| 1. |
- Bremdal, Patrik, 1980-
(author)
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Riksdagens kontroll av regeringsmakten
- 2011
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Doctoral thesis (other academic/artistic)abstract
- With power comes responsibility, which requires both information about actions taken by those in power, and mechanisms for effective accountability. The possibility for the elected representatives to review and take action against the government and its exercise of power is central in our constitution. In this thesis the author demonstrates the opportunities that members of parliament have at their disposal to control and to hold government accountable. These are interpellations, questions, the review of the Committee on the Constitution, specific debates, the vote of confidence, and the prosecution of ministers. Together they form a system of rules that constitutes the basis for parliamentary control of power in and also for this thesis.In this thesis the author discuss the role and function of the parliamentary control of power in Sweden. It is important to consider all forms such control in order to optimize the performance of the control system as a whole. It is also important to see the linkage between control and democratic and constitutional values in order to understand its role and significance. One aim of this thesis is to analyze the parliamentary review of government with a partly new approach. The author place the discussion within a theoretical framwork of accountability and thereby put the mecanisms of control in context. This creates a deeper understanding of the power of control and its function and significance.The author want to bring a principled and theoretical dimension into the analysis of both the various elements that make up the Riksdag's control power, and the whole that these elements cronstitutes. A systematic model is constructed to enhance the understanding of the Riksdags’s direct control of governmental power. The analysis of the individual institutions of control also aims to create a more realistic pictures of those institutions.
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| 2. |
- Friederich Persson, Malou, 1983-
(author)
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The Role of Mitochondrial Uncoupling in the Development of Diabetic Nephropathy
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Diabetes is closely associated with increased oxidative stress, especially originating from the mitochondria. A mechanism to reduce increased mitochondria superoxide production is to reduce the mitochondria membrane potential by releasing protons across the mitochondria membrane. This phenomenon is referred to as mitochondria uncoupling since oxygen is consumed independently of ATP being produced and can be mediated by Uncoupling Proteins (UCPs). However, increased oxygen consumption is potentially detrimental for the kidney since it can cause tissue hypoxia. Therefore, this thesis aimed to investigate the role of mitochondria uncoupling for development of diabetic nephropathy. UCP-2 was demonstrated to be the only isoform expressed in the kidney, and localized to tubular segments performing the majority of tubular electrolyte transport. Streptozotocin-induced diabetes in rats increased UCP-2 protein expression and correlated to increased non-transport dependent oxygen consumption in isolated proximal tubular cells. These effects were prevented by intense insulin treatment to the diabetic animals demonstrating a pivotal role of hyperglycemia. Importantly, elevated UCP-2 protein expression increased mitochondria uncoupling in mitochondria isolated from diabetic kidneys. Mitochondria uncoupling and altered morphology was also evident in kidneys from db/db-mice, a model of type-2 diabetes, together with proteinuria and glomerular hyperfiltration which are both clinical manifestations of diabetic nephropathy. Treatment with the antioxidant coenzyme Q10 prevented mitochondria uncoupling as well as morphological and functional alterations in these kidneys. Acute knockdown of UCP-2 paradoxically increased mitochondria uncoupling in a mechanism involving the adenosine nucleotide transporter. Increased uncoupling via adenosine nucleotide transporter decreased mitochondria membrane potential and kidney oxidative stress but did not affect glomerular filtration rate, renal blood flow, total kidney oxygen consumption or intrarenal tissue oxygen tension. The role of increased mitochondria oxygen consumption was investigated by administering the chemical uncoupler dinitrophenol to healthy rats. Importantly, increased mitochondria oxygen consumption resulted in kidney tissue hypoxia, proteinuria and increased staining of the tubular injury marker vimentin, demonstrating a crucial role of increased oxygen consumption per se and the resulting kidney tissue hypoxia for the development of nephropathy. Taken together, the data presented in this thesis establishes an important role of mitochondria uncoupling for the development of diabetic nephropathy.
