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  • Public defence: 2016-12-07 09:00 Gunnesalen, Uppsala
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    ­­­Visual assessment of perfusion and metabolism in neurodegenerative dementia2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A worldwide demographic shift is currently occurring, with rapidly increasing numbers of elderly individuals. Since the incidence of neurodegenerative disease generally increases with age, this entails an increase in dementia prevalence. There are several strong incentives for establishing robust and widely available imaging methods for the early diagnosis of these diseases. Atrophy patterns are evident only late in the disease process, and the distinction from healthy ageing can often be elusive. For early diagnosis, physiologic parameters such as perfusion or metabolism must be assessed. The available modalities all have restricted clinical usefulness. The main aim of this thesis was to advance the clinical usefulness of perfusion and metabolism imaging in patients with neurodegenerative dementia, with a focus on visual assessment.

    A cohort of patients with neurodegenerative dementia was included, along with an age-matched control group. All subjects underwent MRI, including a pseudocontinuous ASL sequence and FDG-PET. In papers II and III, a subgroup containing both patients and controls underwent a second FDG-PET with reduced dose. In paper IV, the material was combined with a similar cohort from Amsterdam.

    Paper I showed that spatial smoothing increased the correlation between visually assessed perfusion and metabolism levels as displayed with FDG-PET. However, the distinction between patients and healthy controls was less satisfactory due to false positives.

    Paper II showed that differences in regional standard uptake value ratios between normal- and low-dose FDG-PET were small and without clinically significant bias.

    Paper III showed that the diagnostic performance of Z-score maps showing regions of significant deficits in metabolism was highly similar in normal- and low-dose FDG-PET images. 

    Paper IV showed that ASL perfusion-based Z-score maps can be used for diagnostic purposes with high specificity, but inferior sensitivity, compared to FDG-PET.

    In conclusion, the included studies address aspects of the visual assessment of perfusion and metabolism neuroimaging, with a focus on clinical usefulness in diagnosing neurodegenerative dementia.

  • Public defence: 2016-12-07 13:00 80101, Uppsala
    Hong, Yue
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Hong, Yue
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Numerical Modelling and Mechanical Studies on a Point Absorber Type Wave Energy Converter2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Oceans cover two thirds of the Earth’s surface and the energy potential of ocean waves as a renewable energy source is huge. It would therefore be a tremendous achievement if the vast mechanical energy in waves was converted into a form of energy that could be used successfully by society. For years, scientists and engineers have endeavored to exploit this renewable energy by inventing various generators designed to transform wave energy into electrical energy. Generally, this sort of generator is called a Wave Energy Converter (WEC).

    In this thesis, the research is based on the WEC developed in the Lysekil Project. The Lysekil Project is led by a research group at Uppsala University and has a test site located on the west coast of Sweden. The project started in 2002. So far, more than ten prototypes of the WEC have been deployed and relevant experiments have been carried out at the test site. The WEC developed at Uppsala University can be categorized as a point absorber. It consists of a direct-drive linear generator connected to a floating buoy. The linear generator is deployed on the seabed and driven by a floating buoy to extract wave energy. The absorbed energy is converted to electricity and transmitted to a measuring station on land.

    The work presented in this thesis focuses on building a linear generator model which is able to predict the performance of the Lysekil WEC. Studies are also carried out on the damping behavior of the WEC under the impact of different sea climates. The purpose is to optimize the energy absorption with a specific optimal damping coefficient. The obtained results indicate an optimal damping for the Lysekil WEC which can be used for optimizing the damping control.

    Additionally, the impact two central engineering design features (the translator weight and the stroke length) are investigated. The aim is to find a reasonable structural design for the generator which balances the cost and the energy production.

  • Public defence: 2016-12-08 09:15 Enghoffsalen, Uppsala
    Kretzschmar, Moritz Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Kretzschmar, Moritz Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ventilation/Perfusion Matching and its Effect on Volatile Pharmacokinetics2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The mismatching of alveolar ventilation and perfusion (VA/Q) is the major determinant of impaired gas exchange. The gold standard for analyzing VA/Q distribution is the multiple inert gas elimination technique (MIGET), conventionally based on gas chromatography (GC), and, although simple in principle, a technically demanding procedure limiting its use. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) combined MIGET with mass spectrometry, simplifying the sample handling process, and potentially providing VA/Q distributions for a general clinical approach.

    The kinetics of volatile anesthetics are well known in patients with healthy lungs. The uptake and distribution of inhaled anesthetics have usually been modeled by physiologic models. However, these models have limitations, and they do not consider ventilation/perfusion matching. Respiratory diseases account for a large part of morbidity and mortality and are associated with pulmonary VA/Q mismatch that may affect uptake and elimination of volatile anesthetics.

    The objectives of the studies were firstly to investigate assessment of VA/Q mismatch by MMIMS and secondly to investigate the effects of asthma-like VA/Q mismatch on the kinetics of volatile anesthetics in an experimental porcine model.

    Anesthetized and mechanically ventilated piglets were studied.

    In study I, a direct comparison of MIGET by MMIMS with the conventional MIGET by GC in three animal models that covered a wide range of VA/Q distributions was preformed. The two methods agreed well, and parameters derived from both methods showed good agreement with externally measured references.

    In studies II–IV, a stable method of inducing and maintaining asthma-like VA/Q mismatch with methacholine (MCh) administration was established, and the effect of VA/Q mismatch on the pharmacokinetics of desflurane and isoflurane was investigated. The present model of bronchoconstriction demonstrates a delay in volatile anesthetic uptake and elimination, related to the heterogeneity of MCh-inhalation induced ventilation. The difference in solubility of volatile anesthetics has a significant influence on their uptake and elimination under VA/Q mismatch. The higher blood soluble isoflurane is affected to a lesser degree than the fairly insoluble desflurane.

  • Public defence: 2016-12-09 09:15 Häggsalen, Uppsala
    Sjökvist, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Sjökvist, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Demagnetization and Fault Simulations of Permanent Magnet Generators2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Permanent magnets are today widely used in electrical machines of all sorts. With their increase in popularity, the amount of research has increased as well. In the wind power project at Uppsala University permanent magnet synchronous generators have been studied for over a decade. However, a tool for studying demagnetization has not been available. This Ph.D. thesis covers the development of a simulation model in a commercial finite element method software capable of studying demagnetization. Further, the model is also capable of simulating the connected electrical circuit of the generator. The simulation model has continuously been developed throughout the project. The simulation model showed good agreement compared to experiment, see paper IV, and has in paper III and V successfully been utilized in case studies. The main focus of these case studies has been different types of short-circuit faults in the electrical system of the generator, at normal or at an elevated temperature. Paper I includes a case study with the latest version of the model capable of handling multiple short-circuits events, which was not possible in earlier versions of the simulation model. The influence of the electrical system on the working point ripple of the permanent magnets was evaluated in paper II. In paper III and VI, an evaluation study of the possibility of creating a generator with an interchangeable rotor is presented.  A Neodymium-Iron-Boron (Nd-Fe-B) rotor was exchanged for a ferrite rotor with the electrical properties almost maintained.

  • Public defence: 2016-12-09 09:15 B/A1:107a, Uppsala
    Dosne, Anne-Gaëlle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Dosne, Anne-Gaëlle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Improved Methods for Pharmacometric Model-Based Decision-Making in Clinical Drug Development2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pharmacometric model-based analysis using nonlinear mixed-effects models (NLMEM) has to date mainly been applied to learning activities in drug development. However, such analyses can also serve as the primary analysis in confirmatory studies, which is expected to bring higher power than traditional analysis methods, among other advantages. Because of the high expertise in designing and interpreting confirmatory studies with other types of analyses and because of a number of unresolved uncertainties regarding the magnitude of potential gains and risks, pharmacometric analyses are traditionally not used as primary analysis in confirmatory trials.

    The aim of this thesis was to address current hurdles hampering the use of pharmacometric model-based analysis in confirmatory settings by developing strategies to increase model compliance to distributional assumptions regarding the residual error, to improve the quantification of parameter uncertainty and to enable model prespecification.

