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(2023)The APOE4 gene variant of apolipoprotein E (apoE) has been identified as a predisposing factor for late-onset Alzheimer’s disease (AD). ApoE is known to interact with one of the classically characterized hallmarks of AD, the amyloid-beta (Aβ) protein. Aβ activates the classical complement pathway by binding to C1q that may sustain inflammation, hamper Aβ clearance and therefore promote accumulation of Aβ deposits in the brain and affect the integrity of the blood-brain barrier. Depending on context, binding of apoE to C1q can either activate or inhibit complement activation. ApoE can also interact with the complement regulator factor H (FH) which colocalizes with C1q on Aβ plaques. The interactions between these proteins and their role in the AD pathogenesis has not been fully explored. This thesis aimed at unraveling the complex formation between Aβ1-42, apoE, FH, and C1q, and their role in complement activation to provide novel insights on the mechanisms contributing to AD pathophysiology. By conducting enzyme-linked immunosorbent assays and Western Blotting of native PAGE, I was able to show that FH bound to apoE and forms a complex with Aβ1-42/apoE in an isoform- specific manner (apoE2 > apoE3 > apoE4) whereas C1q bound all Aβ1-42/apoE complexes with same affinity. FH did not bind Aβ1-42 alone, thus the results indicated that binding of FH in Aβ1-42/apoE complex took place via apoE2 and apoE3. In the absence of FH and C1q, immobilized Aβ1-42/apoE4 complexes led to higher serum complement activation levels when compared to Aβ1-42/apoE2 and Aβ1-42/apoE3 complexes or Aβ1-42 alone. C1q activated serum complement especially in the presence of Aβ1-42/apoE3 and Aβ1-42/apoE4. Further functional analysis with flow cytometry revealed that in fluid phase the presence of FH could restrict Aβ1-42-induced complement activation, the subsequent formation of C5a and activation of C5a receptor (C5aR) expressed on Human embryonic kidney (HEK) 293 cells. The presence of all apoE isoforms on Aβ1-42/C1q complexes led to reduced C5aR activation. Surprisingly, however, the reduction was the largest with apoE4, and the presence of C1q on Aβ1-42 alone could also decrease C5aR activation. The results of this thesis elucidated the effects of Aβ1-42, apoE, C1q and FH in complement activation and proposed a mechanism by which FH regulates complement activation and cell-mediated inflammation through isoform-specific binding to apoE associated with Aβ1-42. Further work is required to analyze the functional effects of these complexes, whether Aβ1-42, apoE, FH, and C1q can all bind simultaneously to form a large complex and whether this complex affects C5aR activation. This study provides important insights on how APOE4 may predispose to the neurotoxicity and neuroinflammatory changes in AD pathophysiology early in the disease process. Yet, the findings are only preliminary and therefore further studies are required to validate these results and to demonstrate whether promoting FH binding to apoE/Aβ complex could provide a novel target for AD therapy.
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(2013)Nursery grown seedlings are an essential part of the forestry industry. These seedlings are grown under high nutrient conditions caused by fertilization. Though grown in a controlled environment, symbionts such as ectomycorrhizal fungi (EcMF) are often found in these conditions. To examine the effects of EcMF in these conditions, colonized Picea glauca seedlings were collected from Toumey Nursery in Watersmeet, MI. After collection, the EcMF present were morphotyped, and seedlings with different morphotypes were divided equally into two treatment types- fertilized and unfertilized. Seedlings received treatment for one growing season. After that time, seedlings were collected, ectomycorrhizas identified using 1morphotyping and DNA sequencing, and seedlings were analyzed for differences in leaf nutrient concentration, content, root to shoot ratio, total biomass, and EcMF community structure. DNA sequencing identified 5 unique species groups- Amphinema sp. 1, Amphinema sp. 5, Thelephora terrestris, Sphaerosporella brunnea, and Boletus variipes. In the unfertilized treatment it was found that Amphinema sp. 1 strongly negatively impacted foliar N concentration. In fertilized seedlings, Thelephora terrestris had a strong negative impact on foliar phosphorus concentration, while Amphinema sp. 1 positively impacted foliar boron, magnesium, manganese, and phosphorus concentration. In terms of content, Amphinema sp. 1 led to significantly higher content of manganese and boron in fertilized treatments, as well as elevated phosphorus in unfertilized seedlings. Amphinema sp. 5 had a significant negative effect on phosphorus content. When examining root to shoot ratio and biomass, those seedlings with more non-mycorrhizal tips had a higher root to shoot ratio. Findings from the study shed light on the interactions of the species. Amphinema sp. 5 shows very different functionality than Amphinema sp. 1. Amphinema sp. 1 appears to have the highest positive effect on seedling nutrition when in both fertilized and unfertilized environments. Amphinema sp. 5 and T. terrestris appear to behave parasitically in both fertilized and unfertilized conditions.
