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Coming theses from other universities

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.
  • Robust Low-Power Wide Area Networks for Sports and Health

    Author: Charalampos Orfanidis
    Publication date: 2020-09-04 14:59

    Low-Power Wide Area Networks (LPWANs) has enriched the IoT ecosystem with new features and application scenarios. LPWANs offer long range communication and can be used to connect devices that are divided by long distances and offer connectivity to remote areas where cellular networks are not accessible. They utilize their long range, low-power robust communication to enable popular application scenarios, such as smart cities and smart agriculture.

    However, the environment that most of these networks operate in is unlicensed spectrum, which might be crowded and noisy due to the co-existence of other networks and technologies that operate in the same frequency band. Therefore, one of the goals of this thesis is to investigate the degree of robustness in LPWANs and propose seamless mechanisms that ensure robust communication in case of high degree of interference. Another goal is to support application scenarios in sports technology and health, which require robust and long-range communication. Hence, the second goal of this thesis is to explore how to take advantage of the robust communication that LPWANs offer, and use it in application scenarios in sports technology and health.

    To realize the aforementioned goals, this thesis is quantifying the tolerance level of LPWANs in high interference level environments and suggests methods that will make the co-existence of these networks more sustainable. It also demonstrates that LPWANs can be used in healthcare and safety contexts with a use case of a long-range emergency system. Finally, this thesis provides evidence that LPWAN is a good fit for sports technology applications as it presents a use case where long range time synchronization is offered for a kayak training application using LPWAN.

  • The emerging phase of young star clusters, constraints for UV photons leakage in local galaxies

    Author: Lorenza Della Bruna
    Publication date: 2020-09-04 11:48
  • NK Cell Cytotoxicity at the Single Cell Level

    Author: Ludwig Brandt
    Publication date: 2020-09-03 14:05

    Natural killer (NK) cells are innate immune cells with the ability to recognize and eliminate virally infected cells and cancer cells without prior sensitization. There is a functional heterogeneity between individual NK cells, where some NK cells are more efficient at killing cancer cells than others. Methods that allow studies of single NK cells are required to understand the functional differences and how they correlate with the activation and development status of the NK cell.

    This thesis focuses on the development and implementation of microchip- based imaging of NK cells, which is covered in five papers. Paper I presents a microchip screening platform for assessment of the cytotoxic potential of individual NK cells, by confining single NK cells together with target cells in microwells, followed by microscopy screening over extended time periods and automated image analysis. In paper II, the microchip platform was applied to test the ability of a novel trispecific killer engager (TriKE) to mediate an NK cell-dependent immune response. The process of NK cell education was studied in paper III and for that the image analysis methods for the microchip platform was further developed, in order to reveal new insight into how the education process affects the cytotoxic function of single NK cells. In paper IV, a previously developed microchip assay was extended to study NK cell migration and cytotoxicity in a more in vivo-like 3D collagen matrix. Paper V shows how NK cells can eliminate platelets in the presence of anti-platelet antibodies.

    In summary, this thesis covers the development and applications of time- lapse imaging using microwells for studying important NK cell functions in different settings. Understanding NK cell heterogeneity has the potential for improving e.g. cancer cell therapies.

  • Dynamic soil-structure interaction of simply supported high-speed railway bridges

    Author: Johan Lind Östlund
    Publication date: 2020-09-03 12:31

    Research performed on the subject of dynamic soil-structure interaction (SS) concerning railway bridges is presented in this thesis with the focus on simply supported railway bridges supported by shallow foundations in soil strata on bedrock. The research aims to obtain insight into the SSI of high-speed railway bridges and to provide recommendations on how to model the soil-bridge system from a design perspective.

    A three-dimensional (3D) simply supported soil-bridge model was first developed and the effects from model assumptions made on the soil-foundation system was evaluated in a 3D setting (paper I). The soil-foundation system was then refined and a model assumptions study was performed in order to evaluate the effects of model assumptions on impedance functions, including the influence of the permanent load acting on the soil-foundation system (paper II). Finally, a study of the assembled soil-bridge system was performed in an extensive parametric study including a set of 2D bridge models in combination with a set of shallow foundations in soil strata on bedrock (paper III). A supplementary section related to paper III was also added in this thesis, showing the effects of the substructure mass.

    The model assumptions made when creating the soil-foundation model and the soil-bridge model can be very important and must be made with care. The permanent load acting on the soil-foundation systems of shallow foundations may alter the impedance functions significantly. The substructure mass may alter the behavior of the soil-bridge system depending on its magnitude, and neglecting it gives inaccurate results. The 3D effects of SSI do not cause high vibrations due to modes other than the first bending mode, and assuming a 2D bridge model is generally acceptable.

