Browsing by Title
Now showing items 3749-3768 of 32623
-
(2016)Metagenomics promises to shed light on the functioning of microbial communities and their surrounding ecosystem. In metagenomic studies the genomic sequences of a collection of microorganisms are directly extracted from a specific environment. Up to 99% of microbes cannot be cultivated in the lab; thus, traditional analysis techniques have very limited applicability in this challenging setting. By directly extracting the sequences from the environment, metagenomic studies circumvents this dilemma. Thus, metagenomics has become a powerful tool in the analysis of the diversity and metabolic capability of environmental microbes. However, metagenomic studies have challenges of their own. In this thesis we investigate several aspects of metagenomic data set analysis, focusing on means of (1) verifying adequacy of taxonomic unit and enzyme representation and annotation in the sample, (2) highlighting similarities between samples by principal component analysis, (3) visualizing metabolic pathways with manually drawn metabolic maps from the Kyoto Encyclopedia of Genes and Genomes, and (4) estimating taxonomic distributions of pathways with a novel strategy. A case study of deep bedrock groundwater metagenomic samples will illustrate these methods. Water samples from boreholes, up to 2500 meter deep, of two different sites of Finland display the applicability and limitations of aforementioned methods. In addition publicly available metagenomic and genomic samples serve as baseline references. Our analysis resulted in a taxonomic and metabolic characterization of the samples. We were able to adequately retrieve and annotate the metabolic content based on the deep bedrock samples. The visualization provided a tool for further investigation. The microbial community distribution could be characterized on higher levels of abstraction. Previously suspected similarities to fungi or archaea were not verified. First promising results were observed with the novel strategy in estimating taxonomic distributions of pathways. Further results can be found at: http://www.cs.helsinki.fi/group/urenzyme/deepfun/
-
(2023)This work examines how neural networks can be used to qualitatively analyze systems of differential equations depicting population dynamics. We present a novel numerical method derived from physics informed learning, capable of extracting equilibria and bifurcations from population dynamics models. The potential of the framework is showcased three different example problems, a logistic model with outside inference, the Rosenzweig-MacArthur model and one model from a recent population dynamics paper. The key idea behind the method is having a neural network learn the dynamics of a free parameter ODE system, and then using the derivatives of the neural network to find equilibria and bifurcations. We, a bit clunkily, refer to these networks as physics informed neural networks with free parameters and variable initial conditions. In addition to these examples, we also survey how and where these neural networks could be further utilized in the context of population dynamics. To answer the how, we document our experiences choosing good hyperparameters for these networks, even venturing into previously unexplored territory. For the where, we suggest potentially useful neural network frameworks to answer questions from an external survey concerning contemporary open questions in population dynamics. The research of the work is preceded by a short dive on qualitative population dynamics, where we ponder what are the problems we want to solve and what are the tools we have available for that. Special attention is paid to parameter sensitivity analysis of ordinary differential equation systems through bifurcation theory. We also provide a beginner friendly introduction to deep learning, so that the research can be understood even by someone not previously familiar with the field. The work was written, and all included contents were selected, with the goal of establishing a basis for future research.
-
(2024)This thesis presents DeepGT, a 3D Convolutional Neural Network designed to enhance the spatial resolution of GNSS Tropospheric Tomography, a technique for estimating atmospheric water vapor distribution using GNSS signals. By utilizing Slant Wet Delays from dense GNSS networks and boundary meteorological data from Numerical Weather Prediction models, DeepGT refines low-resolution tomographic wet refractivity fields. The proposed method quadruples the horizontal resolution, while improving the accuracy of the tomographic reconstruction. Two experiments are conducted to validate this: one with real-world SWEPOS data and another with a hypothetical dense GNSS network. The results demonstrate the potential of deep learning models such as DeepGT in enhancing GNSS Meteorology, with implications for improved weather forecasting and climate studies.
-
(2024)Anxiety disorders are the most prevalent mental disorders in the world and often show comorbidity with sleep disorders. The bidirectionality of sleep disturbances and anxiety disorders is a hot topic in research and the understanding of the underlying mechanisms is crucial for the development of successful methods of intervention. Studies on the effect of sleep disturbances on anxiety-like behaviour in rodents, however, are limited and have been so far inconclusive. One factor behind this could relate to the limitations that exist when studying behaviour, hindering the replicability of results. Recently, novel behavioural approaches based on deep learning have been introduced, aiming to automate behavioural tracking, thus minimising the subjectivity of manual scoring that is often required for the assessment of more complex behaviours. The aim of this thesis was to use one of the recently developed deep learning tools, namely DeepLabCut (DLC), as well as a DLC data analysis tool, DeepOF, to examine whether chronic (14-day) sleep fragmentation (SF) affects anxiety-like behaviour in female mice and if one week of recovery period affects this phenotype. For the assessment of behaviour, a battery of behavioural tests was conducted immediately after SF and repeated after a week of recovery. The behavioural test data was then analysed using conventional methods, as well as using DLC and DeepOF for supervised analysis of more complex behaviours. These results show that SF does not increase anxiety-like behaviour in female mice, in both conventional and deep learning measurements of behaviour, but may affect locomotor activity, results which contradict previous findings. Despite this, DLC and DeepOF were found to be reliable and valuable tools for the identification and comparison of complex behaviours in mice, overcoming the oversimplified nature of the conventional behavioural tests.