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(2012)The purpose of this research was to investigate the role of electronic word of mouth (eWOM) in shaping consumer attitudes towards various products and services with concentration on the consumer attitude change. eWOM has long been proven to play an important role in influencing consumer attitudes and has been researched from a variety of perspectives. This study attempts to look deeper into the process of consumer attitude change by applying as the central theory of the study the Elaboration Likelihood Model of Persuasion by Petty and Cacioppo. In the processes of examining the background academic and empirical research the Internet and Web 2.0 are closely depicted in order to understand how throughout the past centuries technology allowed the rise of various mediums where consumers can not only share their opinions online about products and services but also communicate with other consumers. Manuel Castel’s Internet Galaxy, Gildin’s, Carl and Noland’s, Hennig-Thurau, Gwinner, Walsh and Gremler’s researches on eWOM are the central works that helped to shape both the theoretical and empirical parts of this study. The mixed method approach was chosen as a research method for this study. An online survey was conducted via the Surveymonkey.com platform and eight qualitative in-depth interviews were conducted. The results of the study show that central route queues as text quality and text argumentativeness are more prominent among the research subjects and the peripheral route queues: source credibility and source expertise did not show considerable significance. Also more experience and participation consumers have with user-rating websites and applications more inclined they are to elaborate on the central route cues and are more likely to search for opinions that they consider rational and credible. Also these respondents are less inclined to search for ratings that confirm their existing beliefs about products or services. Less experience/participation they have about eWOM more likely they are to search for reviews confirmatory to their own.
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(2022)The use of emotion is becoming increasingly relevant in the fields of international relations and political communication. While new research has been attentive to the use and dissemination of emotion, it has failed to establish emotion as an individual category of study, thus mostly neglecting its role within political discourses. This thesis argues that emotion is key to understanding why some discourses are more appealing than others, using the theories of Ernesto Laclau, Jacques Lacan and Simon Koschut as theoretical framework. By combining the qualitative methods of Emotion Discourse Analysis and Pragmatics of Emotive Communication, this thesis studies how emotion is embedded within the Manifesto “The Programme of Change”, published by Podemos at the beginning of 2015 with the objective of inspiring the political campaigns of the multiple elections that were going to take place that year. My analysis is specifically focused on two topics. First, it aims to understand how emotions were used within the Manifesto to create the antagonistic groups “the people” and “the elite”. Second, it aims to expose the new feeling rules that the party proposed to challenge the narrative of the status quo. The results of my analysis show that Podemos created an image of a corrupted, self-serving and extravagant elite, while defining the people as a group of honest, trustworthy and capable citizens. The antagonism between both groups is sustained by a sense of unfairness and humiliation of the latter towards the former and it is built through a political discourse that puts forward five new feeling rules that challenge the elite’s power. The first feeling rule appeals to unfairness, turning it into anger towards the elite. The second appeals to anxiety, stressing the need for a quick change. The third evokes frustration, converting it into strength to gain power. The fourth relies on hope to draw and image of an optimistic future. The last evokes self-awareness to create a new order where ordinary people feel recognised and represented. The findings of this thesis add value to existing literature on Podemos, while also proving that emotion needs to be considered a valid unit of analysis in discourse analytical methodologies. It defines emotion as key to uncovering patterns in international relations, and it defends its role in sustaining and challenging structures of power.
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The role of employee and customer satisfaction in explaining profitability in Finnish grocery retail (2020)The relationship between employee job satisfaction and customer satisfaction and the impact of these measures on the profitability of a company has been studied extensively. It has been shown that for companies with high levels of job satisfaction, customer satisfaction can be higher compared to companies with lower levels of employee job satisfaction. Similarly, previous works have documented that customer satisfaction can improve the profitability of a company. Furthermore, some scholars have found that job satisfaction enhances customer satisfaction while some have found an impact with opposite direction. This Master’s thesis was conducted with the aim to find out how job satisfaction, customer satisfaction and profitability are related in the Finnish grocery retail industry. The empirical part of the study consists of analyses of employee satisfaction and customer satisfaction surveys that were conducted by third parties before this master thesis was started. These surveys were combined and matched with profitability data, where operating margin was used as a proxy for profitability. This combined data is based on 374 Finnish supermarket grocery stores which means approximately one third of all stores in this category. As the sales of supermarkets is together nearly one half of the Finnish grocery sales, is this study representing about one sixth of all grocery purchases of Finns. The study applied the service-profit chain model (Heskett et al., 2008) as a conceptual framework. The model considers the interrelationships between internal service quality of the company, job satisfaction, retention of employees, productivity of employees, external service value, customer satisfaction, customer loyalty, revenue growth and profitability. The main research method applied was qualitative comparative analysis (Fs/QCA). The results suggest that the internal service quality of the company under investigation has an impact on the job satisfaction of employees. Job satisfaction improved when the employees experienced their job interesting and felt that the work they do is important. In addition, especially the work atmosphere but also leadership and good work conditions positively influence job satisfaction. According to this study, job satisfaction did not, however, have a direct impact on customer satisfaction, efficiency or profitability of the company. Customer satisfaction increased customer loyalty as expected. In light of this study, and for the specific context investigated, it seems possible by the focal company to positively affect employee job satisfaction by supporting a good work atmosphere. Although this research found no robust evidence on the relationships between job satisfaction and customer satisfaction, job satisfaction and efficiency of the company nor job satisfaction and company profitability, it is notable that the analyses gave some indication that work atmosphere, leadership and good work conditions might have a positive impact on financial performance of the focal company. These are the same factors that were highlighted as drivers of job satisfaction. Thus, the inter-relationship between these concepts should be further explored in the future.
