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Coming dissertations at Uppsala university

Please note that the date and time given on these pages is the time of electronic publication, and not the date of the public defense. To find the time and venue of the public defense, please follow the link to DiVA of the thesis in question.
  • “This is the Face of an Atheist” : Performing Private Truths in Precarious Publics

    Author: Evelina Lundmark
    Publication date: 2019-01-10 12:38

    The primary aim of this dissertation is to gain a greater understanding of the particular vulnerabilities attached to wo/men publicly performing atheist selves on YouTube. The purpose is to examine lived non-religion as a performance of a personal and stigmatized identity in a digitally mediated public. I thus examine 60 vloggers’ videos and comment sections in relation to their experiences of, on the one hand, publicly performing atheist identity in the US context – a culture that strongly ties the idea of good citizenship to religiosity – and on the other hand, to what it means to speak out as a woman, agendered, or gender queer person in a minority discourse dominated by men. By use of qualitative feminist intertextual analysis, this study focuses three empirical questions: What characterizes the process of the performances of selves in videos made by non-religious wo/men in the US context? What socio-technological affordances are made visible in the videos, and how do they structure the performances? What characterizes vloggers’ interactions with commenters, and how does this process shape the construction of a space for their self-performances? The findings and their significance for sociology of religion – more precisely the subfields of digital religion and nonreligious and secular studies – is discussed through the fourth and fifth research questions: How can theories of self-performance, counterpublics, and third spaces in digital religion help us understand what is happening in these types of spaces? What theoretical implications follow from these results for understanding visibility of religion as a public phenomenon in current sociology of religion? The study finds that vloggers co-effect third spaces of emotive resonance that enable a precarious counterpublicness of performing atheist visibility. This dissertation can thereby open up a new intellectual space within sociology of religion and digital media studies for engaging with non-religious identity in a mediatized society. Further, it provides novel understandings of the visibility and publicness of atheist identity and the socio-technological conditions that both afford and constrain them.

  • Biological Aspects of Peripartum Depression

    Author: Åsa Edvinsson
    Publication date: 2019-01-09 13:44

    Peripartum depression affects around 12% of women in pregnancy and postpartum, and about 2–3% of European pregnant women use antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). An increased risk of poor pregnancy outcomes has been described in women with antenatal depression and SSRI treatment during pregnancy. The biological mechanisms behind these complications are not fully understood and here we investigated several biological correlates of peripartum depression, and discriminated between the effects of antidepressant treatment and depression itself.

    In Paper I, attentional biases in pregnant and postpartum women were studied by using the Emotional Stroop Task, measuring reaction times to different stimuli. The major finding was shorter reaction times in postpartum depressed women, for emotionally valenced stimuli, which can be interpreted as emotional numbing.

    In Paper II, peripheral inflammatory markers were assessed by proximity extension assay technology in depressed, SSRI-treated and healthy pregnant women. Lower levels of 23 markers were found in women with antenatal depression, independent of treatment, compared with healthy controls. These findings suggest a dysregulated switch to the anti-inflammatory M2 milieu characterizing a normal third trimester.

    In Paper III, normal changes in inflammatory markers across pregnancy and postpartum were assessed in healthy pregnant and postpartum women. The majority (41) of the 50 markers that differed between groups were lower postpartum. These results clearly reflect the change in the immune system in pregnancy to postpartum transition.

    In Paper IV, placental gene and protein expression were investigated and nominally significant findings were noted for serotonin receptor 1A (HTR1A) and neuropeptide Y2 receptor (NPY2R), where women with untreated depression displayed higher gene expression than healthy controls. Protein expression analyses revealed higher levels of HTR1A in placentas from SSRI-treated women, compared with healthy controls and women with untreated depression. This suggests possible involvement of HTR1A in the effect of antenatal depression on the placenta.

    Overall, peripartum depression is associated with altered cognitive-emotional processing, lower levels of several mostly anti-inflammatory markers, and altered placental gene and protein expression. However, we found no major differences between untreated and treated depression.