    A dynamic transform-both-sides approach capable of handling skewed and/or heteroscedastic residuals and a t-distribution approach allowing for symmetric heavy tails were developed and proved relevant tools to increase model compliance to distributional assumptions regarding the residual error. A diagnostic capable of assessing the appropriateness of parameter uncertainty distributions was developed, showing that currently used uncertainty methods such as bootstrap have limitations for NLMEM. A method based on sampling importance resampling (SIR) was thus proposed, which could provide parameter uncertainty in many situations where other methods fail such as with small datasets, highly nonlinear models or meta-analysis. SIR was successfully applied to predict the uncertainty in human plasma concentrations for the antibiotic colistin and its prodrug colistin methanesulfonate based on an interspecies whole-body physiologically based pharmacokinetic model. Lastly, strategies based on model-averaging were proposed to enable full model prespecification and proved to be valid alternatives to standard methodologies for studies assessing the QT prolongation potential of a drug and for phase III trials in rheumatoid arthritis.

    In conclusion, improved methods for handling residual error, parameter uncertainty and model uncertainty in NLMEM were successfully developed. As confirmatory trials are among the most demanding in terms of patient-participation, cost and time in drug development, allowing (some of) these trials to be analyzed with pharmacometric model-based methods will help improve the safety and efficiency of drug development.

  • Public defence: 2016-12-09 09:15 Rosensalen, Kvinnokliniken, Uppsala
    Elenis, Evangelia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Elenis, Evangelia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Genetic and epidemiological aspects of implantation defects: Studies on recurrent miscarriage, preeclampsia and oocyte donation2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Implantation requires complex molecular and cellular events involving coagulation, angiogenesis and immunological processes that need to be well regulated for a pregnancy to establish and progress normally.  The overall aim of this thesis was to study different models associated with atypical angiogenesis, impaired implantation and/or placentation, such as recurrent miscarriage (RM), oocyte donation (OD) and preeclampsia.

    Histidine-rich glycoprotein (HRG), a serum protein with angiogenic potential has been previously shown to have an impact on implantation and fertility.  In two retrospective case-control studies, women suffering from RM (Study I) and gestational hypertensive disorders (GHD) (Study IV) have been compared to healthy control women, regarding carriership of HRG genotypes (HRG A1042G and C633T SNP, respectively).  According to the findings of this thesis, heterozygous carriers of the HRG A1042G SNP suffer from RM more seldom than homozygous carriers (Study I).  Additionally, the presence of the HRG 633T allele was associated with increased odds of GHD (GHD IV).  Studies II and III comprised a national cohort of relatively young women with optimal health status conceiving singletons with donated oocytes versus autologous oocytes (spontaneously or via IVF).  We explored differences in various obstetric (Study II) and neonatal (Study III) outcomes from the Swedish Medical Birth Register.  Women conceiving with donated oocytes had a higher risk of GHD, induction of labor and cesarean section, as well as postpartum hemorrhage and retained placenta, when compared to autologously conceiving women.  OD infants had higher odds of prematurity and lower birthweight and length when born preterm, compared to neonates from autologous oocytes.  With regard to the indication of OD treatment, higher intervention but neverthelss favourable neonatal outcomes were observed in women with diminished ovarian reserve; the risk of GHD did not differ among OD recipients after adjustment.

    In conclusion, HRG genetic variation appears to contribute to placental dysfunction disorders.  HRG is potential biomarker that may contribute in the prediction of the individual susceptibility for RM and GHD.  Regarding OD in Sweden, the recipients-despite being of optimal age and health status- need careful preconceptional counselling and closer prenatal monitoring, mainly due to increased prevalence of hypertensive disorders and prematurity.

  • Public defence: 2016-12-09 09:15 Polhemsalen, Uppsala
    Frisk, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Frisk, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    The Importance of Controlling Composition to Tailor the Properties of Magnetic Thin Films2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Many physical properties, for example structural or magnetic, of a material are directly dependent on elemental composition. Tailoring of properties through highly accurate composition control is possible in thin films. This work exemplifies such tailoring.

    A short review is given of the current status for research in the area of permanent magnets, focusing on rare earth element free alternatives, where FeNi in the L10 phase is a possible candidate. Epitaxial FeNi L10 thin films were successfully synthesized by magnetron sputtering deposition of monoatomic layers of Fe and Ni on HF-etched Si(001) substrates with Cu or Cu100-xNix/Cu buffers. The in-plane lattice parameter aCuNi of the Cu100-xNix buffer layer was tuned by the Ni content. Through matching of aFeNi to aCuNi, the strain state (c/a)FeNi was controlled, where c is the out-of-plane lattice parameter. The 001 reflection indicative of chemical order, as measured by resonant x-ray diffraction, was in most cases split in two peaks due to a composition modulation of Fe and Ni. This chemical disorder contributed to that the uniaxial magnetocrystalline anisotropy energy, KU≈0.35 MJ/m3, was smaller than predicted. In later experiments the composition modulation could partly be compensated for. Remaining discrepancies with respect to predicted KU values were attributed to additional disorder induced by surface roughness of the buffer layer.

    The interface sharpness between Fe and Ni was explored by producing epitaxial symmetric multilayers with individual layer thicknesses n = 4-48 monolayers (ML). For n ≤ 8 ML the films had pure fcc structure, with antiferromagnetic Fe layers. For n ≥ 8 ML the Fe layers relaxed to bcc structure.

    A combinatorial sputter chamber, which has the capability to deposit samples with composition and thickness gradients, was assembled. A model for simulation of composition and thickness across large substrates, for the conditions in this chamber, is presented. The model is verified by comparison to experimental data. Some challenges inherent in combinatorial sputtering are discussed, and two experimental studies employing the technique are presented as examples. These investigated magnetic and structural properties of Tb-Co films, with 7-95 at.% Tb, and of amorphous and crystalline ternary gradient Co-Fe-Zr films, respectively.

  • Public defence: 2016-12-09 09:30 Geijersalen, Engelska Parken, Uppsala
    Jonbäck, Francis
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology, Studies in Faith and Ideologies, Philosophy of Religion.
    Jonbäck, Francis
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology, Studies in Faith and Ideologies, Philosophy of Religion.
    The God who Seeks but Seems to Hide2016Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The purpose of this study is to reconstruct and evaluate two types of responses to an evidential argument from divine hiding, namely the ‘value agnostic’ response and the ‘theodicy’ response. In the study, the term ‘divine hiding’ refers to the experience of all those who find themselves having inconclusive evidence for the existence of God.

    According to the argument in focus, the fact that there is divine hiding that does not seem to be necessary for any particular greater good, or to avoid a worse evil, makes it improbable that God exists.

    In accordance with the value agnostic response, it is argued that it would not be surprising if divine hiding were necessary to realise greater goods or to avoid worse evils that are beyond our ken. In which case the goods or avoidance of evils in question could figure in a reason God might have for hiding. It is concluded that the value agnostic response is successful.

    The theodicy response states that divine hiding is probably necessary to realise greater goods or to avoid worse evils that are within our ken. It is argued that it would not be surprising if the realisation of the goods or avoidance of evils in question would in turn be sufficient for the realisation of worse evils that are beyond our ken. In which case the goods and avoidance of evils referred to in the theodicy response could not figure in a reason God might have for hiding. It is concluded that the theodicy response is a failure

    Finally, some further problems and prospects on which the study sheds light are discussed. In particular, it is argued that – although believers do not seem to have an evidential problem with believing in a God who seems to hide there might be an existential or practical problem, in particular for non-believers, when seeking a God who seems to hide.

  • Public defence: 2016-12-09 10:15 Eva Netzeliussalen, Blåsenhus, Uppsala
    Malafry, Melina
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Malafry, Melina
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Biodiversity Protection in an Aspiring Carbon-Neutral Society: A Legal Study on the Relationship between Renewable Energy and Biodiversity in a European Union Context2016Doctoral thesis, monograph (Other academic)
    Abstract [en]

    There is a vision in the EU for a transition to a low carbon society, including a carbon-neutral energy system, containing a high share of renewable energy. However, this vision is not isolated from other political goals, such as halting the loss of biodiversity by 2020. Both of these goals are accompanied by EU legislation promoting their respective aims.

