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Kohdunkaulan syöpä on maailmanlaajuisesti yleinen naisten syöpä. Suomessa sen kokonaisilmaantuvuus on laskenut, mutta nuorilla naisilla ilmaantuvuus on nousussa meillä ja muualla maailmassa. Ikäjakauma on myös kaksihuippuinen, jonka toinen huippu koskee hedelmällisessä iässä olevia naisia. Perinteinen kohdunkaulan syövän hoitomuoto on ollut radikaali kohdunpoisto aina 2000 -luvulle asti, jonka myötä potilaiden hedelmällisyys menetettiin. Trakelektomia on hedelmällisyyden säästävä kohdunkaulan syövän leikkaus. Leikkauksia on tehty Helsingissä vuodesta 2004 asti 24 kappaletta. Tarkastelimme retrospektiivisesti potilaiden gynekologista, onkologista ja obstetrista vointia. Verrokkiryhmänä toimivat iältään vakioidut CIN 3 – kohdunkaulan muutoksen takia loop-hoidon läpikäyneet potilaat. Tautivapaana seurannan aikana säilyi 21 potilasta eli 87,5 %. Tauti uusiutui yhdellä potilaalla, ja yhden potilaan vartijaimusolmukkeesta löytyi tautia myöhemmässä tarkastuksessa. Yhden potilaan primäärileikkaus oli riittömötön. Potilailla todettiin 10 raskautta, joista vain yksi päättyi keskenmenoon ja yksi syntyi ennenaikaisesti. Intra-operatiivisia komplikaatioita ei todettu. Postoperatiivisia komplikaatioita oli noin kolmasosalla potilaita.

The history of tractor in Finland is 100 years old and in the whole world 120 years old. Development of tractors is continually ongoing. During the first decades it concentrated on engines. The introduction of air-filled tyres made it possible to increase speed on the road, which in turn lead to an increase in the number of gears. Most of the inventions within transmissions were made during the 1950s. The first powershift gears, stepless hydrostatic transmissions, fuell-sell tractor, range-gear and the power shuttle were all introduced during this time. Over the next decades these features were improved and presented as new inventions. The hydrostatic-mechanical power split continuously variable transmission (CVT) has become more common in recent years, but the basic invention was already in use elsewhere during the 1910s. The first CVT tractor was the Fendt 926, which was launched in 1995. Later introductions came in 1999, when ZF’s Eccom and the S-Matic both came to the market. Of all the CVT tractors that were introduced to the market up until 2008, only the John Deere IVT ant the Valtra Direct machines were equipped with the manufacturer’s own diesel engines and CVT transmissions. All other CVT tractors were manufactured using five different transmissions and engines. In the coming years, several more transmissions and brands will appear on the market. Mechanical Torotraks and steel belt variators will be available for low-horsepower tractors in the sub-75 kW class. At the same time the number of brands seen in the CVT arena is increasing and the differences in the construction of stepless transmissions will grow. Current CVT transmissions differ from each greatly, with different functional principles, functionality and structure. Transmissions are divided into two main categories on the basis on functional principle, either summing up torque or summing up speed. The functionality division in mostly based on the hydrostatic part. In a full-CVT transmission, the percentage decrease of hydrostatic transmission has s linear relationship with the percentage increase in running speed. The function of the hydrostat in a semi-CVT transmission in to balance the speed differences between different gearing rations. In these transmissions the hydrostatic part of the transmission in around 20–40%. The percentage of hydrostatic transmission in double-CVT transmission varies with the driving speed. Double-CVT transmissions can have several driving speeds where the percentage of mechanical transmission is very close to 100%. The theoretical predictions about how common new features will become is based upon a study of four-wheel tractors in Western Europe and Finland. This can be precisely calculated using Logistic-funktion the result would be better if the source data covered a longer time period. The regular S-curve depicts how common the new features will become in tractors of the future. The real growth area is during the period when the market share of 4wd tractors increase from 10 to 90 %. This shows that the annual growth in Western Europe was 4,0% and in Finland 7,5%. Within the next few years it will become necessary to study further new entrants of the CVT transmission market and to make predictions more precise by means of increasing the amount of source data. The users driving with conventional transmissions could utilise the driving strategies of CVT transmissions. Tractor manufacturers should ensure that their customers are fully educated in the use of their new machines, in order that they develop the correct driving habits. This in an important part of postmarketing strategy.

