Dissertations and theses

 

Digital dissertations and theses from the University of Helsinki. Contains both open access theses as well as metadata records.

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  • Rasola, Miika (Helsingin yliopisto, 2020)
    Resonant inelastic X-ray scattering (RIXS) is one of the most powerful synchrotron based methods for attaining information of the electronic structure of materials. Novel ultra-brilliant X-ray sources, X-ray free electron lasers (XFEL), offer new intriguing possibilities beyond the traditional synchrotron based techniques facilitating the transition of X-ray spectroscopic methods to the nonlinear intensity regime. Such nonlinear phenomena are well known in the optical energy range, less so in X-ray energies. The transition of RIXS to the nonlinear region could have significant impact on X-ray based materials research by enabling more accurate measurements of previously observed transitions, allowing the detection of weakly coupled transitions on dilute samples and possibly uncovering completely unforeseen information or working as a platform for novel intricate methods of the future. The nonlinear RIXS or stimulated RIXS (SRIXS) on XFEL has already been demonstrated in the simplest possible proof of concept case. In this work a comprehensive introduction to SRIXS is presented from a theoretical point of view starting from the very beginning, thus making it suitable for anyone with the basic understanding of quantum mechanics and spectroscopy. To start off, the principles of many body quantum mechanics are revised and the configuration interactions method for representing molecular states is introduced. No previous familiarity with X-ray matter interaction or RIXS is required as the molecular and interaction Hamiltonians are carefully derived, based on which a thorough analysis of the traditional RIXS theory is presented. In order to stay in touch with the real world, the basic experimental facts are recapped before moving on to SRIXS. First, an intuitive picture of the nonlinear process is presented shedding some light onto the term \textit{stimulated} while introducing basic terminology and some X-ray pulse schemes along with futuristic theoretical examples of SRIXS experiments. After this, a careful derivation of the Maxwell-Liouville-von Neumann theory up to quadrupole order is presented for the first time ever. Finally, the chapter is concluded with a short analysis of the experimental status quo on XFELs and some speculation on possible transition metal samples where SRIXS in its current state could be applied to observe quadrupole transitions advancing the field remarkably.
  • Autio, Antti (Helsingin yliopisto, 2020)
    Hiukkasfysiikan standardimalli kuvaa alkeishiukkasia ja niiden välisiä vuorovaikutuksia. Higgsin bosonin löydön (2012) jälkeen kaikki standardimallin ennustamat hiukkaset on havaittu. Standardimalli on hyvin tarkka teoria, mutta kaikkia havaittuja asioita ei voida kuitenkaan selittää standardimallin puitteissa. Supersymmetria on yksi houkutteleva tapa laajentaa standardimallia. Matalan energian supersymmetriaa ei kuitenkaan ole havaittu. Supersymmetria vaatii toimiakseen niin sanotun kahden Higgsin dubletin mallin. Tavallisessa standardimallissa on yksi Higgsin dublettikenttä. Higgsin dubletissa on kaksi kompleksista kenttää eli yhteensä neljä vapausastetta, joten voisi olettaa, että siitä syntyy neljä hiukkasta. Kolme vapausasteista kuitenkin sitoutuu välibosoneihin W+, W− ja Z, jolloin jäljelle jää yksi Higgsin bosoni. Kahden Higgsin dubletin malleissa dublettikenttiä on kaksi. Koska se lisää teoriaan yhden neljän vapausasteen dubletin, Higgsin hiukkasia on siinä kaiken kaikkiaan viisi: kolme sähköisesti neutraalia (h, H ja A) sekä kaksi sähköisesti varattua (H+ ja H−). Tässä työssä keskitytään varattujen Higgsin hiukkasten etsintään malliriippumattomasti. Tutkimuksessa käytetään LHC-kiihdyttimen (Large Hadron Collider, suuri hadronitörmäytin) CMS-ilmaisimen (Compact Muon Solenoid, kompakti myonisolenoidi) keräämää dataa. Sähkövarauksellisten Higgsin bosonien etsintä keskittyy lopputiloihin, joissa varattu Higgsin bosoni hajoaa hadroniseksi tau-leptoniksi (eli tau-leptoniksi, joka puolestaan hajoaa hadroneiksi) sekä taun neutriinoksi. Niin sanottu liipaisu on tapa suodattaa dataa tallennusvaiheessa, sillä dataa tulee törmäyksistä niin paljon, ettei kaiken tallentaminen ole mahdollista. Eri liipaisimet hyväksyvät törmäystapauksia eri kriteerien perusteella. Liipaisusta aiheutuu merkittäviä systemaattisia epävarmuuksia. Tässä työssä liipaisun epävarmuuksia pyritään pienentämään käyttämällä sellaisia liipaisimia, joiden epävarmuudet ovat pienempiä. Tätä varten analyysi on jaettava riippumattomiin osiin, joiden epävarmuudet käsitellään erikseen. Lopuksi osat yhdistetään tilastollisesti toisiinsa, jolloin kokonaisepävarmuuden oletetaan pienenevän. Tässä työssä tutkitaan, pieneneekö tämä epävarmuus ja kuinka paljon. Näitä menetelmiä käyttäen kykenimme löytämään pieniä parannuksia analyysin tarkkuuteen raskaiden varattujen Higgsin bosonien kohdalla. Lisäksi odotettu raja, jota suurempi varatun Higgsin hiukkasen tuotto tässä lopputilassa olisi havaittavissa, paranee yllättävästi. Tätä rajan paranemista tutkitaan liipaisua emuloimalla. Työ on tarkoitus sisällyttää koko Run2:n datasta julkaistaviin tuloksiin.
  • Pelttari, Hannu (Helsingin yliopisto, 2020)
    Federated learning is a method to train a machine learning model on multiple remote datasets without the need to gather the data from the remote sites to a central location. In healthcare, gathering the data from different hospitals into a central location can be a difficult and time-consuming task, due to privacy concerns and regulations regarding the use of sensitive data, making federated learning an attractive alternative to more traditional methods. This thesis adapted an existing federated gradient boosting model and developed a new federated random forest model and applied them to mortality prediction in intensive care units. The results were then compared to the centralized counterparts of the models. The results showed that while the federated models did not perform as well as the centralized models on a similar sized dataset, the federated random forest model can achieve superior performance when trained on multiple hospitals' data compared to centralized models trained on a single hospital. In scenarios where the centralized models had data from multiple hospitals the federated models could not perform as well as the centralized models. It was also found that the performance of the centralized models could not be improved with further federated training. In addition to practical advantages such as possibility of parallel or asynchronous training without modifications to the algorithm, the federated random forest performed better in all scenarios compared to the federated gradient boosting. The performance of the federated random forest was also found to be more consistent over different scenarios than the performance of federated gradient boosting, which was highly dependent on factors such as the order with the hospitals were traversed.
