| 11. |
- Kawde, Anurag Y., 1984-
(author)
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Advanced silicon photoelectrodes for water splitting devices : design, preparation and functional characterization by photo-electrochemistry and high-energy X-ray spectroscopy
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- For the last century, mankind has been hugely dependent on fossil fuels to meet its energy needs. Harnessing energy from fossil fuels led to the emission of greenhouse gases. Greenhouse gases such as CO2 are a major contributor to global warming. Since the last decade, the global annual average temperature has increased by almost 1 oC, while the annual average temperature of Europe has increased by almost 1.7 oC. It is high time to find an alternative source of energy. Such an energy source must be renewable, sustainable, robust and free of greenhouse gases. Our earth has a non-stop supply of solar energy and water in oceans, harvesting energies from such resources will not only be clean but also inexpensive. Solar fuels such as H2 generated from sunlight and seawater using earth-abundant materials are expected to be a crucial component of a next generation renewable energy mix.My PhD research was thus focused on the use of solar energy to split water into molecular hydrogen and oxygen, a process that is referred to as ‘artificial photosynthesis’. This can be achieved with the help of semiconductor photocatalysts. As most of the earth crust has a high abundance of silicon (Si), I prepared my semiconductor photoelectrodes using Si. However, Si tends to degrade in an aqueous environment. Thus, my PhD research comprises the synthesis of microstructured Si photoelectrodes and their protection with a TiO2 inter layer followed by functionalization with various earth abundant co-catalysts. The study on the synthesis, morphology and elemental characterization of the photoelectrodes was carried out under the supervision of Prof. Dr. Johannes Messinger at the Chemistry Department of Umeå University. Deep insight on the electronic and atomic structure of the functionalized Si photoelectrodes was obtained by careful experiments at the European Synchrotron Radiation Facility (ESRF) under the supervision of Dr. Pieter Glatzel. I investigated the electronic and geometric structural properties of my photocatalysts using inner shell electron spectroscopy, which is also referred to as ‘X-ray spectroscopy’. Thus, my PhD thesis falls under the broad title of “Artificial Photosynthesis and X-Ray Spectroscopy”. With the motivation of developing a bias free photoelectrochemical device for overall water splitting, I first developed cost effective earth abundant photocathodes. The experimental data and detailed analysis of the photocathodes are presented in Paper I. The best photocathode obtained in Paper I (p-Si/TiO2/NiOx) was then coupled with a well-studied FTO/α-Fe2O3 photoanode in parallel-illumination mode. The two most significant information obtained in Paper II were: 1) p-Si/TiO2/NiOx outcompetes Pt as a counter electrode and 2) a space charge region in the pristine hematite can be enhanced using p-Si/TiO2/NiOx as photocathode without bias or using any dopant. The proof of concept device studied in Paper II was further optimized in Paper III by replacing the FTO substrate with the n-Si MW to a obtain n-Si MW/TiO2/α-Fe2O3 photoanode. A record high photocurrent density of 5.6 mA/cm2 was achieved for the undoped hematite photoanode. I also found out that the TiO2 inter layer plays a crucial role in enhancing the overall device performance. The role of TiO2 was thus further studied using valence to core X-ray emission spectroscopy, which opened a new avenue for identifying and investigating the prime components in such devices. Paper I to III discuss the role of TiO2 and of the co-catalysts towards solar water splitting and thus the only material left to study was the Si substrate. For paper IV, a detailed analysis on Si substrate was performed. The electronic structural changes on Si LII, III edge was studied using X-ray Raman spectroscopy. The X-ray spectroscopic studies presented in papers I to III were performed at the ID-26 beamline at ESRF, while the X-ray Raman Spectroscopy presented in Paper IV was performed at the ID-20 beamline at ESRF. The data presented in Paper IV is preliminary and needs to be processed and analyzed further.
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| 12. |
- Kazen, Thomas, 1960-
(author)
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Jesus and Purity Halakhah : Was Jesus Indifferent to Impurity?