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| 3. |
- Grönberg, Fredrik
(author)
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Spectral Photon-Counting Computed Tomography with Silicon Detectors: New Models and Applications
- 2022
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Doctoral thesis (other academic/artistic)abstract
- X-ray computed tomography (CT) is a widely used imaging modality that enables visualization of nearly every part of the human body. It is used for diagnosis of disease and injury as well as medical treatment planning. The vast majority of CT scanners in clinical use today have energy-integrating x-ray detectors, which measure the total incident energy in a given measurement.Spectral photon-counting detectors operate by counting individual photons and measuring their energy, and are expected to yield the next major advance in CT, with improvements in spatial resolution, dose efficiency, material differentiation and quantitative imaging capabilities compared to the current state-of-the-art.In this Thesis, a set of new models and applications for a spectral photon-counting silicon detector developed for CT is investigated. The first part of the Thesis is dedicated to the modeling of spectral photon-counting silicon detectors. A new statistical model for the effects of pulse pileup is presented. Also, the effects on image quality from intra-detector Compton scatter in silicon detectors are investigated via spatio-energetic modeling. In the second part of the Thesis, potential applications for spectral photon-counting detectors are investigated. An experimental study of ex vivo CT imaging of an excised human heart with calcified plaque is presented. It demonstrates the feasibility of unconstrained projection-based three-material decomposition with iodine as a third basis material and explores the potential improvements in spatial resolution and material differentiation that can be achieved with a spectral photon-counting silicon detector compared to a conventional dual-energy CTsystem. Two other applications are investigated with simulations: a method for reconstructing CT images from spectral photon-counting CT data that accurately mimic conventional CT images; and a method for estimating iron concentration in mixtures of liver and adipose tissue when using three basis functions instead of only two to describe the linear attenuation coefficient of tissues in the human body. Although the methods presented in this Thesis have been specifically developed for a spectral photon-counting silicon detector, they are also applicable for other types of photon-counting detectors.
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| 4. |
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| 5. |
- Kentson, Magnus
(author)
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Fatigue and Peripheral Muscle Dysfunction: Studies on Vitamin D Status, Muscle Metabolism and Systemic Inflammation in Patients with COPD : Aspects of COPD severity beyond FEV1 and exacerbations
- 2022
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Doctoral thesis (other academic/artistic)abstract
- BackgroundThe severity of Chronic Obstructive Pulmonary Disease (COPD) is usually described in terms of forced expiratory volume in one second (FEV1) and number of exacerbations. However, COPD is a complex disease with different ways of expression, involving pulmonary symptoms, extra pulmonal manifestations and comorbidities, which altogether affect the patient by contributing to reduced functional capacity, increased shortness of breath, reduced health-related quality of life and increased mortality. Systemic inflammation is common in COPD and can potentially constitute a link between the lungs and other organs. The aim of this thesis was to broaden the aspects of COPD severity beyond FEV1 and exacerbations by studying fatigue, the role of vitamin D, nutritional factors, systemic inflammation and peripheral muscle function in patients with COPD. Methods and ResultsIn paper I, we included 101 patients with COPD, and 34 control subjects. Assessment of experience of fatigue, functional limitation due to fatigue, and the relationships to physiological, psychological and situational variables and quality of life (QoL) were evaluated. We found that experience of fatigue was highly prevalent (72% versus 56% in control subjects) and a troublesome symptom in COPD. Patients with COPD and fatigue had lower lung function, shorter walking distance, more dyspnoea, anxiety and depressive symptoms and poorer health status compared to patients without fatigue (all p < 0.01). Several contributing factors were identified to experience of fatigue and functional limitations of fatigue with dyspnoea, depressive symptoms and insomnia as the most prominent factors. No clear association with systemic inflammation was found. Paper II evaluated vitamin D status in 66 patients with advanced COPD (28 with long-term oxygen therapy (LTOT)) and 47 control subjects. 25-hydroxyvitamin 25(OH)D were deter-mined in early fall in a short period of seven weeks. Questionnaires about COPD symptoms, general health, lifestyle, dietary habits and QoL were answered. Lung function tests and blood sampling including systemic inflammatory markers, carotenoids and protein carbonylation (PC) were assessed. The peak annual 25(OH)D of COPD patients was significantly lower than in the control subjects, but there was no significant difference between COPD patients with and without LTOT. Among vitamin D-deficient COPD patients, 25(OH)D correlated positively with lung function, blood oxygenation, food portion size, Mediterranean Diet Score and Ultra-violet Score and negatively with dyspnoea and DOSE-index, a composite index for COPD se-verity. Ongoing vitamin D supplementation was the single most important intervention to maintain 25(OH)D levels <50 nmol/L. In paper III, we evaluated in the same cohort as paper II oxidative damage and levels of carotenoids. Patients with COPD (±LTOT) did not demonstrate increased oxidative damage. Com-pared with the control group, levels of several carotenoids