| 26. |
- Ahmadi, Omid, 1980-
(författare)
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Application of the Seismic Reflection Method in Mineral Exploration and Crustal Imaging : Contributions to Hardrock Seismic Imaging
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The seismic reflection method has been used extensively in mineral exploration and for imaging crustal structures within hardrock environments. In this research the seismic reflection method has been used and studied to address problems associated with hardrock settings. Papers I and II, address delineating and imaging a sulfide ore body and its surrounding rocks and structures in Garpenberg, central Sweden, at an active mine. 3D ray-tracing and finite-difference modeling were performed and the results suggest that although the detection of the ore body by the seismic reflection method is possible in the area, the presence of backfilled stopes in the mine makes seismic imaging of it difficult. In paper III the deeper structures of the Pärvie fault system in northern Sweden were revealed down to about 8 km through 2D seismic reflection profiling. The resulting images were interpreted using microearthquake data as a constraint. Based on the interpretation, some locations were suggested for future scientific deep drilling into the fault system. In paper IV, the seismic signature of complex geological structures of the Cue-Weld Range area in Western Australia was studied using a portion of a deep 2D seismic reflection profile. The pronounced reflections on the seismic images were correlated to their corresponding rock units on an available surface geological map of the study area. 3D constant velocity ray-tracing was performed to constrain the interpretation. Furthermore, the proposed structural model was tested using a 2D acoustic finite-difference seismic modeling method. Based on this study, a new 3D structural model was proposed for the subsurface of the area. These studies have investigated the capability of the seismic reflection method for imaging crustal structures within challenging hardrock and complex geological settings and show some its potential, but also its limitations.
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| 27. |
- Ahmadova, Nigar
(författare)
-
Studies of the two redox active tyrosines in Photosystem II
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Photosystem II is a unique enzyme which catalyzes light induced water oxidation. This process is driven by highly oxidizing ensemble of four Chl molecules, PD1, PD2, ChlD1 and ChlD2 called, P680. Excitation of one of the Chls in P680 leads to the primary charge separation, P680+Pheo-. Pheo- transfers electrons sequentially to the primary quinone acceptor QA and the secondary quinone acceptor QB. P680+ in turn extracts electrons from Mn4CaO5 cluster, a site for the water oxidation. There are two redox active tyrosines, TyrZ and TyrD, found in PSII. They are symmetrically located on the D1 and D2 central proteins. Only TyrZ acts as intermediate electron carrier between P680 and Mn4CaO5 cluster, while TyrD does not participate in the linear electron flow and stays oxidized under light conditions. Both tyrosines are involved in PCET.The reduced TyrD undergoes biphasic oxidation with the fast (msec-sec time range) and the slow (tens of seconds time range) kinetic phases. We assign these phases to two populations of PSII centers with proximal or distal water positions. We also suggest that the TyrD oxidation and stability is regulated by the new small lumenal protein subunit, PsbTn. The possible involvement of PsbTn protein in the proton translocation mechanism from TyrD is suggested.To assess the possible localization of primary cation in P680 the formation of the triplet state of P680 and the oxidation of TyrZ and TyrD were followed under visible and far-red light. We proposed that far-red light induces the cation formation on ChlD1.Transmembrane interaction between QB and TyrZ has been studied. The different oxidation yield of TyrZ, measured as a S1 split EPR signal was correlated to the conformational change of protein induced by the QB presence at the QB-site. The change is transferred via H-bonds to the corresponding His-residues via helix D of the D1 protein.
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| 28. |
- Ahmed, Taha, 1984-
(författare)
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Nanostructured ZnO and metal chalcogenide films for solar photocatalysis
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The increasing demand for clean energy and safe water resources has driven the development of efficient and sustainable technologies. Among these technologies, photocatalysis using semiconducting materials has emerged as a promising solution for both solar hydrogen generation and water purification. Low-dimensional ZnO, including nanorods, nanoparticles, and quantum confined particles (so called quantum dots), has demonstrated excellent photocatalytic properties due to their large surface area, high electron mobility, and tunable band gap.The work in this thesis aims to investigate the potential of low-dimensional ZnO alone and in combination with CdS and Fe2O3 for solar hydrogen generation and photocatalytic water purification. The thesis includes a comprehensive analysis of the synthesis, characterization, and optimization of low-dimensional ZnO-based photocatalyst systems for solar hydrogen generation and photocatalytic water purification. Additionally, the thesis will evaluate the performance of the ZnO-based photocatalysts under different experimental conditions, either as photoelectrodes or as distributed particle systems for water purification. The work includes detailed size control of ZnO by itself in dimensions below 10 nm using a hydrothermal method, to provide an increased total surface area and introduce quantum confinement effects that increase the band gap to enable degradation of chemical bonds in a model pollutant in a distributed system for water purification. The work also includes a relatively detailed study of the phonon–phonon and electron–phonon coupling as a function of dimension from 10 nm to 150 nm for ZnO using non-resonant and resonant Raman spectroscopy. Ultimately, the thesis aims to provide insight into the potential of low-dimensional ZnO alone and in combination with other inorganic materials for solar hydrogen generation and photocatalytic water purification and pave the way for the development of efficient and sustainable technologies for clean energy and safe water resources.