    One of the central challenges, in light of this transition, is the very nature of the legal system – that it is rather fragmented – both regarding the substantive law applicable to renewable energy activities and the legal processes that renewable energy activities face. The aim is therefore to discuss certain challenges arising from the fragmented legal system applicable to renewable energy activities.

    The dissertation is based on EU and Swedish law. First, I investigate the EU’s competence in the field of renewable energy and address how such policy may better reflect the protection of biodiversity. Thereafter, in a Swedish context, I analyse the relationship between protection of biodiversity and promotion of renewable energy. Finally, I address the problems arising from the fragmented legal procedures of renewable energy activities, with the main example of wind power installations and new transmission lines.

    In general, this study suggests that the current system lacks consistency between renewable energy and nature protection legislation and there is a coordination problem with regards to the permit processes of the development of renewable energy activities. These conclusions point towards a need for a broader perspective on the development of renewable energy activities, which could include: a more integrated planning system for renewable energy activities; exploring the use of derogation rules from the Water Framework Directive; and a more integrated EU renewable energy policy with specific sustainability criteria.

  • Public defence: 2016-12-09 13:00 Hörsal 2, Ekonomikum, Uppsala
    Hierofani, Patricia Yocie
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Social and Economic Geography.
    Hierofani, Patricia Yocie
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Social and Economic Geography.
    "How dare you talk back?!": Spatialised Power Practices in the Case of Indonesian Domestic Workers in Malaysia2016Doctoral thesis, monograph (Other academic)
    Abstract [en]

    By taking the experiences and narratives of Indonesian women in Malaysia as the empirical material, this dissertation offers an analysis on spatialised power practices in the context of paid domestic workers. Family survival prompts these women to work abroad, but patriarchal norms shift their economic contribution as supplementary to the men’s role as the breadwinner. The interviews reveal that these women chose Malaysia as their destination country after having listened to oral stories, but despite the transnational mobility involved in their decisions, they are rendered immobile in the employers’ house.

    Furthermore, the analysis shows an intricate ensemble of power relations in which gender, class and nationality/ethnicity interact with each other, inform and reproduce spatialised domination and labour exploitation practices by the employers. Immigration status of the workers, meanwhile, puts them in a subordinated position in relation to the employers, citizens of the host country. Without the recognition from the state on this particular form of embodied labour, the employers are responsible for defining the working conditions of the workers, leading to precarious conditions.

    Findings on several resistance practices by the workers complete the analysis of power practices, where resistance is treated as an entangled part of power. Contributing to the study of gendered geographies of exploitation, the study identifies the home and the body as the main levels of analysis; meanwhile, practices at the national level by the state, media and recruitment/placement agencies and globalisation processes are identified as interrelated factors that legitimate the employers’ practices of exploitation.

    Finally, the dissertation contributes to feminist geography analysis on gender, space, and power through South-South migration empirics.

  • Public defence: 2016-12-09 13:15 Polhemsalen, Uppsala
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    On Directed Random Graphs and Greedy Walks on Point Processes2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis consists of an introduction and five papers, of which two contribute to the theory of directed random graphs and three to the theory of greedy walks on point processes.          

    We consider a directed random graph on a partially ordered vertex set, with an edge between any two comparable vertices present with probability p, independently of all other edges, and each edge is directed from the vertex with smaller label to the vertex with larger label. In Paper I we consider a directed random graph on ℤ2 with the vertices ordered according to the product order and we show that the limiting distribution of the centered and rescaled length of the longest path from (0,0) to (n, [na] ), a<3/14, is the Tracy-Widom distribution. In Paper II we show that, under a suitable rescaling, the closure of vertex 0 of a directed random graph on ℤ with edge probability n−1 converges in distribution to the Poisson-weighted infinite tree. Moreover, we derive limit theorems for the length of the longest path of the Poisson-weighted infinite tree.          

    The greedy walk is a deterministic walk on a point process that always moves from its current position to the nearest not yet visited point. Since the greedy walk on a homogeneous Poisson process on the real line, starting from 0, almost surely does not visit all points, in Paper III we find the distribution of the number of visited points on the negative half-line and the distribution of the index at which the walk achieves its minimum. In Paper IV we place homogeneous Poisson processes first on two intersecting lines and then on two parallel lines and we study whether the greedy walk visits all points of the processes. In Paper V we consider the greedy walk on an inhomogeneous Poisson process on the real line and we determine sufficient and necessary conditions on the mean measure of the process for the walk to visit all points.

  • Public defence: 2016-12-09 13:15 Häggsalen, Uppsala
    Björnson, Kristofer
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Björnson, Kristofer
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Topological band theory and Majorana fermions: With focus on self-consistent lattice models2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    One of the most central concepts in condensed matter physics is the electronic band structure. Although band theory was established more than 80 years ago, recent developments have led to new insights that are formulated in the framework of topological band theory. In this thesis a subset of topological band theory is presented, with particular focus on topological supercon- ductors and accompanying Majorana fermions. While simple models are used to introduce basic concepts, a physically more realistic model is also studied intensely in the papers. Through self- consistent tight-binding calculations it is confirmed that Majorana fermions appear in vortex cores and at wire end points when the superconductor is in the topologically non-trivial phase. Many other properties such as the topological invariant, experimental signatures in the local density of states and spectral function, unconventional and odd-frequency pairing, the precense of spin-polarized currents and spin-polarization of the Majorana fermions, and a local π-phase shift in the order parameter at magnetic impurities are also investigated. 

  • Public defence: 2016-12-09 14:00 Ekonomikum, hörsal 1, Uppsala
    Holmefur, Niklas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology, Church and Mission studies, Science of Mission.
    Holmefur, Niklas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology, Church and Mission studies, Science of Mission.
    Den osynliga religionen: Analys av policy för svensk utvecklingspolitik 2010–20142016Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Sweden boasts a rich history of cooperating with civil organisations in advancing international development cooperation with high rates of support from its citizens. Religious institutions are an active component of this government-civil society cooperation. In fact, the early beginnings of Sweden’s development work were closely intertwined with Christian mission enterprises, especially in the areas of education and health ministries. This background circumstance has led to an increasing unease about the interface between the secular exercise of public authority and religious groups’ vested interests. This dissertation aims to explore Swedish development cooperation policies for the presence of religion and for the evaluation of religion’s impact.  It is theoretically placed within the sociological shift that emphasizes the visibility of religion, rather than secularising of religion. The dissertation analyses nine government development cooperation policies plus additional documents that further explore policy issues. While using quantitative and qualitative content analysis, the study searches for explicit references to: 1) religious agency, 2) religious identity, 3) religious rights as part of human rights, and 4) religious ideas.  The results indicate that religion, in the four analysed categories, tends to be poorly represented, non-existent or anonymous under the generic term ‘civil society’. Evaluation of religion’s impact varies according to policy area, with the overall conclusion that Swedish development cooperation has an ambivalent relationship with religion. The dissertation further analyses the specific policy areas of civil society, economic growth, and sexual and reproductive health and rights. It finds higher sensitivity to religious components in parts. It compares results with those of other studies that have focused on religion in the selected areas. The dissertation concludes that Swedish development cooperation needs to develop a higher sensitivity to the religious aspects of development work. This will mean that the ‘secular’ and the ‘religious’ in development cooperation need further clarification from the theoretical premise of the new visibility of religion.

  • Public defence: 2016-12-10 10:15 Ihresalen, Uppsala
    Kalm, Mikael
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Languages, Department of Scandinavian Languages.
    Kalm, Mikael
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Languages, Department of Scandinavian Languages.
    Satsekvivalenta infinitivfraser i svenskan: En synkron och diakron undersökning2016Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis investigates control infinitives and ECM-infinitives in the history of Swedish. Both constructions are non-finite, based on infinitives with or without complements, but share some properties and functions with finite subordinate clauses. Control infinitives (to-infinitives) are headed by the infinitive marker att (which in some cases may be omitted) and have invisible PRO-subjects (“controlled” by, i.e. co-referential with, the subject or object of the matrix), whereas ECM-infinitives are headed by overt subjects, distinguished by their “exceptional case marking” (ECM) from the matrix verb, and never contain the infinitive marker.