were significantly lower in COPD, and the diet contained significantly less fruit and vegetables. Lycopene correlated positively with saturation and lutein correlated positively with some inflammatory markers but negatively with IL-6, an important marker for systemic inflammation. The study highlights the importance of dietary factors in COPD. In paper IV, 32 patients with COPD answered questionnaires, and were subjected to lung function tests and blood analysis including systemic inflammatory markers. Magnetic resonance imaging (MRI) for analysis of whole-body and thigh muscle composition was performed. Bioenergetics in the resting thigh muscle, (PCr/Pi ratio), were analysed using 31phosphorus magnetic resonance spectroscopy (31P-MRS). We found that adverse muscle composition was common in the COPD group. Clinical characteristics reflecting COPD severity were all associated with a raise of the PCr/Pi ratio in the thigh muscle. Increased MFIa correlated positively to systemic inflammatory markers, negative to physical activity and PCr/Pi ratio. We compared the COPD group with a virtual control group from UK Biobank (n= 3200). ConclusionsSevere COPD is much more than airway obstruction and exacerbations. The presence of fatigue is associated, as well as vitamin D status and nutritional factors, with important clinical out-comes reflecting COPD severity. Adverse muscle composition is common in COPD and there seems to be a link between systemic inflammation, muscle fat infiltration and bioenergetics.
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| 6. |
- Lysholm, Fredrik, 1981-
(author)
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Bioinformatic methods for characterization of viral pathogens in metagenomic samples
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Virus infections impose a huge disease burden on humanity and new viruses are continuously found. As most studies of viral disease are limited to theinvestigation of known viruses, it is important to characterize all circulating viruses. Thus, a broad and unselective exploration of the virus flora would be the most productive development of modern virology. Fueled by the reduction in sequencing costs and the unbiased nature of shotgun sequencing, viral metagenomics has rapidly become the strategy of choice for this exploration.This thesis mainly focuses on improving key methods used in viral metagenomics as well as the complete viral characterization of two sets of samples using these methods. The major methods developed are an efficient automated analysis pipeline for metagenomics data and two novel, more accurate, alignment algorithms for 454 sequencing data. The automated pipeline facilitates rapid, complete and effortless analysis of metagenomics samples, which in turn enables detection of potential pathogens, for instance in patient samples. The two new alignment algorithms developed cover comparisons both against nucleotide and protein databases, while retaining the underlying 454 data representation. Furthermore, a simulator for 454 data was developed in order to evaluate these methods. This simulator is currently the fastest and most complete simulator of 454 data, which enables further development of algorithms and methods. Finally, we have successfully used these methods to fully characterize a multitude of samples, including samples collected from children suffering from severe lower respiratory tract infections as well as patients diagnosed with chronic fatigue syndrome, both of which presented in this thesis. In these studies, a complete viral characterization has revealed the presence of both expected and unexpected viral pathogens as well as many potential novel viruses.
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| 7. |
- Nahlen Bose, Catarina
(author)
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Coping and emotional well-being in patients with chronic heart failure
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Background: Chronic heart failure (CHF) is a serious illness, with a profound impact on the patient. Poor health-related quality of life (HRQoL) as well as anxiety and depression are prevalent in CHF and predict mortality and rehospitalization, yet, psychosocial factors are infrequently treated and cared for.Aim: To gather scientific evidence on illness perception and coping strategies to predict emotional well-being in patients with CHF and to establish a measurement model of coping strategies. Furthermore, to evaluate a nurse-led psychoeducational intervention, Coping Effectiveness Training (CET) adapted for patients with CHF.Methods: Studies I-III were cross sectional. Study IV was a randomized controlled trial aimed to improve emotional well-being (one-year follow-up). All studies used patient reported outcome measures and clinical data via medical journals.Results: Younger age and male gender were associated with higher levels of alcohol usage and/or drugs to cope, p < 0.01. Poor sense of coherence was associated with maladaptive coping (I). A four factorial model of Brief COPE displayed the best psychometric properties (II). Avoidant coping influenced negative affect (NA) (I), worse HRQoL (II) and greater anxiety and depression (III). CET (IV) improved personal control in the intervention group (IG) compared to the control group (CG), p = 0.036. Improved scores for the IG were detected in emotional well-being and HRQoL, p = ns. The IG demonstrated reduced NA, p = 0.022, excluding cases with clinical anxiety and depression. Time to cardiovascular readmission or death was non-significantly lower in the IG vs the CG (Hazard ratio 0.58 [0.29-1.18]) adjusted p = 0.135.Conclusions: Personal resources seemed to influence the coping strategies used by patients with CHF. Avoidant coping had an adverse influence on emotional wellbeing and illness perception in CHF. The perceived sense of control and illness burden were of importance for emotional well-being. A CET intervention for patients with CHF increased sense of control over the illness. CET also reduced NA in patients with no or mild symptoms of anxiety and depression.