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| 29. |
- Aihara, Aya, 1989-
(författare)
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Aeroacoustic Prediction for Vertical Axis Wind Turbines
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates the aerodynamic and aeroacoustic prediction of vertical axis wind turbines, using computational fluid dynamics simulations. Noise pollution from wind turbines is one of the disadvantages of wind energy, calling for strategies to reduce noise levels. Yet for vertical axis wind turbines in particular, there is insufficient knowledge of how to identify sound sources and mitigate the sound level. The aim of this study is to predict aerodynamic noise, using large eddy simulation and acoustic analogy, so as to better understand the mechanism of sound generation for vertical axis wind turbines. First, the prediction method is validated for a static single blade in stall. This model is able to capture the dominant frequency, but it does not well reproduce the broadband characteristics. Next, the aerodynamic behavior of the 12 kW H-rotor vertical axis wind turbine is studied, whereby the focus is on the importance of properly modeling the strut influence for an accurate prediction of the blade forces. To achieve this, the flow field is solved for three different tip speed ratios. The results show that the struts significantly affect on the force distribution along the blade. The reduction of the blade force is observed to occur not only at the attachment points of the struts, but also over a large area of the blade section in the downwind side where the blade interacts with the wake created in the upwind. Finally, the noise radiated from the vertical axis wind turbine operating at high tip speed ratio is predicted. Measurements are conducted to validate the prediction, with the experimental data representing the broadband noise characteristics dominant at around 800 Hz. The prediction reproduces the sound pressure level observed at a radial distance of 1.4 rotor diameter, with a few decibels difference. However, these discrepancies become more pronounced at double distance, which can be considered to arise due to the effect of the ground reflection being ignored. The simulation furthermore indicates, that the main sound sources are emitted when the blade rotates in the downwind. It is suggested that future work should properly consider the atmospheric turbulence for more accurate predictions.
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| 30. |
- Aiso, Toshiharu, 1983-
(författare)
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Workpiece steels protecting cutting tools from wear : A study of the effects of alloying elements on material transfer and coating damage mechanisms
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 31. |
- Ajawatanawong, Pravech, 1974-
(författare)
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Mine the Gaps : Evolution of Eukaryotic Protein Indels and their Application for Testing Deep Phylogeny
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Insertions/deletions (indels) are potentially powerful evolutionary markers, but little is known about their evolution and few tools exist to effectively study them. To address this, I developed SeqFIRE, a tool for automated identification and extraction of indels from protein multiple sequence alignments. The program also extracts conserved alignment blocks, thus covering all major steps in preparing multiple sequence alignments for phylogenetic analysis.I then used SeqFIRE to build an indel database, using 299 single copy proteins from a broad taxonomic sampling of mainly multicellular eukaryotes. A total of 4,707 indels were extracted, of which 901 are simple (one genetic event) and 3,806 are complex (multiple events). The most abundant indels are single amino acid simple indels. Indel frequency decreases exponentially with length and shows a linear relationship with host protein size. Singleton indels reveal a strong bias towards insertions (2.31 x deletions on average). These analyses also identify 43 indels marking major clades in Plantae and Fungi (clade defining indels or CDIs), but none for Metazoa.In order to study the 3806 complex indels they were first classified by number of states. Analysis of the 2-state complex and simple indels combined (“bi-state indels”) confirms that insertions are over 2.5 times as frequent as deletions. Three-quarters of the complex indels had three-nine states (“slightly complex indels”). A tree-assisted search method was developed allowing me to identify 1,010 potential CDIs supporting all examined major branches of Plantae and Fungi.Forty-two proteins were also found to host complex indel CDIs for the deepest branches of Metazoa. After expanding the taxon set for these proteins, I identified a total of 49 non-bilaterian specific CDIs. Parsimony analysis of these indels places Ctenophora as sister taxon to all other Metazoa including Porifera. Six CDIs were also found placing Placozoa as sister to Bilateria. I conclude that slightly complex indels are a rich source of CDIs, and my tree-assisted search strategy could be automated and implemented in the program SeqFIRE to facilitate their discovery. This will have important implications for mining the phylogenomic content of the vast resource of protist genome data soon to become available.