  • Understanding Heparan Sulfate Biosynthesis and Functional Implications of Heparanase

    Author: Tianyi Song
    Publication date: 2019-01-09 13:04

    Heparan sulfate (HS) proteoglycans are present on the plasma membrane of all animal cells studied so far and are a major component of extracellular matrices. Heparanase is an endo-ß-glucuronidase that cleaves HS chains at internally located ß-glucuronidic linkages1. Except its conventional enzymatic function, non-enzyme function and its function in the nucleus have been demonstrated recently.

    Regulation of HS biosynthesis has long been a myth. By generating HEK293 cells that overexpress different doses of C5-epimerase and a mutant without catalytic activity we created tools to analyze HS chain structure. We show that HS chain length increases in a dose dependent manner, dependent on the enzymatic activity of C5-epimerase, which can be reversed by co-overexpresssing with 2-O-sulfotransferase.

    Lipoprotein lipase (LpL) is a HS-bound enzyme that processes the triglycerides of lipoproteins from both exogenous and endogenous sources. Underdeveloped adipose tissue was revealed in heparanase transgenic mice, due to compromised LpL activity. Mechanistically, a likely possibility was demonstrated due to HS shedding related to overexpressed heparanase.

    The finding that breast cancer T47D cells which overexpress heparanase adopt a higher rate of aerobic glycolysis fueling cell proliferation and cell survival added up to the diverse functions of heparanase.

    Transcriptomic analysis after knockdown of heparanase in melanoma cells confirmed involvement in inflammatory responses as studied previously, and regulation of cell adhesion, ECM components, apoptosis and nucleosome assembly emerged as novel functional and mechanistic indications of heparanase. Supported by experimental evidence, heparanase’s effect in cell adhesion and apoptosis validated its role in cancer progression. Moreover, regulation of nucleosome assembly prompts further investigation into its action mode in the nucleus.

    Taken together, the present study adds to the elucidation of HS biosynthesis and depicts novel roles of heparanase, highlighting its multifaceted roles in cancer and providing exciting notions for future studies.

  • Dynamics of Magnetic Molecules under Electrical Control

    Author: Henning Hammar
    Publication date: 2019-01-09 09:31

    This thesis theoretically studies the dynamics of molecular magnets under electrical control. Molecular magnets are nanoscale magnets that can, e.g., consist of single-molecules or single-atoms. In these magnets, the electronically mediated exchange and transport can be controlled by external fields. In this thesis, we study the effect of electrical control and voltage pulses on the transport properties, spin dynamics and the exchange of the molecular magnets.

    Nonequilibrium Green's functions is the method used to describe the underlying electronic structure of the magnetic molecule. The studied systems consists of single-molecule magnets in a tunnel junction between metallic leads. Here, the transport characteristics are derived for charge, spin and heat currents in the system for time-dependent voltage pulses. Furthermore, a generalized spin equation of motion is derived for the molecular spin moment, using nonequilibrium field theory. The equation of motion incorporates nonequilibrium conditions and is of nonadiabatic character. The effective model for the spin moment can be decomposed into effective magnetic field, isotropic Heisenberg interaction, and anisotropic Ising and Dzyaloshinskii-Moriya interactions. These effective fields depends on the electronic structure of the molecule and can be controlled by, e.g., gate and bias voltages.

    The thesis encompasses studies on the effect of a sudden on-set of a voltage pulse for a single-molecule magnet and its effect on the spin dynamics and transport properties of the molecule. Different approximations schemes for the spin equation of motion and their regimes of validity are investigated. Moreover, spin-dependent signatures in the heat transport characteristics of the single-molecule magnet are connected to the dynamics of the molecular spin moment. A phase induced switching mechanism of the molecular moment is shown for voltage pulses of varying temporal length. In the stationary limit, it is shown that one can electrically control the interaction and transport of two molecular magnets in a series. Furthermore, investigations on the electrictronically mediated anisotropy in a vibrating single-molecule magnet show that the anisotropy can be tuned by a temperature difference or a voltage bias.

  • Adapting sonar systems for monitoring ocean energy technologies

    Author: Francisco Francisco
    Publication date: 2019-01-08 14:10

    The global energy sector is under profound reforms aiming towards renewable energy sources, clean technologies and expansion of smart grids, all with the additional aim of providing affordable and dependable electricity for everyone. A reduction of carbon dioxide emissions is a priority on the global agenda, and to achieve that, cleaner energy technologies has to be more integrated into the energy mix. This thesis focus on a sustainable implementation of wave, tidal and offshore wind power, wherefore there is a need to investigate more about the prerequisites and consequences ocean energy can have on the marine environment. For that, reliable, cost effective and continuous environmental monitoring framework is necessary in order to support and safeguard ocean energy operations.