  • Toppari, Sanni (Helsingin yliopisto, 2020)
    Tämä lisensiaatintutkielma sisältää kirjallisuuskatsauksen lyhytkasvuisuuden merkittävimmistä taustatekijöistä kotieläimillä sekä kliinisen ja patologisanatomisen kuvauksen eräällä turkistilalla esiintyneistä kääpiökasvuisista suomensupeista. Kirjallisuuskatsauksessa kuvataan lyhytkasvuisuuden tutkimusta laumatasolla sekä esitetään yleisimpiä nutritionaalisia, teratogeenisia sekä geneettisiä syitä kotieläimillä esiintyvään kääpiökasvuisuuteen. Kääpiökasvuisuutta ei ole kuvattu suomensupeilla tai luonnonvaraisilla supikoirilla aiemmin kirjallisuudessa. Kääpiökasvuisia supeja oli alkanut ilmestyä tilalle viimeisen muutaman vuoden aikana ja vuonna 2017 tuottajan arvion mukaan kääpiösupeja oli noin 20 %:ssa pentueita. Kääpiökasvuiset supit jäävät muita lajitovereita pienemmiksi eivätkä kasvata turkkiinsa peitinkarvaa normaalisti. Tutkimuksessa tutkittiin kolmea samalta tilalta olevaa kääpiösupipentua sekä yhtä naapuritilalta olevaa normaalikasvuista verrokkipentua. Pennuilta mitattiin IGF-1-, tyroksiini- sekä TSH-pitoisuudet verinäytteistä. Pennut röntgenkuvattiin ja niille suoritettiin ruumiinavaus. Ruho, iho ja karvapeite sekä vatsaontelon ja rintaontelon elimet sekä aivolisäkkeet tutkittiin histologisesti. Tutkimuksen päälöydöksinä havaittiin alentunut IGF-1- sekä tyroksiinipitoisuus kääpiösupien seerumissa sekä nähtiin röntgenkuvissa hidastunut kasvulevyjen sulkeutuminen ja luutumiskeskusten luutuminen raajojen luissa. Röntgenlöydöksissä havaittiin myös kallon rakenteiden puutteellista kehittymistä kääpiösupeilla. Tutkitulla tilalla oli syötetty samaa kaupallista rehua kuin lähitiloilla, joissa ongelmaa ei oltu raportoitu eikä affektoituneiden lukumäärä tilalla sopinut ravintoaineperäiseen kasvuhäiriöön. Tutkittujen eläinten veristä tutkittiin amdovirusta PCR:llä ja ELISA:lla, ja näytteet olivat negatiivisia. Supeilla ei ole raportoitu teratogeenisia viruksia. Tilallinen oli poistanut jalostuksesta sekä sairaat pennut että niiden emät ja muun pentueen ja mahdollisuuksien mukaan myös isän. Tämän myötä sairausinsidenssi oli laskenut. Tämän perusteella epäilemme sairauden olevan luonteeltaan peittyvästi periytyvä. Tässä tutkimuksessa kuvattua tautia ei ole aiemmin kuvattu kirjallisuudessa, joten kyseessä on merkittävä uusi löydös.
  • Tomberg, Teemu (Helsingin yliopisto, 2020)
    A trace amount of a specific gas in air, breath, or an industrial process can profoundly affect the chemistry and properties of the medium. Therefore, an accurate measurement of the concentration of the trace gas can provide invaluable information. This thesis focuses on the development of trace gas detection methods based on background-free laser absorption spectroscopic techniques. Background-free techniques possess characteristics that greatly benefit the detection of minuscule amounts of gases. These include, for example, scalability with optical power and diminished sensitivity to optical power fluctuations. The thesis deals with two spectroscopic approaches: a novel interferometric method for broadband optical background suppression in absorption spectroscopy, and cantilever-enhanced photo-acoustic spectroscopy. We performed the spectroscopy mainly in the two atmospheric windows of 2000 to 3000 cm^(−1) and 800 to 1200 cm^(−1) found in the mid-infrared region. The employed light sources encompass various broadband and single mode laser devices, including optical parametric oscillators, optical frequency combs, and a quantum cascade laser. The presented results include a demonstration of the interferometric background suppression with a state-of-the-art mid-infrared dual-comb spectrometer. We used the setup to compare the signal-to-noise ratio in direct absorption spectroscopy with and without the background suppression technique. The novel method was found to improve the signal-to-noise ratio by approximately a factor of five. The improvement was limited by the available optical power, and is expected to increase considerably with high power laser light sources. In the cantilever-enhanced photo-acoustic experiments, we investigated the use of high optical power in improving the trace gas detection performance. Using a high power mid-infrared optical parametric oscillator as a laser light source, we reached a record level noise equivalent concentration of 2.5 ppt in 15 s measurement time for hydrogen fluoride. In another work, we reached a record normalised noise equivalent absorption of 1.75×10^(−12) W cm^(−1) Hz^(−1/2) by using an optical build-up cavity to enhance the optical power in the photo-acoustic cell. Lastly, we presented results on hyphenation of the cantilever-enhanced photo-acoustic detector and a gas chromatograph. With the hyphenation, we demonstrated the capability of quantitatively analysing a complex mixture of small to large molecular weight compounds, at a detection sensitivity far better than what can be obtained with a conventional Fourier-transform based infrared detector used in gas chromatography. Quantitative analysis of the sample would have been difficult for laser absorption spectroscopy without the chromatographic separation. The results show a great potential for laser absorption spectroscopy to be used as a detector for gas chromatography in the development of a field deployable multigas analyser.
  • Kurki, Mika (Helsingin yliopisto, 2020)
    The purpose of this study is to analyze performance benefits of Collective Variable-driven Hyperdynamics (CVHD) method over standard molecular dynamics (MD) simulation. Theory of CVHD is an implementation of the hyperdynamics method with some beneficial features of metadynamics. The original implementation of CVHD was modified to work as an addon for COLVARS package of the LAMMPS simulation software with current software versions. About 70 simulations were run and analyzed to verify functionality of CVHD and compare results with CVHD to those without CVHD. The simulated system was the adatom self-diffusion on Copper 001 surface. It was found out that CVHD provides a significant performance boost (several order of magnitudes) over standard MD while preserving physical accuracy for simulation of the diffusion, but only in limited temperature range. With high temperatures CVHD doesn’t speed up the simulation at all compared to standard MD. With low temperatures, it is possible to achieve statistically meaningful number of diffusion events in temperatures where the same with standard MD would require unreasonable long simulations. But also, CVHD slows down at low enough temperatures so that it is impractical. It was also found out that the collective variable used in this context is suitable for counting number of adatom diffusion events, which helps analysis of adatom trajectories. It would be interesting to investigate CVHD more by trying different parametrization and by applying it to also other phenomenon than surface diffusion. The code of CVHD provides possibilities for performance optimizations, for example by utilizing parallel computation.
  • Shahriyer, Ahmed Hasan (Helsingin yliopisto, 2020)
    The local sources influence the spatial distribution of air pollutants in urban settings, and these can be quite diverse. For better air quality forecasting, constant monitoring of pollutants, and a high volume of measurements are necessary at many locations. Building a dense air quality network by only using the reference instruments is expensive and not feasible. The use of complementary sensor like Vaisala AQT 420 can help achieve the goal of creating a robust air quality network. As part of the Helsinki metropolitan Air Quality Testbed (HAQT) project, AQT 420 was tested for its suitability as a complmentary component in an air quality monitoring network. AQT 420 is capable of measuring NO2, PM2.5, PM10, CO, O3, SO2, relative humidity (RH), temperature, wind speed (WS), wind direction (WD), and air pressure (AP). Proxies for condensation sink (CS), black carbon (BC), particles number concentration (N), and Pegasor AQ urban diffusion current (PAQDCLDSA, which can be parameterized to calculate lung deposited surface area (LDSA) concentrations) were developed for an urban background site in Helsinki, Finland. The intention is to use variables measured by the AQT 420 and predict additional variables by using proxies. Proxy variables will help to maximize the output of AQT 420 sensors, and giving extra data extraction capability from the sensors. PM2.5, NO2, RH and temperature yielded reliable proxies for both CS and PAQDCLDSA with the correlation coefficient r, 0.85 and 0.83, respectively. While, PM2.5, NO2, and NO2, RH were enough to produce satisfactory proxy parameters for BC (r, 0.80), and N (r, 0.76), respectively. Additionally, a campaign data for sulfuric acid (SA) from Helsinki, Finland site was used to produce a proxy for SA. SO2, global radiation, CS and RH gave the best version of that proxy (r, 0.85).