Tutkimuksen tavoitteena oli vuoden 2014 oikeuslääketieteellisissä kuolemansyynselvityksissä tramadolilöydöksen sisältäneitä tapauksia tutkimalla selvittää tramadolin korkeaa esiintyvyyttä myrkytyskuoleman aiheuttajana oikeuskemiallisissa raporteissa. Tramadoli oli kyseisenä vuonna buprenorfiinin jälkeen yleisin myrkytyskuolemia aiheuttanut aine suomessa. Tramadolilöydöksen sisältäviä tapauksia ilmeni aineistossa yhteensä 189 kappaletta. Tramadoli mainittiin yhtenä kolmesta tärkeimmästä myrkytyskuoleman aiheuttajasta 44 tapauksessa. Aineistosta haluttiin tarkastella myös päihdekäyttäjien osuutta ja päihdekäytön roolia tramadolikuolemissa. Tyypillisimmin tramadolikuolema oli kuolemanluokaltaan tauti, jossa tramadolilöydös oli kuolemansyyn kannalta merkityksetön sekä veripitoisuudeltaan matala, ja käyttö on ollut lääkinnällistä. Tramadolin keskimääräiset pitoisuudet verinäytteissä olivat korkeimmat itsemurhissa, kuolemanluokaltaan epäselvissä kuolemissa sekä tapaturmissa, laskevassa järjestyksessä lueteltuna. Tramadoli oli yleisin aineistossa ilmennyt myrkytyskuoleman aiheuttaja. Suurin osa myrkytyskuolemista oli useamman kuin yhden aineen aiheuttama. Yleisimmin tramadolimyrkytyksissä ilmenneet muut aineet olivat bentsodiatsepiinit, pregabaliini, psyykenlääkkeet ja muut opioidit. Tramadolin merkitys myrkytyksen aiheuttajana korostui hiukan itsemurhan tehneiden ja selkeästi päihdekäyttäjien keskuudessa. Päihdekäytöstä oli viitteitä 58 tapauksessa. Päihdekäyttäjät olivat kuollessaan muuta aineistoa huomattavasti nuorempia, ja heistä 79,3 % oli miehiä. Päihdekäyttäjien kuolemat olivat muuta aineistoa huomattavasti yleisemmin tapaturmaisia. Päihdekäyttäjien osuus korostui selkeästi myrkytyskuolemissa ja vielä selvemmin tramadolimyrkytyksissä. Tramadolin huomattava yleisyys oikeuskemiallisena löydöksenä vaikutti tutkimuksen perusteella muodostuvat kolmen jokseenkin erillisien huomattavan perustekijän, laajan lääkekäytön, suuren päihdekäyttöpotentiaalin ja itsemurhatarkoituksiin soveltuvuuden seurauksena. Poiketen aiemmista vastaavia aineistoja koskevista tutkimustuloksista, tahattomissa tramadolikuolemissa ei nähty selkeää yhteyttä psyykenlääkkeiden ja alkoholin käyttöön tramadolin ohella.