    According to the proposed analyses, conducted within the theoretical framework of generative grammar, control infinitives are CPs, taking the infinitive marker as a non-finite complementizer in C, but lack the TP of the I-domain, whereas ECM-infinitives have no C-layer but, nevertheless, a (sort of) TP.

    The historical investigation shows that control infinitives have developed more clause like properties over time. In Old Swedish (1220–1526), they only rarely contained e.g. negations or auxiliaries. It is not until the seventeenth century that these elements have come into use in the same way as in modern Swedish. This is accounted for by assuming that the control infinitive in Old Swedish was a recent innovation that did not initially make any use at all of the I-domain. The ECM-infinitives, on the other hand, are taken to have the same structure and function in Old Swedish as in Modern Swedish, as their use and properties have not changed significantly.

    In addition, the status of the infinitive marker has changed through the history of Swedish. Etymologically a preposition, it is here analysed as a verb phrase element in Early Old Swedish, not as a (non-finite) complementizer as in Modern Swedish. In early Modern Swedish (1526–1732), the preposition till is used in much the same function as att giving rise to two new infinitive markers: till att and till. This development of new infinitive markers is also accounted for in the thesis.

  • Public defence: 2016-12-12 13:15 Ångstrom 10132, Uppsala
    Li, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Li, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Numerical Modelling and Statistical Analysis of Ocean Wave Energy Converters and Wave Climates2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ocean wave energy is considered to be one of the important potential renewable energy resources for sustainable development. Various wave energy converter technologies have been proposed to harvest the energy from ocean waves. This thesis is based on the linear generator wave energy converter developed at Uppsala University. The research in this thesis focuses on the foundation optimization and the power absorption optimization of the wave energy converters and on the wave climate modelling at the Lysekil wave converter test site.

    The foundation optimization study of the gravity-based foundation of the linear wave energy converter is based on statistical analysis of wave climate data measured at the Lysekil test site. The 25 years return extreme significant wave height and its associated mean zero-crossing period are chosen as the maximum wave for the maximum heave and surge forces evaluation.

    The power absorption optimization study on the linear generator wave energy converter is based on the wave climate at the Lysekil test site. A frequency-domain simplified numerical model is used with the power take-off damping coefficient chosen as the control parameter for optimizing the power absorption. The results show a large improvement with an optimized power take-off damping coefficient adjusted to the characteristics of the wave climate at the test site.

    The wave climate modelling studies are based on the wave climate data measured at the Lysekil test site. A new mixed distribution method is proposed for modelling the significant wave height. This method gives impressive goodness of fit with the measured wave data. A copula method is applied to the bivariate joint distribution of the significant wave height and the wave period. The results show an excellent goodness of fit for the Gumbel model. The general applicability of the proposed mixed-distribution method and the copula method are illustrated with wave climate data from four other sites. The results confirm the good performance of the mixed-distribution and the Gumbel copula model for the modelling of significant wave height and bivariate wave climate.

  • Public defence: 2016-12-14 10:00 Lilla Hörsalen, 11418 Stockholm
    Weis, Franz A.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Mineralogy Petrology and Tectonics.
    Weis, Franz A.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Mineralogy Petrology and Tectonics.
    Hydrogen in nominally anhydrous silicate minerals: Quantification methods, incorporation mechanisms and geological applications2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis is to increase our knowledge and understanding of trace water concentrations in nominally anhydrous minerals (NAMs). Special focus is put on the de- and rehydration mechanisms of clinopyroxene crystals in volcanic systems, how these minerals can be used to investigate the volatile content of mantle rocks and melts on both Earth and other planetary bodies (e.g., Mars). Various analytical techniques for water concentration analysis were evaluated.

    The first part of the thesis focusses on rehydration experiments in hydrogen gas at 1 atm and under hydrothermal pressures from 0.5 to 3 kbar on volcanic clinopyroxene crystals in order to test hydrogen incorporation and loss from crystals and how their initial water content at crystallization prior to dehydration may be restored. The results show that extensive dehydration may occur during magma ascent and degassing but may be hindered by fast ascent rates with limited volatile loss. De- and rehydration processes are governed by the redox-reaction OH- + Fe2+ ↔ O2- + Fe3+ + ½ H2. Performing rehydration experiments at different pressures can restore the water contents of clinopyroxene at various levels in the volcanic systems. Subsequently water contents of magmas and mantle sources can be deduced based on crystal/melt partition coefficients. This thesis provides examples from the Canary Islands, Merapi volcano in Indonesia and the famous Nakhla meteorite. Using NAMs as a proxy for magmatic and mantle water contents may provide a very good method especially for planetary science where sample material is limited.

    The thesis’ second part focusses on analytical methods to measure the concentration of water in NAMs. Specifically the application of Raman spectroscopy and proton-proton scattering are tested. The hydrated mineral zoisite is thoroughly analyzed in order to be used as an external standard material. Polarized single crystal spectra helped to determine the orientation of the OH-dipole in zoisite. Further, Transmission Raman spectroscopy and a new method for the preparation of very thin samples for proton-proton scattering were developed and tested. The results provide new possibilities for the concentration analysis of water in NAMs such as three dimensional distribution and high spatial resolution.                       

  • Public defence: 2016-12-14 10:15 Hörsal 2, Uppsala
    Öhman, Mattias
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics.
    Öhman, Mattias
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics.
    Essays on Cognitive Development and Medical Care2016Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis consists of four self-contained papers.

    Essay I (with Linuz Aggeborn): Fluoridation of the drinking water is a public policy whose aim is to improve dental health. Although the evidence is clear that fluoride is good for dental health, concerns have been raised regarding potential negative effects on cognitive development. We study the effects of fluoride exposure through the drinking water in early life on cognitive and non-cognitive ability, education and labor market outcomes in a large-scale setting. We use a rich Swedish register dataset for the cohorts born 1985-1992, together with drinking water fluoride data. To estimate the effects, we exploit intra-municipality variation of fluoride, stemming from an exogenous variation in the bedrock. First, we investigate and confirm the long-established positive relationship between fluoride and dental health. Second, we find precisely estimated zero-effects on cognitive ability, non-cognitive ability and education for fluoride levels below 1.5 mg/l. Third, we find evidence that fluoride improves later labor market outcomes, which indicates that good dental health is a positive factor on the labor market.

    Essay II: I study the associations between cognitive and non-cognitive abilities and mortality using a population-wide dataset of almost 700,000 Swedish men born between 1950 and 1965. The abilities were measured at the Swedish military enlistment at age 18-20. In addition, I investigate if income and education are good proxies for the abilities. The results suggest that both cognitive and non-cognitive abilities are strongly associated with mortality, but that non-cognitive ability is a stronger predictor. The associations are only partly mediated through income and education. For middle and high income earners and individuals with a college education there are no associations with mortality. However, for low income earners and individuals without a college education, both abilities are strongly associated with mortality. The associations are mainly driven by the bottom of the distributions.

    Essay III (with Matz Dahlberg, Kevin Mani and Anders Wanhainen): We examine how health information affects individuals' well-being using a regression discontinuity design on data from a screening program for an asymptomatic disease, abdominal aortic aneurysm (AAA). The information provided to the individuals is guided by the measured aorta size and its relation to pre-determined levels. When comparing individuals that receive information that they are healthy with those that receive information that they are in the risk zone for AAA, we find no effects. However, when comparing those that receive information that they have a small AAA, and will be under increased surveillance, with those who receive information that they are in the risk zone, we find a weak positive effect on well-being. This indicates that the positive information about increased surveillance may outweigh the negative information about worse health.