- 2002
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Doctoral thesis (other academic/artistic)abstract
- At the end of the Second Temple period, ritual purity came to play an increasing role in Jewish society. Purity laws were interpreted and expanded, and sources of impurity were generally avoided by many. Signs of that development are discussed in this study and put forward as arguments for an expansionist trend, gaining in influence and support from the common people. Jesus’ attitude to impurity is traced against this historical background. The (in)famous history of historical Jesus-research necessitates a conscious choice of method. The traditional focus on sayings material and criteria of authenticity is modified; narrative traditions with implicit purity issues are appealed to, and extra-canonical traditions are included. The main areas examined are the most important "fathers" of impurity: "leprosy" (skin diseases), genital discharges and corpse-contamination. Jesus is found to have acted in ways easily understood as indifference to these types of impurity. His behaviour is shown on several points to clash with current purity halakhah and dominant expansionist ideals. In an attempt to interpret his actions within the Jewish context and culture of the Second Temple period, three explanatory models are provided. Jesus’ attitude is seen as part of a moral trajectory in Judaism. It is understood as a response to a regional, Galilean dilemma. It is viewed in a power perspective as an expression of Jesus’ eschatological struggle against demonic evil. The result is that Jesus may be understood as operating within the purity paradigm of his time, yet pushing it to the breaking point, at least in the eyes of some. Such a reconstruction makes subsequent developments intelligible, in which various Christian currents drew conflicting conclusions. The function and effect of purity laws change with time, however. While they are irrelevant to most modern people, those looking to Jesus’ behaviour for some sort of guidance may find contemporary analogies.
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| 13. |
- Kurdve, Martin, 1971-
(author)
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Development of collaborative green lean production systems
- 2014
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Doctoral thesis (other academic/artistic)abstract
- This thesis deals with development of lean and green production systems from an action research point of view. The studies focus on Swedish-based automotive and vehicle industries and their aims to integrate sustainable thinking and environmental care into their operations management.Starting from operations management in manufacturing and corporate sustainable development, the research is built on how to integrate these two views into one production system. The systematic structure of a multiple-target improvement process with methodologies and tools designed to achieve the sustainability vision has been studied. Since lean as well as green production is based on the entire value chain, the research has gone beyond legal company limits and included the collaborative efforts between suppliers and customers in the value chain.The thesis includes six papers and describes approaches on how to implement integration, how to structure and integrate improvement management systems, how to set up an integrated monitoring and control system for the business and how to organise and redesign green lean tools and methodologies to support collaboration towards common targets.The results can be used for exploration and hypothesis formulation for further studies and development of integrated production systems and collaboration systems. The thesis helps answering how to integrate and implement company-specific green lean production systems.
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| 14. |
- Lehmann, Manuela, 1986-
(author)
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SOD1 misfolding and aggregation in ALS : in the light of conformation-specific antibodies
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Mutations in the superoxide dismutase 1 (SOD1) gene are linked to the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). ALS-associated mutations affect the stability of the SOD1 protein and promote its unfolding. As a consequence, disordered SOD1 species can misfold and accumulate into insoluble aggregates. Cytoplasmic inclusions containing misfolded SOD1 are a hallmark of ALS pathology in patients as well as transgenic mouse models. However, it remains unclear, which SOD1 species are pathogenic and how they arise and contribute to the disease.The aim of this thesis was to use antibodies as tools to study the role of disordered and aggregated SOD1 species in ALS. These antibodies recognize epitopes exposed in disordered SOD1 species and hence, discriminate between natively folded SOD1 and the disordered or misfolded protein.SOD1 is expressed in all cell types, but aggregates of misfolded SOD1 are predominantly found in motor neurons and associated glial cells in the spinal cord of ALS patients. To understand why misfolded SOD1 targets the motor system, we used ELISA and immunocapture methods to quantify soluble SOD1 species in patient-derived cell models of ALS. The highest levels of soluble disordered SOD1 were detected in induced pluripotent stem cell (iPSC)-derived motor neuron and astrocytes cultures (MNACs) compared to fibroblasts, iPSCs and sensory neuron cultures. These results suggest that the selective vulnerability of motor areas to SOD1-ALS could derive from an enhanced burden of disordered SOD1.To understand factors that might promote SOD1 unfolding, we focussed on the disulfide bond that is required for the stability of natively folded SOD1. Formation of the bond is oxygen-dependent and reduction of the bond promotes SOD1 unfolding. We studied the stability of SOD1 in patient-derived cells exposed to lowered oxygen tensions. This induced increases in