Latterly, the Arctic has transformed from a peripheral region to an area in the focus of the world, especially in terms of oil drilling. Nonetheless, no international legal instrument has addressed the matter of accountability for transnational oil pollution damage. Consequently, this thesis aspires to evaluate whether the current legal constructions, namely State responsibility, international liability, civil liability regimes and multilateral environmental agreements (MEAs), allow establishing accountability or creating a regime of accountability for transboundary environmental harm that results from hydrocarbon exploitation in the Arctic. Finally, the thesis seeks to systematize the law of accountability for environmental harm by providing an examination of the above mentioned current constructions, understood as layers of international accountability in the present thesis. The first layer, which offers an insight into the law of State responsibility for wrongful acts, naturally focuses on the ILC’s Draft Articles on responsibility of States. Both of the main criteria of State responsibility, meaning the attribution of the conduct and the breach of an obligation, will be assessed. However, it quickly becomes apparent that State responsibility faces severe challenges in terms of establishing accountability for oil pollution damage: the exploitation activities are often carried out by private entities whose conduct may only be attributable to States in rare circumstances. Moreover, the environmental obligations remain vague and thus a breach of them hard to prove. Thereby, State responsibility cannot be effectively resorted to in order to enforce accountability for environmental damage. The second layer, international liability, is based on the ILC’s project on international liability of States for injurious consequences. This prominent project, however, ran into difficulties right from the beginning: it was founded on the idea of strict State liability, something the international community was not ready for. Consequently, the project was never finished; instead, separate works on prevention and allocation of loss were concluded. Simultaneously, however, the original scope of the project was weakened: while the idea of State liability was abandoned, the idea of civil liability systems as a means to enforce accountability was welcomed. Thus, also the second layer in its initial from fails to establish accountability for Arctic oil spills. The third layer, in turn, introduces civil liability schemes as a possible solution to executing accountability for oil pollution damage. In this context, special attention will be paid to the vessel-source civil liability system and the approaches adopted in it. The third layer will culminate in assessing whether a civil liability system could become the tool for enforcing accountability. Despite the certain advantages a civil liability system would incorporate, it still constitutes a dissatisfying solution: their scope and territorial applicability leave much to be desired.. Moreover, it allows exonerations and limitations to liability, thus meaning that damage would never be compensated fully. Therefore, neither does a civil liability regime resolve the matter of international accountability for oil spills. Finally, the fourth layer presents the MEAs as the solution to enforcing international accountability. In this context, special attention will be paid to the most remarkable treaty regimes, such as the 1972 Convention on International Liability for Damage Caused by Space Objects, the 1982 Convention on the Law of the Sea and the Antarctic Treaty system as well as the prospects of an Arctic Treaty to develop an effective scheme in order to establish oil pollution damage in the Arctic. As none of these appear particularly useful in terms of determining accountability for an oil spill, however, the present thesis proposes that neither do the MEAs present a workable solution for enforcing accountability for the Arctic oil pollution damage. In conclusion, the thesis indicates that no current regime assists in establishing accountability for transfrontier pollution; thereby, there is need for ‘a new way’ in the law of accountability, one possibility of which could be presented in the form of non-compliance mechanisms. It also appears that two things may indicate to the creation of a system of accountability: either it will be concluded in the aftermath of an environmental disaster or in the event the environmental concerns have transformed into military or security threats. Still, neither of these options appears very appealing; when the problems have escalated into that level, reacting to them might prove impossible. Thus, the time for action is now. Finally, the lack of proper regulation of accountability for transboundary harm resulting from the Arctic oil drilling can actually be deemed an indirect subsidy to the hazardous activity; thereby, once again a collision of the environmental and economic values results in the latter prevailing, thus leaving the environment in an especially vulnerable position.

Psychrotrophic lactic acid bacteria (LAB) play a versatile role in research, food, farming and medicinal applications, but also play a role as a source of food spoilage. The effects of temperature changes has yet to be studied in depth. In this study, to analyze in a transcriptome level, cold and heat shock stress to spoilage lactic acid bacteria, a time-dependent RNA-seq for Lactococcus piscium with a temperature of 0 °C and 28 °C was conducted. The data of protein regulation during the experiment shows that Lactococcus piscium has the essential machinery to survive against different types of environmental stress. I observed known heat shock related genes and stress related genes to be present in the regulated response of both temperature extremes. Cold shock upregulation is observed after 35 minutes, which could indicate that the metabolic response at cold temperatures is related to growth rate. With a clear downregulation of pathways of energy consumption and an adaptation in terms of RNA being more prominent that at 28 ºC. Certain surface, cell wall and transport proteins are noticeable more upregulated at 0 ºC in addition to a downregulation of energy related proteins, which in correlation with its growth curve, we can assume it is part of a mechanism of protection against cold environments, in comparison with the regulation of proteins at 28 ºC. This gives an insight of a well controlled preservation mechanism that Lactococcus piscium exhibits that can be linked to its environment. The findings of this research offer new understandings into the survival skills of Lactococcus piscium to a cold and heat shock. Future studies should focus on analyzing the regulation and function of possible new genes for the response to heat stress, as well as the specific function of proteins related to temperature stress in the events where change of temperature plays a constant role in the environment.