    Essay IV: I estimate the effect of SSRI antidepressants on the risk of mortality for myocardial infarction (MI) patients using Propensity Score Matching on individual health variables such as pharmaceutical drug prescription, patient history and severity of the MI. The effect of antidepressants on mortality is a heavily debated topic. MI patients have an elevated risk of developing depression, and antidepressants are among the most common treatments for depression and anxiety. However, there are indications that some classes of antidepressants may have drug-induced cardiovascular effects and could be harmful for individuals with heart problems, but there is a lack of large-scale studies using credible identification strategies. My findings indicate no increased risk of two-year mortality for MI patients using SSRI. The results are stable for several specifications and robustness checks.

  • Public defence: 2016-12-14 13:00 Å4001, Uppsala
    Qin, Tao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Qin, Tao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Submicron Calcium Phosphate Spheres for Biomedical Applications: Synthesis and Use2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Calcium phosphate spheres as biomaterials have been attracting attention in recent years. Calcium phosphate occurs naturally in bone, and a hollow structure could be advantageous for drug loading and release. The combination of a calcium phosphate chemistry and a spherical-hollow structure could be an optimal strategy for specific biomaterial applications, e.g., certain dental and drug-delivery applications.

    The focus of this thesis is on the synthesis, formation mechanism and applications of hollow, spherical calcium phosphate particles. First, the thesis describes two methods for the synthesis of calcium phosphate (CaP) spherical particles. The first method involves synthesis of hollow calcium phosphate spherical particles via a supersaturated buffer solution based on a previous study. It was utilised to prepare spheres for applications in drug delivery and dentistry. The second method was developed to explain the mechanism of formation of hollow calcium phosphate spheres. It aimed at revealing the particular function of magnesium in the formation of spherical particles. With the use of this modified method, it could be concluded that the only ions active in the formation of CaP spherical particles are calcium ions, phosphate ions and magnesium ions. Compared with the thermodynamics of micellisation, a new model, called three ions virtual micelle effect, was developed to explain the mechanism of the Mg function. Following this mechanism, a series of spherical particles of other compositions were explored. These spherical particles included strontium phosphate, barium phosphate, calcium fluoride, strontium fluoride and barium fluoride.

    In this thesis, CaP spheres were studied for the controlled delivery of active ingredients and as active agent for tooth remineralisation. The first investigated application was to control the release of vancomycin from Poly(methyl methacrylate) (PMMA) cement via strontium-doped CaP spheres (SCPS). The results showed that incorporation of CaP spheres into PMMA could enhance antibiotic release while maintaining the mechanical strength. The second application was to control hydrogen peroxide (HP) release from two bleaching gel, in which CP-loaded CaP spheres were the active ingredient. One gel with low HP concentration was developed as an at-home bleaching gel, and one with high HP concentration was developed as an in-office bleaching gel. The results showed that CaP spheres would give a controlled release of peroxide and thus have a potential to increase the efficacy of the bleaching. The third application was to investigate the potential for an anti-sensitivity effect of the spheres, as active agents in toothpaste. We studied the tooth tubules occlusion and the remineralisation effect of CaP spheres. After 7 days of application, the open dentin tubules and surface were fully covered by a newly formed apatite layer, demonstrating the remineralisation potential of the spheres.

  • Public defence: 2016-12-15 09:15 Gustavianum, Uppsala
    Sembrant, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Computer Systems. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computer Systems.
    Sembrant, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Computer Systems. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computer Systems.
    Hiding and Reducing Memory Latency: Energy-Efficient Pipeline and Memory System Techniques2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Memory accesses in modern processors are both far slower and vastly more energy-expensive than the actual computations. To improve performance, processors spend a significant amount of energy and resources trying to hide and reduce the memory latency. To hide the latency, processors use out-order-order execution to overlap memory accesses with independent work and aggressive speculative instruction scheduling to execute dependent instructions back-to-back. To reduce the latency, processors use several levels of caching that keep frequently used data closer to the processor. However, these optimizations are not for free. Out-of-order execution requires expensive processor resources, and speculative scheduling must re-execute instructions on incorrect speculations, and multi-level caching requires extra energy and latency to search the cache hierarchy. This thesis investigates several energy-efficient techniques for: 1) hiding the latency in the processor pipeline, and 2) reducing the latency in the memory hierarchy.

    Much of the inefficiencies of hiding latency in the processor come from two sources. First, processors need several large and expensive structures to do out-of-order execution (instructions queue, register file, etc.). These resources are typically allocated in program order, effectively giving all instructions equal priority. To reduce the size of these expensive resources without hurting performance, we propose Long Term Parking (LTP). LTP parks non-critical instructions before they allocate resources, thereby making room for critical memory accessing instructions to continue and expose more memory-level parallelism. This enables us to save energy by shrinking the resources sizes without hurting performance. Second, when a load's data returns, the load's dependent instructions need to be scheduled and executed. To execute the dependent instructions back-to-back, the processor will speculatively schedule instructions before the processor knows if the input data will be available at execution time. To save energy, we investigate different scheduling techniques that reduce the number of re-executions due to misspeculation.

    The inefficiencies of traditional memory hierarchies come from the need to do level-by-level searches to locate data. The search starts at the L1 cache, then proceeds level by level until the data is found, or determined not to be in any cache, at which point the processor has to fetch the data from main memory. This wastes time and energy for every level that is searched. To reduce the latency, we propose tracking the location of the data directly in a separate metadata hierarchy. This allows us to directly access the data without needing to search. The processor simply queries the metadata hierarchy for the location information about where the data is stored. Separating metadata into its own hierarchy brings a wide range of additional benefits, including flexibility in how we place data storages in the hierarchy, the ability to intelligently store data in the hierarchy, direct access to remote cores, and many other data-oriented optimizations that can leverage our precise knowledge of where data are located.

  • Public defence: 2016-12-15 09:15 C8:301, Uppsala
    Zarnegar, Behdad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Zarnegar, Behdad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mechanisms triggering the recruitment of mast cell progenitors to the lung and regulation of mast cell degranulation2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mast cells stem from the bone marrow and migrate via the blood as mast cell progenitors. Upon arrival in peripheral tissues, they develop into mast cells. These rare immune cells have numerous granules that contain large amounts of pro-inflammatory mediators. Mast cells accumulate at certain sites in the asthmatic lung, and once activated they release mediators that are thought to induce symptoms. In mouse models of allergic airway inflammation, the increase in lung mast cells in asthma can be mimicked and is mainly caused by the recruitment of mast cell progenitors to the lung. However, whether other types of lung inflammation stimulate the recruitment of mast cell progenitors to the lung was unknown until now.

    Here, using a murine model of influenza A virus infection, this type of virus was demonstrated to trigger an extensive recruitment of mast cell progenitors to the lung, most likely through the induction of VCAM-1 expression in the lung endothelium. Thereafter, some influenza-induced mast cell progenitors developed into an intermediate mast cell stage before they matured into mast cells. However, upon the resolution of inflammation, the mast cells that accumulated in the lung upon influenza infection were gradually lost.

    Because the recruitment of mast cell progenitors started early after influenza infection, the role of innate immune signals in inducing the recruitment of mast cell progenitors was addressed. The intranasal administration of either Poly I:C or IL-33 was sufficient to induce an increase in lung mast cell progenitors in a TLR3- or ST2-dependent fashion. However, the influenza-induced recruitment of mast cell progenitors to the lung occurred independently of TLR3 and ST2.

    VAAT/SLC10A4 is a member of the solute carrier family of proteins that is expressed in nerve cells and mast cells. In this study, murine VAAT was localized to mast cell granules and regulated the IgE/antigen-mediated release of granule-associated mediators and ATP. However, the absence of VAAT did not affect IgE/antigen-mediated de novo synthesis of cytokines and lipid mediators. Additionally, mice lacking VAAT had attenuated passive cutaneous anaphylaxis reactions and scratched less frequently in response to compound 48/80 injections, suggesting that VAAT regulates reactions for which mast cells are implicated in vivo.

