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(2022)This thesis is aimed to investigate the long-run and short-run relationship between renewable, nuclear energy consumption, economic growth and CO2 emissions in Finland. The historic development and current situations of the energy consumption, economic growth and CO2 emissions are discussed. Then Johansen cointegration test and Vector Error Correction Model (VECM) are applied in the empirical analysis to further exploit the causal relationships between the variables. There are four variable employed in this thesis: renewable energy consumption (REC), nuclear energy consumption (NUC), Gross Domestic Product (GDP) and CO2 emissions (COE). The data of the variables span from 1977 to 2020 and mainly come from official databases and reports from the Finnish government and international organizations, such as Statistics Finland, Our World in Data, World Bank, etc. The results indicate that there is the positive bidirectional long-run relationships between NUC, REC and GDP. Also, the unidirectional long-run relationships of GDP, REC, NUC with COE are estimated. The increase in GDP and NUC are estimated to increase COE in the long run, while REC is estimated to decrease COE. Furthermore, the negative short-run relationships between REC, NUC and COE are found, which shows that, in the short run, renewable and nuclear energy consumption in Finland is estimated to reduce the CO2 emissions. The findings from the thesis indicate renewable energy consumption is both economic and environmental-friendly. Nuclear energy is also good for economic growth in the long run and environment in the short run, but needs to be cautiously treated with regard to environmental protection in the long-run strategies. Also, there has been the trend of impact decoupling in Finland in the short term. However, further research is needed to test the EKC hypothesis and its turning point.
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(2023)Plants are vital to all terrestrial ecosystems by providing ecosystem services through photosynthesis- derived compounds. Throughout the millennia, plant metabolism has diversified in the form of all plant secondary metabolites, ranging from metabolite groups such as terpenes to alkaloids to flavonoids. Many of these secondary metabolites are economically valued for their chemical, pharmaceutical and physical properties. The flavonoids are one of the largest groups and are known to provide competitional advantages and increase of survival of many plant species in extreme environments. One of the critical enzymes in the whole biosynthesis pathway of flavonoids is the dihydroflavonol 4- reductase (DFR). DFR regulates the formation of leucoanthocyanidins, predecessors of colourful anthocyanins. Anthocyanins are an economically significant group of molecules, especially for horticulturists and plant breeders, but also for nutritional and health scientists due to their potential health benefits. Dihydroflavonol 4-reductase is a much-studied enzyme due to its significant role in flavonoid biosynthesis and the economic interests of plant breeders and alike. Previous studies have expanded the knowledge of flavonoid biosynthesis and have identified several amino acid residues in the DFR structure affecting the substrate specificity of the enzyme and, consequently, the flower colours. However, only a single crystal structure model of the dihydroflavonol 4-reductase has been solved so far, originating from the grapevine Vitis vinifera. Although a single crystal structure can facilitate further structure-to-function studies associated with dihydroflavonol 4-reductase, further studies need to be carried out to shine a light on the functional basis of the enzyme. Therefore, this study aims to resolve petunia and gerbera dihydroflavonol 4-reductase crystal structures, expanding the knowledge of structural variations within the uncharted families of angiosperms, Solanaceae and Asteraceae. Several recombinant protein expression systems were utilised in my attempts to solve the crystal structure of the DFRs. These systems ranged from the bacterium Escherichia coli to yeast species such as Saccharomyces cerevisiae and Pichia pastoris, as well as the tobacco plant Nicotiana benthamiana. The genes encoding for Petunia wildtype DFRA, three mutants, and three Gerbera DFR variants were cloned to several expression vectors. Their presence and expression were identified using various genetic methodologies and enzymological assays. The expression of DFRs using an E. coli-based expression system was verified. However, the trials with E. coli were deemed unsuccessful due to the majority of the protein ending in inclusion bodies with no detectable activity. An alternative system using agroinfiltration of N. benthamiana was later utilised, as significant amounts were detected in the plant tissue extracts following the agrobacterial infiltration. Although the proteins were expressed in high quantities, no purification procedures have been established to provide plant tissue-extracted protein in crystallography-grade purity. With the protein supplied by a plant-based system and several small- scale purification steps, purified DFR enzymes could be utilised in crystallisation studies. Due to significant contamination by RuBisCO in the protein samples, alternative systems based on S. cerevisiae and Pichia pastoris were investigated, and a successful Pichia-based expression was established. Several sets of plasmids with variable expression systems were constructed in this study, facilitating future experiments into the dynamics and structure of dihydroflavonol 4-reductases. Ground-breaking techniques based on computational modelling were utilised to hypothesise the role of prior determined amino acid residues in enzyme catalysis and substrate recognition. Possible crystallisation-related issues originating from protein structure were approached using the same techniques, opening new windows and possibilities into determining the structure of Petunia hybrida and Gerbera hybrida dihydroflavonol 4-reductase structures using tools of protein engineering.