-
(2021)Cancer is a leading cause of death worldwide. Unlike its name would suggest, cancer is not a single disease. It is a group of diseases that arises from the expansion of a somatic cell clone. This expansion is thought to be a result of mutations that confer a selective advantage to the cell clone. These mutations that are advantageous to cells that result in their proliferation and escape of normal cell constraints are called driver mutations. The genes that contain driver mutations are known as driver genes. Studying these mutations and genes is important for understanding how cancer forms and evolves. Various methods have been developed that can discover these mutations and genes. This thesis focuses on a method called Deep Mutation Modelling, a deep learning based approach to predicting the probability of mutations. Deep Mutation Modelling’s output probabilities offer the possibility of creating sample and cancer type specific probability scores for mutations that reflect the pathogenicity of the mutations. Most methods in the past have made scores that are the same for all cancer types. Deep Mutation Modelling offers the opportunity to make a more personalised score. The main objectives of this thesis were to examine the Deep Mutation Modelling output as it was unknown what kind of features it has, see how the output compares against other scoring methods and how the probabilities work in mutation hotspots. Lastly, could the probabilities be used in a common driver gene discovery method. Overall, the goal was to see if Deep Mutation Modelling works and if it is competitive with other known methods. The findings indicate that Deep Mutation Modelling works in predicting driver mutations, but that it does not have sufficient power to do this reliably and requires further improvements.
-
(2018)The transition towards greener energy- and technology solutions significantly increases the demand for critical minerals. These minerals are found in large quantities in the Area, which is the deep seabed beyond national jurisdiction. The International Seabed Authority (ISA) was established in 1994 under the United Nations Convention on the Law of the Sea (UNLCOS) and its 1994 Implementing Agreement. Under UNCLOS and the 1994 Implementing Agreement, the ISA is mandated to organize, carry out and develop seabed mining in the Area. As a part of this mandate, the ISA is equipped with law making powers, through which it has adopted rules, regulations and procedures regarding mining activities. These rules, regulations and procedures are collectively referred to as the Mining Code. The Mining Code currently consists of regulations for prospecting and exploration of polymetallic nodules, polymetallic sulphides and cobalt-rich ferromanganese crusts, while a new set of regulations are being negotiated regarding the exploitation of the deep seabed. The start of commercial scale deep seabed mining is going to have significant impacts on the deep-sea and deep seabed environment, as the mining operations will remove habitats, disperse sediments in the deep water and cause noise and light pollution. This will impact the deep-sea ecosystems to an extent which is still unknown, due to lack of scientific knowledge. It is highly likely that the start of full-scale mining will result in significant loss of biodiversity. In order to address the negative consequences, the ISA is equipped with a broad environmental mandate to protect and preserve the marine environment. Environmental Impact Assessments (EIA) are a key component to implementing this mandate and is required under the Mining Code prior to conducting activities which may cause significant environmental impacts. However, the EIA process under the Mining Code is general-level and burdened with significant regulatory gaps. A major challenge to fill the regulatory gaps is the lack of knowledge of the deep-sea environment. Addressing these knowledge gaps in the exploitation regulations is crucial for protecting the deep-sea environment from significant and potentially irreversible harm.