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(2021)Tämä tutkielma keskittyy englannin kielen rooliin kahden suomalaisen kauppakeskuksen kielimaisemissa esimerkiksi kauppojen ikkunoissa, mainoksissa ja muissa kylteissä. Tutkimuskohteina ovat Mall of Tripla Helsingissä ja Kauppakeskus Valkea Oulussa. Vaikka englannin on toistuvasti osoitettu olevan tärkein vieras kieli suomalaisille, erityisesti Tripla on saanut osakseen kritiikkiä englannin kielen käytöstään. Tutkimuskohteita vertailemalla pyritään selvittämään erityisesti, miten englannin kieltä käytetään ja mikä funktio sillä on näissä kielimaisemissa. Tutkielma nojaa vahvasti kielimaisemien (linguistic landscapes) teoriaan, joka tutkimussuuntana yhdistää kielitiedettä eri tieteenaloihin, kuten politiikkaan, maantieteeseen ja sosiologiaan. Kielimaisemien tutkimukset keskittyvät perinteisesti kirjoitettuun kieleen kaupungeissa esiintyvissä erilaisissa kylteissä. Kun otetaan huomioon tämän tutkimuksen kaupalliset tutkimuskohteet, on tärkeää tarkastella myös englannin kielen käyttöä mainonnassa. Lisäksi kielen asema sekä Suomessa että maailmalla on tärkeä pohja analyysille ja auttaa selittämään sen roolia paremmin. Tutkimusaineisto kerättiin valokuvaamalla kauppakeskuksista kaikki kyltit, joissa esiintyi englannin kieltä. Lopullinen aineisto muodostui 349 kuvan kokoelmaksi. Analyysissä sovellettiin aiempien kielimaisematutkimusten käyttämää kategorisointimenetelmää, joka tässä tutkimuksessa keskittyi kylteissä esiintyviin kieliin, kielten funktioihin ja kylttien multimodaalisiin ominaisuuksiin. Tutkimuksen perusteella voidaan tunnistaa englannin kielen vahva läsnäolo molemmissa kohteissa. Suurimmassa osassa aineistoa kylteillä esiintyi ainoastaan englannin kieltä, mutta monikielisissä kylteissä näkyi suomen ja englannin lisäksi myös ruotsia, venäjää, italiaa, espanjaa ja thaita. Monikielisissä kylteissä hyödynnettiin sekä käännöksiä että kielten sekoittamista. Kielen valinnan, kylttien asettelun sekä materiaalien havaittiin olevan yhteydessä joko symboliseen tai viittaavaan funktioon, joka nousi suurimmaksi eroksi kohteiden välillä. Viittaava englannin käyttö oli hieman yleisempää Triplassa kuin Oulussa, jossa taas englannin symbolinen rooli korostui. Tulosten perusteella voidaan päätellä, että kohdeyleisöjen oletetuissa kielitaidoissa on eroja Helsingin ja Oulun välillä. Symbolinen kielenkäyttö nojautuu erilaisiin arvoihin ja stereotypioihin, joita englannin kieleen ja englanninkielisiin paikkoihin usein liitetään. Nämä arvot välittyvät yleisölle, vaikka kielitaito olisi heikompaa. Viittaava kielenkäyttö taas näkyy kylteissä, joiden tehtävänä on informoida asiakkaita. Viittaavat kyltit vaativat lukijaltaan edistyneempää kielitaitoa, koska viestin ymmärtäminen on tärkeämpää kuin sen herättämät mielikuvat. Tulokset osoittavat, että kohdeyleisön oletetaan osaavan englantia paremmin Helsingissä kuin Oulussa.
