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Coming dissertations at Uppsala university

Please note that the date and time given on these pages is the time of electronic publication, and not the date of the public defense. To find the time and venue of the public defense, please follow the link to DiVA of the thesis in question.
  • Power transfer in the air gap of linear generators for wave power

    Author: Anna E. Frost
    Publication date: 2019-05-13 10:35

    An increased need for electric energy and share of renewable energy is important for a more sustainable future, to which wave power can contribute. Some concepts for wave power use linear generators, and the studies presented here focus on the power transfer and forces in the air gap of linear generators.

    Based on Poynting's theorem, analytical expressions were derived for how much power is transmitted in the air gap of linear electric machines. The equations were derived for flat linear generators as well as for cylindrical linear generators, and for both the radial and the longitudinal power flows. The radial power flow contributes to the electricity that can be taken from the generator, while the longitudinal contributes to unwanted effects such as vibration. The equations show that for flat linear electric machines, vibrations and other unwanted power transmissions can be reduced by increasing the number of poles in the machine, without decreasing the desired power transfer. Otherwise, the same factors that increase the desired power transfer also increase the unwanted.

    By studying the generator as a damping force and a lumped circuit, it was derived that the absorbed energy of a linear generator is quadratically dependent on the partial stator-translator overlap if the inductance of the generator is not affected by a partial overlap. Consequently, the forces in the air gap also depend quadratically on the relative overlap between the stator and the translator.

    Data were collected during two experiments in order to determine whether the quadratic dependence between partial stator-translator overlap and energy transfer could be seen experimentally. Linear regression analysis of the experimental data shows that the relationship is somewhere between linear and cubic, but did not clearly show a quadratic relationship. The inductance showed no dependence of the partial stator-translator overlap.

  • Oxygen Storage Chemistry of Nanoceria

    Author: Dou Du
    Publication date: 2019-05-10 13:44

    The versatile redox chemistry of ceria (CeO2) originates from its Ce4f electron, which plays the key role in changing the oxidation state of Ce between +IV and +III. Ceria is, among other things, a material that can act as a powerful oxygen buffer with a high oxygen storage capacity (OSC). This is used in many technical applications, such as the three-way catalyst, cleaning exhausts from gasoline vehicles. This thesis is concerned with the dramatic OSC effect observed experimentally in the literature for very small ceria nanoparticles (NPs) at lower temperatures, where the effect was found to be accompanied by the formation of superoxide ions (O2–).

    The main aim of the thesis work was to develop strategies to allow us to discover the origin of the OSC phenomenon, and to simulate temperature-programmed reduction (TPR) and temperature-programmed desorption (TPD) experiments and collect useful mechanistic insight about these processes. Quantum-mechanical (DFT) calculations, partly with modified DFT functionals, and later augmented by microkinetic (MK) modelling building on the DFT-results, made it possible to model the large and complex NP systems needed to make detailed comparisons between theory and experiment feasible.

    At first, a suitable DFT functional for nanoceria was needed. We turned to hybrid functionals, and more specifically, the non-local Fock exchange contribution within the hybrid functional HSE06 was explored. The amount that gave the best overall description was determined (15%, labeled HSE06' below) and was used in subsequent studies. Moreover, an accompanying HSE06'//PBE+U computational protocol was constructed (HSE06' energies calculated for pre-optimized structures at the PBE+U level); this made it possible to use the hybrid functional for large ceria systems.

    With the modified HSE functional, we scrutinized a previously proposed OSC model, namely the "supercharge" model for nanoparticles loaded on the outside with superoxide ions at low-coordinated ridge sites, enabled by the oxidation of Ce3+ to Ce4+. In the previous study, adsorption energies were calculated using the PBE+U density functional, which does not give adsorption energies in agreement with experiment. With the new HSE06' functional, together with the Redhead equation, we obtained an estimated oxygen desorption peak at ca. 415 K, in much better agreement with the experimental TPD peak at 440 K. However, this calculation could still not explain the large broadening of the experimental TPD spectrum. An oxygen adsorption energy model was then formulated which took Ce coordination and superoxide ion coverage into account. With microkinetic simulations based in this energy model, we achieved a broad simulated TPD signal, which was largely in agreement with the experimental spectrum.