-
(2014)Osakeyhtiöiden elinkaari päättyy useimmiten joko yhtiön konkurssiin tai yrityskauppaan, joiden jälkeen yhtiö joko lakkaa olemasta tai muodostaa merkittävässä määrin uuden kokonaisuuden. Yrityskaupat ovat markkinoiden suurimpia tapahtumia, joita valmistellaan ja joiden vaikutuksia selvitellään kuukausia tai jopa vuosia. Ostettavan listayhtiön osakkeenomistajien näkökulmasta olennaista on yrityskaupasta saatavan vastikkeen suuruus heidän omistuksestaan yhtiöstä. Käytännössä kyse on osakkeen markkinahintaan lisättävän preemion suuruudesta, sillä listayhtiön osakkeenomistajan oletetaan saavan osakkeistaan markkinaarvon mukaisen korvauksen, mikäli hän myy omistuksensa julkisilla arvopaperimarkkinoilla. Lähtökohtaisesti yhtiön johdon ajaessa yhtiön ja sen osakkeenomistajien etua heidän tulee pyrkiä maksimoimaan osakkeen arvo. Myös yritysvaltauksessa, normaalissa tai vihamielisessä, yhtiön johdon tulee toimia velvollisuuksiensa mukaan, jolloin osakkeen arvo maksimoidaan maksimoimalla osakkeesta maksettavan preemion määrä. Vihamielisessä yritysvaltauksessa kohdeyhtiön johto ei hyväksy ostotarjouksen tehneen yhtiön tarjousta osakkeista eikä tee yhteistyötä tarjouksen tehneen yhtiön kanssa. Syyt tähän vaihtelevat, mutta eräs merkittävänä pidetty syy tarjouksen vastustamiseen on johtajien riski menettää asemansa yhtiössä, sillä useimmissa tapauksissa kohdeyhtiön johto vaihdetaan onnistuneen yrityskaupan jälkeen. Johdon oman aseman säilyttäminen ei kuitenkaan ole johdon tehtävä ja velvollisuus, vaan sen tulisi säilyä osakkeenomistajille lojaalina huolimatta mahdollisuudesta ja uhasta menettää oma asemansa. Yritysvaltauksessa, jota kohdeyhtiön johto ei hyväksy, vastakkain asettuvat johdon henkilökohtaiset sekä yhtiön ja sen osakkeenomistajien intressit. Oikeus- ja taloustieteellisessä kirjallisuudessa on kyseenalaistettu puolustautumista vihamielistä yritysvaltausyritystä vastaan, mutta käytännössä näitä esiintyy jatkuvasti. Tämän takia on perusteltua tutkia vaihtoehtoisia puolustuskeinoja. Vihamielistä yritysvaltausyritystä vastaan voi puolustautua monin keinoin riippuen sovellettavasta lainsäädännöstä. Suosittuja keinoja ovat valtausta yrittävän yrityksen toimintamahdollisuuksien rajaaminen esimerkiksi yhtiöjärjestykseen sisältyvällä määräyksellä sekä yhtiön taloudellisen aseman uudelleenjärjestely siten, että yhtiön markkina-arvo nousee. Osakeanti nostaa yhtiön markkina-arvoa osakkeista maksettavan vastikkeen verran ilman että yhtiölle aiheutuu muita kuin osakkeiden liikkeelle laskemiseen liittyviä kustannuksia. Yhtiön markkina-arvon noustessa valtaaja joutuu usein hankkimaan ulkopuolista lisärahoitusta, mikä lisää valtauksen kustannuksia jopa siinä määrin, että valtaajan kiinnostus viedä valtaus loppuun vähenee riittävästi. Toisaalta kohdeyhtiölle ei aiheudu merkittävää tai pysyvää haittaa. Koska osakeantipuolustus täytyy toteuttaa suuntaamalla osakeanti tietyille osakkeenomistajille, sen käytössä on huomioitava osakkeenomistajien yhdenvertaisuus. Lähtökohtaisesti suunnattu osakeanti loukkaa osakkeenomistajien yhdenvertaisuutta, joten sille on oltava sovellettavasta laista riippuen riittävän painava syy. Suomen osakeyhtiölaki (21.7.2006/624) ei mahdollista suunnatun osakeannin käyttämistä tilanteissa, joissa tarkoituksena on säilyttää jonkun tai joidenkin omistajien kontrolliasema. Suunnatun osakeannin käyttäminen puolustuskeinona vihamielistä yritysvaltausta vastaan voi periaatteessa kuitenkin pitää mahdollisena poikkeuksena, kunhan yhdenvertaisuusvaatimus otetaan huomioon. Vaikka osakeantipuolustus ei ole puolustuskeinoista tehokkain, se voi olla osakkeenomistajien enemmistölle houkutteleva vaihtoehto sen edullisuuden ja yhtiön toimintaa haittaamattoman vaikutuksen takia.
-
(2013)Collaborative applications like online markets, social network communities, and P2P file sharing sites are in popular use these days. However, in an environment where entities have had no interaction before, it is difficult to make trust decisions on a new transacting partner. To predict the quality of further interactions, we need a reputation system to help establish trust relationships. Meanwhile, motivated by financial profit or personal gain, attackers emerge to manipulate the reputation systems. An attacker may aim to slander others, promote oneself, or undermine the whole reputation system. Vulnerable components in a reputation system might bring in potential threats which might be taken advantage of by attackers. In order to give an accurate reputation estimate and better user satisfaction, a reputation system should properly reflect the behavior of the participants and should be difficult to manipulate. To resist attacks, there are various defense mechanisms, for example, mitigating the generation and spreading of false rumors, reasonably assigning an initial reputation value to newcomers, and gradually discounting old behavior. However, each defense mechanism has limitations. There is no perfect defense mechanism which can resist all attacks in all environments without any trade-offs. As a result, to make a reputation system more robust, we need to analyze its vulnerabilities and limitations, and then utilize the corresponding defense mechanisms into it. This thesis conducts a literature survey on reputation systems, inherent vulnerabilities, different kinds of attack scenarios, and defense mechanisms. It discusses the evolution of attacks and defense mechanisms, evaluates various defense mechanisms, and proposes suggestions on how to utilize defense mechanisms into reputation systems.