    The main objectives of the research presented in this thesis are to develop a multifunctional environmental monitoring platform based on sonar systems for ocean energy applications, by adapting high resolution multibeam, dual beam and split beam sonar systems and also underwater cameras; Propose data acquisition and processing protocols capable of decipher sonar data in order to provide continuous environmental monitoring and reporting; Conduct qualitative and quantitative observations of fish and marine mammals using the built monitoring platform; And investigate the feasibility of utilizing the Uppsala University wave energy converter technology to generate electricity worldwide. As a result, a multifunctional platform was designed, built and tested. This included the hardware, the data acquisition system, and a data analysis framework comprising new algorithms necessary to process the new acoustic data. The multibeam, dual beam, and split beam sonar systems and underwater cameras produced both qualitative and quantitative data of biomass, occurrence and behavior of fish and marine mammals in the vicinity of ocean energy devices. With this platform, it was also possible to conduct seabed and structural inspections within ocean energy devices, observe cavitating flows, etc. One of the most important results of this research was the possibility of extracting visual signatures of fish and marine mammals through acoustic images. This can be valuable for training algorithms for manual or automatic identification and classification of underwater targets through imaging sonar systems, a technique that can be widely used in the offshore activities. Regarding feasibility studies and wave power resource assessment, this study concluded that mild wave climates can provide enough energy to run reverse osmosis desalination systems as well as produce sufficient electricity to integrate into a national grid.

    In summary, this thesis concludes that the implementation of ocean energy can be facilitated by creating environmental monitoring, risk and resource assessment frameworks such as the presented research work that contribute to lowering the risks associated with subsea work and thereby costs of ocean energy projects.

  • Drug discovery against leishmaniasis : Bio- and chemoinformatic guided strategies for target evaluation and hit identification

    Author: Elisabet Vikeved
    Publication date: 2019-01-08 10:53

    Leishmaniasis is a neglected tropical disease mainly affecting poor people in developing countries. It is caused by infections of flagellated protozoa belonging to genus Leishmania. The few available drugs are associated with problems such as low effectiveness, severe side effects and resistance development. The overall aim of this thesis is to aid in drug discovery against leishmaniasis – primarily using bio- and chemoinformtic approaches.

    In the first part of the thesis potential drug targets in Leishmania parasites were identified and hits against these targets were thereafter suggested. In paper I bioinformatics together with experimental work were used to evaluate lateral gene transfer (LGT) in genus Leishmania. LGTs of prokaryote origin often lack human homologs, and are therefore hypothesized to be valuable drug targets. LGT in genus Leishmania is shown to be a dynamic process in which some acquired genes are conserved in the recipient genomes and others are degraded and eventually lost. Some LGTs have also undergone pseudogenization. It is thus important to evaluate LGT products before exploring them as potential drug targets.

    In paper II ligand-based virtual screening and molecular docking were used to suggest potential hits against the LGT product pteridine reductase 1 (PTR1) and the two-domain enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) both involved in folate metabolism. DHFR-TS is not encoded by an LGT but it has been hypothesised that several enzymes in the folate pathway need to be inhibited to affect the viability of Leishmania parasites. One potential hit compound against PTR1 and the DHFR-domain and four hit compounds against PTR1 and the TS-domain were identified and tested on Leishmania tropica promastigotes. The suggested PTR1/TS inhibitors had no effect in the promastigote assay, however one of them enhanced the effect of the PTR1/DHFR inhibitor, which also had effect on its own.

    In the second part of the project, focus shifted towards predictions of targets for compounds with known anti-leishmanial activity but unknown mechanisms of actions. In paper III a ligand-based-target fishing (LBTF) method was developed. The reference compounds were metabolites to metabolic enzymes and similarities were assessed with Euclidean distance calculations in chemical property space. The LBTF approach was used to suggest potential targets to a set of anti-leishmanial agents retrieved from ChEMBL-database. The theory behind the LBTF method developed in paper III was also used in paper IV to predict targets of two sponge-derived alkaloids that where shown to have anti-leishmanial activity.

