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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.
  • Development of rotation electron diffraction as a fully automated and accurate method for structure determination

    Author: Bin Wang
    Publication date: 2019-05-16 09:00

    Over the past decade, electron diffraction methods have aroused more and more interest for micro-crystal structure determination. Compared to traditional X-ray diffraction, electron diffraction breaks the size limitation of the crystals studied, but at the same time it also suffers from much stronger dynamical effects. While X-ray crystallography has been almost thoroughly developed, electron crystallography is still under active development. To be able to perform electron diffraction experiments, adequate skills for using a TEM are usually required, which makes ED experiments less accessible to average users than X-ray diffraction. Moreover, the relatively poor data statistics from ED data prevented electron crystallography from being widely accepted in the crystallography community.

    The thesis focused on both application and method development of continuous rotation electron diffraction (cRED) technique. The cRED method was first applied to a beam sensitive metal-organic framework sample, Co-CAU-36, and the structure was determined and refined within one working day. More importantly, the guest molecules in the pores were also located using only electron diffraction data. To facilitate general users to perform cRED data collection for useful data, software was developed to automate the overall data collection procedure. Through combination of hierarchical cluster analysis tools, the automatically collected data showed comparable quality to those from recent publications, and thus were useful for structure determination and even phase identification. To deal with dynamical refinement for ED data, a frame orientation refinement algorithm was designed to calculate accurate frame orientations for rotation data. Accuracy for the method was validated and compared to an existing software, and the behavior of TEM goniometer was studied by applying the method to an experimental data set.

  • Kan man räkna med PISA och TIMSS? : Relevansen hos internationella storskaliga mätningar i matematik i en nationell kontext

    Author: Samuel Sollerman
    Publication date: 2019-05-16 09:00

    The overall purpose of the thesis is to contribute to the knowledge of relevance of international large-scale assessments (ILSAs) in mathematics, when these are to be used and interpreted in a national context. If a nation is to engage in ILSAs, draw conclusions from them and act on them, one should be aware of what they are measuring and how well it fits in with the national mathematics education and the mathematics they are trying to teach their students.

    The relevance is linked to the validity of the ILSA, which means that the assessment should measure the right things and do that in such a way that the results are as informative and useful as possible. In this thesis, the Swedish context is used as an example of a national context, against which the ILSAs PISA and TIMSS are contrasted.

    One way to study validation is to use an argumentation-based validation method, Assessment Utilization Argument. In this model, an argument consists of making claims on the basis of data and warrants. The claim is an interpretation of assessment results and the assertion of a claim carries with it the duty to support the claim and, if challenged, to defend it. Warrants are created and functions as propositions to justify the inferences from the data that lead to the claim.

    The ILSAs have been contrasted with the Swedish context through studies in three areas; content of the assessments, implementation of the assessments and results from the assessments. Based on these areas, the frameworks and tests from ILSAs were analyzed and compared with policy document and national tests from the Swedish context. Warrants were created based on these three areas.

    The analysis of the warrants showed that the ILSAs had a high level of conformity with the Swedish context and the ILSAs coincide in such a way that the results from these are relevant for studying the development of performance in a Swedish context. The analysis also showed that certain content and abilities in the Swedish context were not covered by the ILSAs. The Swedish students do not have the opportunity to show all those skills that the Swedish mathematical context covers and there were also indications that they do not make full efforts to show their skills. In order to create a more complete picture of Swedish students' mathematical skills, the assessment of students’ skills in mathematics should be complemented with other assessments.

    The results are discussed in relation to the development of national policy documents, including the risk if a nation decides to adapt their policy document to the ILSAs. In the case of Sweden there are indications that policy document develops in the same direction and closer to the frameworks of ILSAs. It becomes important to thoroughly examine the relationship between the ILSAs and a national context so that one can be aware of how, if and it what way the large-scale assessment impact a national context.