-
(2015)Successful vocabulary acquisition requires encoding of newly learned spoken words into a long-term storage. At the neural level, this means optimal establishment of novel neural connections and rapid formation of memory traces for words. In adults the rapid formation of memory traces is seen as an enhanced neural response at 50 ms after word recognition point to novel words after short exposure. To explore the rapid word memory trace formation in children with dyslexia, we recorded online neural activity using electroencephalography (EEG) and event-related potentials (ERPs) during a short (~35mins) session of passive exposure to a novel pseudo-word in school-aged dyslexic children and matched fluently reading controls. The memory trace formation for the novel word was investigated by comparing the average ERPs of trials in the early and late part of the exposure. In fluently reading children, the neural response to the unfamiliar pseudo-word at early latencies after word disambiguation point increased significantly by the end of the session, putatively indicating memory trace formation for the novel word. In contrast, the neural response at the early latencies did not show any change in the group with dyslexia between the early and late stages of the exposure, indicating impaired rapid formation of memory traces for novel words. We propose that rapid neural learning of new spoken words is impaired in dyslexic children, possibly due to deficient phonological processing, development of phonological representations and phonological short-term memory, and hinders efficient vocabulary growth.
-
(2017)Tämän tutkielman tarkoituksena on selvittää, kuinka avioliiton perusteella maahan muuttaneita henkilöitä määritellään Etelä-Korean laki- ja muissa säädösteksteissä ajanjaksona 2008–2016. Sosiaalisen konstruktionismin mukaisesti avioliittomuuttajien määritelmä rakentuu sosiaalisesti, kontekstisidonnaisesti, ja kielenkäytöllä on aina seurauksia tuottava luonne. Avioliittomuutto on sukupuolittunut ja alueellinen ilmiö. Vuonna 2016 Etelä-Koreassa oli 152 374 avioliittomuuttajaa (mikäli Korean kansalaisuuden saaneet henkilöt lasketaan mukaan, luku on noin kaksinkertainen). Heistä naisia oli 84 prosenttia. Suurin osa avioliittomuuttajista asui kaupungeissa. 37 prosentilla heistä on Kiinan kansalaisuus. Analysoin diskurssianalyysin keinoin keskeisiä avioliittomuuttajia koskevia säädöstekstejä. Aineiston ja tulkinnan perusteella tunnistetaan neljä erilaista, osittain toisiinsa sekoittuvaa diskurssia: määräävin diskurssi asemoi avioliittomuuttajat monikulttuuriseen perheeseen, jonka tavoitteena on muun muassa koulutuksen kautta tukea avioliittomuuttajan rooleja perheessä. Tähän liittyy avioliittomuuttajien integraatiota korostava diskurssi. Avioliittomuuttajat kuuluvat erityiseen ryhmään Korean säädösteksteissä esimerkiksi kansalaisuuslain näkökulmasta. Jo maahantulomääräykset kielitaitovaatimuksineen ja tuettu polku aina kansalaistamiseen saakka ohjaavat heitä integroitumaan sekä korealaiseen yhteiskuntaan että perheeseen. Lisäksi aineisto antaa viitteitä riskien ja toiseuden diskursseista. Muista maahanmuuttajaryhmistä poiketen ainoastaan avioliittomuuttajien asemoiminen monikulttuuristen perheiden diskurssiin on myös tätä ryhmää homogenisoiva. Esitän, että tähän monikulttuurisen perheen diskurssiin yhdistyy myös diskursseja traditionaalisesta naiseudesta ja äitiydestä. Vaikka käytössä on tässä yhteydessä käsite damunhwa eli monikulttuurisuus, se ei itsessään kerro tämän poliittisen diskurssin monikulttuurisuudesta. Tämä kategoria saa korealaisessa kontekstissaan erityisen merkityksen avioliittomuuttajien perheiden kuvaajana, joka samalla tuo myös esiin tämän ryhmän keskeisyyden poliittisessa päätöksenteossa.
-
(2017)DRama Queen (DRQ) is an unknown conserved gene that might be involved with sensing cytokinin signalling in the roots of Arabidopsis thaliana. It was originally found in a mutant screen when a mutated version of it – mDRQ – was found to improve the cytokinin sensitivity of plants in a desensitized genetic background. This thesis was done to define the protoxylem phenotype of mDRQ single mutant in Columbia (Col-0) background and to test the functionality of the gene by analyzing the complementation lines. The protoxylem phenotypes were scored from fuchsin stained samples by DIC microscopy. Protoxylem differentiation in the root of A. thaliana is an outcome of a mutually inhibitory signalling mechanism of auxins and cytokinins. Analysis of protoxylem status is a good tool for studying the cytokinin signalling because the differentiation is affected both by increased and reduced signalling levels. High signalling causes loss of protoxylem phenotypes whereas whereas low cytokinin signalling leads to ectopic protoxylem formation. The data of this thesis was analysed by SPSS version 22 software using cumulative logit modelling for the analysis. It was considered to be the most suitable alternative for analysis since the protoxylem phenotype data is ordinal by its nature. A protoxylem phenotype distribution was defined for mDRQ line and it was statistically different from Col-0. Most of the complementation lines were functional at a statistically significant level though the phenotype distributions of the complementation lines were not identical with original background. The difference could possibly be explained by the fact that the mDRQ gene is partially functional and may influence the phenotype distributions.