  • Adhesion-dependent mechanisms regulating mitosis

    Author: Deepesh Kumar Gupta
    Publication date: 2019-01-07 13:43

    Integrin-mediated cell adhesion is required for normal cell cycle progression during G1-S transition and for the completion of cytokinesis. Cancer cells have ability to grow anchorage-independently, but the underlying mechanisms and the functional significance for cancer development are unclear. The current thesis describes new data on the adhesion-linked molecular mechanisms regulating cytokinesis and centrosomes. 

          Non-adherent fibroblast failed in the last step of the cytokinesis process, the abscission. This was due to lack of CEP55-binding of ESCRT-III and its associated proteins to the midbody (MB) in the intercellular bridge (ICB), which in turn correlated with too early disappearance of PLK1 and the consequent premature CEP55 accumulation. Integrin-induced FAK activity was found to be an important upstream step in the regulation of PLK1 and cytokinetic abscission. Under prolonged suspension culture, the MB disappeared but septin filaments kept the ICB in the ingressed state. Upon re-plating on fibronectin, such cells were found to divide through traction-based abscission. Non-adherent cytokinetic cells maintained septin filaments around the ICB for >24 hours, but septin was gradually depolymerized later on and furrow-regressed binucleated cells were generated (<15%). Binucleated non-transformed cells were halted in G1 and became senescent, possibly via PIDDosome formation by two centrosomes merging. In contrast to normal fibroblasts, ras-transformed fibroblasts were able to recruit the ESCRT-III-associated protein ALIX to MB under non-adherent condition. Live-cell imaging and septin-7 immuno-staining showed that cytokinetic abscission occurred in non-adherent ras-transformed fibroblast.  

          Non-adherent fibroblasts, as well as adherent cells lacking FAK expression, were also delayed in early stages of mitosis progression and exhibited defect centrosome separation and abnormal spindle formation. Our data show that integrin-dependent FAK activity promotes centrosome separation via a FAK-PLK1-Eg5 route during early mitosis.

  • Ion dynamics and structure of collisionless shocks in space

    Author: Andreas Johlander
    Publication date: 2019-01-07 13:30

    Shock waves form when supersonic flows encounter an obstacle. Like in regular gases, shock waves can form in a plasma - a gas of electrically charged particles. Shock waves in plasmas where collisions between particles are very rare are referred to as collisionless shock waves. Collisionless shocks are some of the most energetic plasma phenomena in the universe. They are found for example around exploded supernova remnants and in our solar system where the supersonic solar wind encounters obstacles like planets and the interstellar medium. Shock waves in plasmas are very efficient particle accelerators though a process known as diffusive shock acceleration. An example of particles accelerated in shock waves are the extremely energetic galactic cosmic rays that permeate the galaxy. This thesis addresses the physics of collisionless shocks using spacecraft observations of the Earth's bow shock, particularly understanding the ion dynamics and shock structure for different shock conditions. For this we have used data from ESA's four Cluster satellites and NASA's four Magnetospheric Multiscale (MMS) satellites. The first study presents Cluster measurements from the quasi-parallel bow shock, where the angle between the magnetic field and the shock normal is less than 45 degrees. We study the first steps of acceleration of solar wind ions at short large-amplitude magnetic structures (SLAMS). We observe nearly specularly reflected solar wind ions upstream of a SLAMS. By gyration in the solar wind, the reflected ions are accelerated to a few times the solar wind energy. The second and third study are about shock non-stationarity using MMS measurements from the quasi-perpendicular shock, where the angle between the magnetic field and the shock normal is greater than 45 degrees. In the second study we show that the shock is non-stationary in the form of ripples that propagate along the shock surface. In the third study we study closer in detail the dispersive properties of the ripples and find that whether a solar wind ion will be reflected at the shock is dependent on where it impinges on the rippled shock. In the fourth study we quantify the conditions for ion acceleration shocks by using MMS measurements from many encounters with the bow shock. We find that the quasi-parallel shock is efficient with up to 10% of the energy density in energetic ions. We also find that at quasi-parallel shocks, SLAMS can restrict high-energy ions from propagating upstream and convect them back to the shock, potentially increasing acceleration efficiency.