    This thesis contributes to a holistic approach based on a national context, with an overall method and covers the areas content, implementation and results of the ILSAs. It shows that opportunities and limitations can be found in all of these three areas. When the results of ILSAs are to be used in a national context, it is important to thoroughly examine what is meant to be assessed and what is really being assessed in these studies and to compare it with the purposes and content of the national context, so that suitable and valid conclusions could be drawn.

  • Functional genomics of diapause in two temperate butterflies

    Author: Peter Pruisscher
    Publication date: 2019-05-13 09:00

    Natural selection will act on a given phenotype to maximize fitness in a particular environment, even if this would result in reduced fitness in other environments. In insects some of the strongest selection pressures act on timing life cycles to seasonal variation in environmental conditions, in order to maximize growth, reproduction, and to anticipate the onset of winter. Many temperate insects survive winter by entering a pre-programmed state of developmental arrest, called diapause. The decision to induce diapause is predominantly based on measuring day length. Populations have adapted to latitudinal variation in photoperiod, thereby synchronizing with local seasonal variation. However, there is no general understanding of the genetic basis for controlling diapause induction, maintenance and termination. In this thesis I aimed to gain a better understanding of the genetic basis underlying variation in the induction decision, as well as to gain insights into gene expression changes during diapause in temperate butterflies.

     

    I started by revealing local adaptation in the photoperiodic response of two divergent populations of Pieris napi (Paper I). I found that variation in diapause induction among populations of both P. napi and Pararge aegeria showed strong sex-linked inheritance in inter-population crosses (Paper I and II). The genome-wide variation across populations was relatively low in both species. However, there was strong divergence in genomic regions containing the circadian clock genes timeless and period in P. aegeria, and period, cycle, and clock in P. napi. The genetic variation in these specific regions segregated between diapausing and direct developing individuals of inter-population crosses, showing that allelic variation at few genes with known functions in the circadian clock correlated to variation in diapause induction (Paper II and III).

     

    Furthermore, I investigated the transcriptional dynamics in two tissues (head and abdomen) during diapause (Paper IV). Already at the first day of pupal development there are on average 409 differentially expressed genes (DEG) each up and down regulated between the direct development and diapause pathways, and this increases dramatically across these formative stages to an average of 2695. Moreover, gene expression is highly dynamic during diapause, showing more than 2600 DEG’s in the first month of diapause development, but only 20 DEG’s in the third month. Moreover, gene expression is independent of environmental conditions, revealing a pre-programmed transcriptional landscape that is active during the winter. Still, adults emerging from either the direct or diapause pathways do not show large transcriptomic differences, suggesting the adult phenotype is strongly canalized.

     

    Thus, by integrating whole-genome scans with targeted genotyping and bulk-segregant analyses in population crosses, I demonstrate that adaptive variation in seasonal life cycle regulation in the two butterflies P. napi and P. aegeria both converge on genes of the circadian clock, suggesting convergent evolution in these distantly related butterflies.

    Moreover, the diapause program is a dynamic process with a distinct transcriptional profile in comparison to direct development, showing that on a transcriptome level diapause development and direct development are two distinct developmental strategies.

  • Factors modifying cellular response to ionizing radiation

    Author: Lei Cheng
    Publication date: 2019-05-13 09:00

    Many physical factors influence the biological effect of exposure to ionizing radiation, including radiation quality, dose rate and temperature. This thesis focuses on how these factors influence the outcome of exposure and the mechanisms behind the cellular response. 