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| 32. |
- Ajaxon, Ingrid, 1983-
(författare)
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Can Bone Void Fillers Carry Load? : Behaviour of Calcium Phosphate Cements Under Different Loading Scenarios
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Calcium phosphate cements (CPCs) are used as bone void fillers and as complements to hardware in fracture fixation. The aim of this thesis was to investigate the possibilities and limitations of the CPCs’ mechanical properties, and find out if these ceramic bone cements can carry application-specific loads, alone or as part of a construct. Recently developed experimental brushite and apatite cements were found to have a significantly higher strength in compression, tension and flexion compared to the commercially available CPCs chronOS™ Inject and Norian® SRS®. By using a high-resolution measurement technique the elastic moduli of the CPCs were determined and found to be at least twice as high compared to earlier measurements, and closer to cortical bone than trabecular bone. Using the same method, Poisson's ratio for pure CPCs was determined for the first time. A non-destructive porosity measurement method for wet brushite cements was developed, and subsequently used to study the porosity increase during in vitro degradation. The compressive strength of the experimental brushite cement was still higher than that of trabecular bone after 25 weeks of degradation, showing that the cement can carry high loads over a time span sufficiently long for a fracture to heal. This thesis also presents the first ever fatigue results for acidic CPCs, and confirms the importance of testing the materials under cyclic loading as the cements may fail at stress levels much lower than the material’s quasi-static compressive strength. A decrease in fatigue life was found for brushite cements containing higher amounts of monetite. Increasing porosity and testing in a physiological buffer solution (PBS), rather than air, also decreased the fatigue life. However, the experimental brushite cement had a high probability of surviving loads found in the spine when tested in PBS, which has previously never been accomplished for acidic CPCs. In conclusion, available brushite cements may be able to carry the load alone in scenarios where the cortical shell is intact, the loading is mainly compressive, and the expected maximum stress is below 10 MPa. Under such circumstances this CPC may be the preferred choice over less biocompatible and non-degradable materials.
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| 33. |
- Akansel, Serkan, 1983-
(författare)
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Magnetization Dynamics in Ferromagnetic Thin Films : Evaluation of Different Contributions to Damping in Co2FeAl and FeCo Film Structures
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Static and dynamic magnetic properties of Co2FeAl and Fe65Co35 alloys have been investigated. Co2FeAl films were deposited at different temperatures and the deposition parameters were optimized with respect to structural and magnetic properties. As a result, a film with B2 crystalline phase was obtained without any post-annealing process. A lowest magnetic damping parameter of was obtained for the film deposited at 573K. This obtained low value is comparable to the lowest values reported in research literature. After optimizing the deposition parameters of this alloy, different seed layers and capping layers were added adjacent to the Co2FeAl layer and the effect of these layers on the magnetic relaxation was investigated. In addition to adding nonmagnetic layers to Co2FeAl, the dependence of the magnetic damping parameter with respect to the thickness of Co2FeAl was investigated by depositing films with different thicknesses. A temperature dependent study of the magnetic damping parameter was also performed and the measured damping parameters were compared with theoretically calculated intrinsic Gilbert damping parameters. Different extrinsic contributions to the magnetic damping, such as two magnon scattering, spin pumping, eddy-current damping and radiative damping, were identified and subtracted from the experimentally obtained damping parameter. Hence, it was possible to obtain the intrinsic damping parameter, that is called the Gilbert damping parameter.In the second part of the thesis, Fe65Co35 alloys were investigated in terms of static and dynamic magnetic properties. Fe65Co35 films were deposited without and with different seed layers in order to first understand the effect of the seed layer on static magnetic properties of the films, such as the coercivity of the films. Then the films with seed layers yielding the lowest coercivity were investigated in terms of dynamic magnetic properties. Fe65Co35 films with different rhenium dopant concentrations and with ruthenium as the seed and capping layer were also investigated. The purpose of this study was to increase the damping parameter of the films and an increase of about ~230% was obtained by adding the dopant to the structure. This study was performed at different temperatures and after subtraction of the extrinsic contributions to the damping, the experimental values were compared with theoretically calculated values of the Gilbert damping parameter. During the thesis work, magnetic looper and superconducting quantum interference device magnetometers set-ups were used for static magnetic measurements and cavity, broadband in-plane and broadband out-of-plane ferromagnetic resonance set-ups were used for dynamic measurements.