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(2015)Social networking services have become an increasingly central way for people to interact with each other. Facebook, the most popular social networking service in the world, is believed to support the maintenance and creation of social relationships. In order to understand the way these services influence social relationships it is important to take into account the personal uniqueness of the people using them. At the same time concerns have been raised about the development of social capital. Being in contact has never been easier and yet people spend more time alone than before. In this study the relationship between the intensity of Facebook usage, personality trait extraversion and three types of social capital (bridging, bonding and maintained) were studied. The aim was to see whether the intensity of Facebook usage is associated with individuals’ perceived social capital and to examine if extraversion affects this association. The theoretical framework of this study consists of social capital theory and trait theory of personality. They are applied to the context of information and communications technology research. The data was gathered using an online survey (N = 487). The sample consists of adult Finnish Facebook users. Most of the respondents were female (72 %) and students (89 %). The analyses were made using factor analysis and multiple regression analysis. The main finding is that the intensity of Facebook usage is positively associated with perceived bridging and maintained social capital. In addition, extraversion was found to be positively associated with bridging and maintained social capital, even more so than Facebook intensity. However, the relationship between extraversion and social capital is mediated by the intensity of Facebook usage. This means that extraversions relation with social capital can partly be explained by the influence of the intensity of Facebook usage. Moreover, the relationship between the intensity of Facebook usage and bridging social capital is moderated by extraversion. This means that the relationship is stronger for people who perceived themselves as less extraverted in comparison to people who perceived themselves as highly extraverted. Bonding social capital was not found to be a reliable scale so it was deleted from the analyses. These findings support the idea that Facebook can be a useful tool to support the formation and maintenance of individual’s bridging and maintained social capital. It can be particularly useful for people who do not perceive themselves as highly extraverted. Main sources: Ellison, N. B., Steinfield, C. and Lampe, C. (2007). The Benefits of Facebook 'friends:' Social Capital and College Students’ use of online social networking sites. Putnam, R. D. (2000). Bowling alone: The collapse and revival of American community. Wilson, R. E., Gosling, S. D. and Graham, T. L. (2012). A Review of Facebook Research in the Social Sciences. Hanifi, R. (2015). Sosiaaliset suhteet järjestäytyvät uudelleen. Hamburger, Y. A. and Ben-Artzi, E. (2000). The relationship between extraversion and neuroticism and the different uses of the Internet.
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(2018)This study investigates the metabolic consequences of a biomarker for mitochondrial myopathies, using the mouse as a model organism. The studied biomarker is fibroblast growth factor 21 (FGF21), which is secreted in high amounts from the diseased muscle tissue. It is an endocrine hormone that regulates lipid metabolism, and in healthy individuals it is mainly secreted from the liver. I utilized skeletal muscle samples from mice that were either wild type or had a mitochondrial myopathy, both with or without a whole-body knockout of FGF21. I analysed a data set from a targeted metabolomic experiment conducted on the skeletal muscle samples. The experiment was performed by our collaborator Vidya Velagapudi. Additionally I measured protein and mRNA expression of selected enzymes from the muscle samples. This study shows, that the cytokine FGF21 contributes to the disease progression of mitochondrial myopathy. The aspects of pathophysiology it regulates were all found to center on the metabolic pathway of one carbon (1C) metabolism. Serine de novo synthesis shuttles glucose carbons into 1C metabolism. The transsulfuration pathway produces glutathione using carbon units from the 1C pathway. The results of this study show, that FGF21 mediates the upregulation of alternative carbon donors in one carbon metabolism, especially serine biosynthesis, and the elevated utilisation of carbon units in the transsulfuration pathway. Not all of the metabolic changes characteristic of mitochondrial myopathy were affected by FGF21, e.g. the upregulation of acyl carnitines seen in mitochondrial myopathy was not affected by the knock-out of FGF21.
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(2018)Some flavonoids are thought to have antioxidant functions in plants, but this is still controversial because of a lack of in planta evidence. Methyl viologen (MV) sensitivity was assayed in sterile culture by growing seven day old Arabidopsis seedlings on 0.5x MS media supplemented with and without MV. Seedlings grew for 9 days after that, and then were photographed and root growth measured. We used several flavonoid deficient Arabidopsis transparent testa (tt) mutants and found they were hypersensitive to MV that produces reactive oxygen species (ROS) in chloroplasts and mitochondria. Flavonoids are transported into different compartments of the cell via a specific flavonoid transport system but no chloroplastic or mitochondrial transporters are currently known. To identify potential chloroplastic and mitochondrial transporters, knockout mutants of candidate MATE and ABC transporters have been screened for MV sensitivity. Flavonoids modulate auxin transport, which raises the possibility of passive effects through auxin during ROS sensitivity. To test whether auxin or the inhibitions of auxin transport have a role in protecting against ROS stress, MV sensitivity was assayed under exogenous treatment of artificial auxin (NAA) and an auxin transport inhibitor (NPA) during MV stress. From this study, we obtained data about the role of flavonoids and auxin in ROS signalling. The inhibition of auxin transport modulated MV sensitivity. We found that NAA had no effect or very modest effect. However, a protective effect of NPA was observed that helps against ROS formation, mimicking the effect of flavonoids. NPA induced more protection. One MATE transporter also gave the mimic of (tt) phenotype, however their role in the movement of flavonoids into or out of the chloroplast or mitochondria remains unclear, as they may be transporting some other protective agent that helps against oxidative stress. However, At1g54350 is a candidate for further testing.