    Mixed beam exposure, which is the combination of different ionizing radiations, occurs in many situations and the effects are important to understand for radiation protection and effect prediction. Recently, studies show that the effect of simultaneous irradiation with different qualities is greater than simple additivity of single radiation types, which is called a synergistic effect. But its mechanism is unclear. In Paper I, II and III, alpha particles and X-rays were used to study the effect of mixed beams. Paper I shows that mixed exposure induced a synergistic effect in generating double strand breaks (DSB), and these DSB were repaired by slow kinetics in U2OS cells. In Paper II, alkaline comet assay was applied to investigate the induction and repair of DNA lesions including DSB, single strand breaks and alkali labile sites in peripheral blood lymphocytes (PBL). We demonstrate that mixed beams interact in inducing DNA damage and influencing DNA damage response (DDR), which result in a delay of DNA repair. Both in Paper I and II, mixed beams showed a capability in inducing higher activity of DDR proteins than expected from additivity. Paper III investigates selected DDR-related gene expression levels after exposure to mixed beams in PBL from 4 donors. Synergy was present for all donors but the results suggested individual variability in the response to mixed beams, most likely due to life style changes.

    Low temperature at exposure is radioprotective at the level of cytogenetic damage. In Paper IV, data indicate that this effect is through promotion of DNA repair, which leads to reduced transformation of DNA damage into chromosomal aberrations.  

    Paper V aims to compare the biological effectiveness of gamma radiation delivered at a very high dose rate (VHDR) with that of a high dose rate (HDR) in order to optimize chronic exposure risk prediction based on the data of atomic bomb survivors. The results suggest that VHDR gamma radiation is more effective in inducing DNA damage than HDR.     

  • Combinatorics and zeros of multivariate polynomials

    Author: Nima Amini
    Publication date: 2019-05-10 10:26

    This thesis consists of five papers in algebraic and enumerative combinatorics. The objects at the heart of the thesis are combinatorial polynomials in one or more variables. We study their zeros, coefficients and special evaluations. Hyperbolic polynomials may be viewed as multivariate generalizations of real-rooted polynomials in one variable. To each hyperbolic polynomial one may associate a convex cone from which a matroid can be derived - a so called hyperbolic matroid. In Paper A we prove the existence of an infinite family of non-representable hyperbolic matroids parametrized by hypergraphs. We further use special members of our family to investigate consequences to a central conjecture around hyperbolic polynomials, namely the generalized Lax conjecture. Along the way we strengthen and generalize several symmetric function inequalities in the literature, such as the Laguerre-Tur\'an inequality and an inequality due to Jensen. In Paper B we affirm the generalized Lax conjecture for two related classes of combinatorial polynomials: multivariate matching polynomials over arbitrary graphs and multivariate independence polynomials over simplicial graphs. In Paper C we prove that the multivariate $d$-matching polynomial is hyperbolic for arbitrary multigraphs, in particular answering a question by Hall, Puder and Sawin. We also provide a hypergraphic generalization of a classical theorem by Heilmann and Lieb regarding the real-rootedness of the matching polynomial of a graph. In Paper D we establish a number of equidistributions between Mahonian statistics which are given by conic combinations of vincular pattern functions of length at most three, over permutations avoiding a single classical pattern of length three. In Paper E we find necessary and sufficient conditions for a candidate polynomial to be complemented to a cyclic sieving phenomenon (without regards to combinatorial context). We further take a geometric perspective on the phenomenon by associating a convex rational polyhedral cone which has integer lattice points in correspondence with cyclic sieving phenomena. We find the half-space description of this cone and investigate its properties.

  • Statistical methods for detecting gene-gene and gene-environment interactions in genome-wide association studies

    Author: Mattias Frånberg
    Publication date: 2019-05-07 17:03

    Despite considerable effort to elucidate the genetic architecture of multi-factorial traits and diseases, there remains a gap between the estimated heritability (e.g., from twin studies) and the heritability explained by discovered genetic variants. The existence of interactions between different genes, and between genes and the environment, has frequently been hypothesized as a likely cause of this discrepancy. However, the statistical inference of interactions is plagued by limited sample sizes, high computational requirements, and incomplete knowledge of how the measurement scale and parameterization affect the analysis.

