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Chemical Exchange Saturation Transfer (CEST) is a novel Magnetic Resonance Imaging (MRI) technique that utilises exchange reactions between metabolites and tissue water to map metabolite concentration or tissue pH noninvasively. Similarly to Magnetic Resonance Spectroscopy (MRS), CEST is able to detect many endogenous metabolites, but unlike MRS, CEST is based on imaging and thus enjoys the speed of modern MR imaging. On the other hand, CEST also suffers from the same difficulties as MRI and MRS. One of the most common source of image artifacts in MRI is subject motion during imaging. Many different motion correction methods have been devised. Recently, a novel real-time motion correction system was developed for MRS. This method is based on volumetric navigators (vNav) that are performed multiple times interleaved with the parent measurement. Navigator image comparison, affine matrix calculation, and acquisition gradient correction to correct the field of view to match subject head motion are done online and in real-time. The purpose of this thesis is to implement this real-time motion correction method to CEST-MRI and study its efficacy and correction potential in phantoms and in healthy volunteers on 7T MR scanner. Additionally, it is hypothesised that the vNav images may be used to correct for motion related receiver sensitivity (B1-) inhomogeneities. Glutamate was chosen as the metabolite of interest due to it being the most abundant neurotransmitter in the human brain and due to its involvement in both normal cognitive function as well as many brain pathologies. Since glutamate has an amine group, it undergoes chemical exchange with water and is thus a usable metabolite for CEST imaging. A glutamate phantom was constructed to show the glutamate concentration sensitivity of CEST and to test and optimise the CEST sequence. Seven healthy volunteers were imaged over a period of two months. All but one volunteer were imaged more than once (2-4 times). Subjects were measured without voluntary head motion and with controlled left-right and up-down head movements. All measurements were performed with and without motion correction to test the motion and B1- -correction methods. Additionally, three volunteers were measured with a dynamic CEST experiment to assess the reproducibility of CEST. The real-time motion correction method was found to be able to correct for small, involuntary head movements. 18 % of the CEST maps measured without motion correction were found to have motion artifacts whereas the equivalent number for maps with motion correction was 0 % (4/22 maps versus 0/18 maps). Larger (>0.7◦ or >0.7 mm in one coregistration step), voluntary head movements could not be corrected adequately. The vNav images could be used to correct for B1- -inhomogeneities. This was found to improve CEST spectra quality and to remove lateral inhomogeneities from the CEST maps. The reproducibility of the CEST-MRI could not be established, however dynamic CEST measurements were found to be stable with only small contrast fluctuation of 4 % between consecutive maps due to noise.

High-throughput sequencing techniques make it possible to identify DNA variants at a reasonable cost, representing a first-tier diagnostic test for rare mendelian diseases. However, a substantial number of variants identified through the analysis of sequencing data are frequently classified as variants of uncertain significance (VUS). Accordingly, only 30–60% of individuals receive a conclusive molecular diagnosis depending on the clinical phenotype. Reanalysis of older sequencing data has been encouraged by recently developed and improved methodologies for analysis and more robust bioinformatic pipelines to enhance variant interpretation and raise the diagnostic/detection rate. This study focused on reanalyzing data from a targeted gene panel, MYOcap, a targeted gene panel for patients with neuromuscular disorders. The aims were to find elusive (i.e., previously undetected/misinterpreted) variants in patients still missing a molecular diagnosis and, by using novel bioinformatic tools, focusing on pathogenic and likely pathogenic variants (according to ACMG guidelines) in Varsome as well as on variants affecting the splicing as predicted by SpliceAI. With this setting, the detection rate of solved cases increased by 2,7% in the first cohort and 0,5% in the third. This study suggests that additional data, such as segregation data or transcriptomic and proteomic data are essential for reducing the number of VUS and increase the detection rate. Notably, this study represents an essential first step of a larger reanalysis project, aiming at providing a diagnosis to an increasing number of myopathy patients.

Formal argumentation is a vibrant research area within artificial intelligence, in particular in knowledge representation and reasoning. Computational models of argumentation are divided into abstract and structured formalisms. Since its introduction in 1995, abstract argumentation, where the structure of arguments is abstracted away, has been much studied and applied. Structured argumentation formalisms, on the other hand, contain the explicit derivation of arguments. This is motivated by the importance of the construction of arguments in the application of argumentation formalisms, but also makes structured formalisms conceptually and often computationally more complex than abstract argumentation. The focus of this work is on assumption-based argumentation (ABA), a major structured formalism. Specifically we address the relative lack of efficient computational tools for reasoning in ABA compared to abstract argumentation. The computational efficiency of ABA reasoning systems has been markedly lower than the systems for abstract argumentation. In this thesis we introduce a declarative approach to reasoning in ABA via answer set programming (ASP), drawing inspiration from existing tools for abstract argumentation. In addition, we consider ABA+, a generalization of ABA that incorporates preferences into the formalism. The complexity of reasoning in ABA+ is higher than in ABA for most problems. We are able to extend our declarative approach to some ABA+ reasoning problems. We show empirically that our approach vastly outperforms previous reasoning systems for ABA and ABA+.