    The effects of SSI on the soil-bridge systems with shallow soil strata are largely dependent on the ratio between the natural frequency of the bridge and the fundamental frequency of the soil. Depending on the value of this ratio, the effect of including SSI in bridge models may contribute to the bridge obtaining a negligible, conservative, or non-conservative response, as compared to the bridge with the assumption of non-flexible supports.

  • Engineering enzymes towards biotherapeutic applications using ancestral sequence reconstruction

    Author: Natalie Hendrikse
    Publication date: 2020-09-02 15:53

    Enzymes are versatile biocatalysts that fulfill essential functions in all forms of life and, therefore, play an important role in health and disease. One specific application of enzymes in life science is their use as biopharmaceuticals, which typically benefits from high catalytic activity and stability. Increased stability and activity are both desirable properties for biopharmaceuticals as they are directly related to dosage, which in turn affects administration time, cost of production and potency of a drug. The aim of the work presented in this thesis is to enhance the therapeutic potential of enzymes by means of enzyme engineering, in particular using ancestral sequence reconstruction. In Paper I, we established the utility of this method in a model system and obtained ancestral terpene cyclases with increased activity, stability and substrate scope. In Paper II, we described the successful crystallization of the most stable ancestral terpene cyclase, which allowed for rational design of substrate specificity. Finally, we applied the method to two therapeutically relevant enzyme families associated with rare metabolic disorders. We obtained ancestral phenylalanine/tyrosine ammonia-lyases with substantially enhanced thermostability and long-term stability in Paper III and ancestral iduronate-2-sulfatases with increased activity in Paper IV. In summary, the results presented herein highlight the potential of ancestral sequence reconstruction as a method to obtain stable enzyme scaffolds for further engineering and to enhance therapeutic properties of enzymes.

  • Cryo-EM Studies of Macromolecular Complexes from Photosynthetic Organisms

    Author: Annemarie Perez Boerema
    Publication date: 2020-09-02 09:00

    Plants, algae, and cyanobacteria convert light energy into chemical energy through the process of photosynthesis, fueling the planet and making life as we know it possible. Photosystem I (PSI) is one of the main photosynthetic complexes, responsible for this process. PSI uses the energy of light to transfer electrons from the soluble electron carrier plastocyanin, on the lumenal site of the thylakoid membrane, to ferrodoxin, on the stromal site of the membrane. Thus, playing a key role in the light dependent reactions. In order to survive many photosynthetic organisms need to be able to adapt to fluctuations in light and have adapted their photosynthetic machinery accordingly. In recent years many advances have been made in electron cryo-microscopy, making it possible to visualize many previously elusive photosynthetic complexes. This has brought a wealth of information on the structural adaptations of PSI.

    In plants and algae, PSI is hosted by the chloroplast, a specialized organelle that houses the photosynthetic reactions. In the chloroplast, key components of PSI are synthesized by the chloroplasts own translation machinery: the chloroplast ribosome. Translation in the chloroplast is remarkable as it has to synchronize translation in two different genetic compartments as well as adapt to fluctuations in light. A glimpse of how this machinery has evolved to be able to fulfill all of these duties can be obtained from its three dimensional structure and its chloroplast specific features. However, despite all this structural information providing valuable clues as to the functioning of these systems, there are still many aspects of how they play a role that still remain unknown.

  • RNA Polymerase I regulation by chromatin remodelling

    Author: Yuan Guo
    Publication date: 2020-09-02 09:00

    Cell proliferation and growth is correlated with effective protein synthesis and ribosome biogenesis. The transcription of the 47S pre-ribosomal RNA by RNA Polymerase I (RNA Pol I) machinery is the rate-limiting step of ribosome biogenesis and can accounts for more than 50% of total cellular transcription. RNA Polymerase I transcription is a highly energy-consuming process which requires regulation at various stages.