    This thesis addresses the major statistical, computational, and modeling issues that hamper large-scale interaction studies today. Furthermore, it investigates whether gene-gene and gene-environment interactions are significantly involved in the development of diseases linked to atherosclerosis. Firstly, I develop two statistical methods that can be used to study of gene-gene interactions: the first is tailored for limited sample size situations, and the second enables multiple analyses to be combined into large meta-analyses. I perform comprehensive simulation studies to determine that these methods have higher or equal statistical power than contemporary methods, scale-invariance is required to guard against false positives, and that saturated parameterizations perform well in terms of statistical power. In two studies, I apply the two proposed methods to case/control data from myocardial infarction and associated phenotypes. In both studies, we identify putative interactions for myocardial infarction but are unable to replicate the interactions in a separate cohort. In the second study, however, we identify and replicate a putative interaction involved in Lp(a) plasma levels between two variants rs3103353 and rs9458157. Secondly, I develop a multivariate statistical method that simultaneously estimates the effects of genetic variants, environmental variables, and their interactions. I show by extensive simulations that this method achieves statistical power close to the optimal oracle method. We use this method to study the involvement of gene-environment interactions in intima-media thickness, a phenotype relevant for coronary artery disease. We identify a putative interaction between a genetic variant in the KCTD8 gene and alcohol use, thus suggesting an influence on intima-media thickness. The methods developed to support the analyses in this thesis as well as a selection of other prominent methods in the field is implemented in a software package called besiq.

    In conclusion, this thesis presents statistical methods, and the associated software, that allows large-scale studies of gene-gene and gene-environment interactions to be effortlessly undertaken.

  • Theoretical Studies on Water Oxidation Catalysts - from Solvent to Interfaces

    Author: Shaoqi Zhan
    Publication date: 2019-05-06 15:47

    Water splitting contains two half-reactions, the water oxidation reaction and the hydrogen reduction reaction. In water oxidation, protons and electrons will be generated to offer two elemental components for production of fuels, such as H2 and CH3OH. To overcome the overpotential of the reaction, a large amount of water oxidation catalysts (WOCs) have been synthesized. In the second chapter, a variety of homogeneous and heterogenous catalysts have been introduced. The homogeneous catalysts include Ru-based catalysts, Ir-based catalysts, and first-row transition metal-based catalysts. Among these catalysts, a family of Ru(bda)L2 complexes was found in experiment to have a comparable turnover frequency (TOF) at acidic pH with photosystem II. A similar catalyst, Ru(tda)(py)2, was found to have an impressive TOF of 50 000 s-1 at pH 10.0. The heterogenous catalysts include heterogenous oxide and heterogenized molecular catalysts that catalyze the reaction using either electrochemical driving force or photoelectrochemical driving force.

    Understanding the details of the mechanism can help to design a better catalyst with high catalytic performance. For this purpose, several theoretical methods have been applied. Density functional theory (DFT) was employed to study the rate limiting reaction in implicit solvent. The empirical valence bond (EVB) method is a powerful tool for describing environment effects. This approach was used to get insight into the solvent and surface effects on the reaction pathway. Molecular dynamics (MD) and potential of mean force (PMF) methods are applied to perform simulations for large systems at long time-scales.      

    The Ru(bda)L2 catalysts have been found to have high TOF, up to 1000 s-1 and react via an I2M (Interaction of two metal centers) pathway. By using B3LYP-D3 functional to study the diradical coupling of the O-O bond formation, we found that there is no intrinsic barrier between the two RuV=O fragments of RuV=O complexes. On the basis of the study of the solvent role on the reaction using an EVB-MD model, the oxo of the RuV=O species was shown to be hydrophobic. The hydrophobic oxo explained why the Ru(bda)L2 complexes proceed the reaction via the I2M pathway. To study the full dimerization of two separated RuV=O species in fully explicit solvent, we calculated the diffusion of individual catalysts from MD simulations, association of pre-reactive dimer from PMF simulations, and the coupling reaction in explicit solvation using the EVB approach. The formation of the prereactive dimer was found to be the sole determining factor for the efficiency of the Ru(bda)L2 catalysts. In the study of four Ru complexes with different equatorial ligands, the secondary coordination environments, such as flexibility, hydrophilicity were proposed to be the affecting the different catalytic pathways.