Biallelic germline mutations in ERCC6L2 cause bone marrow failure (BMF) and predisposition to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The patients often develop varying cytopenias, and underlying hypoplasia in the bone marrow is usually evident. The aim of this thesis was to characterize the transcriptome of patient -derived fibroblasts with biallelic germline ERCC6L2 mutation. Moreover, the aim was to study changes on the gene expression at the RNA level in fibroblasts in different media conditions, ROS levels in ERCC6L2 -mutated fibroblasts, and whether addition of glutamine impacts the ROS levels. Fibroblasts from 16 skin biopsies were cultured; eight samples were from healthy controls and eight samples from patients with known mutations in ERCC6L2. Fibroblasts were cultured in different media conditions, followed by RNA extraction and RNA sequencing. We observed downregulation in base excision repair, nucleotide excision repair, mismatch repair, DNA replication, homologous recombination, and cell cycle in ERCC6L2 -mutated cells. MAPK signaling pathway, p53 signaling pathway, apoptosis, AMPK signaling pathway, and TGF-beta signaling pathway were in turn upregulated in ERCC6L2 -mutated cells. The medium did not affect the gene expression significantly across samples. We suspect that the effect of medium was not detected at the RNA level, but it might affect post-translational modifications. We also detected increased ROS levels in ERCC6L2 samples compared to control and observed decreased ROS levels in ERCC6L2 and control samples with excess glutamine. This study shows that biallelic mutations in ERCC6L2 do not only affect the bone marrow but can also affect tissues outside of the hematopoietic system. The transcriptomic analysis identified important biological processes, which could be studied with more detail in the future to further explore the pathology of the ERCC6L2 disease.

In order to understand the relationship between organisms and environment, and reconstruct the environment in the past, where occurrence of animal species is known from fossils and climate is unknown, we build predictive models using machine learning algorithms. Our response variable for prediction is terrestrial net primary productivity (NPP) which represents fixed energy stored in vegetation. NPP is one of the main climate determinants and previous research has shown that NPP can be robustly predicted from dental traits of plant-eating mammals. Global occurrence of large plant-eating mammals and their dental traits are used as inputs. Since occurrence of species, their traits and climate characteristic data are not uniformly distributed over time and geographical space, models built on all available training data may generate low prediction accuracy. To achieve accurate prediction, we propose three types of local models such that training data are similar to testing data. They are baseline models, hierarchical clustering based models(HCM) and advanced hierarchical clustering based models(AHCM). Moreover, hierarchical clustering are utilised for clustering data points in HCM and AHCM in order to find training data that match testing data the most. Considering input data are not independently distributed over geographical space and therefore model evaluation is not trivial, we also propose vertical spatial cross validation (VSCV) for evaluating performance of predictive models as well as tuning parameters of models. In experiments, ordinary least squares regression (OLS), decision tree, random forest, rotation forest and gradient boosting regressor are utilised in both global models and local models. Root mean squared error(RMSE) and mean absolute error(MAE) indicates performance of models. In an experiment, we apply VSCV to tune parameters of all models. The baseline is the global model with OLS and Africa continent is testing continent. Experimental results illustrate that there are no models that can perform the best on each small geographic regions. Thus, we develop a scheme to give recommendations on selecting models on different regions. We recommend to use modified hierarchical clustering based models (MHCMs) and global models on the area of Lake Turkana. We propose MHCM as a new strategy to optimize HCMs. In addition, we discover that the prediction on data points in equatorial climate zone is most reliable and prediction error on the Africa continent is equatorial symmetric. Last but not the least, we demonstrate applicability of our models with a case study of fossil data from the Turkana Basin in Africa between 0:01 and 7 millions years ago. The trend of NPP over time for fossil is that NPP firstly decreases slowly and it reaches the lowest value at around 2 to 3 Ma. Then, NPP starts increasing and tends to be stable. NPP in time period between 4 and 7 Ma is higher than in present day.

Neural network based modern language models can reach state of the art performance on wide range of natural language tasks. Their success is based on capability to learn from large unlabeled data by pretraining, using transfer learning to learn strong representations for the language and transferring the learned into new domains and tasks. I look at how language models produce transfer learning for NLP. Especially from the viewpoint of classification. How transfer learning can be formally defined? I compare different LM implementations in theory and also use two example data sets for empirically testing their performance on very small labeled training data.