disulfide-reduced, disordered mutant and wild-type SOD1. The response was time- and concentration-dependent and more pronounced in MNACs, where even increased aggregation of mutant SOD1 was observed. These results are consistent with the enhanced vulnerability of the motor system in ALS and suggest that conditions causing impaired oxygen perfusion could contribute to the initiation and progression of the disease.Inclusions containing aggregated misfolded wild-type SOD1 have been found in sporadic ALS (sALS) patients without SOD1 mutations and those carrying mutations in genes other than SOD1. However, other groups have reported contrasting results and the contribution of misfolded wild-type SOD1 to ALS pathology is controversial. Guidelines for preservation, storage, and analysis of tissues under standardized conditions would facilitate the comparison of results between different laboratories. We established an optimized immunohistochemistry protocol to detect misfolded wild-type SOD1 in paraffin-embedded spinal cord samples from sALS patients. We also developed a method to immunocapture disordered SOD1 from frozen post-mortem tissue. High, but variable, levels of disordered SOD1 were detected in spinal cords from sALS patients. Our data support a possible pathological role of misfolded wild-type SOD1 in sALS.Recent evidence suggests that SOD1 aggregates can induce templated aggregation of disordered SOD1 and spread from cell-to-cell via a prion-like mechanism. To test if antibodies could block this process in vivo, we conducted an immunotherapy study in a model of prion-like spread, where SOD1 aggregate seeds are inoculated into the lumbar spinal cord of SOD1G85R transgenic mice and lead to accelerated disease onset and progression. Novel monoclonal antibodies (mAb) against disordered domains of SOD1 aggregates were developed and validated for their reactivity to disordered and aggregated SOD1 species in vitro and in vivo. Immunotherapy using a mAb against the C-terminal end of SOD1 attenuated the onset and progression of prion-like SOD1 spread. However, no effect was seen on onset, duration or progression of the underlying disease. This suggests that, under the conditions tested, immunotherapy against disordered domains of SOD1 does not affect intracellular aggregation and additional strategies might be needed to reduce intracellular accumulation of misfolded SOD1 aggregation.In conclusion, we show that conformation-specific antibodies are powerful tools to investigate disordered and potentially pathogenic species of SOD1 in various biochemical, cellular and in vivo contexts. The development of the novel immunocapture strategy could facilitate future research on characterizing SOD1 aggregates from mouse tissues, patient-derived cells or post-mortem tissues with the goal of determining their role in ALS disease pathogenesis.
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| 15. |
- Lettner, Thomas
(author)
-
Bright and strain-tunable semiconductor quantum dot devices
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- Optically active semiconductor quantum dots have proven to be excellent single- and entangled-photon sources, with applications in quantum optics and quantum photonics. These sources are considered crucial in the development of future photonic quantum technology, such as quantum communication, quantum computation and quantum metrology. In future quantum networks, they allow to share quantum information through optical fiber links and implement secure communication protocols based on quantum key distribution.However, there are several challenges when developing quantum dot devices in order to unlock the full potential of these quantum emitters. The ideal quantum dot source efficiently generates triggered single- and entangled-photons on-demand. It provides further high collection-efficiency, low multi-photon probability, near-unity indistinguishability and high entanglement fidelity. Finally, it also offers compatibility with other systems by providing photons with the desired spectral properties and enabling efficient photon coupling.In this thesis the development and fabrication of bright and strain-tunable quantum dot devices for single- and entangled-photon generation has been studied. It covers highly-symmetric GaAs quantum dots emitting in the near-infrared, InAs quantum dots generating photons in the telecom C-band and InAsP quantum dots embedded in InP nanowires enabling deterministic integration into photonic circuits. The main aspects of operating these quantum dots in cryogenic micro-photoluminescence experiments are described, with focus on enhancing the collection efficiency using solid immersion lenses. For strain-tunability, the focus lies on the fabrication of piezoelectric actuators as substrates for the integration of quantum dot samples by polymer-based bonding. Finally, this thesis describes the simulation, fabrication and measurement of a novel device featuring quantum dots embedded in broad-band parabolic mirror microcavities for enhanced light collection.Experimental results obtained with a variety of quantum dot devices are included: GaAs quantum dot devices featuring solid immersion lenses demonstrate record-low multi-photon probability and near-unity photon indistinguishability. Piezoelectric strain-tunable devices with InAs quantum dots emitting in the telecom C-band allow for on-demand generation of single- and entangled-photons with tunable quantum dot emission properties and high entanglement fidelity. Piezoelectric strain-tuning actuators enable further the realization of reconfigurable quantum photonic circuits featuring waveguide-integrated InAsP/InP nanowire quantum dots with tunable emission wavelength. Finally, GaAs quantum dots in microcavities with parabolic mirror integrated on piezoelectric actuators achieve an increase in brightness by one order of magnitude over planar structures while allowing to tune the emission wavelength to the atomic transition 87Rb D1 relevant for quantum memory applications.