  • Purhonen, Janne (Helsingin yliopisto, 2020)
    Mitochondrial disorders are rare diseases but collectively the most frequent group of inborn errors of metabolism. These disorders are genetically and phenotypically heterogenous and can manifest in any organ of the body with onset at any age. Mitochondrial functions are also diverse with the ATP production via the oxidative phosphorylation (OXPHOS) being the most notable. At the center of the OXPHOS machinery is the respiratory complex III (CIII, cytochrome bc1 complex). CIII deficiency in GRACILE syndrome belonging to the Finnish disease heritage causes a neonatal-lethal hepatorenal disease. The primary cause of GRACILE syndrome is a c.A232G (p.S78G) mutation in the BCS1L gene, which encodes a translocase required for Rieske Fe-S protein (RISP, UQCRFS1) incorporation into CIII. Homozygous Bcs1lp.S78G mice bearing the GRACILE syndrome mutation recapitulate the human syndrome, but unlike the patients they have a short asymptomatic period and relatively longer lifespan giving a window for therapeutic interventions. In this thesis project, we studied two potential therapies aiming to improve dysfunctional mitochondria in Bcs1lp.S78G mice: ketogenic diet and NAD+ repletion. We also utilized an alternative oxidase (AOX) transgene to bypass the electron-transfer blockade at CIII. Ketogenic diets are low-carbohydrate high-fat diets causing nutritional ketosis. They have been proposed to induce a beneficial starvation-like adaptive mitochondrial response involving increased mitochondrial biogenesis. Bcs1lp.S78G mice tolerated the carbohydrate restriction of ketogenic diet, were able to utilize dietary fat as the main energy source and developed ketosis. Ketogenic diet attenuated the hepatic CIII assembly defect, increased CIII activity and corrected mitochondrial structural aberrations. Our results suggested that these changes were not due to increased mitochondrial biogenesis. In line with the improved CIII function, Bcs1l mutant mice showed attenuated hepatopathy as shown by delayed liver fibrosis, inhibited stellate cell activation and hepatic progenitor cell response, decreased cell death and plasma liver enzyme activities. Liver transcriptomics and subsequent histochemical analyses suggested altered macrophage activation and a normalizing effect by ketogenic diet. In the second study, we characterized NAD+ metabolism in Bcs1lp.S78G mice. We found transcriptionally repressed NAD+ de novo biosynthesis and decreased hepatic NAD+ concentration. Changes in NAD+ consuming processes did not explain the decreased NAD+ levels. Aiming to replete the NAD+ levels, we fed the Bcs1lp.S78G mice a NAD+ precursor nicotinamide riboside (NR). In contrast to previous studies on mitochondrial myopathy models and mouse models with secondary mitochondrial dysfunctions, the hepatic NAD+ depletion of Bcs1lp.S78G mice was refractory to NR supplementation and the disease progression was unaltered. Cellular NAD+ levels regulate mitochondrial functions via sirtuin deacetylases, which are the main targets of NAD+ repletion therapies. Investigation of the upstream effectors of sirtuins showed that a starvation-like metabolic state of Bcs1lp.S78G mice is linked to AMP kinase and cAMP signaling, which likely counterbalances the repressive effect of decreased NAD+ levels on the activity of SIRT1 and SIRT3. In the third study, we introduced Ciona intestinalis AOX transgene into the Bcs1lp.S78G mice. AOXs are non-mammalian enzymes that can bypass a blockade of the CIII-CIV segment of the respiratory electron transfer. The AOX-expressing Bcs1lp.S78G mice were viable, and their CIII-deficiency stimulated AOX-mediated respiration in isolated mitochondria. AOX expression tripled the median lifespan of Bcs1lp.S78G mice from 200 to 600 days. The extension of the lifespan was predominantly due to the complete prevention of late-onset cardiomyopathy. The effects of AOX were tissue specific. In the heart of Bcs1lp.S78G mice, it preserved normal tissue structure and function, mitochondrial morphology, respiratory electron transfer, and wild-type-like transcriptome. In contrast, AOX only minimally affected the late-stage liver disease. Whereas, in the kidneys, AOX normalized an atrophic kidney phenotype and some histological lesions but it did not normalize kidney function or cause global normalization of transcriptome changes. Our results suggest tissue-specific thresholds of CIII deficiency for in vivo AOX-mediated respiration in CIII deficiency. Moreover, our study demonstrates the value of AOX as a research tool to dissect the pathogenesis of CIII deficiency. During our investigations, we observed approximately 5-fold difference in the lifespan of the Bcs1lp.S78G mice on two closely related congenic backgrounds. In the fourth study, we tracked the difference to a spontaneous homoplasmic mitochondrial DNA (mtDNA) variant (mt-Cybp.D254N) in an isolated congenic Lund University mouse colony. The variant changes a highly conserved negative amino acid residue in the only mtDNA-encoded subunit of CIII, cytochrome b (MT-CYB). A crossbreeding experiment utilizing the maternal inheritance of mtDNA verified the novel variant as the determinant of the survival difference. Functional studies showed that the variant exacerbated complex III deficiency in all assessed tissues. In otherwise wild-type mice, it also decreased cardiac CIII activity, caused a slight disturbance in mitochondrial bioenergetics, and decreased whole-body energy expenditure. Molecular dynamics simulations and their verification in isolated mutagenized Rhodobacter capsulatus cytochrome bc1 complex showed that the mt-Cybp.D254N variant restricts the mobility of RISP head domain movement. In summary, these studies provided novel mechanistic and therapeutic insights into CIII deficiency at genetic, molecular, and metabolic level. The results highlight the importance of knowing the underlying tissue-specific pathology and metabolic adaptations when designing therapies for mitochondrial diseases. The genetic epistasis between Bcs1lp.S78G and mt-Cybp.D254N also highlights the role of mitochondrial DNA background as a modifier of mitochondrial disease phenotypes.