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(2022)The variational quantum eigensolver (VQE) is one of the most promising proposals for a hybrid quantum-classical algorithm made to take advantage of near-term quantum computers. With the VQE it is possible to find ground state properties of various of molecules, a task which many classical algorithms have been developed for, but either become too inaccurate or too resource-intensive especially for so called strongly correlated problems. The advantage of the VQE comes in the ability of a quantum computer to represent a complex system with fewer so-called qubits than a classical computer would with bits, thus making the simulation of large molecules possible. One of the major bottlenecks for the VQE to become viable for simulating large molecules however, is the scaling of the number of measurements necessary to estimate expectation values of operators. Numerous solutions have been proposed including the use of adaptive informationally complete positive operator-valued measures (IC-POVMs) by García-Pérez et al. (2021). Adaptive IC-POVMs have shown to improve the precision of estimations of expectation values on quantum computers with better scaling in the number of measurements compared to existing methods. The use of these adaptive IC-POVMs in a VQE allows for more precise energy estimations and additional expectation value estimations of separate operators without any further overhead on the quantum computer. We show that this approach improves upon existing measurement schemes and adds a layer of flexibility, as IC-POVMs represent a form of generalized measurements. In addition to a naive implementation of using IC-POVMs as part of the energy estimations in the VQE, we propose techniques to reduce the number of measurements by adapting the number of measurements necessary for a given energy estimation or through the estimation of the operator variance for a Hamiltonian. We present results for simulations using the former technique, showing that we are able to reduce the number of measurements while retaining the improvement in the measurement precision obtained from IC-POVMs.
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(2021)This MA thesis explores the use of English on Instagram in the Finnish capital region that consists of the municipalities of Helsinki, Vantaa, Espoo and Kauniainen. Building on previous research on Virtual Linguistic Landscapes and English as a lingua franca, this thesis investigates the extent to which English is used in the study area and how different types of areas and locations differ in terms of English use in the study area. For this purpose, I use geotagged social media data and methods from the fields of natural language processing and geoinformatics. Firstly, I analyse the general linguistic make-up of the study area to understand the use of English in relation to other languages. Secondly, I analyse and compare how the use of English and Finnish are spread geographically across the Finnish capital region on Instagram and identify spatial clusters by means of spatial autocorrelation analysis. Lastly, I seek to provide further insights into the different types of locations where English, Finnish and other languages are used by using the Corine Land Cover inventory for categorising different types of locations. The results of this study show that the English language has a very strong presence as the second most used language in the Virtual Linguistic Landscape of the Finnish capital region. English is used especially often by users who use more than one language on Instagram. The spatial patterns of English use show that the language is used particularly often in the Helsinki city centre, western Helsinki and eastern Espoo and least in north-eastern Helsinki and Vantaa. English has a strong presence in essentially all the studied location types, especially in commercial and urban contexts. The relative proportions of English use are highest at airport areas and lowest in various sport and leisure facilities, where Finnish is used significantly more than any other language. In the analysis, I also include frequent observations on Finnish and other languages, which provide further insights into the rich Virtual Linguistic Landscape of the capital city region.
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(2024)Objectives. This article-based master’s thesis explores the use of ChatGPT in educational settings. Previous research on human-LLM remains scarce, and most literature addressing the use of GPT in educational settings is theoretical and lacking empirical evidence. The new technological developments, however, urge for a deeper understanding of its novel dynamics for the development of efficient and safe AI-systems. Consequently, our study aims explore the use of a novel guided interaction design for modeling users’ information foraging behavior when navigating GPT-generated content and the role of Computational Thinking Skills in shaping such behavior. Methods. Conducted with nine educational researchers in a doctoral-level AIEd course, our research used editable prompt templates and keywords to structure the prompt crafting process. We modeled and analyzed participants’ interactions with ChatGPT in terms of exploration (to generate and explore various information landscapes) and exploitation (to delve deeper into a specific landscape). Additionally, we conducted the Computational Thinking Scale survey. We employed descriptive statistics to describe participants’ foraging behavior, and network analysis to explore the relationship between foraging behavior and Computational Thinking Skills. Results and conclusions. Our results suggested that Algorithmic Thinking and Creativity might encourage exploitation behavior, leaning more on AI-generated information rather than pre-defined design elements. Furthermore, including participants' interests in the interaction design seemed to foster a shared conceptual space in prompt construction. This approach encouraged the use and combination of diverse interests for content creation, as opposed to relying solely on individuals' interests. Our findings also suggested that exploitation prompts are predominantly driven by GPT-generated content. While this seems to add value to AI-generated content, it raises concerns about potential overreliance, especially in educational settings. The article, entitled ‘Exploring the Use of GPT-4 when Generating Personalized Case Scenarios for Higher Education.’, follows the guidelines of the International Journal of Artificial Intelligence in Education.