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| 16. |
- Matthiesen, Isabelle
(author)
-
Recreating the microenvironment of the neurovascular unit
- 2022
-
Doctoral thesis (other academic/artistic)abstract
- The neurovascular unit (NVU) comprises the blood-brain-barrier (BBB) and its surrounding astrocytes, pericytes and neurons that are embedded in the extracellular matrix (ECM). As the main function of the BBB is to protect the brain from inlet of pathogens and toxins, the specialized endothelial cells that keep the barrier tight will also hinder the passage of pharmaceuticals. Understanding the detailed microenvironment and cellular interactions involved in the development of the neurovascular unit is, therefore, an important step towards designing CNS-targeting pharmaceuticals that can pass into the brain. At the same time, the initial steps of pharmaceutical development often involve the use of animal based in vitro models with poor human translation; thus, there is a great need for novel methods to better mimic the complexity of the human NVU. Apart from conventional cell culture models, the use of micro-engineered devices, microphysiological systems (MPS), have gained popularity. The use of MPS allows for fabrication of tissue-like structures using stem cells and provide more in vivo-like parameters in terms of physical cues and dynamic flow. Various materials have been explored for chip fabrication, and biological and synthetic ECM-mimicking hydrogels have been developed for cell encapsulation. Unfortunately, models developed to date often lack either: i) relevant and reproducible cell sources, ii) materials that allow for easy chip fabrication where sensors can be integrated to understand metabolic effects and barrier integrity, or iii) animal-free defined ECM-mimicking scaffolds that support the culture of sensitive cells. This thesis presents an isogenic model of the BBB using iPSC-derived endothelial cells and astrocytes cultured in a MPS made from the non-absorbing polymer OSTE+ that allows for easy fabrication and integration of interdigitated gold electrodes for continuous barrier integrity monitoring. The model presents barrier-protective effects of the BBB-penetrating drug NACA. To better understand the metabolic attributes of astrocytes, a flow-cell sensor is evaluated for the measurement of glucose and lactate turnover during a ketogenic diet. The results imply that such a sensor is valuable for the measurement of metabolic changes and can, in the future, be integrated into MPSs.Furthermore, a model of early neuronal development is realized by using defined copper-free click chemistry to conjugate laminin to a hyaluronic-based hydrogel system for the differentiation of neuroepithelial stem cells. The use of the hydrogel is validated for bioprinting, and the first-ever printed neuroepithelial stem cells are presented. In another study astrocyte 3D culture and bioprinting is evaluated in peptide conjugated hyaluronic-based hydrogels. Unique attachment and spreading of human fetal astrocytes is observed while the common glioblastoma U87 cells display a rounded up morphology. The results of the hydrogel study imply that the defined chemistry of the hydrogel is suitable for both neuroepithelial stem cells, U87 and fetal primary astrocytes, and can in the future be integrated into MPS to circumvent the use of animal derived matrices. In summary, these results provide solutions to some of the problems to date and lay the ground work for the continuation of the development of human-relevant MPS of the NVU.