  • Public defence: 2016-12-15 13:15 Hörsal 2 (Lecture Hall 2), Uppsala
    Haq, Hammad ul
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Business Studies.
    Haq, Hammad ul
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Business Studies.
    The Unequal Playing Field: Headquarters’ Attention and Subsidiary Voice in Multinational Corporations2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Attention of top managers has an impact on future direction of an organization according to the attention-based view of the firm. In the context of multinational corporations, headquarters’ attention is likely to influence the actions and behavior of subsidiaries. Thus, in the thesis, I respond to calls for more research on this topic: enhancing the understanding about how a subsidiary’s perception of headquarters’ attention relates to its choice of communication moves when sharing business ideas with headquarters (also known as subsidiary voice). In recent research, subsidiary voice is viewed as a bottom-up tool for subsidiaries to attract headquarters’ attention to issues that they consider important for their local units and the entire organization.

    In line with the research purpose, the data were collected at the subsidiary level through a combination of both, survey and interviews. The findings based on empirical data point out that a subsidiary’s perception of headquarters’ attention engagement has a positive impact on its voice. This means that subsidiaries not having regular interaction with headquarters are unable to select communication moves that can attract headquarters’ attention and hence encounter challenges in adopting an initiative-taking approach to gain influence or a central position in the organization. As a result, contrary to the claims put forth in recent research, the thesis findings highlight that subsidiary voice alone is not enough to attract headquarters’ attention. Instead, subsidiaries can only use their voice when they have power (also called weight) to influence headquarters’ attention and decisions.

    This gives rise to an unequal playing field because subsidiaries that lack considerable weight are unable to contribute to strategy formulation and future planning done by the headquarters, with regard to their own units and the organization in general. On the contrary, subsidiaries with a considerable weight experience a high degree of attention engagement from the headquarters and thus find it easier to attract headquarters’ attention for their business ideas.      

  • Public defence: 2016-12-15 13:15 B22, Uppsala
    Ashrafzadeh, Parham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ashrafzadeh, Parham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Exploring Cellular Dynamics: From Vesicle Tethering to Cell Migration2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cells in the body communicate with each other in order to cooperate efficiently. This communication is in part achieved by regulated secretion of signaling molecules, which when released from a cell may activate receptors present at the plasma membrane of an adjacent cell. Such signals affect both cell fate and behavior. Dysregulated signaling may lead to disease, including cancer. This thesis is focused on how exocytosis and subsequent activation and trafficking of receptors can be regulated, and what the consequences of this regulation may be for cell migration.

    Actin filaments are important transport structures for secretory vesicle trafficking. In Paper 1, actin polymerization was shown to induce formation of ordered lipid domains in the plasma membrane. Accordingly, actin filaments may thus create and stabilize specific membrane domains that enable docking of vesicles containing secretory cargo.

    The RhoGEF FGD5 regulates Cdc42 which can result in cytoskeletal rearrangements. In Paper II, FGD5 was shown to be selectively expressed in blood vessels and required for normal VEGFR2 signaling. FGD5 protected VEGFR2 from proteasome-mediated degradation and was essential for endothelial cells to efficiently respond to chemotactic gradients of VEGFA.

    The exocyst component EXOC7 is essential for tethering secretory vesicles to the plasma membrane prior to SNARE-mediated fusion. In Paper III, EXOC7 was required for trafficking of VEGFR2-containing vesicles to the inner plasma membrane and VEGFR2 presentation at the cell surface.

    The ability of tumor cells to escape the primary tumor and establish metastasis is in part dependent on their capacity to migrate. In Paper IV, a method based on time-lapse microscopy and fluorescent dyes was created to analyze single cancer cell migration in mixed cancer cell cultures, and in particular the influence of different types on neighboring cells was assessed.

    In conclusion, these studies have enhanced our understanding of the mechanisms behind cellular trafficking, and may be applied in the future to develop more specific therapeutics to treat cancer and other diseases associated with abnormal angiogenesis and cellular migration.

  • Public defence: 2016-12-16 09:00 Auditorium minus, Uppsala
    Ljungman, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Department of public health and caring sciences.
    Ljungman, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Department of public health and caring sciences.
    Parents of Children with Cancer: Psychological Long-Term Consequences and Development of a Psychological Treatment for Parents of Survivors2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of this thesis were to increase the knowledge about the long-term psychological consequences in parents of children diagnosed with cancer, including parents of childhood cancer survivors (CCSs) and bereaved parents, and to take the first steps towards developing a psychological treatment for parents of CCSs.

    Study I was a systematic review synthesizing the literature on psychological long-term consequences in parents of CCSs. Study II had a longitudinal design assessing posttraumatic stress symptoms (PTSS) from shortly after the child’s diagnosis (T1, N=259) up to five years after end of the child’s treatment or death (T7, n=169). Study I and II concluded that while most parents show resilience in the long-term, a subgroup report high levels of general distress and/or PTSS. In Study III, interview data from the last assessment in the longitudinal project (T7, n=168) was used. Participants described particularly negative and/or positive experiences in relation to their child’s cancer, and results pointed to the wide range of such experiences involved in parenting a child with cancer. In Study IV and V, parents of CCSs reporting cancer-related psychological distress were included (N=15). In Study IV, a conceptualization of this distress was generated by aggregation of individual behavioral case formulations. The conceptualization consisted of two separate but overlapping paths describing development and maintenance of symptoms of traumatic stress and depressive symptoms. In Study V, cognitive behavior therapy (CBT) based on the individual case formulations were preliminarily evaluated in an open trial. The CBT appeared feasible, and at post-assessment participants reported significant decreases in PTSS (p<.001), depression (p<.001), and anxiety (p<.01) with medium to large effect sizes (Cohen’s d=0.65-0.92).

    Findings indicate that psychological long-term consequences in parents of children with cancer consist of a broad range of negative as well as positive experiences, and that while most parents show resilience in the long-term, a subgroup report high levels of psychological distress. For parents of CCSs this distress is suggested to primarily consist of symptoms of traumatic stress and depression, and a preliminary evaluation of CBT targeting hypothesized maintaining mechanisms showed promise in terms of feasibility and treatment effect.

  • Public defence: 2016-12-16 09:15 B41, Uppsala
    Zhang, Yanyu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zhang, Yanyu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Platelets – Multifaceted players in tumor progression and vascular function2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Platelets play a crucial role for blood hemostasis, the process that prevents bleeding. In addition, platelets have been demonstrated to promote cancer progression and cancer related complications like metastasis and thrombosis. Platelets can affect cancer related diseases either directly or by interacting with other blood cells or molecules in the circulation of individuals with cancer. The current thesis addresses the role of platelets in tumor progression and tumor-induced systemic effects of cancer, with a special focus on the effects on the vasculature.

    In the first paper, the role of platelets in tumor progression in histidine-rich glycoprotein (HRG)-deficient mice was addressed. We report that HRG-deficient mice show enhanced tumor growth, epithelial to mesenchymal transition (EMT) and metastasis. The enhanced platelet activity in the absence of HRG is responsible for the accelerated tumor progression.

    In the second paper, we demonstrate that platelet-derived PDGFB is a central player to keep the tumor vessels functional. Moreover, in a pancreatic neuroendocrine carcinoma model with PDGFB-deficient platelets, spontaneous liver metastasis was enhanced. With this finding we identify a previously unknown role of platelet derived PDGFB.

    In the third paper, we found that TBK1 mediates platelet-induced EMT by activation of NF-kB signaling, which suggest that TBK1 contributes to tumor invasiveness in mammary epithelial tumors.

    In the last paper, we report that the vascular function in organs that are neither affected by the primary tumor, nor represent metastatic sites, is impaired in mice with cancer. We show that tumor-induced formation of intravascular neutrophil extracellular traps (NETs), a fibril matrix consisting of neutrophils with externalized DNA and histones, granule proteases and platelets, are responsible for the impaired peripheral vessel function.

  • Public defence: 2016-12-16 10:15 Auditorium Minus, Uppsala
    Perry, Sharn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Perry, Sharn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Deciphering the Locomotor Network: The Role of Spinal Cord Interneurons2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the spinal cord, an intricate neural network generates and coordinates the patterning of limb movements during locomotion. This network, known as the locomotor central pattern generator (CPG), comprises of various cell populations that together orchestrate the output of motor neurons. Identification of CPG neurons through their specific gene expression is a valuable tool that can provide considerable insight to the character, intrinsic properties and role of a population, which represents a step toward understanding locomotor circuit function and correlating neural activity to behaviour. We selectively targeted two inhibitory CPG populations to investigate their molecular characteristics, circuitry and functional role; Renshaw cells (RCs) marked by their specific expression of the cholinergic nicotinic receptor α2 (Chrna2) and a subset of the dI6 population derived by their selective expression of the Doublesex and mab-3 related transcription factor 3 (Dmrt3).