-
(2023)Dialogue on the definition of Europe is often dominated by geopolitical undertones. However, since the dawn of the Enlightenment era, it has been recognised that such a definition of Europe is insufficient in formulating a comprehensive meaning of Europe which encompasses the wide regional diversity which exists within the continent. This argument gained new relevance during the interwar period, where discourse on Europe as an idea that goes beyond the strict geopolitical implications of the continent, started to emerge. Select interwar studies shone a new light on the idea of Europe as they allowed for the founding of unity amidst diversity; an endeavour which cannot be considered within the geopolitical realm. Additionally, reflecting on the turmoil and crises of the interwar period, the resulting idea of Europe was said to have emerged from a major schism in intellectual trends of the time. In this regard, the formulation of Europe as an idea borne out of crisis and reinvention was perfectly demonstrated within the works of Edmund Husserl and Richard von Coudenhove-Kalergi. Both authors recognised the limitations of adopting only a geopolitical definition of Europe, and thus presented their own theories on what could constitute an all-encompassing idea of Europe. Husserl determined the core of Europe to lay within abstract factors such as universalism. Coudenhove-Kalergi considered concrete politics to be a tool which can bring Europe under the main locus of tolerance. While Husserl and Coudenhove-Kalergi took different routes in tackling this question, their respective answers can be said to highlight the interdependence between philosophical considerations of the former and the latter’s pragmatic solutions to the idea of Europe. At first glance, the only commonality between Husserl and Coudenhove-Kalergi seems to be their time-period. However, the works and theories of these two authors experience a sense of complementarity; while taking on very different approaches, the respective views on idea of Europe of Husserl and Coudenhove-Kalergi could point to a new perspective on the topic of study. While both have their limitations, the side-by-side study of their different views on Europe allows for a unique perspective in which one makes up for the other’s shortcomings in terms of thoroughness and applicability. Such is the benefit of examining and comparing Husserl and Coudenhove-Kalergi; much like their standing on the idea of Europe, their diversity only adds to the credibility of their review.
-
(2024)Drought events will increase in the future due to climate change and thereby threaten agricultural production. The growing world population needs stable yields nonetheless thus, solutions need to be found. One way to do so is to explore mechanisms that allow plants to withstand harsh conditions and recover from them. Autophagy is such a mechanism. It is a bulk degradation pathwaythat allows plants to recycle cell components. During biotic and abiotic stress autophagy pathways are enhanced. Even though this mechanism is very useful and is proven to enhance abiotic stress tolerance, very little is known about it in plants. This thesis aimed at defining the informative time points for drought and autophagy response during drought and recovery in barley. To do so barley plants were subjected to gradual drought by withholding irrigation. They were kept at a level of severe drought for 4 days and were then rewatered. The tip of the third leaf was sampled for RNA extraction followed by qPCR. The genes this thesis focused on were GST and HSP17 as indicators of drought stress and ATG6 as indicator for autophagy. Additionally, phenotypic data was collected via RGB imaging for monitoring wilting and thermal imaging for stomata closure. GST was upregulated during the onset of drought, which seems to make it an early response gene, while HSP17 was upregulated during severe drought. ATG6 had a high transcription rate during all stages of drought and only decreased during recovery. However, because the primer efficiencies calculated in this experiment appear to be very low, and data points were missing due to pipetting practice, the results are not reliable and need to be repeated. Thus, no prediction about the informative time points can be made. The thermal data showed good results and the expected pattern of stomatal closing during drought could be observed. But because the greenhouse is a variable environment a reference would make the data even more precise.