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Exploring transient pockets in membrane bound pyrophosphatases using molecular dynamics simulations (2022)Malaria is a major cause of human mortality, morbidity, and economic loss. P. falciparum is one of six Plasmodium species that cause malaria and is widespread in sub-Saharan Africa. Many of the currently used drugs for malaria have become less effective, have adverse effects, and are highly expensive, so new ones are needed. mPPases are membrane integral pyrophosphatases that are found in the vacuolar membranes of protozoa but not in humans. These enzymes pump sodium ions and/or protons across the membrane and are crucial for parasite survival and proliferation. This makes them promising targets for new drug development. In this study we aimed to identify and characterize transient pockets in mPPases that could offer suitable ligand binding sites. P. falciparum was chosen because of its therapeutical interest, and T. maritima and V. radiata were chosen because they are test systems in compound discovery. The research was performed using molecular modelling techniques, mainly homology modelling, molecular dynamics, and docking. mPPases from three species were used to make five different systems: P. falciparum (apo closed conformation), T. maritima (apo open, open with ligand, and apo closed) and V. radiata (open with ligand). P. falciparum mPPase does not have a 3D structure available, so a homology model was built using the closest structure available from V. radiata mPPase as a template. Runs of 100 ns molecular dynamics simulations were conducted for these five systems: monomeric mPPase from P. falciparum and dimeric mPPases for the others. Two representative 3D structures for each of the five trajectories, the most dissimilar one to another, were selected for further analysis using clustering. The scrutinized 3D structures were first analyzed to identify possible binding pockets using two independent methods, SiteMap and blind docking (where no pre-determined cavity is set for docking). A second set of experiments using different scores (druggability, enclosure, exposure, …) and targeted docking were then run to characterize all the located pockets. As a result, only half of the catalytic pockets were identified. None of the transient pockets were identified in P. falciparum mPPase and all of them were located within the membrane. Docking was performed using compounds that have shown inhibiting behavior in previous studies but did not give good results in the tested structures. In the end none of the transient pockets were interesting for further study.
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Exploring white matter structural anomalies underlying dyslexia : A diffusion tensor imaging study (2018)Developmental dyslexia (DD) affects the accuracy and the fluency of reading without influencing the intelligence of an individual. Problems in phonological awareness (PA), the ability to manipulate the sound structure of words, has been proposed to be the key predictor of DD across languages. Diffusion tensor imaging (DTI) has been used to investigate white matter (WM) structure in DD. The DTI research has concentrated mainly on fractional anisotropy (FA) values, that measure the integrity of WM, and volume of the WM tracts, but also on lateralization differences. Structural alterations have been reported in multiple WM tracts, but left arcuate fasciculus (AF) have most consistently been associated with problems in phonological processing. Also, individuals with DD have been reported to have less prominent leftward lateralization in AF, and inferior fronto-occipital fasciculus (IFOF) compared to non-DD individuals. The participants consisted of 23 individuals with confirmed DD and 21 without DD. In this thesis the reading-related WM tracts were evaluated using deterministic tractography, and the goal was to 1) compare DD and non-DD participants in the FA and volume in reading circuitry, 2) study the associations between reading skills and FA and volume of the WM tracts, and 3) study the lateralization differences in FA and volume. The results of this thesis did not support the current view of the neuroanatomy of DD. Although groups did not differ in FA or in volume of the reading related WM tracts, the groups differed in the lateralization of the WM tracts. Both DD and non-DD participants manifested a rightward lateralization of WM volume in the AF, opposing the earlier findings. Furthermore, DD participants had a unique rightward lateralization of volume in uncinate fasciculus. Subthreshold results in correlations between reading skills and DTI indices also hint toward the heterogeneity found in the DTI research of DD, and do not confirm the role of the AF as the neural correlate of the phonological processing. It seems that no single abnormality in WM structure is responsible of DD. Rather, it seems that DD compiles a vast spectrum of symptoms, with possibly multiple trajectories, and individual compensatory mechanisms in adult samples.