    In the work presented in this thesis, we have investigated the regulation of RNA Pol I transcription, and investigated the stress response triggered by impaired RNA Pol I transcription. We showed in study I that the ATP dependent chromatin remodelling complex B-WICH is required to maintain an open chromatin landscape at the ribosomal DNA (rDNA) gene promoter in order to allow for transcription initiation by RNA Pol I. In absence of B-WICH, the NuRD complex reconfigures the chromatin landscape to an inaccessible state. We showed in study II that impairment of RNA Pol I transcription by deleting WSTF, a core subunit of B-WICH resulted in cell cycle arrest and apoptosis. More severe inhibition of RNA Pol I transcription through chemical compounds resulted in activation of cellular stress response cascades including but not limited to cell cycle arrest, unfolded protein response and oxidative stress response. We showed in study III that RNA Pol I transcription was increased during epithelial-mesenchymal transition (EMT) in the context of development and disease. The association of the EMT-driving transcription factor SNAIL1 with the rDNA gene promoter was shown to be essential in EMT triggered RNA Pol I transcription. The work presented in this thesis demonstrates the importance of RNA Pol I transcription regulation in maintaining cellular homeostasis.

  • The transition to a bio-based economy : Toward an integrated understanding

    Author: Therese Bennich
    Publication date: 2020-09-02 09:00

    The bio-based economy has gained increasing attention in societal and academic debates over the past two decades, and is argued to hold solutions to several pressing sustainability challenges. However, it is not yet clear if the high-reaching aspirations of the bio-based economy can be realized. The bio-based economy discourse has been criticized for being promissory, vague, and single-sector focused, thereby overlooking larger systemic impacts, trade-offs, and unintended consequences that may result from pursuing the goals of the bio-based economy. Against this background, this thesis aims to advance an integrated and systemic understanding of the transition to a bio-based economy and what it implies for sustainability. Sweden is used as an empirical case, where specific bio-based economy goals, as well as their interactions and sustainability outcomes, are examined. The focus is primarily on developments in the forestry, agriculture, and energy sectors. The analysis also seeks to identify how goals related to the bio-based economy are interconnected with goals promoted by parallel sustainability initiatives, specifically the 2030 Agenda and the associated Sustainable Development Goals (SDGs). Integration is achieved by using systems analysis tools and methods. Further, the weak and strong sustainability paradigms, and the opposing definitions of sustainability they provide, are used to assess the contribution of the bio-based economy to sustainability. 

    The integrated analysis provides a detailed and operational conceptualization of transition pathways to a Swedish bio-based economy. The goals of the Swedish bio-based economy are divergent and broad-reaching, emphasizing that there is no general agreement on what the transition to a bio-based economy entails. The results point to multiple barriers that need to be addressed to realize the goals of the Swedish bio-based economy. Goal conflicts constitute one such barrier. These are found internal to as well as across the bio-based economy and the parallel 2030 Agenda. Additional hindrances include policy resistance, negative cross-sectoral spillovers, and patterns of path dependency. However, the results also highlight several opportunities for supporting the transition process in a Swedish context. These opportunities include the identification of goals and interventions with synergetic potential, which offer a basis for developing efficient implementation strategies with high systemic impact. There is also large potential to support cross-sectoral collaboration and learning, based on shared interests and challenges. Finally, the results emphasize the importance of better understanding and addressing perceptions about risk, conflict, legitimacy, and trust in the transition process.

    In terms of the overarching question of what the bio-based economy implies for sustainability, the results find that the bio-based economy has been contributing to developments that align primarily with weak sustainability. From the perspective of the strong sustainability paradigm, the prospects of the bio-based economy are less promising, potentially leading to outcomes that could worsen ongoing environmental and social issues. For the future, fundamental changes to the way the bio-based economy is conceptualized and implemented are needed for it to contribute to sustainability according to the notion of strong sustainability.

  • Random Graph and Growth Models

    Author: Sebastian Rosengren
    Publication date: 2020-09-02 09:00

    Random graphs is a well-studied field of probability theory, and have proven very useful in a range of applications — modeling social networks, epidemics, and structures on the Internet to name a few. However, most random graphs are static in the sense that the network structure does not change over time. Furthermore, standard models also tend to consist of single-type objects. This puts restrictions on possible applications. The first part of this thesis concerns random graphs with a focus on dynamic and multi-type extensions of standard models. The second part of the thesis deals with random growth models. Random growth models are important objects in probability theory and, as the name suggests, models the random growth of some entity. Typical examples include infectious disease spread; how a liquid flows through a random medium; and tumor growth. The growth of these models, properly scaled by time, tends to be deterministic. The second theme of the thesis concerns the final shape of the growing entity for two standard random growth models.

    In Paper I, we study a dynamic version of the famous Erdős-Rényi graph. The graph changes dynamically over time but still has the static Erdős-Rényi graph as its stationary distribution. In studying the dynamic graph we present two results. The first result concerns the time to stationarity, and the second concerns the time it takes for the graph to reach a certain number of edges. We also study the time until a large component emerges, as well as how it emerges.