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| 34. |
- Akhtar, Sultan
(författare)
-
Transmission Electron Microscopy of Graphene and Hydrated Biomaterial Nanostructures : Novel Techniques and Analysis
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Transmission Electron Microscopy (TEM) on light element materials and soft matters is problematic due to electron irradiation damage and low contrast. In this doctoral thesis techniques were developed to address some of those issues and successfully characterize these materials at high resolution. These techniques were demonstrated on graphene flakes, DNA/magnetic beads and a number of water containing biomaterials. The details of these studies are given below.A TEM based method was presented for thickness characterization of graphene flakes. For the thickness characterization, the dynamical theory of electron diffraction is used to obtain an analytical expression for the intensity of the transmitted electron beam as a function of thickness. From JEMS simulations (experiments) the absorption constant λ in a low symmetry orientation was found to be ~ 208 nm (225 ± 9 nm). When compared to standard techniques for thickness determination of graphene/graphite, the method has the advantage of being relatively simple, fast and requiring only the acquisition of bright-field (BF) images. Using the proposed method, it is possible to measure the thickness change due to one monolayer of graphene if the flake has uniform thickness over a larger area.A real-space TEM study on magnetic bead-DNA coil interaction was conducted and a statistical analysis of the number of beads attached to the DNA-coils was performed. The average number of beads per DNA coil was calculated around 6 and slightly above 2 for samples with 40 nm and 130 nm beads, respectively. These results are in good agreement with magnetic measurements. In addition, the TEM analysis supported an earlier hypothesis that 40 nm beads are preferably attached interior of the DNA-coils while 130 nm beads closer to the exterior of the coils.A focused ion-beam in-situ lift-out technique for hydrated biological specimens was developed for cryo-TEM. The technique was demonstrated on frozen Aspergillus niger spores which were frozen with liquid nitrogen to preserve their cellular structures. A thin lamella was prepared, lifted out and welded to a TEM grid. Once the lamella was thinned to electron transparency, the grid was cryogenically transferred to the TEM using a cryo-transfer bath. The structure of the cells was revealed by BF imaging. Also, a series of energy filtered images was acquired and C, N and Mn elemental maps were produced. Furthermore, 3 Å lattice fringes of the underlying Al support were successfully resolved by high resolution imaging, confirming that the technique has the potential to extract structural information down to the atomic scale. The experimental protocol is ready now to be employed on a large variety of samples e.g. soft/hard matter interfaces.
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| 35. |
- Akiyama, Reiko, 1981-
(författare)
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Life History and Tolerance and Resistance against Herbivores in Natural Populations of Arabidopsis thaliana
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, I combined observational studies with field and greenhouse experiments to examine selection on life history traits and variation in tolerance and resistance against herbivores in natural populations of the annual herb Arabidopsis thaliana in its native range. I investigated (1) phenotypic selection on flowering time and plant size, (2) the effects of timing of germination on plant fitness, (3) the effect of leaf damage on seed production, and (4) correlations between resistance against a specialist and a generalist insect herbivore. In all three study populations, flowering time was negatively related to plant fitness, but in only one of the populations, significant selection on flowering time was detected when controlling for size prior to the flowering season. The results show that correlations between flowering time and plant fecundity may be confounded by variation in plant size prior to the reproductive season. A field experiment detected conflicting selection on germination time: Early germination was associated with low seedling survival, but also with large leaf rosette before winter and high survival and fecundity among established plants. The results suggest that low survival among early germinating seeds is the main force opposing the evolution of earlier germination, and that the optimal timing of germination should vary in space and time as a function of the relative strength of selection acting during different life-history stages. Experimental leaf damage demonstrated that tolerance to damage was lowest among vegetative plants early in the season, and highest among flowering plants later in the season. Given similar damage levels, leaf herbivores feeding on plants before flowering should thus exert stronger selection on defence traits than those feeding on plants during flowering. Resistance against larval feeding by the specialist Plutella xylostella was negatively correlated with resistance against larval feeding by the generalist Mamestra brassicae and with resistance against oviposition by P. xylostella when variation in resistance was examined within and among two Swedish and two Italian A. thaliana populations. The results suggest that negative correlations between resistance against different herbivores and different life-history stages of herbivores may contribute to the maintenance of genetic variation in resistance.