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(2013)Foreign direct investment (FDI) is one of the key drivers of globalization. It is generally regarded as beneficial for the host countries to which FDI flows are directed. Experience has shown this to be true for developed countries, but not all developing countries have been able to benefit from inward FDI to the same extent. In addition, empirical studies exploring the effect of FDI on developing host countries have found ambiguous results. As FDI flows are increasingly directed to developing countries and transition economies, it is time to find out what the effect of FDI really is on different host countries, and why the literature has failed to provide a unanimous answer. The purpose of the thesis is to study the effect of inward FDI on developing host countries and the conditions on which the effect depends. The thesis concentrates on the effect of FDI on economic growth. It shows that the FDI-growth relationship is more complex than the literature generally suggests. There are two main themes. First, it is studied how the local conditions (i.e. the absorptive capacity of the host country) influence the effect of FDI on growth. Then, it is shown how the effect of FDI on growth depends on the type of FDI. Two endogenous growth models are presented in the thesis. The models are closely linked to the main themes. The model by Alfaro et al. (2010) focuses on the importance of the absorptive capacity of the host country, which is measured in the model by the development of local financial markets. The model introduces a mechanism through which FDI may lead to a higher growth rate in host countries and shows how the mechanism depends on the development of local financial markets. The second model is a growth model by Beugelsdijk et al. (2008), which takes into account the heterogeneity of FDI and differentiates between the growth effects of horizontal (market seeking) FDI and vertical (efficiency seeking) FDI. The varying effects of different types of FDI and the types of investment certain kinds of countries attract are discussed as well. The main conclusion of the thesis is that the absorptive capacity of the developing host country has to be good enough, so that the host country can (fully) benefit from inward FDI, especially from its growth promoting property. In particular, the local financial markets matter, which is shown in the thesis. Another important conclusion of the thesis is that the type of FDI is important, as the growth effects and the channels through which FDI affects growth are not the same for the different types of FDI. These two aspects are significant in determining the benefits from inward FDI, but they are not enough taken into account in the literature. The thesis suggests that this, at least partly, explains why current literature fails to provide a unanimous answer to the question of the effect of FDI on growth. The findings of the thesis have implications for policy and future research.
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(2020)Forests can sequester large amounts of carbon with relatively low costs. Thus, they are an important instrument for climate policies. The forestry sector can be directly included in an emissions trading system (ETS). Another way is to exclude it but award offsets for additional carbon sinks. The awarded offsets can be used to cover a certain percentage of emissions under the ETS. Offset broaden the scope of an ETS and increase the overall emission reductions at lower cost. However, they face some issues. The main issues are non-additionality, non-permanence and carbon leakage, which are defined in the Kyoto Protocol and scientific literature. The approaches to these issues are compared in three ETS, which are the California Cap-and-Trade Program, the Regional Greenhouse Gas Initiative (RGGI) and the New Zealand Emissions Trading Scheme (NZ ETS). Three research questions are answered. First, how are the forestry related issues of non-additionality, non-permanence and carbon leakage considered in the California Cap-and-Trade Program, the RGGI and the NZ ETS? Second, how these approaches differ between the systems? And third, how could the forestry offset programs be improved in parts of the three main issues based on scientific literature? The approaches to all three issues are almost similar between the California's program and the RGGI. Both programs award only additional sinks. To account for the non-permanence issue, both programs require a 100-year monitoring period after credit issuance. They also require annual reporting and monitoring and a third-party verification every six years. They use a buffer account or reversal risk adjustments for unintentional reversals. Intentional reversals are covered by retiring offset credits in both programs, but the California’s program also requires a penalty. The carbon leakage risk for shifting cropland and grazing activities is determined the same way in both programs and is between zero and 50%. The secondary emissions resulting from these activities are based on the leakage risk, annual difference in actual onsite carbon and annual difference in baseline onsite carbon. The NZ ETS credits all sinks and has not implemented an ETS design to account for carbon leakage. However, non-permanence is addressed. Post-1989 forest owners must repay units if the forest is removed from the program, do a carbon sink inventory every five years and pay units if the number of sinks decreases. Pre-1990 forest owners must repay units in case of deforestation. The California’s program and the RGGI could improve the timing of accounting the onsite carbon sinks and leakage releases, which are inconsistent. Also, the reductions based on the estimated leakage risk may not be high enough because the actual leakage can be up to 80%. The long monitoring periods can be a barrier for participation especially for financially motivated forest owner. On the other hand, the additionality requirements can be a barrier for conservation motivated forest owners. The NZ ETS could be improved by crediting only additional sinks because crediting all sinks increases the government's expenditures, i.e. the taxpayer’s costs, without any environmental benefit. Carbon leakage should also be considered to gain environmental benefits.