  • Haavisto, Anna-Kaisa (Helsingin yliopisto, 2020)
    Eye injuries cause inconvenience at least and permanent disability at worst. Yet most of the injuries are preventable. Therefore, it is essential to have updated information on the circumstances leading to eye injuries. By reporting on the causes and contexts, we can promote proper eye protection and safe behaviour to reduce the number of accidents. In this thesis, the focus of analysis was leisure-time eye injuries; injuries in children and those caused by toy guns, sports and wooden projectiles in Southern Finland. Patients were gathered from all new eye trauma patients (n = 1151) taken into care at the Helsinki University Eye Hospital during a one-year period in 2011-2012. The follow-up time was three months and patients injured by toy guns were examined also five years after the eye injury. Children comprised 18 % (n = 202/1151) of all patients. Eye injury was most likely at the age of 13-16, and the leading causes were a hit of a sporting equipment (15 %), contact with the human body (12 %) and superficial foreign body (11 %). The main diagnosis was mild ocular or periorbital trauma (50 %). Six open globe traumas were caused by fireworks, tools, ski pole and a gun. Permanent disability was estimated for 9 % (n = 19) of children. Toy guns caused 1 % (n = 15/1151) of all eye injuries, consisting of 12 airsoft guns, 2 peashooters and 1 paintball gun. The main diagnosis was contusion (87 %). At the five-year follow-up, 47 % (n = 7) had subjective impairment, and 53 % had (n = 8) abnormal clinical findings. Sports caused 13 % (n = 149/1151) of all eye injuries. Floorball, football and tennis were the main sports to come up in the study. Floorball eye injuries decreased from 45 to 32 % of all sports-eye injuries from the season 2002-2003. The main diagnosis was contusion (77 %). Regarding participants, rink bandy had the highest risk. Permanent disability was diagnosed in 11 % of patients and was more common (p = 0.033) in ice hockey than in other sports in the number of injuries. Wooden projectiles caused 6 % (n = 67/1151) of all eye injuries. Males aged 51-67 were at the highest risk. The most common activity during the accidents was playing (27 %), gardening (18 %) and forest work (16 %). In relation to time spent in the activity, the risk of eye injury was the highest in gardening, forest work and woodwork. Permanent disability was diagnosed for 10 % due to various activities. Children should be guided safe play with sticks, and fireworks and tools should be avoided among children. The sale of toy guns should be more restricted and put under the Firearms Act to increase awareness of the risk. The use of eye protection in floorball is recommended for all age groups, and in ice hockey, the use of visors should be emphasised. In gardening, forest work and woodwork, the use of protective eyewear should be enhanced.
  • Pasanen, Miia (Helsingin yliopisto, 2020)
    The aim of this dissertation was to characterize Pectobacterium strains isolated in Finland. Pectobacterium species cause soft rot and blackleg on wide range of plants in cultivated areas worldwide. Potato is an important food crop and source of food cultivated all over the world. Pectobacterium species interfere with potato production at all stages of cultivation. Pectobacterium species belong to the Pectobacteriaceae family with the soft rot bacteria Dickeya genus. In this study, two Pectobacterium model strains, SCC3193 and SCC1, isolated in Finland during 80s and initially defined as belonging to P. carotovorum species were further examined. Biochemical tests of the strains were conducted to understand their characteristics of the bacterial strains and their differences to closely related bacterial strains. The strain SCC3193, originally determined as belonging to P. carotovorum, was redefined as P. wasabiae in the present study. However, it did not fully share the same biochemical profile with the P. wasabiae type strain and based on genome comparisons it was later placed into a novel species P. parmentieri. Furthermore, phylogenetic position of the Pectobacterium strain SCC1 was determined. Also, the strain SCC1 was originally defined as P. carotovorum, but it was observed in the phylogenetic analysis that it clustered apart from P. carotovorum type strain, and thus its taxonomical status could not be confirmed at the time of the analysis. It was later included into a novel species called Pectobacterium versatile. In addition, Pectobacterium strains isolated from diseased potato tubers in 2004, and initially classified as P. carotovorum, were characterized in this study. According to biochemical analyzes, these bacteria isolated from potato stems resembled P. carotovorum but had a low virulence on potato tuber and citrate-negative phenotype. Two genomes of these atypical Finnish stem isolates were produced to study their genome content and phylogenetic position in Pectobacterium genus. Average nucleotide identity (ANI) analysis showed that these isolates were similar to Pectobacterium polaris, a highly virulent new species recently identified in Norway. However, the Finnish isolates were most similar to atypical P. polaris isolates in ANI analysis and biochemical tests. Genome comparisons showed that the all the atypical isolates harbored similar genomic islands not present in P. polaris type strain. Alltogether, taxonomic and genomic studies placed the atypical P. polaris strains into a new subspecies, here called P. polaris subsp. parvum. One of the P. polaris subsp. parvum strains had been isolated in the Netherlands already in 1970s, but originally misidentified as P. carotovotum, which suggests that similar isolates were present in Europe also before. This study provides novel information about the taxonomy and ecology of Pectobacterium species existing in Finland. Taxonomic status of P. carotovorum isolates redefined in this and other studies show that Pectobacterium strains previously included into P. carotovorum species could be divided into several novel species with genome-based methods. The precise identification of bacterial species poses challenges for plant protection. The information from the study can be used for potato production and plant protection in the future.
  • Savonius, Okko (Helsingin yliopisto, 2020)
    Bacterial meningitis remains a significant cause of childhood morbidity and mortality, despite reductions to the global meningitis burden resulting from immunisations against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Meningitis poses a threat to child health especially in resource-limited settings, where mortality rates can reach up to 50%, even with the use of effective broad-spectrum antibiotics. The extent of the host’s immune response associates with bacterial meningitis outcomes. Consequently, new treatment modalities have focused on controlling the initial inflammatory burst. This doctoral thesis project evaluated the use of a continuous antibiotic infusion, in contrast to conventional boluses, combined with paracetamol as a treatment for childhood bacterial meningitis. In addition, this research attempted to identify new prognostic markers in the cerebrospinal fluid (CSF) of children with meningitis and examined the impact of children’s vitamin D status on disease outcomes. The use of a continuous four-day cefotaxime infusion combined with oral paracetamol was evaluated in a prospective, randomised, double-blind parallel-group trial conducted at the Paediatric Hospital of Luanda in Angola between 2012 and 2017. The control intervention consisted of conventional cefotaxime boluses four times daily and an oral placebo, using mortality by day 7 from treatment initiation as the primary outcome. The prognostic role of matrix metalloproteinases (MMPs), myeloperoxidase (MPO) and the antimicrobial protein cathelicidin in the CSF and vitamin D levels in serum were analysed retrospectively using a cohort from Latin America of children with bacterial meningitis. Our prospective clinical trial showed no benefit from using a continuous cefotaxime infusion combined with paracetamol as a treatment for childhood bacterial meningitis in Angola. By day 7, 61 of 187 (32.6%) children in the intervention group and 64 of 186 (34.4%) children in the control group died (absolute risk difference 1.8%, 95% confidence interval -7.8% to 11.4%). Similarly, no differences emerged between the study groups in terms of neurological sequelae. In addition, the retrospective studies identified MMP-8 as a promising prognostic marker for bacterial meningitis: upon admission, a CSF MMP-8 level greater than the median value increased the odds of death 4.9-fold. The other analysed MMP, MPO and cathelicidin were also expressed in the CSF of children with bacterial meningitis, but did not predict disease outcomes to a similar extent. Furthermore, children’s vitamin D status upon admission did not associate with survival. In conclusion, the prognosis of childhood bacterial meningitis in Angola could not be improved by using a continuous cefotaxime infusion and oral paracetamol. Many of the children in our study were severely ill when presenting at hospital, likely contributing to the poor outcomes and warranting further attention. CSF MMP-8, however, presented as a potential prognostic marker for the disease.