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| 8. |
- Oelker, Melanie, 1988-
(author)
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Disarming bacteria : a structure-based approach to design an anti-virulence drug against Listeria monocytogenes
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Antibiotic resistances are one of the biggest threats to global health and if we don’t change our behavior and way of using antibiotics we will end up in a ‘post-antibiotic era’, in which common infections and minor injuries can once kill again and up to 10 million deaths per year may occur by 2050. Therefore, there is a high need for new anti-bacterial drugs, especially of alternatives to existing antibiotics with already described resistances. Classical antibiotics target the essential processes of survival and growth in bacteria and therefore put a high selective pressure on them to develop resistances. In contrast, the ability to infect or damage a host, the virulence, is less essential for bacteria. Thus, targeting the virulence is supposed to cause a lower selective pressure and this alternative mode-of-action could help to decelerate the development of antibiotic resistances.The aims in this work were to proceed with the structure-based design of an anti-virulence drug against the food-borne pathogen Listeria monocytogenes, but also to deepen our understanding of the complex regulation system for the virulence of this bacterium. PrfA, the master regulator of virulence in Listeria monocytogenes, is a member of a large family of bacterial transcription factors, which are regulated by a conformational change and allosteric modulation by different regulator molecules. Furthermore, its critical role in virulence regulations makes is a suitable target for an anti-virulence drug. In this work new lead compounds based on the previously identified ring-fused 2-pyridone scaffold were designed, synthesized and analyzed by different biological, biophysical, computational and structural biology methods. Three new binding sites and binding modes of these compounds in PrfA were evaluated for their potential use in future designs and a compound with improved activity was identified. In a second study another structurally different lead compound was discovered to inhibit PrfA. Furthermore, the studies on proposed natural regulators of PrfA uncovered the underlying mechanism for the virulence regulation by the peptide signature of the environment and in a follow-up study the structural basis of the binding of inhibitory peptides to PrfA was further investigated. Finally, a structural review on all available structure of PrfA provided more insights into the allosteric regulation mechanism of PrfA activity.This work will hopefully support in the successful development of an anti-virulence drug against Listeria monocytogenes and thus contribute to the reduction of the problem of antibiotic resistances.
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| 9. |
- Persson, Fredrik, 1971-
(author)
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A Study of Parameters and Properties Influencing the Size, Morphology and Oxygen Content of Water Atomized Metal Powders
- 2021
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Doctoral thesis (other academic/artistic)abstract
- The production of metal powders by water atomization is a well-established process, which can be used to produce a wide range of particle sizes for different applications. In general, there is a lack of detailed knowledge about what process parameters that affect the powder properties for water atomized metal powders. More specifically, this thesis focuses on the particle size, morphology and oxygen content of water atomized iron powders. A careful control of the particle size distribution is necessary to atomize powders with a high quality and at a low production cost. Demands on the particle morphologies vary depending on the application for the final product. It is important to control both the melt properties and atomizing parameters, to produce powders with an even particle shape and sintered steel components with tight tolerances. The oxidation of the liquid metal should also be as low as possible during the water atomization, to avoid a large amount of harmful oxide forming in the final powder. Pores are generally considered as defects in metal powders. Therefore, the powder porosity should be as low as possible.The main objective of this thesis is to obtain a more in-depth knowledge of water atomization of metal powders, by investigating some fundamental parts of the process. The study investigates how the median particle size (d50 value) for iron powders is influenced by the water pressure, the melt stream diameter, the jet angle, the water level in the atomizing tank, changed configurations of the water jets, superheat of the melt, and the carbon and sulfur content in the liquid steel. Similarly, the thesis also investigates factors that influence the particle shape, porosity and oxidation of water atomized iron powders.Laboratory and pilot experiments show that the effect on the d50 value was large for the water pressure, medium