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(2019)Cities are responsible for many of the current environmental changes in the world. Even though the need for urban sustainability transitions is apparent, city governments have been, so far, uncapable of governing the change. In this thesis, the possible urban transition and its multi-level governance is examined through the case example of Eko-Viikki neighbourhood and the urban planning changes around it. The framework of multi-level perspective on socio-technical transitions (MLP) is used for the analysis. This theory on transitions is widely used, while criticized for its inadequate conceptualization of the regime (the dominant system) and its spatial application, especially in cities. Traditionally, the framework has not been used to study transitions in cities, due to which, there is a lack of case examples of urban sustainability transitions and their governance. This thesis addresses the deficiency in question and aims to find out which types of policy instruments could be essential in bringing about urban sustainability transitions and whether the dominant regime, in this case the urban planning of Helsinki, can actively influence the steering of the transition. The materials of this thesis consist of two different sources. The document analysis was used to gather the materials for the policy instrument analysis. In addition, six semi-structured expert interviews were conducted to provide supporting material for it, as well as to examine the change of the urban planning context in Finland. The materials were analysed by qualitative content analysis using the MLP framework and a commonly used environmental policy instrument classification as a frame. The results indicate that regime actors can have endogenous power to somewhat steer the urban sustainability transitions. The regime actors of urban planning of Helsinki were active in the Eko-Viikki project, and sustainability issues have become more integrated part of the everyday urban planning in Helsinki. As for the niche level of Eko-Viikki, regulation and collaboration related policy instruments were the most successful in advancing the sustainability issues. In fact, the site transfer conditions containing sustainability demands as well as the area working group method have been scaled up to the use of the regime. The city of Helsinki has, moreover, committed in advancing sustainable city development through international agreements and its own city strategies. As regards the landscape level, the land use and construction legislation changes have remarkably tightened the requirements for sustainability of urban planning, especially for the energy efficiency. On the contrary, the lack of certain types of instruments seem to remarkably hinder the urban sustainability transitions. According to the results, information related instruments need to be developed to make the most of the technical solutions available and, ultimately, to make urban planning more like continuous learning processes rather than individual projects. Also, the issue of short-term profit seeking should be addressed by economic instruments that involve long-term investments and set sustainability issues as a first priority. All in all, it can be concluded, that much has done for promoting sustainability in urban planning of Helsinki even though a profound urban sustainability transition cannot be said to have happened. Particularly, systemic and process focused policy instruments are needed to take into account the multiple different stakeholders involved, and the governance levels where urban sustainability transitions take place. The urban sustainability transitions can be enabled only together with other governmental bodies of the city, state, construction companies, maintenance companies and, ultimately, residents.
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(2019)In current city policies, cultural events take part in urban, social and economic development contributing in place making and city branding. This master thesis examines the role of the forthcoming Helsinki contemporary art biennial within the city strategies to fulfill social, economic and environmentally sustainable development. The vision of the city of Helsinki is to be the world’s most functional city, creating the best conditions for residents and visitors as well as an attractive knowledge hub for companies and individuals. The potential of achieving some of the strategies’ objectives through the contemporary art biennial is analyzed through interviews with experts of Helsinki Art Museum and benchmarking the city of Helsinki with other long-term biennial cities, specifically, Venice, Berlin and Liverpool. For the benchmarking, it has been used data provided by the European Commission’s on line platform “Cultural and Creative Cities Monitor”. Helsinki biennial takes part in the place-making, city branding as well as in the strategic plan for the city. Overall, the event is efficiently related to most of the objectives of the city strategies, of which the maritime strategy, the project for youth social inclusion, exercise and mobility, health and welfare promotion. The convergent outputs of the analysis of Helsinki provided positive scenarios on the creation of new jobs within the creative economy and revealed that human capital and education sectors might undertake a significant increase. Yet, a broad overview on the strategies for the city of Helsinki 2017-2021 revealed contrasting aspects within the sustainable development principles. The new jobs created through the maritime strategy seem not completely fulfill the ambitious aims of the city strategies to create new captivating jobs through new companies and startups. Furthermore, in order to avoid the worst effects of climate change, environmentally sustainable alternatives for the Biennial in the island of Vallisaari should be carefully considered.
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(2017)Background: Atherosclerosis is a common pathological process in arteries causing significant morbidity and mortality due to stroke and myocardial infarction. The progression of atherosclerosis is affected by both genes and external factors that interactively initiate and advance the pathological cascade. Heme oxygenase 1 (HO1) is a protein that degrades toxic heme and thereby plays a role in maintaining normal vascular function. The expression of the heme oxygenase 1 gene (HMOX1) is affected by a (GT)n polymorphism in its promoter area; short (GT)n alleles associate with higher HO1 expression in cell culture studies and are hypothesized to protect vessel wall from hemi-related oxidative damage. Objective: Our research group has previously found that patients that have suffered stroke due to atherosclerotic carotid stenosis show high expression of HMOX1 in their carotid plaques (CPs). The aim of this thesis was to investigate whether this finding is explained by the HMOX1 (GT)n promoter polymorphism, i.e. if the promoter polymorphism is associated to symptomatic carotid disease. Methods: HMOX1 promoter (GT)n polymorphism was genotyped in carotid stenosis patients (HeCES n=92) and population controls (Health 2000 Survey, n=964). HMOX1 mRNA and protein levels were measured from CPs by qRT-PCR and ELISA, respectively. Results: HMOX1 promoter (GT)n alleles in the Finnish population ranged between 20 and 40 repeats, where (GT)30 was the most common allele with a population frequency of 46.6%. When comparing carotid stenosis patients to controls, statistically significant association between a lack of short alleles (< (GT)30) and symptomatic carotid disease was not found (p=0.214). Whereas, carotid stenosis patients with an ulcerative plaque lacked significantly more often a short allele at the HMOX1 promoter variant (p=0.006). However, we did not find correlation between promoter genotypes and HMOX1 mRNA or protein levels in the CPs. Conclusions: Our results support the protective role of short HMOX1 promoter (GT)n variants against symptomatic carotid artery disease (CaD).