Transfer pricing can be described as the internal price setting between multinational group companies. In recent years the issue of jurisdiction’s tax revenue flowing out of the jurisdiction has been closely related with transfer pricing and the tax authorities all over the world have increasingly began to question the arm’s length nature of the intra-group transactions of multinational enterprises. In this thesis the focus is on the transfer pricing issues arising in situations where intangible assets are involved in business restructuring. Multinational enterprises have noticed that in this time of global recession and economic uncertainty in order for them to be able to answer the invariably increasing competition on the global markets the need to restructure their functions, assets, and risks in a way that will rationalize their operations and reduce the related costs. Intangible assets are often the items being transferred to low-cost / low-tax jurisdictions as they are easily transferrable due to their nature. However, intangible assets are commonly also those, which cause the most controversy between tax payers and tax administrations because they are difficult to identify as well as it is difficult to determine the appropriate arm’s length compensation for them. The research questions in this thesis include the question of how intangible assets are defined and who is the owner of the intangible for transfer purposes. Even though it might sound simple, these factors are often difficult to determine, and different countries might have different interpretations even though the OECD Transfer Pricing Guidelines are quite unanimously accepted at least among the OECD Member Countries as leading guidance in the area. The possible inadequate determination of ownership or failure to recognize a certain item as a compensable intangible asset may lead to transfer pricing adjustment by the tax authorities and possible penalties. It may also lead to double taxation especially in the case of jurisdictions disagreeing on the right characterisation of the item or the rightful owner. The main research questions of this thesis are what type of issues generally arise regarding to transfer pricing of intangibles in business restructuring situations and how different (OECD) jurisdictions treat these situations. Issues relating to back-to-back transactions and treatment of business synergies and location savings, which are common in centralization of intangible property, are examined. Also the issues related to transferring intangible assets with no established value are focused on. An issue which is especially closely related to the back-to-back transactions is the recognition or actually the non-recognition of the actual transactions taken by the taxpayer. The research questions the thesis aims at answering are thus also, in what situations should the tax authorities have grounds for restructuring the transaction instead of a pricing adjustment, what are the approaches of various OECD countries to restructuring transactions and what is the relationship of the restructuring according to Art 9 of the OECD Model Tax Convention to domestic anti-avoidance provisions. Finally, as it is established that the risk of transfer pricing disputes in the area of intangible assets and business restructurings exists, the preventative measures and measures for resolution of such disputes should be available to mitigate the risk. However, the conclusion that was reached in this thesis is that there is still a lot more room for improvement in this regard.

In bioinformatics, new genomes are sequenced at an increasing rate. To utilize this data in various bioinformatics problems, it must be annotated first. Genome annotation is a computational problem that has traditionally been approached by using statistical methods such as the Hidden Markov model (HMM). However, implementing these methods is often time-consuming and requires domain knowledge. Neural network-based approaches have also been developed for the task, but they typically require a large amount of pre-labeled data. Genomes and natural language share many properties, not least the fact that they both consist of letters. Genomes also have their own grammar, semantics, and context-based meanings, just like phrases in the natural language. These similarities give motivation to the use of Natural language processing (NLP) techniques in genome annotation. In recent years, pre-trained Transformer neural networks have been widely used in NLP. This thesis shows that due to the linguistic properties of genomic data, Transformer network architecture is also suitable for gene predicting. The model used in the experiments, DNABERT, is pre-trained using the full human genome. Using task-specific labeled data sets, the model is then trained to classify DNA sequences into genes and non-genes. The main fine-tuning dataset is the genome of the Escherichia coli bacterium, but preliminary experiments are also performed on human chromosome data. The fine-tuned models are evaluated for accuracy, F1-score and Matthews correlation coefficient (MCC). A customized estimation method is developed, in which the predictions are compared to ground-truth labels at the nucleotide level. Based on that, the best models achieve a 90.15% accuracy and an MCC value of 0.4683 using the Escherichia coli dataset. The model correctly classifies even the minority label, and the execution times are measured in minutes rather than hours. These suggest that the NLP-based Transformer network is a powerful tool for learning the characteristics of gene and non-gene sequences.