    To make an efficient electrocatalyst, the Ru(bda)L2 catalyst has been modified by Sun and co-workers with pyrene groups at the axial L-ligands to be adhered on the CNT functionalized electrodes. A computational model of the RuV=O catalyst tethered on the CNT surface was built to study the O-O bond formation in heterogenous system. By using the same combination of MD, PMF, and EVB, we studied the full dimerization reaction of the catalyst at CNT-water interfaces with full dynamics. The reasons for the lower the TOF of the surface catalyst and methods to improve the lower TOF were addressed in this study.

    With the pH dependent Ru(tda)(py)2 complex, we used the same combination methods and proposed a conceptually new function of the dangling carboxylate – the oxide relay. The oxide relay provides a highly nucleophilic oxygen atom close to the oxo to facilitate the O-O bond formation at the first step, and a highly electrophilic center to react with the OH- even at neutral pH at the second step. The rate-limiting step is the O-O bond formation at high pH, OH- nucleophilic attack at neutral pH.

    In summary, several key properties of the water oxidation catalyzed by Ru-based complexes, such as solvent and surface effects, hydrophobicity, and oxide relay have been investigated in detail by using several computational techniques. Our studies can shed light on the design of molecular WOCs with high catalytic activity and will help the development of artificial photosysnthesis devices.

  • Exploring fatty acid derivatives from renewable resources as raw materials for coating applications

    Author: Samer Nameer
    Publication date: 2019-05-06 15:33

    In the work presented herein, epoxy fatty acid derivatives were explored in the formation of thermosets for coating applications. The epoxy fatty acid derivatives were obtained from renewable resources such as birch tree bark and epoxidized linseed oil. The birch bark was used to isolate 9,10-epoxy-18-hydroxyoctadecanoic acid (EFA) and the epoxidized linseed oil was used to retrieve methyl stearate and 3 different epoxy methyl esters: epoxy methyl oleate/linoleate/linolenate (EMO/EMLO/EMLEN). The obtained epoxy fatty acid derivatives were used in resin formulations together with other reactants or in the synthesis of multifunctional oligomer resins using enzyme catalysis. All resins were cured using different polymerization techniques to form thermosets with a wide variety of properties.Multifunctional oligomer resin were synthesized using Candida Antarctica lipase-B (CALB) as enzyme. It was demonstrated that the synthesis was efficient and the oligomers were obtained from “one-pot” route. In addition, the selectivity of CALB was useful in preserving a variety of functional groups (epoxides, alkenes and thiols) in the final oligomers. The oligomers were cross-linked by either thiol-ene chemistry or cationic polymerization resulting in functional thermosets. It was further shown that surface properties of the cured thermosets could be changed by using post-functionalization.Pure fatty acid methyl esters cure into soft materials. An approach in increasing the thermal and mechanical properties was investigated. The 3 different epoxy functional methyl esters together with a furan-2,5-dicarboxylic acid derivative were investigated in the formation of thermosets. Glass transition temperature (Tg) below 0 °C and above 100 °C were obtained by varying the stoichiometric feed of the reactants.The thermal curing of EFA as a one-component system was investigated by model studies showing that a self-catalyzed process occur. EFA thermally cures into a thermoset without the need of an added catalyst. Furthermore, the thermoset showed adhesive properties.Crude mixture containing methyl stearate, EMO, EMLO and EMLEN obtained from epoxidized linseed oil were investigated as reactive diluent in coil-coatings. The mixture was also compared with commercially available reactive diluents such as fatty acid methyl esters (FAME) obtained from rapeseed oil. The results obtained showed that more fatty methyl esters could be incorporated in the final thermoset when using the epoxidized linseed oil fatty acid derivatives.Real-time Fourier-transform infrared spectroscopy (RT-FTIR) was used during most of the work presented in the thesis and proved to be a powerful tool in monitoring the different reactions and comparing relative reaction rates.