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| 36. |
- Aktekin, Burak
(författare)
-
The Electrochemistry of LiNi0.5-xMn1.5+xO4-δ in Li-ion Batteries : Structure, Side-reactions and Cross-talk
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of Li-ion batteries in portable electronic products is today widespread and on-going research is extensively dedicated to improve their performance and energy density for use in electric vehicles. The largest contribution to the overall cell weight comes from the positive electrode material, and improvements regarding this component thereby render a high potential for the development of these types of batteries. A promising candidate is LiNi0.5Mn1.5O4 (LMNO), which offers both high power capability and energy density. However, the instability of conventional electrolytes at the high operating potential (~4.7 V vs. Li+/Li) associated with this electrode material currently prevents its use in commercial applications.This thesis work aims to investigate practical approaches which have the potential of overcoming issues related to fast degradation of LNMO-based batteries. This, in turn, necessitates a comprehensive understanding of degradation mechanisms. First, the effect of a well-known electrolyte additive, fluoroethylene carbonate is investigated in LNMO-Li4Ti5O12 (LTO) cells with a focus on the positive electrode. Relatively poor cycling performance is found with 5 wt% additive while 1 wt% additive does not show a significant difference as compared to additive-free electrolytes. Second, a more fundamental study is performed to understand the effect of capacity fading mechanisms contributing to overall cell failure in high-voltage based full-cells. Electrochemical characterization of LNMO-LTO cells in different configurations show how important the electrode interactions (cross-talk) can be for the overall cell behaviour. Unexpectedly fast capacity fading at elevated temperatures is found to originate from a high sensitivity of LTO to cross-talk.Third, in situ studies of LNMO are conducted with neutron diffraction and electron microscopy. These show that the oxygen release is not directly related to cation disordering. Moreover, microstructural changes upon heating are observed. These findings suggest new sample preparation strategies, which allow the control of cation disorder without oxygen loss. Following this guidance, ordered and disordered samples with the same oxygen content are prepared. The negative effect of ordering on electrochemical performance is investigated and changes in bulk electronic structure following cycling are found in ordered samples, accompanied by thick surface films on surface and rock-salt phase domains near surface.
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| 37. |
- Akula, Srinivas
(författare)
-
The mast cell transcriptome and the evolution of granule proteins and Fc receptors
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Protection against disease-causing pathogens, known as immunity, involves numerous cells organs, tissues and their products. To able to understand the biology of immune cells (hematopoietic cells) and their role in an immune system, we have used several different methods, including transcriptome analyses, bioinformatics, production of recombinant proteins and analyses of some of them, focusing on the granule proteases by substrate phage display.Hematopoietic cells express surface receptors interacting with the constant region of immunoglobulins (Igs) known as Fc receptors (FcRs). These receptors play major roles in the immune system, including enhancing phagocytosis, activating antibody dependent cellular cytotoxicity and cell activation. A detailed bioinformatics analysis of FcRs reveals that the poly-Ig receptors (PIGR), FcR-like molecules and common signalling γ chain all appeared very early with the appearance of the bony fishes, and thereby represent the first major evolutionary step in FcR evolution. The FcμR, FcαμR, FcγR and FcεR receptors most likely appeared in reptiles or early mammals, representing the second major step in FcR evolution.Cells of several of the hematopoietic cell lineages contain large numbers of cytoplasmic granules, and serine proteases constitute the major protein content of these granules. In mammals, these proteases are encoded from four different loci: the chymase, the met-ase, the granzyme (A/K) and the mast cell tryptase loci. The granzyme (A/K) locus was the first to appear and came with the cartilaginous fishes. This locus is also the most conserved of the three. The second most conserved locus is the met-ase locus, which is found in bony fishes. The chymase locus appeared relatively late, and we find the first traces in frogs, indicating it appeared in early tetrapods.To study the early events in the diversification of these hematopoietic serine proteases we have analyzed key characteristics of a protease expressed by an NK-like cell in the channel catfish, catfish granzyme–like I. We have used phage display and further validated the results using a panel of recombinant substrates. This protease showed a strict preference for Met at the P1 (cleavage) position, which indicates met-ase specificity. From the screening of potential in vivo substrates, we found an interesting potential target caspase 6, which indicates that caspase-dependent apoptosis mechanisms have been conserved from fishes to mammals.A larger quantitative transcriptome analysis of purified mouse peritoneal mast cells, cultured mast cells (BMMCs), and mast cells isolated from mouse ear and lung tissue identified the major tissue specific transcripts in these mast cells as the granule proteases. Mast cell specific receptors and processing enzymes were expressed at approximately 2 orders of magnitude lower levels. The levels of a few proteases were quite different at various anatomical sites between in vivo and cultured BMMCs. These studies have given us a new insights into mast cells in different tissues, as well as key evolutionary aspects concerning the origins of a number of granule proteases and FcRs.