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(2020)The applied mathematical field of inverse problems studies how to recover unknown function from a set of possibly incomplete and noisy observations. One example of real-life inverse problem is image destriping, which is the process of removing stripes from images. The stripe noise is a very common phenomenon in various of fields such as satellite remote sensing or in dental x-ray imaging. In this thesis we study methods to remove the stripe noise from dental x-ray images. The stripes in the images are consequence of the geometry of our measurement and the sensor. In the x-ray imaging, the x-rays are sent on certain intensity through the measurable object and then the remaining intensity is measured using the x-ray detector. The detectors used in this thesis convert the remaining x-rays directly into electrical signals, which are then measured and finally processed into an image. We notice that the gained values behave according to an exponential model and use this knowledge to transform this into a nonlinear fitting problem. We study two linearization methods and three iterative methods. We examine the performance of the correction algorithms with both simulated and real stripe images. The results of the experiments show that although some of the fitting methods give better results in the least squares sense, the exponential prior leaves some visible line artefacts. This suggests that the methods can be further improved by applying suitable regularization method. We believe that this study is a good baseline for a better correction method.
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(2016)We study growth estimates for the Riemann zeta function on the critical strip and their implications to the distribution of prime numbers. In particular, we use the growth estimates to prove the Hoheisel-Ingham Theorem, which gives an upper bound for the difference between consecutive prime numbers. We also investigate the distribution of prime pairs, in connection which we offer original ideas. The Riemann zeta function is defined as ζ(s) := \sum_{n =1}^{∞} n^{-s} in the half-plane Re s > 1. We extend it to a meromorphic function on the whole plane with a simple pole at s=1, and show that it satisfies the functional equation. We discuss two methods, van der Corput's and Vinogradov's, to give upper bounds for the growth of the zeta function on the critical strip 0 ≤ Re s ≤ 1. Both of these are based on the observation that ζ(s) is well approximated on the critical strip by a finite exponential sum \sum_{n =1}^{T} n^{-s} = \sum_{n =1}^{T} exp\{ -s log n \}. Van der Corput's method uses the Poisson summation formula to transform this sum into a sum of integrals, which can be easily estimated. This yields the estimate ζ(1/2 + it) = \mathcal{O} (t^{\frac{1}{6}} log t), as t → ∞. Vinogradov's method transforms the problem of estimating an exponential sum into a combinatorial problem. It is needed to give a strong bound for the growth of the zeta function near the vertical line Re s = 1. We use complex analysis to prove the Hoheisel-Ingham Theorem, which states that if ζ(1/2 + it) = \mathcal{O} (t^{c}) for some constant c > 0, then for any θ > \frac{1+4c}{2+4c}, and for any function x^{θ} << h(x) << x, we have ψ (x+h) - ψ (x) ∼ h, as x → ∞. The proof of this relies heavily on the growth estimate obtained by the Vinogradov's method. Here ψ(x) := \sum_{n ≤ x} Λ (n) = \sum_{p^k ≤ x} log p is the summatory function of the von Mangoldt's function. From this we obtain by using van der Corput's estimate that the difference between consecutive primes satisfies p_{n+1} - p_{n} < p_{n}^{\frac{5}{8} + \epsilon} for all large enough n, and for any \epsilon > 0. Finally, we study prime pairs, and the Hardy-Littlewood Conjecture on their distribution. More precisely, let π _{2k}(x) stand for the number of prime numbers p ≤ x such that p+2k is also a prime. The following ideas are all original contributions of this thesis: We show that the average of π _{2k}(x) over 2k ≤ x^{θ} is exactly what is expected by the Hardy-Littlewood Conjecture. Here we can choose θ > \frac{1+4c}{2+4c} as above. We also give a lower bound of π _{2k}(x) for the averages over much smaller intervals 2k ≤ E log x, and give interpretations of our results using the concept of equidistribution. In addition, we study prime pairs by using the discrete Fourier transform. We express the function π _{2k}(n) as an exponential sum, and extract from this sum the term predicted by the Hardy-Littlewood Conjecture. This is interpreted as a discrete analog of the method of major and minor arcs, which is often used to tackle problems of additive number theory.
