Osallistujien tuli valita mihin sukupuoleen he yhdistävät kunkin vuorosanasitaatin kolmesta vaihtoehdosta: nainen, mies ja en osaa sanoa. Lisäksi osallistujilla oli mahdollisuus vastata vapaaehtoiseen avoimeen kysymykseen, jossa pyydettiin kommentoimaan annettua vastausta. Kyselyyn oli mahdollista osallistua, mikäli henkilö puhui äidinkielenään joko Amerikan englantia tai suomea. Kyselyyn osallistui 100 henkilöä ja sen tulosten analyysi toteutettiin vertaamalla saatuja vastauksia vastaajien iän, sukupuoli-identiteetin ja äidinkielen perusteella. Tutkielman päälöydöksiä olivat se, että perinteisesti sukupuolittuneiksi koetut kielen piirteet tunnistettiin pääosin hyvin, sekä se, että osallistujien vastaukset eivät muutamaa poikkeusta lukuun ottamatta eronneet merkittävästi toisistaan. Ensin mainittu löydös osoittaa, että osallistujat tunnistavat kielen piirteet ja yhdistävät ne siihen sukupuoleen, johon stereotypiat on perinteisesti liitetty. Jälkimmäinen löydös puolestaan merkitsee sitä, että englannin kielen sukupuolistereotypioiden tunnistaminen ei katso ikää, sukupuoli-identiteettia eikä äidinkieltä. Lisäksi kyselyn laadullisesta aineistosta nousi esille kiinnostava sivulöydös: vuorosanasitaattien semanttinen sisältö sekä kyselytutkimukseen vastanneiden sitaateille luomat kuvitteelliset kontekstit vaikuttivat suuresti siihen, mihin sukupuoleen vuorosanasitaatit yhdistettiin. Löydös on merkityksellinen, sillä se viittaa siihen, että kielelliset sukupuolistereotypiat pohjautuvat mahdollisesti enemmän kielen semanttisiin ja pragmaattisiin ominaisuuksiin kuin näihin vuosikymmeniä tutkittuihin, perinteisesti sukupuolittuneina pidettyihin kielen piirteisiin.

Cyanobacteria of the order Nostocales, including Baltic Sea bloom-forming species Nodularia spumigena, Aphanizomenon flosaquae, Dolichospermum spp., produce resting stages, known as akinetes, under unfavorable conditions. These akinetes can persist in the sediment and germinate if favorable conditions return, simultaneously representing past blooms and possibly contributing to future bloom formation. The present study characterized cyanobacterial akinete survival, germination, and potential toxin production in 40-to-175- year-old brackish water sediment archives in order to understand historical bloom expansion, akinete persistence, and cyanobacteria life cycles in the northern Baltic Sea. Results showed that cyanobacterial akinetes can persist in and germinate from northern Baltic Sea sediment up to 424 and 174 years old, at coastal and open-sea locations respectively. Akinete abundance and viability decreased with age and depth of vertical sediment layers. Increases in sediment organic matter content and akinete abundance largely corresponded with the historical expansion of anthropogenic eutrophication-fueled blooms of cyanobacteria in the northern Baltic Sea, beginning in the mid-twentieth century. The detection of potential hepatotoxin production from akinetes and revived cultures was minimal and restricted to the coastal sediment core. Phylogenetic analysis of culturable cyanobacteria from the coastal sediment core indicated that the majority of strains likely belonged to benthic genera Anabaena. Findings also supported the notion that, in comparison with Nodularia and Aphanizomenon spp. akinetes, Anabaena/Dolichospermum spp. akinetes play a more significant role in their life cycle and bloom initiation strategies. Further research is recommended to accurately quantify akinetes and create a higher rate of toxin gene detection from brackish water sediment samples in order to further describe species-specific benthic archives of cyanobacteria. Overall, measuring cyanobacterial akinete abundance, germination experiments, and genetic methods can be effectively used to determine akinete persistence, viability, and potential toxin production in brackish water sediment samples. This study highlights the prolonged survival of cyanobacterial akinetes in northern Baltic Sea sediment samples, up to 174 years old.