Introduction: When the decision of admitting a patient into an inpatient ward has been made but the patient remains waiting in the emergency department, the term boarding is used to describe this phenomenon. Boarding is associated with higher mortality, prolonged length of stay and increased hospital expenditure. The objective of this study is to examine the patient transfer conventions used for adult, non-ICU-bound ED patients and to uncover specific targetable causes of patient boarding. The study hospital emergency department treats internal medicine, neurological and surgical adult patients. The information provided by this study is to be used to improve the study hospital’s practices. Methods: The methods for this study were both qualitative and quantitative. The study was conducted in June and July of 2018 by directly observing the practices of the study ED and by measuring the time used for completing the steps relating to patient transfer to inpatient wards from the emergency department. The perceived reasons for delays during the transfer process were observed and logged. Results: The study hospital uses a patient transfer system where nurses communicate directly with each other. Patients could be moved to the wards only after a ward nurse approved it. The observed mean duration of the entire patient transfer process was 106 minutes. Most of this time was spent waiting for the go-ahead to transfer the patient and the mean for time for this part of the transfer process was 64 minutes. Nurses from the inpatient wards did not usually specify the exact cause for delays from their side. Discussion: Some limitations of this study included the small sample size and the fact that the operation of the ED was mostly observed during office hours on weekdays. Most of the boarding time consisted of waiting for the ward’s go-ahead to bring a patient in. To alleviate the problem of boarding in the study hospital, we think that giving the ED nurses a more active role in the admitting process is a key solution. Communication between the ED and the wards should also be improved.

As the esports scene has grown in the past ten years, so has the legal problems surrounding it. Because esports does not have the same kind of structure surrounding it as other sports, it lacks the committees and bylaws that could help in solving different legal issues. Instead esports relies on the more common legal avenues to solve problems that might be completely unheard of in other sports. This study will consider the contractual and legal relationships between different parties in an event where an unauthorized party is using a third party program to ‘rebroadcast’ the gameplay footage of a professional esports player on a streaming site. To thoroughly consider all the angles in an event like this, the author has to consider legal standing of all the parties involved. However, the study will focus on the legality and possible ramifications that an event like this might cause. As most of the more important service providers to date, especially the ones focused on streaming esports, have their base of operations in the United States, the study will focus on the legislation and the case law of the United States. Some legal points from foreign intellectual property legislations will be introduced, and the broader effects of different harmonization processes of international copyright treaties will be explained, but for the sake of clarity, the focus will be locked on the legislation of the United States and especially the Digital millennium copyright act and the Lanham Act. Also some watershed cases from U.S. case law will also be introduced to give some intelligibility to the actual applicability of the legal points that are made. As the contractual relationships between the video game developer, the professional videogame player (esports player) and the creator of the third party software are among the most important parts of the study, there is a separate chapter for the Terms of service agreements (TOS) and the End user license agreements (EULA). This is done to give the reader a basic understanding of the ways that video game companies establish and impose control over their intellectual property in the video game industry. Case law and interpretations of different court cases regarding the Terms of service agreements and End user license agreements will be introduced. As the subject matter is unavoidably intertwined with the use of worldwide web, it is important to look at the current legislation that is used to control things like e-commerce, and converse on the different aspects of intellectual property protection used in the digital age. For the reader to understand the basics of the harmonization of different intellectual property legislations in the internet age, the study will introduce some of the most important international intellectual property treaties, which form the basis for harmonized intellectual property protection in different countries worldwide. For clarity’s sake, a real life event where an individual used a third party program to stream a pro esports player’s gameplay on a streaming site will be introduced. The legal actions of each legal subject will be covered and the legal validity of their actions will be analyzed and used as a base for broader legal analysis on the subject of rebroadcasting via third party programs.