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(2019)Cameroon is a country located in Central Africa. The country has an export-led economy, which means that the country highly depends on exports to ensure its population well-being. Sawnwood exports represent 14% of Cameroon’s total exports. Sawnwood is therefore one of the most important export products for Cameroon. Since Cameroon signed the EU-Cameroon voluntary partnership agreement policy in 2010, Cameroon’s sawnwood exports were impacted. The aim of this study is therefore, to examine the export competitive performance of Cameroon’s sawnwood industry from 2001 to 2017. Based on the literature, a set of three methods analyzing the competitiveness of Cameroon’s sawnwood exports were chosen. These methods are: The Revealed Comparative Advantage Index (RCA) and RSCA index which were used to analyze the competitiveness and international specialization of Cameroon in exporting sawnwood. The Spearman Rank Correlation was used to study the export competitive performance of Cameroon’s sawnwood across years and to analyze the level of competition between Cameroon, Finland, China and Ghana. Lastly, the Constant Market Share Analysis was used to explain the drivers of Cameroon’s sawnwood export competitiveness. This study also compiles information on forest in Cameroon and provides an overview of Cameroon sawnwood industry, it can therefore serve as a base for further studies on sawnwood in Cameroon. Results show that Cameroon has a competitive advantage and is the highest specialized in exporting sawnwood compared to Finland, China and Ghana. Nevertheless, the export competitive performance of Cameroon across years is not continuous and highly depends on external factors. Results also show that Cameroon has reduced its exports to EU and has diversified its importers portfolio by redirecting its exports trade flows towards Asia, especially China which has less stringent imports policies compared to EU. Cameroon will need to improve its production technologies and management practices to ensure a long run competitiveness on the global sawnwood market.
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(2022)In the 2020s, environmental degradation and human rights issues in the context of globalized economy and trade have turned sustainability and responsibility into a trend in politics and business. In the context of trade, the EU portrays itself as a global leader in fair and sustainable trade through its ‘new generation’ free trade agreements (FTA) which include commitments on environmental and labor rights. This thesis studies the role of values, norms, and ideas in the EU’s trade policy, particularly in the EU’s ‘new generation’ free trade agreements. The main research question seeks to answer how the EU promotes its fundamental values in its trade policy with third partners. The sub-questions offer the scope for the research problem: How does the EU diffuse its founding normative values in trade agreements? Which other values and norms does the EU promote in its trade relations? How does the transference of norms appear in trade relations with the EU? The research problem is placed in the constructivist tradition in international relations and global political economy, followed by the discussion of Normative Power Europe (NPE) which explores the EU’s non-coercive power to influence norms and values globally. The methodology is focused on explaining-outcome process tracing in which evidence from the case of EU-South Korea FTA is analyzed through a theorized explanation of norm diffusion as a causal mechanism. In addition to the original FTA document, academic literature about the FTA and the final report of the FTA’s panel of experts procedure were used to examine the theorized explanation. The main findings show that in the case of the EU-South Korea FTA, the EU prioritizes economic and political interests over its fundamental values of human rights and environmental issues in its FTA strategy, negotiations, and the final agreement. Business groups have had a stronger influence on the EU’s policy positions during FTA negotiations compared to non-business organizations. There is also a discrepancy between the EU’s communiqués about its leading role in sustainable trade and the legal capacity of the final agreement: the sustainable development chapter of the EU-South Korea FTA includes commitments on multilateral agreements instead of EU-specific rules, a weaker dispute settlement system compared to its trade-related chapters and a civil society mechanism which in practice has received criticism due to its ineffectiveness in environmental and labor rights questions. Competition with the US could also have influenced the modest normative demands for the FTA. Ultimately, combining an agenda of sustainable development with the management of the EU’s trade relationships is a balancing act between political and economic interests over normative interests. If a normative agenda is not set in the center of the EU’s trade policy, it is likely to remain as a tool for communication for domestic audiences.
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(2017)In this research I am going to target an important topic of media influence and propaganda. In this research, my goal is to identify and analyze the main strategies of Russian disinformation and propaganda actions and how do they affect the politics of the aforementioned countries under review. At the same time, I will go into the analysis of the Russian internal framework and how do polittechnologies and informal policies at home set a narrative, which is built to support the flywheel of propaganda. Generally, during the course of my thesis, I`ll target four main topics. The phenomenon of Russian informal politics and media propaganda, main channels and approaches existing in the field of informational warfare, the importance and relevance in the modern world of such concepts as hybrid warfare and the politics of disinformation, in order to demonstrate how the export of Russian disinformation and propaganda shape the politics of Ukraine, Finland and Germany. The period under review is 2014-2018. I see the main significance of my research in its relevance. The events and political technologies, which are going to be discussed in my dissertation, have occurred very recently and are still happening, what makes them very relevant for the contemporary studies. I hope that this research can bring a significant input into the study of informal politics and propaganda, demonstrate the experience of the countries under review and expand on the potential political decisions against Russian disinformation strategies both by the measures of politics and media policies. The selection of countries aims to represent different aspects of the Russian political technologies, specific for each of the aforementioned region. Ukraine, Finland and Germany belong to different geographic regions, have different mentalities, and thus experience heterogeneous effects of Russian propaganda and political influence. The dissertation is going to be conducted through the research-based method, including articles and databases produced in 2014-18 in the aforementioned region and specific literature on the subject. The methodology of my research is going to consist of analysis of the politics, party building, social media, elections and activity of the private and governmental organisations in the region under review. The language of the publications used in my research include English, Russian, Ukrainian and German. My analysis is supported by the relevant images and graphs, which are set to support my argument where it is going to be necessary. Main conclusion, which can be drawn from this thesis, is that nowadays, Russian disinformation is a very topical and important subject. The strategies of influence in their majority are not new, but they are evolving, same as the informal and hybrid warfare, unleashed in 2014. Taking into the account the slice of the literature and media publications, analyzed in this thesis, it is possible to argue that the threat will continue. It is also possible to argue that the channels of this influence are likely to remain the same as those, discussed in this thesis.