-
(2020)Lithuanian neo-pagan community “Romuva” approached the Lithuanian parliament to grant it state’s recognition. According to the Ministry of Justice, the religious community met all necessary requirements – it has been registered for 25 years, its customs and creeds do not contradict law and morals, and it has support in the society. However, the Lithuanian parliament voted against granting the new status. This thesis aims on how was the legal recognition of the “Romuva” argued for and against in the public media and the Lithuanian parliament and what kind of understanding of neo-paganism in particular and religion in general was constructed in these arguments. To achieve the goal two sets of data were analyzed: all articles related with “Romuva” recognition appeared on the most popular as well as pro-christian and pro-romuvian media sites from 2018-2020. Also public records from the Lithuanian parliament during submission and consideration phases, letters to parliamentarians. The data was also structured in a timeline to track the development of arguments. Findings show that even though the question for recognition is legal, during the debate historical and political arguments were dominating. Many of them did not relate with requirements for the recognition officially set by the Ministry of Justice. The biggest involvement in the question was demonstrated by pro-christian community’s members – politicians, scholars. The recognition for neo-pagans was strongly resisted by the dominant religion in Lithuania Christian Church
-
(2018)Kaposi’s sarcoma herpesvirus (KSHV), also called human herpesvirus 8 (HHV-8), was discovered following the AIDS-epidemic as the causative agent of Kaposi’s sarcoma (KS), an angiogenic endothelial tumor of the skin, and of two rare lymphoproliferative diseases, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). Infection by KSHV displays two life cycle phases; latent and lytic replication. In latency, the virus stays dormant within the host, expressing only a few genes and no viral particles are produced. Latency is the default mode of infection, however, upon appropriate induction the virus reactivates to express all of its genes and replicate viral DNA during the productive lytic replication, culminating with the release of infectious progeny particles and lysis of the host cells. Virus reactivation from latency to the lytic replication is an essential step in the KS pathogenesis. Upon KSHV infection, endothelial cells (EC) undergo reprogramming towards spindle cell, the principal proliferating cell in advanced KS lesions. The transcription factor prospero related homeobox gene Prox1 has an important role in mediating the effects of KSHV on EC reprogramming, contributing to the KS development. Prox1 is the master regulator of lymphatic endothelial cell fate, and its expression is manipulated during the KSHV infection. However, the role of Prox1 in the KSHV life cycle and lytic reactivation has not been studied. To elucidate the role of Prox1 in KSHV reactivation from latency, the effect of ectopic expression of Prox1 on the lytic gene and protein expression in both latent and reactivated KSHV-infected cells was studied. This led to a significant increase in KSHV lytic gene and protein expression, suggesting Prox1 as a positive regulator of KSHV lytic replication. Moreover, Prox1 wild-type, but not its DNA-binding deficient mutant, could significantly increase the release of infectious virions. To investigate the expression levels of Prox1 during KSHV infection, infection kinetics assay was performed, which showed an increase in the Prox1 levels during acute infection. Intriguingly, this was followed by a progressive decrease in the Prox1 levels as latency was established. In conclusion, the focus of this thesis is to investigate the role of Prox1 in KSHV reactivation, and to provide a deeper insight into the virus reactivation mechanisms that can be utilized for future therapeutic strategies against KSHV-mediated tumorigenesis of KS. Keywords: KSHV, Kaposi’s sarcoma, Prox1, virus reactivation, lytic replication
-
(2021)Aging is the progressive accumulation of cellular dysfunction, stress and inflammation. The mitochondrial network plays a central role in the maintenance of cellular homeostasis, with a growing body of evidence assigning dysfunctional regulation of this network as cause or effect of age-related diseases including metabolic disorders, neuropathies, various forms of cancer and neurodegenerative diseases. Neuronal sensitivity to changes in energy supply and metabolic homeostasis make neurons especially susceptible to alterations in the mitochondrial network. Mitophagy, a specified form of autophagy, is the selective degradation and quality control mechanism of mitochondria by engulfment and fusion with acidic endolysosomal compartments of the cell. Mitophagy has been extensively characterised in cultured cells and short-lived model organisms. However, our understanding of physiological mitophagy during mammalian aging is unknown. This study utilizes mito-QC mitophagy reporter mice that enable in vivo detection and monitoring of mitochondrial turnover due to the distinct physicochemical properties of the tandem GFP-mCherry reporter. Using cohort groups of young and aged reporter mice, age-dependent alterations of mitophagy were quantified in the cerebellum and the outer nuclear layer (ONL) of the retina. Specific autophagy and mitophagy markers were used to assess the longitudinal alterations in the mitophagic landscape. Images of fixed brain tissue sections were attained by high-speed spinning disc confocal microscopy for the quantitative and histological analysis. This study characterises the longitudinal alterations of mitophagy in distinct regions of the central nervous system (CNS) of mitophagy reporter mice, demonstrating tissue-specific alterations in mitochondrial turnover throughout physiological time. Åldrande kan definieras som den successiva ackumuleringen av cellulär dysfunktion, stress och inflammation. I upprätthållandet av cellens funktioner och homeostas har det mitokondriella nätverket en central roll. Omfattande forskning visar att åldersrelaterade sjukdomar såsom neuropati, ämnesomsättningssjukdomar, olika cancerformer samt neurodegenerativa sjukdomar föranleds av mitokondriell dysfunktion. Neuroner är beroende av oavbruten energitillförsel och upprätthållen metabolisk homeostas, vilket gör dem speciellt mottagliga för förändringar i det mitokondriella nätverket. Mitofagi är en selektiv form av autofagi som degenererar och kvalitetskontrollerar mitokondrier genom att leverera dem till lysosomer där de bryts ned av hydrolytiska enzymer. Den aktuella kunskapen inom regleringen av och mekanismerna bakom mitofagi baserar sig på gedigen forskning av kortlivade organismer och cellkulturer. Däremot är vår kunskap inom åldrandets inverkan på mitofagi i däggdjur begränsad. I denna studie används musmodellen mito-QC vars rapportörgen består av ett binärt GFP-mCherry-komplex som besitter olika fysikaliska och kemikaliska egenskaper, vilket möjliggör upptäckt och analys av mitofagi in vivo. En kvantitativ jämförelse av mitofagi i unga och åldrande möss genomfördes i vävnadssnitt av cerebellum och av det yttre nukleära lagret av retinan. Specifika autofagi- och mitofagimarkörer användes för att utvärdera de longitudinella förändringarna i mitokondriell degenerering. Bilder för kvantitativ och histologisk analys erhölls med höghastighets spinning-disk-konfokalmikroskop. Denna forskning karaktäriserar de longitudinella förändringarna av mitofagi i definierade regioner av det centrala nervsystemet i musmodellen mito-QC och presenterar vävnadsspecifika förändringar i degenereringen av mitokondrier under åldrandets framskridande.