for the viscosity, surface tension and water to metal ratio, and small for the melt stream diameter. Calculations indicate that the water jet angle has a large effect on the d50 value. In practice, this effect cannot be exploited beyond certain limits caused by instabilities in the atomizing system, which occur if the jet angle is too large.The particle size decreases when the carbon and sulfur contents in the liquid iron are increased. This is attributed to decreased viscosities and surface tensions, respectively. An alternative explanation could be that the superheats at increased carbon contents result in a longer time spent in the molten state before the atomization is completed. This may also lead to a decrease in the particle size. Calculations using a developed d50 model estimate that a decreased viscosity from 6.8 mPa s to 4.3 mPa s leads to a reduction in the d50 value by 33%. Similarly, a decreased surface tension from 1840 mN/m to 900 mN m-1 reduces the d50 value by 27%.The distribution of oxides in pilot water atomized Fe-Mn-C powders was determined by using optical and scanning electron microscopy, combined with energy dispersive X-ray microanalysis. The oxygen in the atomized powders was mainly present as thin surface oxide layers, which increase in thickness from 10 nm to 50 nm as the particle sizes increase from 10 microns to 750 microns. Manganese oxides were observed to be unevenly distributed at the surface of several particles, when the alloy contained 0.3 wt.% manganese. Experimental data indicate that between 10 - 20% of the manganese was present as oxides in the powders. However, equilibrium calculations at 1550 °C estimate that only 4% of the initial manganese content remained in the steel after a completed atomization.The sphericity of the atomized powders decreases as the particle size increases. One feasible explanation is that some larger particles are irregular, since they are formed by collisions of smaller particles. Conversely, smaller particles are formed directly from breakups of the melt and are not the product of collisions between droplets. The sphericity of the size fraction 20-45 microns increases as the carbon content in the iron increases from 0.2 wt.% to 4.2 wt.%. The atomized droplets with larger carbon contents spend a longer time in the molten state, which allows them more time to form a spherical shape during the atomization process. The porosity of iron-carbon powders increases with increasing carbon contents in the melt. Dissociation of steam to hydrogen at the melt surface and precipitation of hydrogen pores in the melt were the most likely mechanisms to cause a pore formation in the powders.Keywords: water atomization; metal powder: particle size; oxygen content; particle shape; porosity; steelmaking
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| 10. |
- Persson, Fredrik, 1978
(author)
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Fast dynamics and measurements of single-charge devices
- 2010
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Doctoral thesis (other academic/artistic)abstract
- In this thesis we present measurements on several different devices, including the single-Cooper-pair box (SCB), the single-electron box, tunable superconducting resonators and so called transmon qubits.By exploiting the quantum capacitance of the SCB, its state was measured by embedding the box in a radio-frequency resonator. The state dependent change in the quantum capacitance then leads to a measurable shift in the resonator’s frequency. On-chip, lumped-element resonators, optimized for speed, were fabricated together with the SCB, which allowed for very fast measurements of the state. We have performed pulsed measurements, and were able to show that the state of the SCB can be measured in approximately 50 ns.The normal state of the box was also measured. We observed a gate dependent absorption in the single-electron box, centered around its degeneracy points, when it was driven by an radio-frequency signal. The internal dynamics of the system was analyzed by solving a two-level master equation. We model the dissipation in the box by defining an effective resistance, which we name the “Sisyphus resistance”. With the developed model, we were able tovery accurately reproduce the measured response over a wide range of RF amplitudes and temperatures.Measurements on a strongly driven SCB are presented. The response of the driven SCB is explained in terms of longitudinal dressed states, defining an effective two-level system. The coherence times of the dressed two-level system are extracted. Relaxation and dephasing in the dressed basis was analyzed.We analyze the possibility of using tunable superconducting resonators for coupling qubits. The resonance frequency is changed by modifying the inductance of a superconducting quantum interference device incorporated into the resonator. The tunability and tuning speed are investigated.We also present measurements on transmon qubits coupled to the tunable cavity. We show Rabi oscillations and observe coherent interaction between two coupled transmon qubits.
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