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(2023)Due to population growth, urbanization, and increase in life expectancy, the urban population is growing, and by 2050 68% of the global population is expected to live in urban areas. Even though the air quality in urban settings has greatly improved in recent decades due to increased legislation, restriction, and monitoring, the negative health impacts associated with pollutants have not completely diminished. Air quality varies on a local scale due to urban form and function, that creates differences in experienced exposure among individuals. These exposure differences among socio-economic groups have been studied, but no clear consensus has been found, as the results have been very diverse and even contradictory. Therefore, conducting local level studies is important in order to identify local patterns of exposure and to recognize them in urban planning. However, previous literature on the topic in Finnish context is lacking. This thesis studies interpolated air pollutant exposure among one susceptible socio-economic group – the elderly – and aims to identify possible hotspots of both in Helsinki, Finland. The distribution of the elderly and air quality is assessed through Moran’s I calculations. Global Moran’s I is used to assess for spatial autocorrelation, and local Moran’s I is applied to identify local clusters. To further examine the relationship, correlation coefficients are calculated through Spearman’s rank correlation coefficient. According to the results, there is a weak positive correlation between the elderly and air quality, indicating that generally air quality tends to be worse when the number of elderly people increase. However, the relationship is stronger among younger age groups, although the differences between age groups is very small. The exposure was also assessed through overlapping high value clusters, which indicate that elderly clusters in the city center are located in areas with low air quality, while elderly clusters in Lauttasaari and Vuosaari are located in areas with good air quality. Previous studies regarding the relationship between age and air pollution exposure have been contradicting in different cities, and therefore these results provide important knowledge about the problem specifically in the context of Helsinki. Additionally, the results are be observed in the light of the larger discourse around socio-economic status and air pollution, but further studies on the topic are still needed. Including multiple socio-economic variables and the dimension of negative health outcomes would aid in identifying 1) the most important socio-economic factors in the context of negative health outcomes associated with air pollution, and 2) those areas where multiple important socio-economic factors and low air quality are overlapping and therefore might have higher risk for negative health outcomes.
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(2021)Histamine receptors are known to be expressed throughout the peripheral nervous system and are involved in regulating the gut and immune system. The gut-brain axis, which consists of bidirectional signaling between the central nervous system and gastrointestinal tract, links gut functions to emotional and cognitive controls in the brain. Many animal models are known to express histamine receptors in their gut and brain tissue which can be altered by a compromised gut-brain axis like stress. Histamine receptors also play an important role in many gastric and intestinal disorders. However, the precise expression pattern of histamine receptors in zebrafish gut tissue is unknown, as is whether their expression levels also change with stress. Here, I show that zebrafish gut contains several histamine receptors, but their role involving stress within the gut remains unknown. I found that histamine receptors hrh1 and hrh3 as well as the enzyme that synthesizes histamine, histidine decarboxylase (hdc), are expressed in zebrafish gut and brain in wildtype and hdc knockout adult zebrafish using in situ hybridization. Stress induction on wildtype male zebrafish through chronic social defeat and analysis of histamine receptor and hdc mRNA levels using quantitative real time PCR showed no differences in subordinate, dominate, or control fish. However, it did provide quantitative data that hrh1, hrh2, and hdc mRNA expresses in the adult gut. My results demonstrate the first data to suggest histamine receptors are expressed in zebrafish gut, and that even though stress can alter the gut-brain axis, it may not do so through the regulation of these receptors.