Global warming is changing the ecohydrology and carbon fluxes of northern peatlands. If the soil moisture level remains high enough, peatland carbon sequestration may increase under longer and warming growing seasons, enhancing the cooling climate impact of peatlands. However, in case the evaporation overcomes precipitation, peatlands will dry. This leads to increased carbon dioxide emissions and the weakening of the cooling climate effect of peatlands. In addition, peatland methane fluxes are regulated by temperature and moisture conditions. What remains unknown, is which changes will be the most prominent and to which direction the climate impact of peatlands will develop in the future. The purpose of this thesis is to gain a better understanding of the peatland climate responses by investigating the recent vegetation development of a subarctic aapa mire. In August 2020, four surface peat cores were collected from the margin of Lompolojänkkä fen in Finnish Lapland. Recent changes in plant communities and carbon accumulation rates were investigated. Pb-210 dating method was applied to establish the chronology. A shift from a Cyperaceae-dominated community into a Sphagnum-dominated community in the beginning of the 1960s was detected. The shift indicates drying habitat conditions. Recent drying has been reported from several other northern peatlands. On the other hand, a similar expansion of Sphagna has been interpreted to be caused not only by hydrological changes but also directly by increasing temperatures, which cannot be ruled out in Lompolojänkkä either. Carbon accumulation in Lompolojänkkä seems to have increased following the change in the vegetation. However, the inferred increase might largely reflect an incomplete level of decomposing characteristic to surface peat. In contrast to the peatland margins, no drying signals or vegetation changes were observed in the central parts of Lompolojänkkä. This variation within a single peatland highlights the heterogeneous nature of peatland climate responses and carbon dynamics.

The literature part of this thesis consists of a review of recently introduced forms of solid phase microextraction (SPME): thin film microextraction (TFME), in-tube solid phase microextraction(IT-SPME) and the closely related techniques of capillary in tube adsorption trap/solid phase dynamic extraction (INCAT/SPDE). The experimental part covers the study of reagents for on-fiber derivatization of low molecular weight aliphatic amines in atmospheric concentrations. In TFME a thin film of sorbent is used for extraction instead of a rod-like sorbent as in fiber-SPME. This increases analyte uptake and capacity compared to fiber-SPME, making TFME suitable for non-equilibrium extraction. TFME is used with both gas and liquid chromatography, although the large size of the film presents problems in desorption, especially in gas chromatography. Common applications of TFME are environmental monitoring and in vivo extraction. IT-SPME is a dynamic type of SPME most often coupled with liquid chromatography, in which a liquid sample is pumped through an extraction capillary. It is relatively easily automated with most autosamplers. In the most common form a sorbent is coated on the inside walls of the capillary. Recently, packed types of IT-SPME have been introduced, which can achieve very high extraction efficiencies. In addition, sorbent materials which change their properties according to environmental factors such as temperature, potential and magnetic field seem promising for future development. INCAT/SPDE utilizes internally coated metal needles for extraction. Although similar to IT-SPME, it is used for sampling gaseous compounds by pumping them through the needle. Desorption and analysis is usually performed with a gas chromatograph. INCAT/SPDE has some advantages over fiber-SPME, such as larger sorbent volume and robustness. However, it is currently limited to only polydimethylsiloxane-based sorbents, which limits possible applications. In the experimental part, the possibilities of using allyl isothiocyanate, pentafluorobenzaldehyde(PFBAY) and pentafluorobenzyl chloroformate (PFBCF) in simultaneous extraction and on-fiber derivatization of low molecular weight aliphatic amines were explored. Separation and analysis was performed with gas chromatography-mass spectrometry. Allyl isothiocyanate did not derivatize the analytes. On-fiber derivatization with PFBAY was successful for both ethylamine and methylamine, but the concentrations required to observe signal from the derivatives were too high to use PFBAY for air samples. PFBCF was identified as the most promising reagent, working for both dimethylamine and ethylamine. It was also possible to construct a calibration function for gaseous dimethylamine.