  • Hänninen, Ulrika (Helsingin yliopisto, 2020)
    Colorectal cancer (CRC) is the third most common cancer and the second main cause of cancer mortality worldwide. The colorectum and the small bowel are part of a continuous passageway called the gastrointestinal (GI) tract, however, the cancer incidence varies greatly between these two organs. Although the small bowel constitutes three quarters of the length of the GI tract, only 3% of GI cancers are located in the small bowel. These cancers develop due to both somatic and inherited germline mutations. Thus, characterizing the genetic events that drive tumorigenesis is crucial to provide ways to improve prevention and clinical management of the disease. The general aim of this thesis was to gain new insights into the molecular genetic backgrounds of CRC and small bowel adenocarcinoma (SBA). The first aim of the thesis was to characterize the somatic mutation patterns of the AT-Rich Interaction Domain (ARID) family genes in CRCs with microsatellite instability (MSI). Approximately 15% of CRCs display MSI which arises due to a defective DNA mismatch repair system. These tumors accumulate a high number of mutations, especially small insertions and deletions in repetitive genomic areas called microsatellites. The ARID gene family comprises 15 members, including a known tumor suppressor gene ARID1A. We utilized exome sequencing data of 25 MSI CRCs and their corresponding normal tissues and identified 12 of the ARID genes to display mutations with a frequency of 4-52%. Four genes were selected for further analysis in 21 additional MSI CRCs. We found that, in addition to ARID1A, also ARID1B, ARID2, and ARID4A were frequently mutated and might play a role in MSI CRC. However, additional studies are warranted to further scrutinize the function of these mutations in MSI CRC genesis. The second aim of the thesis was to identify novel oncogenes in MSI CRC. These tumors represent a sensitive system for studying the generation and selection of oncogenic mutations. In contrast to many reported MSI target genes, few oncogenes are known in MSI CRC and they often display specific mutation hotspots. Thus, we used the exome sequencing data of 25 MSI CRCs and their corresponding normal tissues to search for genes with recurrent somatic missense mutations. We identified 33 novel candidate oncogenes of which the following fourteen genes displayed hotspot mutations also in the validation set of 254 MSI CRCs: ANTXR1, CEP135, CRYBB1, MORC2, SLC36A1, GALNT9, PI15, KRT82, CNTF, GLDC, MBTPS1, OR9Q2, R3HDM1, and TTPAL. This work revealed a variety of novel recurrent candidate oncogene mutations that might potentially be used to develop personalized therapies. Further research is still needed to confirm their pathogenic role and detailed function in tumorigenesis. The third aim of the thesis was to study the genetic overlap within synchronous CRCs (SCRCs). Approximately 4% of CRC patients display multiple simultaneous primary cancers in the colorectum. Understanding whether SCRCs within a patient are genetically similar or distinct is essential when designing personalized treatments. Exome sequencing data of 23 SCRC pairs and their corresponding healthy tissues revealed that the paired tumors shared a maximum of only a few somatic mutations. This indicated that the tumors have independent origins. Furthermore, paired tumors favored different somatic mutations in known CRC genes and signaling pathways. Variation was observed among clinically relevant genes, such as the discordant KRAS mutation status in a quarter of patients. Tumors within pairs also displayed variation in their mutational signature content suggesting that, regardless of the shared environment, some pairs might have undergone different mutational processes. Finally, by analyzing immune cell counts, we observed that the intratumor immune response varied within most tumor pairs. This was not explained by mutation burden or clinicopathological variables. Overall, this work revealed major diversity within SCRCs and highlights the need to evaluate all synchronous lesions within an individual for optimized therapeutic approach. Additional studies are still required to further elucidate the reasons underlying tumor multiplicity. The fourth aim of the thesis was to characterize the somatic mutation content in SBA. Due to its rarity, knowledge on the genetic background of SBA has remained somewhat elusive. We conducted the first large exome sequencing effort of 106 population-based SBAs representing all three small bowel segments. This work revealed significantly mutated genes previously associated with SBA (TP53, KRAS, APC, SMAD4, and BRAF), as well as novel candidate drivers, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We identified clear mutation hotspot patterns in ERBB2 and BRAF. Interestingly, we observed no V600E mutations, the most common BRAF mutation hotspot in CRC. Other clinically relevant aspects included mutations in ERBB family genes in over a quarter of SBAs as well as mutations in multiple genes that could predict anti-EGFR treatment resistance. We performed the first comprehensive mutation signature analysis on SBA that highlighted four signatures: 1A, 6, 17, and U2. Comparison of the three small bowel segments unveiled some variation in tumor characteristics. Further studies are needed to robustly clarify these differences and their clinical relevance. This comprehensive characterization provided further evidence that SBA is a distinct tumor type and singled out many potential therapeutic targets that could be utilized in SBA treatment development.
  • Mäkitaipale, Johanna (Helsingin yliopisto, 2020)
    The main function of vitamin D is the maintenance of serum calcium concentration and skeletal calcium balance. Diet, vitamin D supplements, and endogenous synthesis are possible sources of vitamin D in pet rabbits, but studies regarding the vitamin D concentrations, main sources of vitamin D, and vitamin D deficiency levels in rabbits are lacking. Vitamin D deficiency and the existence of metabolic bone diseases in pet rabbits are topics of intermittent debate. The question regarding the existence of metabolic bone diseases in rabbits arose 20 years ago, after decreased bone density was observed in prepared skulls and radiographs of pet rabbits with advanced stages of dental disease. Dental disease is still one of the most common health disorders in pet rabbits. Observations that rabbits with dental disease had higher parathyroid hormone and lower total calcium concentrations compared to rabbits in free-range conditions, and that pet rabbits housed in hutches had low 1,25-dihydroxyvitamin D3 concentrations, were associated with the theory of vitamin D and calcium deficiency as a common problem in pet rabbits, and a possible predisposing factor for dental disease. This thesis aimed to study serum 25-hydroxyvitamin D (25(OH)D) concentrations and sources of vitamin D in 140 pet rabbits aged 0.1 to 9.3 years. Several tibial bone parameters, including cortical bone density, were measured in 87 rabbits using peripheral quantitative computed tomography. Possible breakpoints were searched in 139 rabbits for serum 25(OH)D concentration when compared to parathyroid hormone concentration and cortical bone density, which indicates a threshold for vitamin D deficiency. Dental disease was diagnosed after examination of the oral cavity and a lateral skull radiograph. Association between dental disease and serum 25(OH)D concentration and tibial bone parameters were compared. Serum 25(OH)D concentration varied from 4.5 to 67.5 ng/ml (mean 26.0 ng/ml). According to GLM analysis adjusted for body weight, age, and season of sample collection, diet was significantly associated with serum 25(OH)D concentration, but outdoor access was not. Serum 25(OH)D concentration was higher in rabbits that received diets with lots of hay and commercial rabbit food, >1dl daily, compared to rabbits with lower amounts of these vitamin D–containing diets. The suppression of parathyroid hormone concentration occurred at a serum 25(OH)D concentration of 17 ng/ml, whereas the breakpoint for cortical bone density occurred at a serum 25(OH)D concentration of 19 ng/ml. No breakpoints were found for ionised calcium, total calcium, or phosphorus. Results suggest a serum 25-hydroxyvitamin D concentration of 17 ng/ml as a threshold for vitamin D deficiency in pet rabbits. One-third of the rabbits participating in this study had serum 25(OH)D concentrations below this threshold, which raises concern regarding the high prevalence of vitamin D deficiency in Finnish pet rabbits. The mean diaphyseal tibial cortical density in rabbits was high (about 1400 mg/cm3). There was no tendency for an age-related decrease in trabecular or cortical bone density, at least up to six years of age. No statistically significant group differences were observed in bone parameters between intact females and males or between intact and castrated males after controlling for body weight and age. Of 140 rabbits, 47 (33.6%, 95% CI: 25.5-41.7) were diagnosed with dental disease. Bone parameters were measured from 87 rabbits, of which 26 rabbits (29.9%, 95% CI 20.3-39.5) had dental disease. After controlling for body weight, age, and season of sample collection, no differences existed in serum 25(OH)D concentrations between healthy rabbits and rabbits with dental disease. Additionally, no statistically significant group differences in tibial bone parameters occurred between healthy rabbits and rabbits with dental disease after controlling for body weight and age. Our results conclude that vitamin D deficiency, diagnosed as serum 25(OH)D concentration below 17 ng/ml, is common in Finnish pet rabbits. Diet is the main source of vitamin D, as outdoor access is too limited to provide them with adequate vitamin D synthesis. Vitamin D deficiency may increase their risk for metabolic bone disease and other health disorders. This study failed to support the theory of vitamin D deficiency as a predisposing factor for dental disease. The results of this study should be used to increase pet rabbits’ health and well-being by preventing vitamin D deficiency and should advocate for further studies regarding the supply of adequate concentrations of vitamin D and consequences of chronic vitamin D deficiency in pet rabbits. Further prospective case-control studies are needed to evaluate the aetiology of dental disease.