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(2020)Norway spruce is commonly cultivated throughout Europe, Russia, and Japan. Cultivation of Norway spruce often faces the issue of fungal diseases, one of which is cherry rust disease caused by Thekopsora areolata. The gene model MA_10g0010 encoding an uncharacterized peroxidase (PabPrx86) has previously been associated with the presence of this pathogen. The aim of this study was to describe and assay the protein produced from this gene model, observe its localization in the cell, and determine its relative expression level in different tissues of Norway spruce. Experiments were performed by isolating the full length cDNA for PabPrx86 and cloning the cDNA into destination vectors pEAQ-HT-DEST1 and pK7FWG2 leading to a hypertranslatable transcript and a C-terminal GFP fusion, respectively. The plasmid constructs were transformed to Agrobacterium tumefaciens and agro-infiltrated to Nicotiana benthamiana. In addition, the relative expression level of this gene in different spruce tissues at different times of the year was determined using the qRT-PCR method. Sequencing showed that there were two allelic variants of this gene in the spruce individual sampled for RNA. Results showed that both alleles code for a peroxidase with basic pI. Subcellular localization with the GFP tag detected that PabPrx86 protein was located out of cytoplasm, indicating that the protein was translated in the ER-ribosomes, whereas relative expression level analysis revealed that PabPrx86 was highest expressed in the bud and lateral bud in June. Peroxidases are known to relate with plant defense, but further experiments are required to determine the role of PabPrx86 in Norway spruce and what the association with T. areolata means.
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(2021)The endoplasmic reticulum (ER) is an important organelle of the cell where a high number of proteins are synthesized and modified to obtain their final structure. Therefore, the ER stress, which is caused by accumulation of unfolded proteins in the ER, is not to be taken lightly since it could contribute to many diseases, such as cancer and neurodegenerative diseases. The response to the ER stress is the unfolded protein response (UPR), which is an adaptive system that helps in adjusting for increased folding needs within the ER. One of the main protein branches in the UPR is inositol requiring enzyme 1 (IRE1). IRE1 detects the status of protein folding inside the ER and initiates the UPR signaling pathway to achieve either normal folding status or cell death. The aim of this research was to express yeast IRE1 in E.coli and human IRE1 in insect cells, purify with affinity chromatography and study the IRE1’s crystal structure with a small molecule modulator that could possibly enhance its activity. The protein was expressed successfully and purified with glutathione S-transferase (GST) tag, and the activity of the pure protein was determined. The structural studies were not fully completed since the absolute purity and yield that was necessary for crystallization was not achieved due to loss of protein during gel filtration and precipitation. Based on the results it is likely that the structure of the protein could be solved and further biochemical and structural studies with F10 are possible.
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(2023)Membrane-bound pyrophosphatases (M-PPases) catalyse the reversible hydrolysis of pyrophosphate into two inorganic phosphate molecules. This hydrolysis is coupled to the transport of protons and/or sodium ions across the biological membrane, generating an electrochemical gradient, which can be utilized by the host organism as an energy source under different stress conditions. The essential physiological roles of M-PPases in agriculturally relevant plants and various human pathogens, such as Bacteroides fragilis, Plasmodium falciparum, Toxoplasma gondii, and Trypanosoma brucei, make them an important research area. Despite the biochemical studies conducted with several M-PPases and structural characterization of Thermotoga maritima and Vigna radiata M-PPases, there remain several questions regarding the biochemistry and catalytic mechanism of M-PPases, one being the basis of K+ dependence. Mutational studies have suggested that a single residue at position 495 is the sole determinant of K+ dependence in M-PPases. In K+-dependent M-PPases this residue is an alanine and a K+ ion binding in close proximity of it, has been shown of having stimulatory effect on K+- dependent M-PPases by increasing the maximal rate of pyrophosphate hydrolysis. In K+-independent M-PPases, a lysine residue resides at 495 position, where the ε-NH3+ group of the lysine residue has been suggested, based on structural modelling and AlaàLys (A495K) mutational studies, to structurally and functionally mimic the activating function of K+ in K+-dependent M-PPases. In order to provide structural basis to this, in this study, a M-PPase belonging to a hyperthermophilic deep- sea bacterium T. maritima containing a single A495K point mutation was expressed in Saccharomyces cerevisiae, solubilized using the high-temperature (“Hot-solve”) method, purified with metal affinity chromatography and structurally characterized using X-ray crystallography. As suggested, the ε-NH3+ group of the introduced lysine was shown to occupy the same space and form the same interactions at the active site as the K+ ion in K+-dependent M-PPases. However, these structural findings were in contradiction with the conducted hydrolytic activity assay which showed that the A495K mutation, besides abolishing K+ dependence, significantly reduced the overall activity compared to the wild type by ~2-10-fold, depending on the K+ concentration. These findings suggest that additional factor(s) besides the 495 residue determine the K+ dependence in M-PPases.