    Finally, an improved “supercharge” model was assessed concerning its ability to mimic the temperature-programmed reduction (TPR) experiments reported in the literature for H2 interacting with ceria nanoparticles. We proposed that the reduction process follows a Langmuir-Hinshelwood reaction mechanism, which gave a simulated TPR spectrum in good agreement with the experimental results.

    In summary, the goals listed above were achieved: we managed to simulate TPD and TPR spectra, using a DFT-based MK approach; the results were in good agreement with experiment and useful mechanistic insight about these processes and the OSC mechanism was derived from the MK simulations and the DFT analyses.

  • Pharmacometric Approaches to Improve Dose Individualization Methods in Hemophilia A

    Author: João A. Abrantes
    Publication date: 2019-05-06 14:36

    Hemophilia A is a bleeding disorder caused by the lack of functional coagulation factor VIII (FVIII). The overall aim of this thesis was to improve dose individualization of FVIII replacement therapy in hemophilia A using pharmacometric approaches.

    A population pharmacokinetic (PK) model of FVIII activity following the administration of moroctocog alfa was developed based on data from a large heterogeneous cohort of moderate to severe hemophilia A patients. Body weight, age, neutralizing anti-FVIII inhibitors, race, and analytical assay were found to be significant predictors of FVIII activity PK. In addition, large inter-individual variability (IIV) and inter-occasion variability (IOV) was identified highlighting the need for dose individualization.

    High magnitudes of IOV are known to impair model-based therapeutic drug monitoring. Using a population PK model of FVIII activity, several approaches to handle IOV in Bayesian forecasting of individual PK parameters were assessed across a wide range of features. Considering IOV in Bayesian forecasting, but ignoring IOV in dose calculation, led to the most precise individualized doses, in particular, when sparse data was used.

    The dose-exposure-response relationship of FVIII replacement therapy remains unclear. A parametric repeated time-to-categorical event (RTTCE) model was developed to characterize the relationship between the dose of octocog alfa, plasma FVIII activity, bleeding frequency and severity, and covariates, using data from clinical trials. The bleeding hazard was found to decrease throughout time and to be affected by plasma FVIII activity and number of previous bleeds. Unexplained IIV in the bleeding hazard was found to be large.

    Bayesian forecasting based on the RTTCE model was used to predict the future occurrence of bleeds, and to contrast the predicted outcome using individual i) PK, ii) bleeding, and iii) PK, bleeding and covariate information, from data collected in clinical trials. The results support that individual bleed information can inform the optimization of prophylactic dosing regimens in severe hemophilia A patients.

    In summary, the pharmacometric approaches presented provide a valuable quantitative framework to improve dose individualization in hemophilia A. Furthermore, enhanced dosing has the potential to reduce bleeding frequency and to lower the high costs associated to treatment.

  • Molecular detection and epidemiological studies of atypical bacteria causing respiratory tract infections

    Author: Karolina Gullsby
    Publication date: 2019-05-06 12:00

    Respiratory infections are common causes of morbidity and mortality. Chlamydia pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis cause respiratory infection, often with similar symptoms. Molecular diagnostic methods are preferred since these bacteria are difficult to culture. The aim of this thesis was to evaluate and improve the diagnostics and knowledge of the epidemiology of these bacteria.

    A real-time polymerase chain reaction (PCR) method targeting the IS481 element present in the genome of B. pertussis was compared to culture and serology results, and a duplex real-time PCR method was constructed for detecting C. pneumoniae and M. pneumoniae, which was compared to two endpoint PCR methods. Both real-time PCR methods showed high sensitivity and specificity.

    Typing of 624 M. pneumoniae samples, collected from 1996 to 2017 from four counties, was performed by P1 typing and multiple-locus variable number tandem repeat analysis (MLVA). A polyclonal distribution of strains was seen over all epidemic periods, but strains of P1 type 2/variant 2 and MLVA types 3-5-6-2 and 4-5-7-2 predominated in 2010−2013. A shift from type 2 strains to different variant 2 strains was seen and a new variant, 2e, was detected in 2016−2017. An A2063G mutation associated with macrolide resistance was detected by a fluorescence resonance energy transfer (FRET) PCR method in one (0.16%) of 608 M. pneumoniae strains.