    In Paper II, we introduce and study an extension of the preferential attachment tree. The standard version is already dynamic, but its vertices are only allowed to be of one type. We introduce a multi-type analog of the preferential attachment tree and study its asymptotic degree distributions as well as its asymptotic composition.

    Paper III concerns the configuration model — a random graph neither dynamic nor multi-type — and we break with the first theme of the thesis since no extensions are made to the model. Instead, we argue that the size of the largest component in the model does not depend on the tail of the degree distribution, but rather on the distribution over small degrees. This is quantified in some detail.

    In Paper IV, we consider the frog model on Zd and a two-type extension of it. For the one-type model, we show that the asymptotic shape does not depend on the initial set and the particle configuration there. For the two-type model, we show that the possibility of both types to coexist also does not depend on the initial sets and the particle configurations there.

    Paper V is concerned with the predictability of the set of discovered sites generated by the first passage percolation model. First passage percolation has the property that the set of discovered sites, scaled properly by time, converges to some deterministic set as time grows. Typically, not much is known about this set, and to get an impression of it simulations are needed. Using simulated data we show that it is possible to use a neural network to adequately predict the shape, on this dataset, from some easily calculable properties of the passage times. The purpose of the paper is to give researchers a proof of concept of this method as wells as a new tool for quickly getting an impression of the shape.

  • Short and long-term effects of exposure to low dose and low dose rate of gamma radiation : using in vitro and in vivo models

    Author: Traimate Sangsuwan
    Publication date: 2020-09-02 09:00

    Assessment of human health risks from exposure to ionizing radiation (IR) is mainly based on the extrapolation of results from epidemiological studies on populations exposed to relatively high doses and often at high dose rates (HDR). Risk estimates after exposure to low doses and in particular at low dose rates (LDR) remain controversial due to a lack of epidemiological evidence. Therefore, high priority is given to strengthening the evidence on which risk assessments can be based for low doses and LDR. It is known that the cytotoxicity of radiation decreases by decreasing dose rate. Less is known about the effects of LDR on mutation rates and premature senescence compared to HDR. We established 2 cell lines with low expression of two proteins, MTH1 or MYH, both involved in the protection of cells from mutation induction by reactive oxygen species (ROS). The cells were exposed to different doses at different dose rates, and the levels of mutation were studied. The results showed a possible dose-rate threshold for mutations for the MTH1/MYH double knockdown cells.

    Next, we studied the effect of dose rate on adaptive response (AR). AR is defined as the ability of a low dose of ionizing radiation to induce enhanced resistance in cells subsequently exposed to a high dose. We established dose response relations for survival and mutations for MCF-10A cells exposed/non-exposed to an adaptive dose of 50 mGy at different dose rates, followed by exposure to different high doses. We found no protective effect of 50 mGy on survival. However, we observed that 50 mGy the adaptive dose reduced the mutation frequency induced by 1 Gy challenging dose. The protection level was higher when 50 mGy was delivered at LDR.

    A significant amount of data suggests that oxidative stress, induced for example by LDR, can contribute to senescence. We cultured VH10 cells, beginning with passage 13, during chronic LDR exposure. The cells were passaged every week for 6 weeks until they stopped proliferating due to premature senescence at passage 19. Passage 8 VH10 cells were cultured correspondingly but without irradiation until they stopped proliferating at passage 23 in response to replicative senescence. The DNA repair kinetics and the levels of DNA damage that were localized in the telomeres of young, middle-aged, premature senescent and replicative senescent cells were investigated. The young cells repaired DSB significantly faster than the senescent cells; premature and replicative senescent cells accumulated more DNA damage in the telomeres; and as compared to middle-aged cells, young cells cope with oxidative stress of chronic irradiation more effectively.

    The transgenerational effects of IR were studied in Drosophila embryos. The exposed embryos were followed up for abnormality during embryogenesis until adult stage and up to 12 generations. We found that radiation induced an A5pig- phenotype (depigmented area in the A5 segment of the male body) that was transmitted up to 12 generations. This phenomenon did not follow the Mendelian inheritance model, which indicates the influence of mechanisms other than mutagenesis e.g. epigenetic mechanism.

    We showed that; LDR is less cytotoxic than HDR but both induce equal levels of mutation per unit dose; LDR induces premature senescence; LDR may be more effective than HDR in inducing adaptive response; and LDR and HDR exposure of Drosophila embryos can induce an abnormal phenotype that can be transmitted through generations.

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