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(2020)Histamine and hypocretin/orexin are neuromodulators important for regulation of alertness and wakefulness. These systems project to major areas of the brain, are highly conserved among vertebrates and they significantly innervate each other. Different studies have indicated an interaction between the histaminergic and orexin systems, however the role of histamine in this interaction is still not well-established. The goal of this study was to examine possible changes in orexin neurons development and larvae behaviour, after genetic loss of histamine decarboxylase (hdc), the histamine-synthesizing enzyme. Using whole-mount in-situ hybridization and immunofluorescence staining we observed a significant reduction in the expression of the hcrt mRNA and the orexin A peptide in 6 dpf hdcKO zebrafish larvae. However, KO of hdc had no effect on startle response, dark flash response and sleeping behaviour of 6 dpf larvae. To further investigate the regulatory role of the histaminergic system, we employed treatment of hdcWT and KO larvae with ciproxifan, a histamine H3 receptor inverse agonist. Ciproxifan treatment increased darkness habituation in 7 dpf hdcWT and KO larvae but reduced the intensity of the dark flash response only on hdcWT larvae. Furthermore, ciproxifan treatment differentially affected the expression of the orexin A peptide in 7 dpf hdcWT and KO larvae but had no effect on the expression levels of the hcrt mRNA. Collectively, these findings suggest the significance of histaminergic signaling for normal development of orexin neurons and the implication of histamine in the execution of the dark flash response. Lastly, this study indicates the complex role of the histamine H3 receptor and the requirement of further studies for better characterization of its function.
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(2018)Host factors play crucial roles in virus infections. Viruses exploit various cellular processes and are counteracted by an arsenal of host antiviral defenses. Characterization of these interactions is crucial for understanding the viral life cycle and developing novel antiviral treatments. Semliki Forest virus (SFV) is a positive-strand RNA alphavirus that has been used as a model virus for multiple clinically significant diseases such as lethal encephalitis. The aim of this thesis was to identify host factors that affect SFV infection to better understand the biology of SFV, and to provide candidate targets for therapies against more serious alphavirus infections. Here I have conducted follow up studies on a previously performed genome-wide siRNA screen that hinted that a number of genes have novel functions in SFV infection. I used an automated high-throughput imaging-based approach to confirm the roles of these host factors in SFV infection. For comparison, I also used a similar strategy to test if these genes affect negative-strand RNA virus infections, using vesicular stomatitis virus (VSV). Additionally, I studied whether the host factors affecting SFV infections perform their roles in the entry and penetration, or post-penetration steps using a previously developed endocytic bypass assay. I identified the γ-aminobutyric acid (GABA) transporter, SLC6A13, as a potential receptor for SFV. I also describe other novel genes that have roles in SFV or VSV infections. In addition, I show that TNP01, RPL18, ETF1, DMN2, and GNDPA1 promote, and HDAC6 counteracts SFV infection in the entry and membrane penetration steps. Furthermore, I report that in the later stages of the infection DDX54 boosts and EIF2B3, EIF4G1, PHB2, EDF1, DDX47, and DHX57 hinder SFV.
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The Role of Hypoxia-Induced Carbonic anhydrase 9 and the Effect of SLC-0111 in Hepatoblastoma Cells (2021)Hepatoblastoma (HB) is the most common malignant pediatric liver tumor. Although developed treatments have increased the survival rate of HB patients, 20-30 % of the patients show lack of response to the currently used treatment. Due to rapid growth and insufficient blood flow, solid tumors, like HB, develop areas with low oxygen levels. This condition is called tumor hypoxia. Tumor hypoxia correlates with poor prognosis, higher metastasis rate and resistance to cancer treatments. In response to hypoxia, cancer cells start to express carbonic anhydrase 9 (CA9) via HIF1. CA9 contributes to the maintenance of alkaline intracellular pH. That promotes tumor development, while the increasingly acidic extracellular space promotes tumor cell invasiveness. CA9 has historically been related to carcinogenic processes in a variety of cancers, and it has been hypothesized that it may be a possible target for cancer therapy. Substances for the inhibition of CA9 already exist, and one of them, SLC-0111, has given promising results in phase I clinical trials as well as several pre-clinical studies. The aim of this study is to describe the expression of CA9 in HB and study their relationship to pathological features in cellular level, especially the viability and migration of cancer cells. Another purpose of the study is to investigate the effect of SLC-0111 on HB cells and to consider its significance as a potential treatment. CA9 is expressed in two different HB cell lines, HUH6 and HB-303-LEF when exposed to hypoxic conditions. Cells show more aggressive behavior under hypoxic conditions. HB-303-LEF migrates more abruptly in hypoxia compared to normoxic cells. Cells from both cell lines in spheroid modeling, in which CA9 was inhibited by SLC-0111, showed lower viability. HB-303-LEF also showed slower migration in hypoxia where it had received the SLC-0111 inhibitor compared to hypoxic cells. HUH6 results were parallel but not statistically significant. Cells behave more aggressively in hypoxia. The use of SLC-0111 contributes to the reduction of viability and migration. It can be considered an interesting discovery for future treatments against HB.