    Molecular characterisation using whole-genome sequencing of 93 B. pertussis isolates, collected between 1986 and 2016 from three counties showed that there were polyclonal strains in the county of Dalarna, Gävleborg and Uppsala in the years 2014−2016. Changes in virulence-related genes were detected: a shift from isolates harbouring the ptxP3 allele in favour of ptxP1 was seen, and almost all isolates had a disrupted prn gene. No detection of macrolide resistance in B. pertussis was detected.

    In conclusion, the validated real-time PCR methods for detection of B. pertussis, C. pneumoniae and M. pneumoniae have led to improved diagnostic methods for use in clinical laboratories. The molecular characterisation of M. pneumoniae and B. pertussis strains has contributed to the wider understanding of the genetic changes that has occurred over the epidemic periods, but further studies is needed.

  • Impact of the inflammatory response on specific immunity in neurosurgical patients

    Author: Anna Ljunghill Hedberg
    Publication date: 2019-05-06 10:41

    Vaccination with a T-cell-dependent pneumococcal conjugate vaccine (PCV) followed by a T-cell-independent pneumococcal polysaccharide vaccine (PPSV) is recommended after basilar skull fracture to reduce the risk of meningitis. The optimal time frame for vaccination has not yet been established and varies widely in practice. Because the risk of meningitis is at its peak shortly after the trauma incident, early vaccination might be more desirable. After trauma and central nervous system (CNS) injury, T-cell defects leading to trauma and CNS injury-induced immune deficiency syndromes may affect the vaccine response. In light of the above information, the overall aim of this thesis was to investigate the impact of neurotrauma and neurosurgery on the response to T-cell-dependent and T-cell-independent vaccines.

    In Paper I, we compared the antibody response to a T-cell-dependent conjugate vaccine in patients vaccinated within 10 days after neurotrauma or neurosurgery with those vaccinated after >3 weeks. To avoid interference with pneumococcal vaccination, a conjugate vaccine against Haemophilus influenzae type b (Hib) was chosen for the study. The majority of the patients responded to the vaccination, although the number of responders was significantly lower in patients vaccinated early.

    In Paper II, we investigated the antibody response to the T-cell-independent vaccine PPSV in patients vaccinated within 10 days after neurotrauma or neurosurgery and in patients vaccinated after >3 weeks. Patients vaccinated early responded similarly to those vaccinated after the acute period, indicating that PPSV can be administered early after neurotrauma or neurosurgery.

    In Paper III, we compared the response to Hib vaccine with the response to PPSV. We also examined whether individual clinical or immunological parameters might predict the response to T-cell-dependent vaccine and thereby help identify non-responders before vaccination. No correlation between Hib vaccine and PPSV responses was found, indicating that B-cell function is not similarly depressed as T-cell function. It was not possible to predict the T-cell-dependent vaccine response by standardized grading of the trauma or by parameters reflecting the innate immune response.

    In Paper IV, we found a significant reduction in the ex vivo CD4+ T-lymphocyte response to PCV in patients after neurotrauma or neurosurgery as compared with healthy controls.

    Our results suggest that PPSV might be a viable alternative to T-cell-dependent PCV in early vaccination after neurotrauma.

  • Plants as Sources of Natural and Effective Acaricides : Against Ixodes ricinus  (Acari: Ixodidae)

    Author: Fawzeia Elmhalli
    Publication date: 2019-05-02 14:02

    Ticks and tick-borne diseases are major health hazards worldwide, with increasing numbers of cases of Lyme disease and tick-borne encephalitis reported yearly. Meanwhile, concerns about the environmental impact and safety of chemical acaricides are driving research into alternative control methods, such as plant-based acaricides. I evaluated eight plant species for their toxicity and repellency against nymphs of Ixodes ricinus (Acari: Ixodidae), the most important life cycle stage of tick-borne infection of humans.