This research will be comprised of five main parts which are directly correlated to achieve some well-based conclusions. The first part will be regarding cybersecurity in general and cybersecurity in the European Union. Here we will give some data that will show the relevance of the topic in our daily life, while at the same time demonstrating why it is so important to have a good cybersecurity strategy to protect the Union’s citizens. In the second part, we will analyse the cybersecurity-related legislation in the European Union, which will give us a good head start as to how we stand in the European Union. The third part will consist of the analysis and description of the law enforcement agencies cooperation with companies in the European Union and how this cooperation can be successful enough for the benefit of the whole Union. In the fourth part we will discuss injunctions in the European Union, in general, and then we will specifically discuss injunctions in the United Kingdom, Germany and Spain. Last, but not least, we will analyse the United States’ legislation and law enforcement agency regarding cybersecurity. Also, during the course of our research, we will interview two Associate General Counsels of one of the biggest technology firms in the world, Microsoft. Microsoft is a leading company in the cybersecurity space with a broad range of experience of working to disrupt malware and botnets, through private law and through law enforcement partnership.

Complications of atherosclerosis such as myocardial infarction and stroke are the primary cause of death in Western societies. The development of atherosclerotic lesions is a complex process, including endothelial cell dysfunction, inflammation, extracellular matrix alteration and vascular smooth muscle cell (VSMC) proliferation and migration. Various cell cycle regulatory proteins control VSMC proliferation. Protein kinases called cyclin dependent kinases (CDKs) play a major role in regulation of cell cycle progression. At specific phases of the cell cycle, CDKs pair with cyclins to become catalytically active and phosphorylate numerous substrates contributing to cell cycle progression. CDKs are also regulated by cyclin dependent kinase inhibitors, activating and inhibitory phosphorylation, proteolysis and transcription factors. This tight regulation of cell cycle is essential; thus its deregulation is connected to the development of cancer and other proliferative disorders such as atherosclerosis and restenosis as well as neurodegenerative diseases. Proteins of the cell cycle provide potential and attractive targets for drug development. Consequently, various low molecular weight CDK inhibitors have been identified and are in clinical development. Tylophorine is a phenanthroindolizidine alkaloid, which has been shown to inhibit the growth of several human cancer cell lines. It was used in Ayurvedic medicine to treat inflammatory disorders. The aim of this study was to investigate the effect of tylophorine on human umbilical vein smooth muscle cell (HUVSMC) proliferation, cell cycle progression and the expression of various cell cycle regulatory proteins in order to confirm the findings made with tylophorine in rat cells. We used several methods to determine our hypothesis, including cell proliferation assay, western blot and flow cytometric cell cycle distribution analysis. We demonstrated by cell proliferation assay that tylophorine inhibits HUVSMC proliferation dose-dependently with an IC50 value of 164 nM ± 50. Western blot analysis was used to determine the effect of tylophorine on expression of cell cycle regulatory proteins. Tylophorine downregulates cyclin D1 and p21 expression levels. The results of tylophorine's effect on phosphorylation sites of p53 were not consistent. More sensitive methods are required in order to completely determine this effect. We used flow cytometric cell cycle analysis to investigate whether tylophorine interferes with cell cycle progression and arrests cells in a specific cell cycle phase. Tylophorine was shown to induce the accumulation of asynchronized HUVSMCs in S phase. Tylophorine has a significant effect on cell cycle, but its role as cell cycle regulator in treatment of vascular proliferative diseases and cancer requires more experiments in vitro and in vivo.