    We found that RCs have hyperpolarisation-activated cation (Ih) and small calcium-activated potassium (ISK) modulatory currents that differentially regulate their excitation and firing properties, which influence the instantaneous feedback to motor neurons through the recurrent inhibition circuit. Due to previous difficulties isolating RCs from the surrounding locomotor circuits, their functional role remains poorly defined. For the first time, we selectively silenced RC inhibition and found that all aspects of motor behaviour, including coordination and gait were normal. The deletion of RC signalling instead altered the electrical and synaptic properties of the recurrent inhibitory circuit, suggesting that developmental plasticity compensates for the loss of RC inhibition.

    We reveal Dmrt3 neurons comprise a population of glycinergic inhibitory, spike-frequency adapting commissural interneurons active during locomotion. Conditional silencing of the Dmrt3 population resulted in considerable gait abnormalities in the neonatal and adult mouse. This manifested as an uncoordinated CPG output in vitro, impaired limb coordination in pups and increased fore- and hindlimb synchrony in adults that was exacerbated at faster locomotor speeds. Dmrt3 mediated inhibition subsequently impacts locomotion and suggests the Dmrt3 population contribute to coordinating speed dependent left-right limb alternation. This thesis provides cellular, circuit and behavioural insights into the Renshaw cell and Dmrt3 populations and enhances our knowledge regarding their probable function within the locomotor CPG.

  • Public defence: 2016-12-16 13:00 Ihresalen, Uppsala
    Santell, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology.
    Santell, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology.
    Svenska kyrkans diakonistyrelse: Tillflöden och tillkomst, organisation och verksamhet intill 19382016Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This study is focused on the way in which the Church of Sweden emerged as an overall national unit in support of the pastoral activities in the dioceses and parishes through the work of the Church of Sweden National Board for Parish Life (Svenska kyrkans diakonistyrelse). This Board was established in 1910 as one of three Central Boards of the Church of Sweden. The incentives and origin of this Board as well as its organisation and activities are investigated for the period from its inception up until 1938.

    The Board was shaped by the Swedish Practical and Pastoral Theologian Olof Holmström (1854–1921) on the basis of his National Church Programme (folkkyrkoprogram). The establishment of the General Swedish Corporation of Priests (Allmänna svenska prästföreningen) in 1903 was the first limited outflow of Holmström’s programme. The interpretation of the Youth Church Movement (ungkyrkorörelsen) as the primary revitalising factor in the Church of Sweden during the first two decades of the 20th century has been rejected as one of the organisational myths identified in this thesis. The establishment of the National Board for Parish Life was the result of an informal collaboration between representatives for the Parish Movement (församlingsrörelsen) and formal initiatives, primarily taken by Archbishop J A Ekman (1845–1913) and the Minister of Ecclesiastical Affairs, Hugo Hammarskjöld (1845–1937).

    The work of the Board was extensive with many branches carried out alongside the parish work line (församlingsvårdslinjen) and the social ethics line (socialetiska linjen). The work was adapted over time, due to changing theological as well as general organisational patterns in the Swedish state and society, such as changing ideas of Sweden as a ’National Home’ (folkhem).

    Different operational levels of the organisation are investigated, such as the Governing Body, a number of Committees for the ongoing work in limited areas and the corporation of diocesan representatives (stiftsombud). The high-ranking First Secretaries’ influence on the daily work was important.

    The Church of Sweden National Board for Parish Life is one of the roots of the current Church of Sweden administrative headquarters at Uppsala. 

  • Public defence: 2016-12-16 13:15 Aros Congress Center, Västerås
    Vadlin, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Centre for Clinical Research, County of Västmanland.
    Vadlin, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Centre for Clinical Research, County of Västmanland.
    Problematic Gaming and Gambling among Adolescents2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aims of this thesis were to develop and evaluate a screening instrument designed to detect gaming addiction symptoms in adolescents, to study associations between problematic gaming and psychiatric symptoms, to investigate the stability of problematic gaming, and to examine possible associations between gaming at baseline (W1) with problem gambling three years later (W2).

    The study population consisted of adolescents from the Survey of Adolescent Life in Västmanland SALVe Cohort (adolescents in Västmanland born in 1997 and 1999, and their parents), in two waves (2012, n = 1887; 2015, n = 1576), and adolescents from child and adolescent psychiatric clinics in Västmanland (2014, n = 242).

    The development of the Gaming Addiction Identification Test (GAIT) was based upon the research literature on gaming, gambling, and addiction. An expert panel estimated the content validity of the GAIT and found it to be excellent. Additional psychometric evaluations of the GAIT and the parent version, GAIT-P, were conducted and it was found that both versions showed promising psychometric results, with high internal consistency, high concurrent validity, high concordance, unidimensionality, and high factor loadings, although poor model fit in exploratory factor analysis. Self- and parent-rated prevalence of gaming addiction symptoms were estimated at 1.3% with the GAIT and 2.4% with the GAIT-P in 13- and 15-year-olds.

    Self-rated problematic gaming above the cutoff had a boy to girl ratio of approximately 5:1 in both the SALVe Cohort and the clinical sample, whereas more girls than boys reported symptoms above the cutoff for ADHD, depression, anxiety, and psychotic-like-experiences. ADHD, depression, and anxiety symptoms were associated with odds ratios of 2.43, 2.47, and 2.06, respectively, in relation to coexisting problematic gaming. Furthermore, problematic gaming was stable over time, and problematic gaming at the first wave was associated with problem gambling three years later.

    It is important to screen for possible co-occurring symptoms among those who seek treatment and among those who appear to have symptoms of gaming, gambling, or psychiatric symptoms. Ongoing evaluation of adequate screening and diagnostic measurements, and the development and evaluation of treatments for problematic gaming, gaming addiction, and comorbid conditions are needed.

  • Public defence: 2016-12-16 13:15 Häggsalen, Uppsala
    Aiso, Toshiharu
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Aiso, Toshiharu
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Workpiece steels protecting cutting tools from wear: A study of the effects of alloying elements on material transfer and coating damage mechanisms2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The vision of this thesis is to improve the machinability of workpiece steels. Workpiece material frequently transfers to the cutting tools during machining, and the transfer layers then forming on the tools may give both good and bad effects on machining performance and tool life. The objective of this work is to understand the effects of alloying element additions to workpiece steels on material transfer and the roles of the formed transfer layers on friction characteristics and wear of tools.

    To isolate and study the influence of the individual alloying elements, model steels are specifically designed. These steels include one reference with C as the only alloying element and others alloyed also with single additions or combined additions of 1 mass% Si, Mn, Cr and Al. The experiments are performed using both a sliding test, simulating the material transfer in milling, and a turning test.

    In a sliding contact, the mode of transfer is strongly dependent on the normal load and sliding speed. Material transfer initiates extremely fast, in less than 0.025 s, and characteristic transfer layers develop during the first few seconds. The different steel compositions result in the formation of different types of oxides in the transfer layers. At the workpiece/tool interface where the conditions involve high temperature, high pressure and low oxygen supply, easily oxidized alloying elements in the steel are preferentially transferred, enriched and form a stable oxide on the tool surface. The degree of enrichment of the alloying elements in the oxides is strongly related to their tendencies to become oxidized.

    The difference in melting temperature of the oxides, and thus the tendency to soften during sliding, explains the difference in the resulting friction coefficient. The widest differences in friction coefficients are found between the Si and Al additions. A Si containing oxide shows the lowest friction and an Al containing oxide the highest.