    Paper I examines the toxicity of the principal active component of the essential oil (EO) of lemon eucalyptus (Corymbia citriodora), p-menthane-3,8-diol (PMD). At 4 h of exposure time (ET), lethal PMD concentrations for 50% mortality (LC50) were 0.035–0.037 mg/cm² and for 95% mortality (LC95) were 0.095-0.097 mg/cm². For 0.1 mg/cm², lethal times for 50% mortality (LT50) were 2.1-2.8 h and for 95% mortality (LT95) were 3.9-4.2 h. An open filter assay gave the most consistent results of five methods tried. Paper II investigated the toxicity of ylang-ylang oil (YYO) and star anise oil (SAO), two naturally occurring, commercially available and inexpensive EOs. Oils were tested at 0.05, 0.1, 0.2, and 0.4μl/cm², and dead nymphs counted at 30-min intervals up to 5h and then at 24, 48 and 72h. For YYO, an exposure of 4.4h resulted in LC95 for 0.4 μl/cm² and LC50 for 0.2μl/cm². The LT95 was 3h for 0.4 μl YYO/cm² and 4.3 h for 0.2 μl/cm². For SAO, the highest concentration (0.4 μl/cm²) only reached LC50 at 14 h and LT95 was 24h. Thus, YYO is a much stronger acaricide but SAO still showed significant toxicity.

    Paper III investigated two plants of traditional medicinal or economic importance in Libya -Salvadora persica, (Miswak) and Rosmarinus officinalis (Libyan Rosemary). EOs were extracted from wild-collected leaves by steam distillation. Oils were tested on I. ricinus nymphs and their chemical composition analysed by GC-MS. R. officinalis EO at 0.5 and 1µl/cm² exhibited 20% and 100% mortality, respectively, after about 5h of ET. The LC50 and LC95 for 1µl/cm² R. officinalis oil were 0.7 and 0.95 µl/cm², respectively. S. persica oil at 1µl/cm² gave 95% repellency up to 1.5h, reducing to 50% at around 5.45 h, but no significant mortality even after 24h ET. GC-MS analysis showed both oils to be rich in the monoterpenes 1,8 cineol, α-pinene and β-pinene with values of 20.8%, 5.9% and 16.8 %, respectively, for S. persica and 24.07%, 13.03% and 2.45%, respectively, for R. officinalis.

    Paper IV investigated EOs extracted from leaves of three additional native Libyan plants - Artemisia herba alba (white wormwood), Origanum majorana (oregano) and Juniperus phoenicea (Ar-aar). At 1µl/cm², the LT95 for both A. herba and J. phoenicea EO was 2h versus 72 h for O. majorana oil. GC-MS analyses gave plant specific combinations of the monoterenoids α-pinene, 1,8-cineol, camphor, linalool, terpinene-4-ol, α-terpinol, β-caryophyllene and β-thujanone. EO of A.herba alba contained most of the oxygenated monoterpenes, which all are all known to have insecticidal activity.

    Taken together, all the EOs used in this study show a broad spectrum of effects against I. ricinus nymphs, making them good candidates for controlling ticks and, thereby, the diseases they carry.

  • Silicon Nanowire Field-Effect Devices as Low-Noise Sensors

    Author: Xi Chen
    Publication date: 2019-05-02 12:54

    In the past decades, silicon nanowire field-effect transistors (SiNWFETs) have been explored for label-free, highly sensitive, and real-time detections of chemical and biological species. The SiNWFETs are anticipated for sensing analyte at ultralow concentrations, even at single-molecule level, owing to their significantly improved charge sensitivity over large-area FETs. In a SiNWFET sensor, a change in electrical potential associated with biomolecular interactions in close proximity to the SiNW gate terminal can effectively control the underlying channel and modulate the drain-to-source current (IDS) of the SiNWFET. A readout signal is therefore generated. This signal is primarily determined by the surface properties of the sensing layer on the gate terminal, with sensitivity close up to the Nernstian limit widely demonstrated. To achieve a high signal-to-noise ratio (SNR), it is essential for the SiNWFETs to possess low noise of which intrinsic device noise is one of the major components. In metal-oxide-semiconductor (MOS)-type FETs, the intrinsic noise mainly results from carrier trapping/detrapping at the gate oxide/semiconductor interface and it is inversely proportional to the device area.