-
(2018)På värdepappersmarknaden har information en alldeles kritisk funktion. För att handeln med värdepapper ska kunna fortgå och aktörerna vara villiga att delta i handeln krävs att information om de finansiella instrumenten finns tillgänglig. Information ligger till grund för varje handelsbeslut som fattas. Ifall rimlig information om de finansiella instrumenten inte fanns att tillgå, skulle aktörerna på marknaden inte vara villiga att bedriva handel. Endast på detta sätt, genom att information de facto finns att tillgå, kan en effektiv marknad uppnås och upprätthållas. På värdepappersmarknaden utgör informationen en fördel som innehavaren av informationen har gentemot dem som saknar motsvarande information. Eftersom information spelar en så central roll för värdepappersmarknadens funktionalitet, spelar regleringen av information och dess utnyttjande på värdepappersmarknaden en viktig roll. Det är av största vikt för marknadsaktörerna att veta var gränsen mellan tillåtet och otillåtet informationsutnyttjande går, samt att det finns fungerande normer för att förhindra marknadsmissbruk och effektiva och klara åtgärder att vidta i de fall då marknadsmissbruk är ett faktum. Då normerna som reglerar marknadsbeteendet är öppna och flexibilitetseftersträvande accentueras rättsdoktrinens och rättsdogmatikens funktion som leverantör av välmotiverade systematiseringar och tolkningsrekommendationer. Målet med denna avhandling är att systematisera och tolka definitionen av insiderinformation. Infallsvinkeln är dock inte en ”traditionell” rättsdogmatisk analys av definitionen, där varje beståndsdel ingående granskas skilt för sig. Även om ett dylikt tacklande av forskningsfrågan säkerligen vore motiverat med tanke på en fullständig analys av undersökningsobjektet, är sen sådan analys emellertid utmanande att framgångsrikt genomföra för definitionen i sin helhet på det spaltutrymme som en magisteravhandling medger. I stället tar avhandlingen avstamp i den historiska utvecklingen av insiderregleringen ur ett internationellt perspektiv. Granskningsobjektet i den kontextualiserande delen utgörs således av insiderregleringen i USA. De två primära syftena med denna infallsvinkel är dels att erbjuda läsaren en bredare kontext och en djupare förståelse för den företeelse och de koncept som diskuteras, dels att sålla fram och analysera de ideologier som ligger till grund för utvecklingen av insiderregleringen i USA. Enligt det synsätt som avhandlingen omfattar utgör ideologierna tolkningsmässiga verktyg som kan utnyttjas vid systematiseringen av den europeiska insiderregleringen och definitionen av insiderinformation. Synsättet kan motiveras bland annat med det inflytande som värdepappersmarknadsregleringen i USA haft på den europeiska regleringen. I den systematiserande delen av avhandlingen ställs definitionen av insiderinformation i den nödvändiga relationen till de definitionsstyrda normerna i den europeiska regleringen – med andra ord förbudet mot insiderhandel och röjande av insiderinformation, samt emittenters fortlöpande skyldighet att offentliggöra insiderinformation. Detta sker genom att de definitionsstyrda normernas innehåll granskas och analyseras. Analysen finner att innehållet i dessa normer är expansivt betingade. Vidare analyseras den europeiska definitionen i samklang med de tolkningsverktyg som utgörs av de ideologier som identifierades i granskningen av insiderregleringen i USA. Analysen finner på denna punkt att den egalitetsbetonade ideologi som den europeiska insiderregleringen bottnar i leder till en insiderreglering som på det hela taget är särdeles expansiv. Avhandlingen argumenterar för att definitionen av insiderinformation, för att uppnå en optimalt fungerande marknad, med fördel kan tolkas i en restriktiv riktning inom det tolkningsutrymme som medges av övriga tolkningsstyrande faktorer. Analysen av avhandlingen utmynnar i en konkret tolkningsrekommendation som framhåller att även den europeiska definitionen, i likhet med andra på detta område betydande jurisdiktioner (såsom USA och Australien), kan systematiseras så att den primärt består av ett krav på att informationen inte är allmänt tillgänglig (monopolistisk) och att den är väsentlig. Informationens monopolistiska natur utgör enligt avhandlingens systematisering en tillgänglighetsdimension, varvid den gemensamma nämnaren för de tre övriga kriterierna i substansdimensionen utgörs av väsentlighet. Informationens väsentlighet gestaltas bäst genom ett krav på att informationen har en kurspåverkande potential, vilket i sin tur lämpligen bedöms med hjälp av total mix-standarden.