Tutkimuksen tavoitteena oli parantaa aivojen takaverenkierron aivoverenkiertohäiriöiden tunnistusta ja hoitoon ohjauksen tehokkuutta. Luotettavampi aikainen tunnistus on tarpeen takaverenkierron aivoverenkiertohäiriöiden hoidossa, sillä takaverenkierron iskeemisistä häiriöistä kärsivillä potilailla voidaan hyödyntää pidempää trombolyysihoidon aikaikkunaa, kun taas takaverenkierron aivoverenvuotopotilaat saattavat tarvita neurokirurgista hoitoa muualla kuin neurologian yksikössä. Tutkimusta varten kerättiin 2262 potilaan kohortti Helsinki Stroke Thrombolysis- sekä Helsinki ICH -tietokannoista vuosilta 2005-2010. Retrospektiivisesti kohortin potilaista kerättiin potilasasiakirjoista tietoja potilaiden demografisista tekijöistä, sairaushistoriasta, aivotapahtuman alkuoireista ja -hoidosta sekä fysiologisista parametreista. Edellä mainittuja tekijöitä analysoitiin SPSS-ohjelmiston avulla. Analyysissä vertailtiin sekä aivojen etu- ja takaverenkiertohäiriöpotilaita, sekä erikseen takaverenkiertohäiriöpotilaiden osalta aivoverenvuoto- ja iskeemisistä häiriöstä kärsineitä potilaita. Tutkimuksessa oli yhteensä 1641 etuverenkierron (75%) ja 553 takaverenkierron aivoverenkiertohäiriöpotilasta. Takaverenkiertohäiriöpotilaat olivat nuorempia (65v vs. 70v) kuin etuverenkiertohäiriöpotilaat, ja harvemmalla oli aiemmin todettu verenpainetauti (51% vs. 61%). Takaverenkiertohäiriöpotilailla esiintyi yli kolminkertaisesti enemmän kouristelua, viidenkertaisesti enemmän oksentelua ja heillä oli päänsärkyä kaksi kertaa useammin kuin etuverenkiertopotilailla. Takaverenkiertopotilaiden joukosta iskeemisistä häiriöistä kärsivät potilaat (34%) olivat nuorempia, ja heillä oli useammin aiemmin todettu eteisvärinä (25%) tai dyslipidemia (40%). Takaverenkierron alueen aivoverenvuotopotilaista kolmasosa oireili oksentelulla ja päänsäryllä. Heidän verenpaineensa mediaani oli 177/92 mmHg ja varfariinilääkitys oli kaksi kertaa yleisempää heidän joukossaan. Tutkimuksessa havaittiin, että vaikka potilaat olivat sydän- ja verisuonitautien riskitekijöiden suhteen tyypillisessä iässä, takaverenkierron alueen aivoverenvuotopotilailla oli harvemmin todettu eteisvärinä tai dyslipidemia verrattuna iskeemisistä häiriöistä kärsiviin potilaisiin. Oksentelevalla, hypertensiiivisellä aivoverenvuotopotilaalla oli usein päänsärkyä, ja varfariinilääkitystä voidaan pitää aivoverenvuodon varoitustekijänä. Tutkimuksen perusteella ei voitu kuitenkaan löytää tekijöitä takaverenkierron aivoverenkiertohäiriöpotilaiden luotettavaan tunnistamiseen.

Fungal ferulic acid esterases (FAEs) are important accessory enzymes that participate in degradation of plant cell wall hemicellulose in grasses, including cereals and many energy crops. They could be used to convert agricultural wastes into a variety of value-added products such as biofuel, feed and paper. In non-aqueous media, they have been shown to act as catalysts for enantioselective reactions. Putative faes are widespread in genomes of plant pathogenic and saprotrophic fungi. However, only few FAEs have been characterized in detail. Additionally, despite of their diverse biotechnological potential, fungal FAEs have not been produced recombinantly on a bioreactor scale, which is a necessary step for their commercial applications. The aim of the present study was recombinant production on a bioreactor scale and biochemical characterization of a putative FAE from Aspergillus terreus. The enzyme demonstrated a broad substrate profile and an excellent storage stability. Its catalytic activity was highest against methyl 3,4-dimethoxycinnamate, but the enzyme was also active against methyl ferulate. It preferred methoxy groups to hydroxyl groups on the substrate’s phenyl ring, while shortening of the aliphatic side chain diminished the activity. The enzyme was observed to be fully stable at 37 °C for 1 h, and it demonstrated thermal activation at the same temperature. At 45 ˚C, it retained 75 % of its initial activity for 1 h. McIlvaine’s buffer was observed to increase the activity by 85 % compared to the standardly used MOPS buffer. The results of this study have contributed to the biochemical knowledge of fungal FAEs and elucidated their substrate preferences.

Users of large online dating sites are confronted with vast numbers of candidates to browse through and communicate with. To help them in their endeavor and to cope with information overload, recommender systems can be utilized. This thesis introduces reciprocal recommender systems that are aimed towards the domain of online dating. An overview of previously developed methods is presented, and five methods are described in detail, one of which is a novel method developed in this thesis. The five methods are evaluated and compared on a historical data set collected from an online dating website operating in Finland. Additionally, factors influencing the design of online dating recommenders are described, and support for these characteristics are derived from our historical data set and previous research on other data sets. The empirical comparison of the five methods on different recommendation quality criteria shows that no method is overwhelmingly better than the others and that a trade-off need be taken when choosing one for a live system. However, making that trade-off decision is something that warrants future research, as it is not clear how different criteria affect user experience and likelihood of finding a partner in a live online dating context.