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| 38. |
- Al-Adili, Ali
(författare)
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Measurements of the 234U(n,f) Reaction with a Frisch-Grid Ionization Chamber up to En=5 MeV
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study on the neutron-induced fission of 234U was carried out at the 7 MV Van de Graaff accelerator of IRMM in Belgium. A Twin Frisch-Grid Ionization Chamber (TFGIC) was used to study 234U(n,f) between En = 0.2 and 5.0 MeV. The reaction is important for fission modelling of the second-chance fission in 235U(n,f). The fission fragment (FF) angular-, energy and mass distributions were determined using the 2E-method highlighting especially the region of the vibrational resonance at En = 0.77 MeV.The experiment used both conventional analogue and modern digital acquisition systems in parallel. Several advantages were found in the digital case, especially a successful pile-up correction. The shielding limitations of the Frisch-grid, called "grid-inefficiency", result in an angular-dependent energy signal. The correction of this effect has been a long-standing debate and a solution was recently proposed using the Ramo-Shockley theorem. Theoretical predictions from the latter were tested and verified in this work using two different grids. Also the neutron-emission corrections as a function of excitation energy were investigated. Neutron corrections are crucial for the determination of FF masses. Recent theoretical considerations attribute the enhancement of neutron emission to the heavier fragments exclusively, contrary to the average increase assumed earlier. Both methods were compared and the impact of the neutron multiplicities was assessed. The effects found are significant and highlight the importance of further experimental and theoretical investigation.In this work, the strong angular anisotropy of 234U(n,f ) was confirmed. In addition, and quite surprisingly, the mass distribution was found to be angular-dependent and correlated to the vibrational resonances. The anisotropy found in the mass distribution was consistent with an anisotropy in the total kinetic energy (TKE), also correlated to the resonances. The experimental data were parametrized assuming fission modes based on the Multi-Modal Random Neck-Rupture model. The resonance showed an increased yield from the Standard-1 fission mode and a consistent increased TKE. The discovered correlation between the vibrational resonances and the angular-dependent mass distributions for the asymmetric fission modes may imply different outer fission-barrier heights for the two standard modes.
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| 39. |
- Al-Ramadan, Khalid, 1976-
(författare)
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Impact of Diagenetic Alterations on Reservoir Quality and Heterogeneity of Paralic and Shallow Marine Sandstones : Links to Depositional Facies and Sequence Stratigraphy
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis constrains the distribution of diagenetic alterations and their impact on reservoir-quality and heterogeneity evolution pathways in relation to depositional environments and sequence stratigraphy (systems tracts and key sequence stratigraphic surfaces) of four selected paralic and shallow marine siliciclastic successions. Typical eogenetic alterations encountered include the dissolution and kaolinitization of framework silicates, which are closely associated to shoreface facies of forced regressive systems tract (FRWST), lowstand systems tract (LST), upper part of the highstand systems tract (HST), and below the sequence boundary (SB). These alterations are attributed to incursion of meteoric water owing to rapid and considerable fall in the relative sea level. Extensive carbonate cementation is most evident below marine and maximum flooding surfaces (MFS), whereas dissolution of carbonate cement and detrital dolomite occur in LST, HST and below SB. Parameters controlling the patterns and texture (microcrystalline vs. poikilotopic) of calcite cement have been constrained within sequence stratigraphic framework of the sandstones. Coarse crystalline to poikilotopic calcite textures of meteoric water origin are thus closely linked to the FRWST, LST and upper part of the HST sandstones and occur mainly as stratabound concretions, whereas microcrystalline calcite, which was precipitated from marine porewaters, occurs as continuously cemented layers in the transgressive systems tract (TST) and lower part of the HST sandstones.Eogenetic alterations impose, in turn, profound control on the distribution pattern of mesogenetic alterations, and hence on reservoir quality evolution (destruction vs. preservation) pathways of sandstones. Eogenetic infiltrated clays, which occur in the tidal estuarine TST and HST sandstones, have helped preserving porosity in deeply buried sandstone reservoirs (≈ 5 km) through inhibition of extensive cementation by quartz overgrowths. Other essential findings of this thesis include deciphering the control on the formation of authigenic illite and chlorite by ultra-thin (≤ 1 µm thick), grain-coating clay mineral substrate.