    The damage mechanism of coated tools is chiefly influenced by the form and shear strength of the transferred material. Absence of transfer layer or non-continuous transferred material leads to continuous wear of the coating. Contrastingly, continuous transfer layers protect it from wear. However, transfer layers with very high shear strength result in high friction heat and a large amount of steel transfer. This leads to rapid coating cracking or adhesive wear.

  • Public defence: 2016-12-17 09:15 Gustavianum, Uppsala
    Påfs, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Påfs, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The Quest for Maternal Survival in Rwanda: Paradoxes in Policy and Practice from the Perspective of Near-Miss Women, Recent Fathers and Healthcare Providers2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rwanda has made significant progress in decreasing the number of maternal deaths and increasing the number of antenatal care visits and childbirths at health facilities. This thesis seeks to illuminate potential barriers for Rwanda’s goal for maternal survival. The studies explore the bottom-up perspective of policies and practices in regards to maternal care in Kigali. Semi-structured interviews were conducted between 2013 and 2016 with women who nearly died (‘near-miss’) during pregnancy, their partners, and with other recent fathers and community members, as well as healthcare providers who work within abortion care. The framework of naturalistic inquiry guided the study design and data collection. Analysis was conducted using framework analysis, thematic analysis and naturalistic inquiry.

    The findings identify paradoxical outcomes in the implementation of maternal care policies. Despite recent amendments of the abortion law, safe abortion was identified as being non-accessible. Abortion-related symptoms continue to carry a criminalized and stigmatized label, which encourages risk-taking and clandestine solutions to unwanted pregnancies, and causes care-seeking delays for women with obstetric complications in early pregnancy. Healthcare providers had limited awareness of the current abortion law, and described tensions in exercising their profession due to fear of litigation. The first antenatal care visit appeared to require the accompaniment of a male partner, which underpinned women’s reliance on men in their care-seeking. Men expressed interest in taking part in maternal care, but faced resistance for further engagement from healthcare providers. Giving birth at a health facility was identified as mandatory, yet care was experienced as suboptimal. Disrespect during counseling and care was identified, leading to repeated care-seeking and may underpin the uptake of traditional medicine.

    An enhanced implementation of the current abortion law is recommended. Reconsideration of policy is recommended to ensure equitable and complete access to antenatal care: women should be able to seek care accompanied by their person of choice. These findings further recommend action for improved policy to better address men’s preferred inclusion in maternal health matters. The findings of this thesis promote continued attention to implementing changes to strengthen quality, and trust, in public maternal care.

  • Public defence: 2016-12-17 10:15 Ihresalen, Uppsala
    Larsson, Tove
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Languages, Department of English.
    Larsson, Tove
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Languages, Department of English.
    The introductory it pattern in academic writing by non-native-speaker students, native-speaker students and published writers: A corpus-based study2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The present compilation thesis investigates the use of a pattern that is commonly found in academic writing, namely the introductory it pattern (e.g. it is interesting to note the difference). The main aim is to shed further light on the formal and functional characteristics of the pattern in academic writing. When relevant, the thesis also investigates functionally related constructions. The focus is on learner use, but reference corpora of published writing and non-native-speaker student writing have also been utilized for comparison. The thesis encompasses an introductory survey (a “kappa”) and four articles.

    The material comes from six different corpora: ALEC, BATMAT, BAWE, LOCRA, MICUSP and VESPA. Factors such as native-speaker status, discipline, level of achievement (lower-graded vs. higher-graded texts) and level of expertise in academic writing are investigated in the articles. In more detail, Articles 1 and 2 examine the formal (syntactic) characteristics of the introductory it pattern. The pattern is studied using modified versions of two previous syntactic classifications. Articles 3 and 4 investigate the functional characteristics of the pattern. In Article 3, a functional classification is developed and used to categorize the instances. Article 4 examines the stance-marking function of the pattern in relation to functionally related constructions (e.g. stance adverbs such as possibly and stance noun + prepositional phrase combinations like the possibility of).

    The introductory it pattern was found to be relatively invariable in the sense that a small set of formal and functional realizations made up the bulk of the tokens. The learners, especially those whose texts received a lower grade, made particularly frequent use of high-frequency realizations of the pattern. The thesis highlights the importance of not limiting investigations of this kind to comparisons across native-speaker status, as this is only one of the several factors that can influence the distribution. By exploring the potential importance of many different factors from both a formal and a functional perspective, the thesis paints a more complete picture of the introductory it pattern in academic writing, of use in, for instance, second-language instruction.

  • Public defence: 2016-12-19 09:15 B21, Uppsala
    Knöppel, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Knöppel, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Experimental Evolution: and Fitness Effects of Mutations2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bacteria have small, streamlined genomes and evolve rapidly. Their large population sizes allow selection to be the main driver of evolution. With advances in sequencing technologies and precise methods for genetic engineering, many bacteria are excellent models for studying elementary questions in evolutionary biology. The work in this thesis has broadly been devoted to adaptive evolution and fitness effects of different types of mutations.

    In Paper I we experimentally tested the fitness constrains of horizontal gene transfer (HGT), which could be used to predict how the fixation of HGT events are affected by selection and fitness effects. We found that the majority of the examined HGT inserts were indistinguishable from neutral, implying that extra DNA transferred by HGT, even though it does not confer an immediate selective advantage, could be maintained at transfer-selection balance and serve as a reservoir for the evolution of novel beneficial functions.

    Paper II examined why four synonymous mutations in rpsT (encoding ribosomal protein S20) reduced fitness, and how this cost could be genetically compensated. We found that the cause for the fitness reduction was low S20 levels and that this lead to a defective subpopulation of 30S subunits lacking S20. In an adaptive evolution experiment, these impairments were compensated by up-regulation of S20 though various types of mutations.

    In Paper III we continued the studies of how the deleterious rpsT mutations could be compensated. The mutations either down-regulated the global regulator Fis or altered a subunit of the RNA polymerase (rpoA). We found that the decreased S20 levels in the cells causes an assembly defect of the 30S particles and that the fis and rpoA mutations restored the skewed S20:ribosome ratio by both increasing S20 levels and decreasing other ribosomal components.

    Paper IV examined adaptation of two bacterial species to different growth media. A total of 142 different adaptive mutations were identified and 112 mutants were characterized in terms of fitness. We found that the experimental variation in fitness measurements could be reduced 10-fold by introducing some adaptive mutations prior to the experiment, allowing measurements of fitness differences as small as 0.04%.

  • Public defence: 2016-12-19 09:30 E10:1307-E10:1309, Biomedical Centre, Uppsala
    Hantke, Max Felix
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Hantke, Max Felix
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Coherent Diffractive Imaging with X-ray Lasers2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The newly emerging technology of X-ray free-electron lasers (XFELs) has the potential to revolutionise molecular imaging. XFELs generate very intense X-ray pulses and predictions suggest that they may be used for structure determination to atomic resolution even for single molecules. XFELs produce femtosecond pulses that outrun processes of radiation damage and permit the study of structures at room temperature and of structural dynamics.

    While the first demonstrations of flash X-ray diffractive imaging (FXI) on biological particles were encouraging, they also revealed technical challenges. In this work we demonstrated how some of these challenges can be overcome. We exemplified, with heterogeneous cell organelles, how tens of thousands of FXI diffraction patterns can be collected, sorted, and analysed in an automatic data processing pipeline. We improved  image resolution and reduced problems with missing data. We validated, described, and deposited the experimental data in the Coherent X-ray Imaging Data Bank.

    We demonstrated that aerosol injection can be used to collect FXI data at high hit ratios and with low background. We reduced problems with non-volatile sample contaminants by decreasing aerosol droplet sizes from ~1000 nm to ~150 nm. We achieved this by adapting an electrospray aerosoliser to the Uppsala sample injector. Mie scattering imaging was used as a diagnostic tool to measure positions, sizes, and velocities of individual injected particles.

    XFEL experiments generate large amounts of data at high rates. Preparation, execution, and data analysis of these experiments benefits from specialised software. In this work we present new open-source software tools that facilitates prediction, online-monitoring, display, and pre-processing of XFEL diffraction data.

    We hope that this work is a valuable contribution in the quest of transitioning FXI from its first experimental demonstration into a technique that fulfills its potentials.