  • Friman, Marika (Helsingin yliopisto, 2020)
    Hevosen sacroiliaca (SI) eli risti-suoliluunivelen ongelmia on alettu hiljattain diagnosoimaan yhä enemmän. Tieto alueen toiminnasta ja liikkeestä on lisääntynyt, mutta tiedon puute on edelleen rajoittava tekijä alueen patologisten tilojen ymmärryksessä. Tämän kirjallisuuskatsauksen tarkoitus on esitellä tarkasti alueen anatomia ja perehtyä alueen tyypillisimpiin ongelmiin. Hevosen SI-nivel on synoviaaliliitos suoliluun siiven ventraalipinnan ja ristiluun siiven dorsaalipinnan välillä. Sen kautta takaraajojen työntövoima välittyy muualle vartaloon. Nivelen rakennetta tukee dorsaalinen, interosseaalinen ja ventraalinen ligamentti. Nämä ligamentit rajoittavat nivelen liikettä ja tekevät siitä hyvin vakaan nivelen. SI-nivelen alueen ongelmat jaetaan usein ligamenttien vaurioihin ja nivelrikkoon. Ligamenttivammat voivat johtua kroonisista toistuvista voimista tai akuutista venähdyksestä. Yleisin alueen pehmytkudosvamma on dorsaalisen SI-ligamentin vaurio. SI-nivelen nivelrikon taustalla on ajateltu olevan alueen pehmytkudosten riittämätön tuki nivelelle. Nivelen nivelrikkomuutosten diagnostiseen kuvantamiseen käytetään usein ultraääntä tai skintigrafiaa. Muutosten merkittävyyden arviointi on kuitenkin vaikeaa, koska samankaltaisia muutoksia löytyy sekä terveiltä, että sairailta hevosilta. Yhdessä kuvantamisen kanssa suositellaankin nivelten diagnostista puudutusta muutosten merkittävyyden arvioimiseksi. SI-nivelten luksaatio on myös mahdollinen, mutta harvinainen. SI-nivelen ongelmat ovat yleisimpiä puoliverisillä ratsuhevosilla. Ne voivat olla myös sekundaarisia jonkun muun syyn aiheuttamalle takajalan ontumalle. SI-nivelen kipu aiheuttaa hyvin epämääräisiä oireita. Hevonen ei usein onnu vaan se tulee tutkimuksiin suorituskyvyn heikkenemisen takia. Muita oireita voivat olla muun muassa vastustelu ratsastaessa, huonolaatuinen laukka tai vaikeudet seistä toinen takajalka ylösnostettuna. Tarkan diagnoosin saavuttaminen SI-nivelen alueen patologiassa on usein vaikeaa, joten hoitosuosituksetkin ovat oireenmukaisia. Systeemisiä lääkkeitä ja paikallisia lääkkeitä voidaan käyttää joko yhdessä tai erikseen. Akuutissa ligamenttivammassa lepo on indikoitua, mutta pitkäaikainen lepo alueen patologiassa ei ole hyväksi, koska vähentynyt lihasjännitys saattaa pahentaa vammaa. Ennuste akuuteissa vammoissa on hyvä, jos hevonen saadaan välittömästi lepoon. Kroonisissa tapauksissa ennuste on usein huonompi, koska ne usein uusivat liikunnan vaatimustason noustessa. Käytännössä diagnoosi vaatisi aina sekä diagnostisen kuvantamisen, että nivelten puuduttamisen, mutta tämänkään jälkeen vain harvoin päästään tarkkaan diagnoosiin.
  • Hannus, Hanna (Helsingfors universitet, 2014)
    Tutkielmani käsittelee Helsingissä sijaitsevaa vuonna 1928 valmistunutta Yrjönkadun uimahallia. Uimahallin rakennutti yksityinen Uimahalli Oy, jonka aktiiveihin kuului muun muassa urheiluvaikuttaja Toivo Aro. Uimahallin suunnitellut arkkitehti Väinö Vähäkallio kuului myös uimahallin johtokuntaan. Uimahallista rakennettiin monitoimitalo, joka vastasi moniin tarpeisiin: se oli niin uimaharrastajien harjoitusallaskin kuin kaupunkilaisten virkistäytymispaikka monine oheispalveluineen. Uimahallilla oli myös sosiaalisia pyrkimyksiä parantaa uimataitoa ja yleistä hygieniaa. Yrjönkadun uimahalli siirtyi Helsingin kaupungin omistukseen vuonna 1967, ja se peruskorjattiin vuosina 1997 1999. Nykyisin uimahalli tunnetaan kylpylätunnelmastaan sekä erillisistä miesten ja naisten vuoroistaan, joiden vuoksi uimahallissa on mahdollisuus uida alasti. Tarkastelen Yrjönkadun uimahallin arkkitehtuuria keskittyen tilaan ja sen käyttäjiin liittyviin kysymyksiin. Kolme näkökulmaani uimahallin tilaan ovat tila eri ihmisryhmien ja sukupuolten kontrolloijana, tilan suhde aikaan ja alastomuuden merkitys tilassa. Pohdin myös ihanteita, jotka saivat uimahallin aikaan sekä ihanteita, joita uimahalli loi. Analysoin uimahallia sen valmistumisajankohdan ja nykyajan perspektiiveistä. Keskeinen tutkimusaineistoni koostuu 1920-luvun lopun ja 1930-luvun alun aikakaus- ja urheilulehdistä, Yrjönkadun uimahallia käsittelevästä arkistomateriaalista, Toivo Aron laatimista kirjoituksista sekä 1990-luvun ja 2000-luvun vaihteen uimahallia käsittelevistä mielipidekirjoituksista. Uimahallin tilojen osalta tarkastelen uimahallikävijöiden kannalta keskeisimpiä tiloja eli isoa ja pientä allashuonetta sekä suihku- ja pesutiloja. Yrjönkadun uimahallin arkkitehtuuriin vaikuttivat nähdäkseni ulkomaalaisten uimahalliesikuvien lisäksi suomalaiset yleiset saunat. Laitoksen nimeksi tuli uimahalli, mutta se sisälsi alusta lähtien myös kylpylämäisiä piirteitä. Uimahallin iso allashuone jakaantuu ensimmäiseen ja toiseen kerrokseen, joita 1920-luvun kontekstissa merkitsivät myös eri yhteiskuntaluokkien sosiaalisia tiloja. Uimahalliin rakennettiin alun perin erilliset osastot miehille ja naisille. Miesten ja naisten osastot erosivat arkkitehtuuriltaan tavoilla, joka heijastelee 1920-luvun urheilupiireissä vallalla olleita käsityksiä sukupuolista. Miesten osasto eli iso allashuone mahdollistaa esimerkiksi kilpaurheilun, joita ei pidetty 1920-luvulla urheiluvaikuttajien keskuudessa naisille sopivina. Naisten osasto on miesten osastoa suojaisampi, pienempi ja koristeellisempi. Tulkitsen näiden piirteiden viittaavaan myös ajan naisoletukseen. Miesten osasto eli iso allashuone on kuitenkin alusta asti ollut muutamia vuoroja viikossa myös naisten käytössä, ja ajan myötä