    This thesis presents a comprehensive study on design, fabrication, and noise reduction of SiNWFET-based sensors on silicon-on-oxide (SOI) substrate. A novel Schottky junction gated SiNWFET (SJGFET) is designed and experimentally demonstrated for low noise applications. Firstly, a robust process employing photo- and electron-beam mixed-lithography was developed to reliably produce sub-10 nm SiNW structures for SiNWFET fabrication. For a proof-of-concept demonstration, MOS-type SiNWFET sensors were fabricated and applied for multiplexed ion detection using ionophore-doped mixed-matrix membranes as sensing layers. To address the fundamental noise issue of the MOS-type SiNWFETs, SJGFETs were fabricated with a Schottky (PtSi/silicon) junction gate on the top surface of the SiNW channel, replacing the noisy gate oxide/silicon interface in the MOS-type SiNWFETs. The resultant SJGFETs exhibited a close-to-ideal gate coupling efficiency (60 mV/dec) and significantly reduced device noise compared to reference MOS-type SiNWFETs. Further optimization was performed by implementing a three-dimensional Schottky junction gate wrapping both top surface and two sidewalls of the SiNW channel. The tri-gate SJGFETs with optimized geometry exhibited significantly enhanced electrostatic control over the channel, thereby confined IDS in the SiNW bulk, which greatly improved the device noise immunity to the traps at bottom buried oxide/silicon interface. Finally, a lateral bipolar junction transistor (LBJT) was also designed and fabricated on a SOI substrate aiming for immediate sensor current amplification. Integrating SJGFETs with LBJTs is expected to significantly suppress environmental interference and improve the overall SNR especially under low sensor current situations.

  • Alexandria: A General Drude Polarizable Force Field with Spherical Charge Density

    Author: Mohammad Mehdi Ghahremanpour
    Publication date: 2019-05-02 10:37

    Molecular-mechanical (MM) force fields are mathematical functions that map the geometry of a molecule to its associated energy. MM force fields have been extensively used for an atomistic view into the dynamic and thermodynamics of large molecular systems in their condensed phase. Nevertheless, the grand challenge in force field development—which remains to be addressed—is to predict­­­­ properties of materials with different chemistries and in all their physical phases. 

    Force fields are, in principle, derived through supervised machine learning methods. Therefore, the first step toward more accurate force fields is to provide high-quality reference data from which the force fields can learn. Thus, we benchmarked quantum-mechanical methods—at different levels of theory—in predicting of molecular energetics and electrostatic properties. As the result, the Alexandria library was released as an open access database of molecular properties.  

    The second step is to use potential functions describing interactions between molecules accurately. For this, we incorporated electronic polarization and charge penetration effects into the Alexandria force field. The Drude model was used for the explicit inclusion of electronic polarization. The distribution of the atomic charges was described by either a 1s-Gaussian or an ns-Slater density function to account for charge penetration effects. Moreover, the 12-6 Lennard-Jones (LJ) potential function, commonly used in force fields, was replaced by the Wang-Buckingham (WBK) function to describe the interaction of two particles at very short distances.  In contrast to the 12-6 LJ function, the WBK function is well behaved at short distances because it has a finite limit as the distance between two particles approaches zero. 

    The third step is free and open source software (FOSS) for systematic optimization of the built-in force field parameters. For this, we developed the Alexandria chemistry toolkit that is currently part of the GROMACS software package. 

    With these three steps, the Alexandria force field was developed for alkali halides and for organic compounds consisting of (H, C, N, O, S, P) and halogens (F, Cl, Br, I). We demonstrated that the Alexandria force field described alkali halides in gas, liquid, and solid phases with an overall performance better than the benchmarked reference force fields. We also showed that the Alexandria force field predicted the electrostatics of isolated molecules and molecular complexes in agreement with the density functional theory at the B3LYP/aug-cc-pVTZ level of theory. 