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| 17. |
- Mukwaya, Anthony
(author)
-
Regulation of inflammation and angiogenesis in the cornea
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- Inflammation and angiogenesis, the growth of new blood vessels from pre-existing ones, are involved in tumor growth, ocular diseases and wound healing. In ocular angiogenesis, new pathological vessels grow into a specific eye tissue, leak fluid, and disrupt vision. The development of safe and effective therapies for ocular angiogenesis is of great importance for preventing blindness, given that current treatments have limited efficacy or are associated with undesirable side effects. The search for alternative treatment targets requires a deeper understanding of inflammation and how it can lead to angiogenesis in the eye in pathologic situations. This thesis provides new insights into the regulation of inflammation and angiogenesis, particularly at the gene expression and phenotypic levels, in different situations characterized by angiogenesis of the cornea, often called corneal neovascularization. For instance, specific genes and pathways are either endogenously activated or suppressed during active inflammation, wound healing, and during resolution of inflammation and angiogenesis, serving as potential targets to modulate the inflammatory and angiogenic response. In addition, as part of the healing response to restore corneal transparency, inflammation and angiogenesis subside with time in the cornea. In this context, LXR/RXR signaling was found to be activated in a time-dependent manner, to potentially regulate resolution of inflammation and angiogenesis. During regression of new angiogenic capillaries, ghost vessels and empty basement membrane sleeves are formed, which can persist in the cornea for a long time. Here, ghost vessels were found to facilitate subsequent revascularization of the cornea, while empty basement membrane sleeves did not revascularize. The revascularization response observed here was characterised by vasodilation, increased inflammatory cell infiltration and by sprouting at the front of the reperfused vessels. Importantly, reactive oxygen species and nitrous oxide signaling among other pro-inflammatory pathways were activated, and at the same time anti-inflammatory LXR/RXR signaling was inhibited. The interplay between activation and inhibition of these pathways highlights potential mechanisms that regulate corneal revascularization. When treating corneal neovascularization clinically, corticosteroids are in widespread use due to their effectiveness. To minimize the many undesirable side effects associated with corticosteroid use, however, identifying new and more selective agents is of great importance. Here, it was observed that corticosteroids not only suppressed pro-inflammatory chemokines and cytokines, but also activated the classical complement pathway. Classical complement may represent a candidate for further selective therapeutic manipulation to investigate its effect on treatment of corneal neovascularization.In summary, this thesis identifies genes, pathways, and phenotypic responses involved in sprouting and remodeling of corneal capillaries, highlights novel pathways and factors that may regulate inflammation and angiogenesis in the cornea, and provides insights into regulation of capillary regression and reactivation. Further investigation of these regulatory mechanisms may offer alternative and effective treatment targets for the treatment of corneal inflammation and angiogenesis.
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| 18. |
- Thomas, Laura D K
(author)
-
Cadmium exposure and risk of kidney effects and bone fractures : population-based studies in England and Sweden
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- Cadmium (Cd) is a toxic metal with no beneficial biological function. The dissemination of cadmium to the surface environment, by industrial and agricultural practices, has led to increased human exposure. Food is the main source of exposure in the general non-smoking population however in areas close to industrial sources, contact with contaminated environmental media may also be important. Previous studies have shown toxic effects of cadmium on the kidneys and bone, however, considerable uncertainty remains over the exposure levels at which these toxic effects may start to occur and the clinical relevance of the early effects observed following long-term, low-level cadmium exposure. The aims of this thesis were: 1) To assess cadmium body burden and early signs of kidney dysfunction in a population exposed to industrial cadmium emissions and to develop and validate an air dispersion model of these emissions. 2) To identify urinary metabolites, associated with cadmium exposure, using metabolic profiling techniques. 