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| 40. |
- Al-Smadi, Derar, 1983-
(författare)
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Carboligation using the aldol reaction : A comparison of stereoselectivity and methods
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The research summarized in this thesis focuses on synthesizing aldehyde and aldol compounds as substrates and products for the enzyme D-fructose-6-aldolase (FSA). Aldolases are important enzymes for the formation of carbon-carbon bonds in nature. In biological systems, aldol reactions, both cleavage and formation play central roles in sugar metabolism. Aldolases exhibit high degrees of stereoselectivity and can steer the product configurations to a given enantiomeric and diastereomeric form. To become truly useful synthetic tools, the substrate scope of these enzymes needs to become broadened.In the first project, phenylacetaldehyde derivatives were synthesized for the use as test substrates for E. coli FSA. Different methods were discussed to prepare phenylacetaldehyde derivatives, the addition of a one carbon unit to benzaldehyde derivatives using a homologation reaction was successful and was proven efficient and non-sensitive to the moisture. The analogues were prepared through two steps with 75-80 % yields for both meta- and para-substituted compounds.The second project focuses on synthesizing aldol compound using FSA enzymes, both wild type and mutated variants selected from library screening, the assay has been successfully used to identify a hit with 10-fold improvement in an R134V/S166G variant. This enzyme produces one out of four possible stereoisomers.The third project focuses on the synthesis of a range of aldol compounds using two different approaches reductive cross-coupling of aldehydes by SmI2 or by organocatalysts using cinchonine. Phenylacetaldehydes were reacted with hydroxy-, dihydroxyacetone and hydroxyacetophenone in presence of cinchonine, the reaction was successful with hydroxyacetophenone in moderate yields and 60-99 % de ratio. On the other hand, the aldehydes reacting with methyl- and phenylglyoxal in the presence of SmI2 resulted in moderate yields and without stereoselectivity.
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| 41. |
- Alavioon, Ghazal, 1986-
(författare)
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Haploid selection in animals : Exploring the fitness consequences and underlying mechanisms
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A consequence of sexual reproduction in eukaryotes is the evolution of a biphasic life cycle with alternating diploid and haploid gametic phases. While our focus in evolutionary biology is on selection during the diploid phase, we know relatively little about selection occurring during the haploid gametic stage. This is particularly true in predominantly diploid animals, where gene expression and hence selection have long been thought to be absent in haploid cells like gametes and particularly sperm. During my PhD, I tested the idea of selection during the haploid gametic phase using zebrafish Danio rario as a study species. I combined a large-scale selection experiment over three generations with fitness assays and next-generation sequencing to assess the importance of haploid selection. We measured offspring fitness in all three generations. In addition, we compared gene expression in brain and testes of F1 and F3 adult male from each treatment by RNA sequencing. We found that offspring sired by longer-lived sperm showed higher survival rate and higher early- and late-life reproductive fitness compared to offspring sired by shorter-lived sperm. We also found differentially expressed genes between the two treatments with functions in metabolic and developmental pathways. These findings suggest that the observed fitness differences to be caused by small expression changes in many basic genes. We also tested for a genetic underpinning of the selected sperm phenotypes and identified allelic differences across the entire genome. Finally, we investigated the additive genetic component and parental effect of different sperm phenotypes. We found generally low additive genetic variation and high parental effects on sperm performance traits. In conclusion, this thesis provides evidence that the phenotypic variation among intact fertile sperm within an ejaculate affects offspring fitness throughout life and provides a clear link between sperm phenotype and offspring fitness and between sperm phenotype and sperm genotype.
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| 42. |
- Alfimov, Vasily, 1978-
(författare)
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Accelerator Mass Spectrometry of 36Cl and 129I : Analytical Aspects and Applications
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Two long-lived halogen radionuclides (36Cl, T1/2 = 301 kyr, and 129I, T1/2 = 15.7 Myr) have been studied by means of Accelerator Mass Spectrometry (AMS) at the Uppsala Tandem Laboratory. The 36Cl measurements in natural samples using a medium-sized tandem accelerator (~1 MeV/amu) have been considered. A gas-filled magnetic spectrometer (GFM) was proposed for the separation of 36Cl from its isobar, 36S. Semi-empirical Monte-Carlo ion optical calculations were conducted to define optimal conditions for separating 36Cl and 36S. A 180° GFM was constructed and installed at the dedicated AMS beam line. 129I has been measured in waters from the Arctic and North Atlantic Oceans. Most of the 129I currently present in the Earth's surface environment can be traced back to liquid and gaseous releases from the nuclear reprocessing facilities at Sellafield (UK) and La Hague (France). The anthropogenic 129I inventory in the central Arctic Ocean was found to increase proportionally to the integrated 129I releases from these reprocessing facilities. The interaction and origin of water masses in the region have been clearly distinguished with the help of 129I labeling. Predictions based on a compartment model calculation showed that the Atlantic Ocean and deep Arctic Ocean are the major sinks for the reprocessed 129I. The variability in 129I concentration measured in seawater along a transect from the Baltic Sea to the North Atlantic suggests strong enrichment in the Skagerrak–Kattegat basin. The 129I inventory in the Baltic and Bothnian Seas is equal to ~0.3% of the total liquid releases from the reprocessing facilities. A lake sediment core sampled in northeastern Ireland was analyzed for 129I to study the history of the Sellafield releases, in particular the nuclear accident of 1957. High 129I concentration was observed corresponding to 1990 and later, while no indication of the accident was found. The results of this thesis research clearly demonstrate the uniqueness and future potential of 129I as a tracer of processes in both marine and continental archives.