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(2023)IER3IP1 is a protein located in the endoplasmic reticulum (ER) transmembrane, and it is highly expressed in pancreatic beta cells and developing brain cortex. The loss-of-function mutations in IER3IP1 cause monogenic neonatal diabetes together with brain linked diseases such as epilepsy and microcephaly. The aim of this thesis is to study the role of IER3IP1 in the development and function of human beta cells using hESC-derived pancreatic islets. Using CRISPR/Cas9, IER3IP1 knockout (KO) and IER3IP1 loss-of-function mutation knock-in (KI) hESC clones were generated. For KO, the first exon of IER3IP1 was deleted whereas for KI, the 21. valine of IER3IP1 was changed to glycine. The clones together with their unedited controls (H1), were differentiated into pancreatic stem cell (SC)-islets following the optimized 7-stage differentiation protocol. The differentiation was followed during the protocol and the SC-islets were tested at the end of the protocol. In vitro, IER3IP1 KO-islets contained less beta cells and more alpha cells when compared to the H1-islets, as shown by immunostainings for insulin and glucagon. The beta cells of KO-islet accumulated more proinsulin compared to H1-islets and had significantly higher level of ER-stress shown by elevated ER-stress marker BiP. Moreover, the KO-islets showed drastically lower amount of insulin secretion and diminished insulin content. The IER3IP1 KI-islets did not significantly differ from H1-islets. Thus, this master’s thesis shows that IER3IP1 is essential for maintaining normal ER homeostasis and beta cell function in vitro. In future, these results should be confirmed using in vivo model.
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(2013)This thesis examines the role that contemporary international criminal courts play in the formation of customary international law. It addresses applicable law and the case law of the International Criminal Tribunal for the former Yugoslavia (ICTY) and Rwanda (ICTR), the Special Court for Sierra Leone (SCSL), and the (permanent) International Criminal Court (ICC). More specifically, this thesis provides answers as to the role customary law plays as a source of applicable law in these courts and further, the role these courts play in developing the content of customary law. International criminal courts serve as important entities in discovering and interpreting existing rules of customary international law. Although these courts’ primary function is to apply existing law, not to create it, their case law forms an essential part of the formation process of customary international law. But uniting the legislative and judicial processes together diminishes the legitimacy of the resulting rules. The problem comes to the fore when international criminal courts broaden the scope of individual criminal liability by expanding the definitions of international crimes. The principle of legality –inherent to criminal law– prohibits retroactive crime creation and punishment and thus seems to prohibit courts from interpreting law expansively. However, throughout the history of international criminal law international criminal courts have been remarkably productive in their interpretations. This thesis examines the role of customary law in the practice of contemporary international criminal courts. It elaborates on the interplay between customary law and judicial decision and examines how traditional and modern approaches to custom formation deal with international courts as entities capable of forming new rules of customary law. Finally, it analyzes critically how rules of customary law have been discovered and identified in contemporary international criminal courts. By addressing the methods and arguments used in judicial reasoning it examines whether international criminal courts have fulfilled the requirements of the principle of legality in their work. The main argument of this thesis is that international criminal courts operate in the very heart of the customary law-making process. Their contribution to the corpus of international criminal law has been indispensable. However, the judicial creativity practiced by the modern international criminal courts seems to be on the decline as the ad hoc Tribunals (ICTY and ICTR) are concluding their work and the ICC begins to lead the way for the future application of international criminal law.
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(2022)Sensory systems display a topographical organization, and in the murine somatosensory system there is oneto-one correspondence between individual whiskers and individual cortical columns called barrels. Functional connectivity in the whisker-to-barrel system is formed prenatally and refined after birth, guided by both spontaneous and whisker-evoked activity. GABAergic connectivity emerges already prenatally and includes transient circuits, but the exact role of GABAergic signalling in early development is elusive. The neuronal, major chloride extruder, potassium-chloride cotransporter (KCC2) is heavily upregulated in the cortex during the first two postnatal weeks resulting in the emergence of hyperpolarizing inhibition. However, in cortical interneurons (INs) KCC2 expression can be detected already at the time of birth. The role of this early interneuronal KCC2 expression is unclear. The aim of this thesis was to study the role of KCC2 in the network activity of cortical INs during the perinatal period. Transgenic mice with conditional inactivation of Kcc2 gene, and expression of the calcium indicator GCaMP6f in GAD2+ neurons (INs) were used to image cortical Ca2+ activity. Transcranial widefield Ca2+ imaging in awake head-fixed mice was performed at the day of birth (P0) and showed that spontaneous, but not evoked, activity was significantly reduced in the knock-out animals. Moreover, immunostaining for the activity-induced transcription factor Egr1 showed that thalamic network activity was significantly decreased in the knock-out and heterozygous animals, suggesting involvement of subcortical areas in the decreased cortical activity. Additional experiments are needed to elucidate the role of other mechanisms contributing to the observed change in activity.
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