3) To prospectively assess the association between validated estimates of dietary cadmium exposure and chronic kidney disease (CKD) incidence, kidney stone incidence, and fracture incidence, in two large population-based cohorts of men and women. In a population-based sample of 180 subjects, living close to a zinc smelter in Avonmouth, Southwest England, urinary cadmium concentrations (median = 0.22 nmol Cd/mmol creatinine) were in the same range as those where associations with kidney and/or bone effects have been observed previously. Three percent had concentrations above 1nmol Cd/mmol creatinine (~1μg/g) – the point of departure for tubular proteinuria set by the European Food Safety Authority in 2009. Modelled air cadmium concentrations from the smelter were strongly correlated with those from air monitoring sites (R2=0.84) and were a significant predictor of urinary cadmium (p=0.04). In a cross-sectional analysis, a significant dose-response relationship between urinary cadmium and one of the biomarkers of early tubular dysfunction (N- acetyl-β-d-glucosaminidase) was observed. Metabolic profiling identified six urinary metabolites, either related to mitochondrial metabolism or one carbon metabolism, associated with urinary cadmium. Two large population-based cohorts of men and women from Central Sweden were used to investigate the association between dietary cadmium exposure and incidence of CKD, kidney stones and fractures. Median dietary cadmium exposure levels in our study populations were 19μg/day in men and 13μg/day women. During an average of 12 years of follow-up, we ascertained 599 incident cases of CKD among men (481,591 person-years) and 253 among women (415,432 person-years). We did not observe an association between dietary Cd and rate of CKD in men, hazard ratio (HR) 0.97 (95% CI 0.77-1.21) or women HR 0.74 (95% CI 0.53-1.04), either before or after adjustment for potential confounders. During an average of 13 years of follow-up, we ascertained 707 incident cases of kidney stone among men (421,611 person-years) and 290 among women (403,575 person-years). Likewise, we did not observe an association between dietary Cd and rate of kidney stones in men HR 0.97 (95% CI 0.77-1.23) or women HR 0.99 (95%CI 0.89-1.43), either before or after adjustment for potential confounders. We ascertained 2,183 cases of any fracture and 374 cases of hip fracture, during a 10- year follow-up of 20,173 Swedish men. In the multivariable adjusted model, dietary cadmium was associated with a statistically significant 19% (HR: 1.19, 95%CI: 1.06- 1.34) higher rate of any fracture, comparing highest tertile with lowest. Hip fracture rates were also higher in the highest tertile of cadmium exposure but only statistically significant among never smokers, with a 70% (HR: 1.70, 95%CI: 1.04-2.77) higher rate. This study provides the first data on hip fracture rates in relation to cadmium exposure and is the first to report an excess risk of any fracture associated with long- term low-level cadmium exposure in men. The results of this thesis suggest that the adverse effects of cadmium exposure around the Avonmouth smelter may be detected in urinary biomarkers. In addition, the results of the prospective studies do not support a role of dietary cadmium exposure, at the level seen in the general population, in the development of CKD or kidney stones. However, the results do provide further evidence of increase fracture risk in relation to cadmium exposure. In conjunction with recent findings, the results of this thesis suggest that bone may be a more sensitive target of cadmium toxicity than the kidney, in terms of clinically relevant outcomes.
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| 19. |
- Wendell, Joakim, 1976-
(author)
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Teaching and Learning Historical Explanation : Teacher and Student Cases from Lower and Upper Secondary History
- 2020
-
Doctoral thesis (other academic/artistic)abstract
- The purpose of this thesis is to investigate and analyse how teachers and students understand the concept of historical explanation in the context of classroom teaching practices. The thesis is made up of four studies that investigate different aspects of understanding, focusing on either teacher or student understanding as expressed in words and actions. The different studies employ differing methods, including classroom observations, interviews with teachers, and analysis of student answers to prompts intended for assessment. The studies include cases from both lower and upper secondary school in Sweden. The four studies provide empirical results that are presented in each individual study, and furthermore subjected to an aggregated analysis in order to find patterns of commonality. The aggregated analysis draws upon Rüsen's theory of historical knowledge, as well as a progression model for historical explanation based on results from previous research. The results of the study show a clear difference between lower and upper secondary school in how students at each stage construct historical explanations, indicating differing expectations of what students are supposed to do with explanations in each stage. Teachers' practices are more varied: while a majority of the included teachers manifest a disciplinary understanding of historical explanation, in line with previous research about historical explanation in educational contexts, other approaches with other emphases are also present. These include an emphasis of learning explanations as sets of facts, as well as approaches that aim for making the knowledge of historical explanation useful outside of the history subject. Examples of such aims found in the study are to enhance empathetic understanding of other people, and helping students to orient themselves in relation to present-day issues.
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