  • Study of biomarkers for improved diagnosis and therapy monitoring in young asthmatics

    Author: Nikolaos Tsolakis
    Publication date: 2018-12-28 09:11

    Background: Type-2 asthma is often related to atopy and is characterized by elevated type-2 biomarkers. However, less is known about the pathophysiology of non-type 2 asthma, factors associated therewith, and the stability of different asthma phenotypes over time.

    Aims: To identify an IgE antibody concentration and putative biomarkers that better separate non-type 2 from type-2 asthma. To study the association between longitudinal changes in inflammatory biomarkers and clinical outcomes. To investigate the pattern of IgE sensitization to different cat allergen components and its impact on type-2 biomarkers in young asthmatics.

    Methods: The present thesis is based on the MIDAS asthma cohort, which includes asthmatics (n = 408) and healthy controls (n = 118), aged 10–35 years at baseline, with a follow-up visit 43{23-65} months later. All the subjects were characterized with regard to IgE sensitization, inflammation was assessed based on fractional exhaled NO (FeNO), blood eosinophil count (B-Eos) and other biomarkers, both type-2 and non-type 2, and lung function was evaluated with spirometry.

    Results: FeNO and B-Eos maintained associations with clinical asthma outcomes in the IgE antibody concentration range 0.10–0.34 kUA/L, but not below 0.10 kUA/L. Non-atopic asthmatics with perceived cow’s milk hypersensitivity had poorer asthma-related quality of life than those with atopic asthma, and were characterized by clinically significant non-type 2 inflammation. Furthermore, longitudinal increase in height-adjusted FeNO associated independently with decline in lung function. IgE sensitization to cat lipocalins and/or cat serum albumin were independently associated with FeNO and B-Eos.

    Conclusions: Our findings demonstrated that a cut-off of 0.10 kUA/L for IgE antibodies appeared to be useful for ruling out type-2 asthma in young subjects. A subgroup of non-atopic asthmatics was characterized by perceived cow’s milk hypersensitivity and non-type 2 inflammation. Longitudinal changes in FeNO associated with lung function decline in asthmatics. IgE sensitization to minor cat allergen components may promote both local and systemic type 2 inflammation.

  • Norges Våpen : Cultural Memory and Uses of History in Norwegian Black Metal

    Author: Christopher Thompson
    Publication date: 2018-12-21 10:52

    This dissertation examines uses of history and expressions of cultural memory in Norwegian black metal. Formed in the late 1980s and early 1990s, Norwegian black metal seemed at odds with many of the stereotypes of Norway. The genre is an extreme style of heavy metal music that has been associated with burning churches, desecrating graves, and committing murders. Yet, Norway is often perceived as wealthy with sublime natural beauty and high levels of equality. Since the late 1990s, Norwegian black metal has increasingly received positive recognition and support from Norwegian government agencies and cultural institutions who have deemed this style of music a cultural product of Norway.

    In exploring the relationship between Norwegian black metal and Norway, two primary questions are asked: what makes Norwegian black metal ‘Norwegian’ and what are its influences? To answer these questions, a theoretical approach based on Astrid Erll’s cultural memory complex is used. Included in this cultural memory complex are notions of individual and collective memory, both of which include concepts of nationalism as outlined by Benedict Anderson and Michael Billig. The source base for this dissertation includes the musical releases of over five hundred Norwegian black metal bands which were gathered and analyzed. Three primary categories, with corresponding subcategories, were identified to account for the ways Norwegian black metal bands have used history and expressed cultural memory over a twenty-five-year period from 1988 to 2013.

    This dissertation shows that Norwegian black metal has made frequent use of history and has actively negotiated parts of the identity-making process from nineteenth-century Norway. In connecting to Norwegian identity in such a way, these bands link to historically construed notions of likhet and egalitarian individualism as identified by the Norwegian anthropologists Marianne Gullestad and Thomas Hylland Eriksen. They actively reproduce many of the same essentialized notions of Norwegian identity that create and maintain ethnic boundaries on Norwegian identity. By using history and expressing cultural memory in the way that they do, Norwegian black metal bands communicate that they are firmly Norwegian while, at the same time, reinforcing ethnocentric notions of Norwegian identity.