-
(2021)Psychological pain is a concept, that describes pain in the mind, also know as psyache. It is a phenomenon closely related to suicidal acts (Shneidman, 1996; Baumeister, 1990, Troister and Holden 2010). Psycyhological pain is a relatively new concept and not yet that well known, atleast among general practicioners. For example in the USA 5,6% of the general population and 53% of the patients with severe mental illness are thought to suffer from psychological pain (American Psychiatric Association, 2003). Depression and hopelessness are perhaps the most well known factors in the development of suicidal ideation, atleast for people not familiar with the research literature of this field. However Troister and Holden (Troister and Holden, 2012) compared the effects of psychological pain, depression and hopelessness. The results were that out of depression, hopelessness and psychological pain psychological pain is the only variable that contributes significantly to a change in suicidal ideation. In this study the contributions of depression and hopelessness were reduced to statistically nonsignificant levels. Furthermore psycological pain has been identified as a high risk factor for suicide with a greater predictive power than depression (Olié et al., 2010; Pereira et al., 2010; Troister and Holden, 2010; Li et al., 2014; Troister et al., 2015). Neuroimaging can be used in psychiatric diagnostics and also in psychiatric research. In diagnostics neuroimaging can be used to for differentiate between psychiatric and somatic causes of a psychosis, as psychosis can arise from a psychiatric disorder or from for example a brain tumor. Neuroimaging can be used for example in the field of pain research. There is overlap between neural networks of physical and psychological pain, but it seems like these different types of pain have some unique brain areas as well (Meerwijk et al., 2013). In addition to neuroimaging one of the ways of measuring psychological pain is through questionnaires, of which there are several. Perhaps because of these overlapping neural networks of pain some of the medication used to treat physical pain seems to have a positive effect on suicidal population suffering from psychological pain. It seems like the dose needed to treat psychological pain is a lot smaller than a dose needed to treat equivalent physical pain (Yovell et al., 2016).
-
(2018)The aim of this study is to define the concept of existing aid. Existing aid relates to state aid control in the European Union. Existing aid is a form of state aid to which the obligation to recover illegal state aid does not apply. The definition of existing aid is, therefore, important. In determining whether an aid can be an existing aid, it must be put into effect prior to the entry into force of the Treaty on the Functioning of the European Union, or another event listed in Article 1(b) of the Procedural Regulation of 2015. This study seeks to find when is an aid considered “put into effect” within the meaning of the said provision. Aid should be considered put into effect when the aid beneficiary is legally entitled, under national law, to receive the aid, instead of the traditional view of only looking at the time the legislation providing for the aid entered into force. Pursuant to Article 1(b)(v) of the Procedural Regulation of 2015, aid, which was not considered aid when it was put into effect but later became aid due to the evolution of the internal market, is existing aid. The scope of application of the said provision is examined in this study. The interpretation proposed by this study is that the provision primarily applies, when evolution of the internal market takes place by a liberalisation of national law, which renders an aid recipient an undertaking within the meaning of European Union competition law. The traditional view of applying the provision when trade between member states within the meaning of Article 107(1) of the Treaty on the Functioning of the European Union emerges, should not be considered the typical situation of applying the provision. This is because that is not likely to ever happen. Pursuant to Article 1(c) of the Procedural Regulation of 2015, existing aid can lose its status as existing, if it is altered. The form, in which the alteration must take place, and the substance of the alteration serious enough to trigger the application of Article 1(c) of the Procedural Regulation of 2015, are examined. The form of alteration should be viewed the same way as putting into effect of aid. The alteration can be substantial without any effect on the conditions of compatibility with the internal market.
-
(2016)As the core task of competition law is to protect the freedom of economic action of various market participants, definition of the relevant market plays an important role for the enforcement of competition law. This thesis mainly discuss existing laws and regulations regarding the definition of relevant market in the European Union and China. The most efficient test method to define the relevant market, that is the Small but Significant and Non-transitory Increase in Price test will be analysed. As one of the most innovative invention during the past decades, the Internet changes operating model of enterprises in many ways. And to define the relevant market in the Internet industry is different from which in the traditional market because of the properties of the Internet market. Such as the Internet is a bilateral market, asymmetry price structure and so on. This thesis provides answers for how the existing rules and principles of competition policy could be applicable under the Internet industry and whether the Internet forms a new relevant market, or whether the Internet industry shapes a new market, which competes with traditional market, and lies within the same market.
Now showing items 3749-3768 of 32623