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(2018)Allograft hud är kadaverhud som används som ett tillfälligt skydd på det brända och opererade hudområdet. Den tillfälliga allograften vaskulariseras i det rena sårbottnet inom några dagar och stöts bort efter 1-4 veckor. Förvaringen i glycerol dödar cellerna och har antibakteriella och antivirala egenskaper, men man vet inte om allografthudens immunogenicitet minskar om förvaringstiden i glycerol förlängs. Blodtransfusioner och användning av allograft hud är de vanligaste orsakerna till HLA-sensitisering hos brännskadepatienter. I denna avhandling utreder vi allograft hudens immunopositivitet med immunohistokemiska metoder, för att kunna förstå oss bättre på hud allograftens immunogenicitet. Vi vill utreda om lagringstiden i glycerol eller donatorns livslängd ändrar den glycerolförvarade allograftens immuniserande egenskaper. Vi analyserade fem Toll-lika receptorer (TLR2, 4, 5, 7 och 9) och cd45 receptorer i glycerolförvarad allograft hud för att se om det fanns ett samband mellan immunopositiviteten och förvaringstiden i glycerol och donatrons livslängd. Analysen gjordes för att kunna ge direktiv om förvaring och användning av glycerolförvarad allograft hud i hopp om att minska patientens immunisering. Vårt begränsade material minskade på möjligheterna att påvisa de samband, som var målsättningen för studien. Vi fann inte ett samband, men vi kunde se immunopositivitet i allograften, vilket tyder på att det finns proteiner i allograften som kan aktivera immunförsvaret.
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(2019)Programmed death protein 1 (PD-1) är en immunsuppressiv ytreceptor på aktiverade mördar-T-celler. På de flesta av kroppens egna celler finns en ligand, programmed death ligand 1 (PD-L1), som binder till PD-1, och inaktiverar mördar-T-cellerna. Detta är en viktig mekanism med vilken kroppen förhindrar autoimmunitet. Tumörceller kan undgå mördar-T-cellerna genom att uppreglera expressionen av PD-L1 på sin yta. I den här studien undersöks hur stor del av mjukvävnadssarkom som uttrycker PD-L1 på sin yta, och hur många fall som innehåller PD-1-aktiverade CD8-celler. Mjukvävnadssarkom omfattar under en procent av all cancer hos vuxna. Sammanlagt 1128 fall inkluderade i 13 TMA-block färgades immunohistokemiskt med PD-1 respektive PD-L1 antikroppar. Preparatens mikropskopbilder skannades och undersöktes i CaseViewer, ett program som stöder digital histopatologisk undersökning. Av de undersökta preparaten var PD-1 expressionen överlag låg, mest PD-1 uttrycktes bland synovialsarkomen. Expressionen av PD-L1 var varierande, den högsta expressionen hade myxofibrosarkomen (53,2%). Idag finns det ännu inte någon specifik vård för sarkom, vården består av kirurgisk excision, strålbehandling och kemoterapi. Då patientens vård planeras är det essentiellt att veta ifall tumörcellerna uttrycker PD-L1, i vilka fall patienten kan vara passande för immunoterapi med PD-L1 antikroppar. Antikropparna binder till PD-1, utan att inaktivera CD8-cellen, vilket möjliggör dess immunologiska funktion och förstörelse av tumörcellen. Patienter vars tumörceller uttrycker PD-L1 har en bättre prognos med immunoterapi.
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(2021)The autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), caused by mutations in the autoimmune regulator (AIRE) impairing the development of T cell tolerance, is characterized by damage towards multiple endocrine and cutaneous tissues, driven by autoreactive T cells and autoantibodies. Furthermore, neutralizing autoantibodies towards type I interferons (IFNs), which are thought to be crucial in the immune modulating function of the skin, are found in practically all APECED patients. Although the expression and role of thymic AIRE have been widely studied, the extra-thymic role of AIRE remains unclear. Previous studies suggest that AIRE is expressed in skin keratinocytes in association with cytokeratin K17 and that AIRE-expressing skin tissue cultivations can thymus-independently facilitate the formation of functional self-tolerant T cells highlighting the importance of skin for immune tolerance. The goal of this research was to study the co-expression of AIRE and K17 or IFNα2 in cultivated primary keratinocytes from healthy individuals and in HaCaT cells through immunohistochemistry to better understand the role of cutaneous AIRE. The results show that AIRE is indeed co-expressed in human keratinocytes where it contributes in a yet unknown manner to the function of these cells.
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