Pharmacogenetics is the study of variations in DNA sequence as related to drug response, i.e. pharmacokinetics, drug efficacy and adverse effects. The literature review of the thesis covers pharmacogenetics of analgesics. The most studied genetic variations affecting the analgesics response are the 118A>G variant of µ-opioid receptor gene (OPRM1) and several variations in the genes coding for cytochrome (CYP) P450 enzymes. Also variations in the COMT gene and the ABCB1 gene coding for P-glycoprotein have been shown to modify the response to analgesics. Genetic polymorphism of CYP2D6, CYP3A4 and CYP3A5 enzymes was studied in the experimental part of the thesis. The aim of the study was to determine if the allele and haplotype frequencies of the CYP2D6, CYP3A4 and CYP3A5 gene variations are different between Finnish breast cancer patients and healthy volunteers. The results will be further used to explore whether the genetic polymorphism of these metabolic enzymes affects the response to a certain drug substance. The study population consisted of 996 Finnish breast cancer patients. Common genetic variants affecting the enzymatic activity of CYP2D6, CYP3A4 and CYP3A5 were studied. In addition to gene copy number, ten single nucleotide polymorphisms (SNP) of the CYP2D6 gene were genotyped. For CYP3A4 gene, genotyping was done for intron 6 SNP rs35599367 shown to decrease CYP3A4 gene expression. CYP3A5 SNP 6986A>G leading to splicing defect and premature STOP codon was also genotyped. Genotyping and copy number determination was done using PCR-based TaqMan® 5'-nuclease method. CYP2D6 haplotype analysis and phenotype predictions were derived based on genotype data. According to CYP2D6 enzyme activity individuals are commonly classified as poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM) or ultra-rapid metabolizers (UM). The frequencies of CYP2D6 phenotypic classes in our study population were the following: PM, 2.8%; IM 2.0 %; EM 87.7% and UM 7.6%. The haplotype and phenotype frequencies determined for breast cancer patients coincide with the values observed earlier for Finnish healthy volunteers. In our study population, the minor allele frequency (MAF) of the CYP3A4 rs35599367 SNP was 2.7% and the MAF of the CYP3A5 6986G>A SNP 7.6%. The MAF of CYP3A5 6986G>A SNP found in our study is in line with the previous findings for Finnish healthy volunteers. There are no previous publications on the frequency of CYP3A4 rs35599367 SNP in Finnish population. In conclusion, no differences were detected in the frequency of the studied CYP2D6 and CYP3A5 genetic variations between Finnish breast cancer patients and healthy volunteers. Frequency of CYP3A4 rs35599367 SNP in Finnish healthy volunteers should be determined in order to compare it with our findings in the population comprising of breast cancer patients. The results of this study can be further used to explore the effects of CYP2D6, CYP3A4 and CYP3A5 genetic polymorphism on drug response.

Emerging research suggests that bacteriophages (phages) may exhibit alternative infection strategies that deviate from the preconceived lytic or lysogenic life cycles. Carrier cell infection is an alternative phage life cycle where complete virus particles are formed and remain within host cells, without cell lysis or integration into the host genome. Phage Φ6 (Φ6), the type member of the double-stranded RNA (dsRNA) virus family Cystoviridae, is a lytic phage that can also establish a carrier cell within its plant pathogenic host, Pseudomonas syringae pathovar (pv.) phaseolicola strain HB10Y (HB10Y). This thesis contributes to current limited knowledge and provides an insight on the underlying mechanisms of the Φ6 carrier cell infection. This study has agricultural and ecological relevance and may contribute to future plant therapeutic options. Synthetic carrier cell lines harboring Φ6 tri-segmented genome or Φ6 genomic constructs in which the coding regions in the S- and/or M- segments were replaced by heterologous sequences from tobacco mosaic virus (TMV) were created using a reverse genetics method. Spontaneous Φ6 carrier cell lines were also isolated from HB10Y after exposure of the host to excess phage. Spontaneous carrier cells were not stable, but rather occasionally released phage into liquid culture. Synthetic carrier cell lines were subjected to secondary phage infection and were found to be less susceptible than wild type (WT) to Φ6 but not Φ8, a more distant member of Cystoviridae. Studies suggest that carrier cell resistance to secondary infection (superinfection exclusion) is exhibited through the Φ6 S-segment gene 8. To test how temperature affects the stability of Φ6 carrier cells, spontaneous carrier cell line culture was incubated at RT and 30°C, and phage productivity was compared. Elevated temperature induced carrier cell stability. Comparison of the growth curves between Φ6 synthetic and spontaneous carrier cell lines and their respective WT strains showed that Φ6 carrier cell infection does not greatly affect host growth.