vuorojen määrää on lisätty. Naisten osalta ihanteet eivät siis olleet niin yksiselitteisiä. Tarkastelen arkkitehtonista tilaa siis myös prosessina, joka osallistuu merkitysten tuottamiseen. Yleisölle avautuessaan Yrjönkadun uimahalli piti sisällään monia viittauksia antiikkiin, erityisesti antiikin Roomaan. Isoa allashuonetta hallitsevien arkadien lisäksi uimahallissa oli roomalaisia saunoja, ja kävijät saivat päälleen roomalaiset kylpykaavut. Uimahallissa ainoa sallittu uintitapa aina vuoteen 2001 saakka oli uida ilman uimapukua. Nähdäkseni 1920-luvulla uimahallin uimapukukielto johtui hygienian ohella suomalaisen saunaperinteen luontevasta pohjasta, ajan muodikkaasta alastomuus- eli ruumiinkulttuurista sekä antiikin ihailusta. Esitän, että Yrjönkadun uimahalli rakennettiin 1920-luvulla paikaksi, jossa ajan aateilmaston mukaisesti antiikki ja suomalaisuus, perinne ja modernius kietoutuivat toisiinsa. Uimahallin tilaratkaisut, käyttötavat ja arkkitehtuuri loivat ja pitivät yllä ihanteita miehistä ja naisista. Uimahallissa käyminen toteutti ja vahvisti näitä ihanteita, mutta erityisesti naiskävijät saattoivat myös asettua niitä vastaan. Nykyisin Yrjönkadun uimahallissa alastomuus voi saada aikaan ajattomuuden tunteen, sillä merkit ajallisuudesta hälvenevät sen myötä. Alastomuus myös korostaa koskien ja oman ruumiillisuuden kautta syntyvää yhteyttä tilaan. Tilan käyttämisessä keskeisiä ovat myös muut moniaistiset kokemukset tuoksuista lämpötilaan. Yrjönkadun uimahalli on osa helsinkiläistä kaupunkikulttuuria ja sitä tulisikin nähdäkseni ajatella kulttuurikohteena.
  • Ruhanen, Hanna (Helsingin yliopisto, 2020)
    Cardiometabolic diseases such as metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) are risk factors for cardiovascular disease and type 2 diabetes. NAFLD can be seen as the hepatic manifestation of the metabolic syndrome and obesity increases the disease risk, but also a genetic component plays a role in the development of NAFLD. The I148M variant of PNPLA3 (PNPLA3-I148M) and E167K variant of TM6SF2 (TM6SF2-E167K) have been strongly associated with NAFLD. However, these variants cause a fatty liver without systemic metabolic complications, and TM6SF2-E167K has even been shown to protect from myocardial infarction. New treatment possibilities for cardiovascular diseases have risen from studies of loss-of-function (LOF) variants of ANGPTL3. Subjects lacking ANGPTL3 have increased activity of lipoprotein lipase (LPL), low plasma levels of VLDL, LDL and HDL as well as increased insulin sensitivity. In this thesis study we aimed to elucidate the function of PNPLA3 and TM6SF2 in lipid metabolism of human hepatocytes, and to clarify the mechanism underlying the association between the variants of these genes and increased hepatic lipid accumulation. We also investigated the function of ANGPTL3 in human hepatocytes and characterized the plasma lipoprotein lipidomes of subjects homozygous for ANGPTL3 LOF variants. In these studies, we utilized different lipidomics approaches as well as complementary methods such as microscopy and transcriptomics. We found using labelled lipid precursors that overexpression of PNPLA3-I148M in hepatocytes leads to a net accumulation of unlabelled triacylglycerols (TAGs) when compared to PNPLA3 wild type (PNPLA3-WT) overexpressing or control cells, but the level of newly synthesized TAGs did not change. Closer examination of the lipid species profiles and further experiments led us to the conclusion that PNPLA3 is a remodelling protein that transfers fatty acids from TAG to phosphatidylcholine (PC) and that PNPLA3-I148M performs this function less efficiently, which may lead to increased hepatic TAG levels. The noticed lipid accumulation could also be related to a more extensive association of PNPLA3-I148M to lipid droplets compared to PNPLA3-WT, which was also observed in our study. We mimicked the effect of TM6SF2-E167K by knocking down TM6SF2 in hepatocytes. TM6SF2 depletion increased the level of TAGs and cholesterol esters (CEs) and changed the membrane lipid composition of the cells by reducing the amount of polyunsaturated fatty acids (PUFAs) and increasing the levels of saturated and monounsaturated fatty acids in the lipids. The size of the lipoprotein-like particles secreted by the TM6SF2 deficient cells was reduced, as was β-oxidation of fatty acids. Both of these observations could explain the increased lipid accumulation caused by TM6SF2 depletion. In addition, TM6SF2 knock-down increased lipid turnover and the amount of late endosomes/lysosomes in the cells. Depletion of ANGPTL3 in hepatocytes lead to PUFA enrichment in major membrane phospholipids and CEs, and the production of PUFA-derived lipid mediators was also increased. In addition, the total level of CEs as well as their synthesis was reduced in ANGPTL3 depleted cells. An examination of the lipidome of lipoproteins derived from ANGPTL3 deficient or control subjects revealed that, in addition to reducing the total levels of all lipid classes, ANGPTL3 deficiency modifies the species composition of the core and surface lipids of lipoproteins, which likely reflects the increased activity of LPL. These findings increase the knowledge on how genetic NAFDL caused by PNPLA3-I148M or TM6SF2-E167K variant develops and how ANGPTL3 depletion affects the liver and the secreted lipoproteins. This information provides tools for creating future prevention and treatment strategies for cardiometabolic diseases.