  • Transition Metal-Based Electrocatalysts for Alkaline Water Splitting and CO2 Reduction

    Author: Zhen Qiu
    Publication date: 2019-04-29 14:39

    With excessive usage of fossil fuels and ever-increasing environmental issues, numerous efforts have been devoted to the development of renewable energies for the replacement of traditional fossil fuels to reduce greenhouse gas emission and realize the rapidly growing demand for global energy. Renewable energies, however, often show diurnal and seasonal variations in power output, forming a need for energy storage to meet people’s continuous energy supply. One approach is to use electrolysis and produce a fuel that can be used on demand at a later stage. A full realization of effective electricity-to-fuel conversion, however, is still limited by the large overpotential requirements as well as concerns with the usage of scarce platinum group elements. This thesis presents studies on transition metal-based electrocatalysts for alkaline water splitting and CO2 reduction, which are two technologies to produce a chemical fuel from renewable electricity. Our aim is to develop efficient, inexpensive, and robust electrocatalysts based on earth-abundant elements with high energy conversion efficiencies.

    In the first part, we develop and investigate three different electrocatalysts intended for high-performance electrocatalysis of water; NiO nanoflakes (NFs) with tuneable surface morphologies, Fe doped NiO nanosheets (NSs), and self-optimized NiFe layered double hydroxide (LDH) NSs. The self-assembled NiO NFs show drastically different performance for the oxygen evolution reaction (OER). Besides the morphology effect on the catalytic property, the presence of Fe is also functional to improve the catalytic activity for both OER and hydrogen evolution reaction (HER). The NiFe LDH NSs form the most effective system for the overall catalytic performance and is dramatically improved via a dynamic self-optimization, especially for HER, where the overpotential decreases from 206 mV to 59 mV at 10 mA cm-2. In order to get insight into the interfacial reaction processes, a variety of techniques were performed to explore the underlying reasons for the catalytic improvement. Ex-situ X-ray photoelectron spectroscopy, transmission electron microscope and in-situ Raman spectroscopy were utilized to characterize and understand the oxidations states, the crystallinity and the active phases. Electrochemical impedance spectroscopy was applied to investigate the dominating reaction mechanisms during high-performance and stable electrocatalysis.

    In the second part, dynamically formed CuInO2 nanoparticles were demonstrated to be high-performance electrocatalysts for CO2 reduction. In-situ Raman spectroscopy was utilized to reveal and understand the formation of CuInO2 nanoparticles based on the Cu2O pre-catalyst onto an interlayer of indium tin oxide under the electrochemical reaction. Density function theory calculation and ex-situ X-ray diffraction further prove the formation of CuInO2 nanoparticles during vigorous catalysis. The findings give important clues on how Cu-based electrocatalysts can be formed into more active materials and can provide inspiration for other Cu-based intermetallic oxides for high-efficiency CO2 reduction.

  • Partial and General Equilibrium Effects of Unemployment Insurance : Identification, Estimation and Inference

    Author: Mathias von Buxhoeveden
    Publication date: 2019-04-29 14:35

    Essay I: Wage setting models typically posit a tight relationship between the generosity of unemployment insurance (UI) and equilibrium wages. This paper estimates the effect of UI on workers’ wages. I build on a unique feature of the unemployment policy in Sweden, where workers can opt to buy supplement UI coverage above a minimum mandated level. In January 2007, the government sharply increased the price of UI, and the share of workers with supplement coverage fell from 90% to 80%. I exploit variation in the price of UI across industries to measure the effect of industry level UI-coverage on wages. My estimates suggest that a 10 percentage point reduction in the share of workers covered by supplement UI reduce wages by 5%. Since I rely on variation in UI-coverage at the industry level, these estimates contain wage adjustments from collective and individual level bargaining. Finally, I use the estimated UI-wage effect to derive bounds on worker bargaining power in a simple DMP model and find that it can be at most 0.12. This evidence supports wage setting mechanisms that tie wages to the generosity of UI.