  • Structural and Functional Studies of Membrane Proteins : From Characterisation of a Fatty Acyl-CoA Synthetase to the Discovery of Superoxide Oxidase

    Author: Camilla A.K. Lundgren
    Publication date: 2019-05-06 09:00

    This thesis is divided into three parts; the first part describes a method for efficient screening of membrane proteins for crystallography. By utilising the properties of a folding reporter GFP it is possible to quickly and accurately screen the stability of a protein in a range of conditions without full purification. This allows rapid assessment of the suitability of a protein for crystallography and a parallel optimisation of purification conditions for subsequent large-scale protein production.

    The second part describes the discovery of a membrane bound superoxide oxidase (SOO), a novel scavenger of membrane proximal superoxide. SOO is a kinetically perfect enzyme, reacting at rates close to the diffusion limit in a similar fashion to other superoxide scavengers, such as superoxide dismutase. We propose that SOO rescues electrons “lost” to superoxide and recycles them back into the respiratory chain, releasing oxygen. At the same time SOO contributes to the proton motive force by uptake of protons from the cytoplasmic side of the membrane.

    The third part concerns the fatty acyl-CoA synthetase FadD13 from Mycobacterium tuberculosis (M. tuberculosis). It represents a critical node point in M. tuberculosis lipid metabolism and has been suggested to be a vital component of M. tuberculosis survival in host cell macrophages. FadD13 harbours a hydrophobic cavity that is unable to house the very-long-chain substrates the enzyme has preference for. We propose that FadD13 is a peripheral membrane protein, utilising the membrane to house the very-long-chain fatty acid substrates during the activation reaction.

  • Unravelling Sustainability : The complex dynamics of emergent environmental governance and management systems at multiple scales

    Author: Lucas Dawson
    Publication date: 2019-05-06 09:00

    This thesis adopts a complex systems approach to investigate the dynamic emergence of sustainable environmental governance and management systems in multiple contexts in Europe. Accelerating rates of environmental degradation across the world have called the legitimacy of previous environmental governance and management arrangements into question. Top-down, linear optimisation approaches have failed to account for the inherent complexity of social-ecological systems, upon which human society is entirely reliant for long-term survival. Systemic interdependence between ecological and human systems underscores the “wicked” nature of environmental problems, which are characterised by multi-dimensional values and competing interests among stakeholders and actors at multiple levels and across divergent spatial and temporal scales. Sustainability objectives therefore mandate the evolution of new environmental governance and management systems that are capable of engaging with complexity and dynamism. Employing a methodology based on comprehensive literature assessment, case studies and qualitative systems modelling methods, this thesis clearly identifies the structurally complex systems within which studied environmental governance and management arrangements took place. However, the degree to which these systems indicated the emergence of integrated and/or adaptive approaches, proposed by recent sustainability theories, was more uneven across governance levels and contexts. Key constraints related to the continued dominance of top-down institutional and regulatory frameworks, the availability of adequate inputs (primarily financial) for new approaches and initiatives, socio-cultural influences, and to the complexity and concomitant uncertainty of social-ecological system dynamics. Identified opportunities from across cases related to supra-national institutions, a shift of value preferences amongst stakeholders, and the perverse opportunities arising from chronic environmental degradation and/or acute social/ecological crises. Strategies enabling emergent governance and management approaches included strengthening the legitimacy of new actors, actively managing and integrating the perceptions of stakeholders, learning by doing and sharing, and recruiting and enabling active, hybridised leadership. Importantly, key constraints and opportunities remain largely out of reach for actors and stakeholders at lower levels. Feedback mechanisms by which bottom-up initiatives can influence higher level institutional development are lacking, poorly understood, or are dominated by long delays. These dynamics impede sustainability transitions.

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