  • Hynninen, Mika (Helsingin yliopisto, 2020)
    The main research question of this study is to examine the formation of Christian anti-Judaism, and in particular the claim that the Jews murdered Christ in the light of the evidence preserved in the Gospel of Peter. The text of the Gospel of Peter is analyzed through source and redaction criticism. It is concluded that a literary dependence of the Gospel of Peter on the canonical gospels is the most plausible explanation for the existing evidence. The cumulative evidence of unique features of the canonical gospels, verbal agreements, inconsistencies in the narrative and the redaction of the author of the Gospel of Peter explain the similarities and the differences between the Gospel of Peter and the canonical gospels. The redaction critical analysis shows that the author of the Gospel of Peter solves problems within and between the canonical gospels in such an insightful manner that it requires a profound knowledge of their content. The redaction critical examination of the evidence also demonstrates a consistent apologetic and polemical redaction of the author of the Gospel of Peter. This redaction critical analysis provides evidence for a hypothesis that the Gospel of Peter was written in a social context where Christians were engaged in verbal disputes with Jewish critics of Christianity. The hypothesis that the Gospel of Peter was written in a social context that included verbal disputes between Christians and Jews is examined by comparing the apologetic redaction of the author to the criticism of early Christianity. This comparison demonstrates that the apologetic redaction of the Gospel of Peter responds to criticism that is preserved in the sources of the first two centuries. These sources attribute this criticism consistently to Jewish critics of Christianity. A distinction between the historical situation and the rhetorical situation provides a solution to the debates of previous scholarship on the social context and purpose of the Gospel of Peter. The author of the Gospel of Peter responds to Jewish criticism of the Christian community, but his response is directed to the members of the Christian community. This solution explains the connection between the apologetic redaction of the author of the Gospel of Peter and Jewish criticism, and the polemical description of the Jewish people and leaders in the Gospel of Peter. The social identity approach is applied to analyze the identity construction of Christians in the face of the above-mentioned challenges. The social identity approach explains the intergroup interaction and particularly the intergroup discrimination between Christians and Jews. This approach explains why Christians constructed a self-conception of their own group as loyal followers of Jesus in relation to the Jewish group, who are represented as demonic murderers of Jesus. This polarized Christian identity is seen as a norm that governed the community’s orientation in a complex social reality where divisions between the respective groups were not clearly defined.
  • Waltari, Otto (Helsingin yliopisto, 2020)
    Over the past decade Internet connectivity has become an increasingly essential feature on modern mobile devices. Many use-cases representing the state of the art depend on connectivity. Smartphones, tablets, and other devices alike can even be seen as access devices to Internet services and applications. Getting a device connected requires either a data plan from a mobile network operator (MNO), or alternatively connecting over Wi-Fi wherever feasible. Data plans offered by MNO's vary in terms of price, quota size, and service quality based on regional causes. Expensive data, poor cell coverage, or a limited quota has driven many users to look for free Wi-Fis in hopes of finding a decent connection to satisfy the ever-growing transmission need of modern Internet applications. The standard for wireless local area networks (WLAN, IEEE 802.11) specifies a network discovery protocol for wireless devices to find surrounding networks. The principle behind this discovery protocol dates back to the early days of wireless networking. However, the scale at which Wi-Fi is deployed and being utilized today is magnitudes larger than what it used to be. In more recent years it was realized that the primitive network discovery protocol combined with the large scale can be used for privacy violations. Device manufacturers have acknowledged this issue and developed mechanisms, such as MAC address randomization, for preventing e.g. user tracking based on Wi-Fi background traffic. These mechanisms have been proven to be inefficient. The contributions of this thesis are two-fold. First, this thesis exposes problems related to the 802.11 network discovery protocol. It presents a highly efficient Wi-Fi traffic capturing system, through which we can show distinct characteristics in the way how different mobile devices from various brands and models scan for available networks. This thesis also looks at the potentially privacy-compromising elements in these queries, and provides a mechanism to quantify the information leak. Such collected information combined with public crowdsourced data can pinpoint locations of interest, such as home, workplace, or affiliation without user consent. Secondly, this thesis proposes a novel mechanism, WiPush, to deliver messages over Wi-Fi without association in order to avoid network discovery entirely. This mechanism leverages the existing, yet mostly inaccessible Wi-Fi infrastructure to serve a wider scope of users. Lastly, this thesis provides a communication system for privacy-preserving, opportunistic, and lightweight Wi-Fi communication without association. This system is built around an inexpensive companion device, which makes the concept adaptable for various opportunistic short-range communication systems, such as smart traffic and delay-tolerant networks.
  • Ala-Kurikka, Eve (Helsingin yliopisto, 2020)
    Lameness of sows is a very common problem in the modern pig industry. It impairs both health and welfare of sows and production economics of farms. Lameness is a clinical sign caused by various problems associated with the locomotor system. However, the exact cause of lameness often remains undetermined and lame sows do not always get the necessary attention and treatment. The overall aim of this thesis was to gather information and add to the scientific knowledge on sow lameness. The specific aims of the studies were to investigate pathological-anatomical findings in the locomotor system of euthanized and spontaneously dead sows, to examine the effect of oral ketoprofen in treatment of lameness, and to study the effect of lameness on behavior of the sows. The pathological-anatomical findings in the locomotor system were examined in a descriptive study. The convenience sample consisted of 38 euthanized and 27 spontaneously dead sows from 15 Finnish farms. The majority (91%) of sows had one or more lesions in their locomotor system. The most common primary pathological-anatomical diagnosis (PAD) was inflammatory arthritis, with a prevalence of 9%. Degenerative joint disease (DJD) was diagnosed in 71% of the animals. DJD was the most frequent incidental finding, and its association with lameness remains in question. Lameness was however the most commonly reported clinical sign observed by the farmer within 30 days preceding death. The effect of oral ketoprofen in treatment of non-infectious lameness was evaluated in a randomized, double-blinded, controlled field trial. Altogether 141 lame sows were allocated to three groups: two dose rates of oral ketoprofen (2 mg/kg and 4 mg/kg) were compared with placebo treatment over five consecutive days. Lameness was assessed using a five-grade scoring system prior to and on the last day of the treatment. Treatment of lameness was considered successful for 54% of the sows in the ketoprofen 4 mg/kg group, for 53% in the ketoprofen 2 mg/kg group and for 21% of the sows in the placebo group. Parallel with the above-mentioned study, a randomized, double-blinded, controlled field trial was conducted to evaluate the effects of lameness and ketoprofen treatment on behavior of sows. Thirteen lame sows were allocated to treatment groups and paired with a healthy, non-lame control sows. Behavior was observed using a scan-sampling method prior to and after the treatment. Before the treatment on day 0, lame sows were observed to be more passive, lie down more and stand and explore pen fixtures less than the healthy control sows. On day 5 of the treatment, the behavior of sows with relieved lameness did not differ from that of healthy control sows, indicating that these sows had most likely been in pain before treatment. Some behavioral differences were apparent between sows with relieved and non-relieved lameness, showing that the latter sows were still in pain. The sows with non-relieved lameness were in contact with the wall and lay down significantly more often and moved and stood less than healthy control sows on day 5 of the treatment. In conclusion, pathological-anatomical findings in the locomotor system were very common in on-farm-dead sows. In future, more research is needed to evaluate the clinical relevance of these diagnoses and their association to lameness. Oral ketoprofen proved to be an effective treatment in alleviating the non-infectious lameness of sows. The differences in behavior between lame and healthy control sows and also between the ones with relieved and non-relieved lameness indicated that most of the lame sows were in pain and that the treatment of lameness is important from the animal welfare point of view.

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