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| 43. |
- Alfredsson, Ylvi, 1973-
(författare)
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Electronic and Structural Properties of Thin Films of Phthalocyanines and Titanium Dioxide
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on experimental studies in chemical physics. Titanium dioxide (TiO2) and phthalocyanine’s (Pc’s), interesting in many future perspectives, have been deposited as thin films and studied as follows. Information has been obtained on e.g. molecular orientation, crystal structure, depth profile of the chemical composition, electrochemical properties and electronic structure. This has been achieved by means of a combination of techniques: X-ray photoelectron spectroscopy (XPS), near edge x-ray absorption fine structure (NEXAFS), density functional theory calculations (DFT), UV-visible absorption spectroscopy (UVVIS) and cyclic voltammetry (CV).Metal-free phthalcyanine (H2Pc) has been shown to form films with different crystal structure and molecular orientation depending on deposition method, evaporation/sublimation or powder deposition, on commercial conducting glass (fluorine doped tin oxide, FTO), which is used e.g. in solar cells and organic light emitting devices (OLEDs). The unoccupied molecular orbitals are divided in x, y and z space coordinates of the molecule and also divided in inequivalent nitrogen components.The electronic structure is also studied for a sublimated titanyl phthalocyanine (TiOPc) film and related to the metal-free phthalocyanine. The ligand field around the titanium atom in TiOPc is compared with that of TiO2 to delineate the unoccupied levels recorded by means of x-ray absorption spectroscopy.Nanostructured TiO2 films were manufactured by screen printing/doctor blading on FTO. Such films were additionally covered with lutetium diphthalocyanine (LuPc2) by means of surface assembly from solution. LuPc2-, LuPc2+ and LuPc2H were identified and the stability of the electrochromic reactions in this system was monitored.Chemical vapor deposition (CVD) has been used to grow nanometer sized anatase TiO2 crystals on pre-oxidized Si (111) without formation of interfacial carbon and with an interface layer of the size of 15- 25Å. The interface layer was found to be amorphous TiSixOy with graded stoichiometry.
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| 44. |
- Alghamdi, Fayiq, 1985-
(författare)
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Dimensions of Professionalism : A Study of Computer Science Teaching in Saudi Arabia
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Saudi Arabia, new computing education programs have been introduced in alignment with the Saudi Vision 2030, which is a plan launched in 2017 to reduce Saudi Arabia's reliance on oil, diversify its economy, and develop its health, education, recreation, infrastructure and tourism. Computer science is a rapidly changing area, which places high demands on teachers in the subject to develop both their subject and pedagogical competence. This thesis explores computer science teachers’ perspectives on professional development from three viewpoints—the Saudi Teaching Competencies Standard, engagement in teachers’ awards and self-directed learning. The thesis examines the efforts of computer science teachers as they develop new pedagogies during their teaching careers as a result of the new regulations. The main question is ‘How do Saudi Arabian computer science teachers develop their teaching professionalism?’ Conclusions draw on the outcomes of four sub-studies. A mixed-methods approach consisting of interviews and questionnaires was used to collect data. The participants comprised 389 computer science teachers from different Saudi Arabian cities with different demographics and different teaching experience. The analysis drew on a theoretical framework that integrates elements of the Theory of Reasoned Action, the Theory of Planned Behaviour and the Adult Learning Theory. A model for pedagogical change was developed and used to understand how and why computer science teachers change their educational pedagogy. The model explains the teachers’ shift in pedagogy and answers the question of how and why computer science teachers adopt a new pedagogical strategy. The studies show that both internal and external factors motivate the study participants to engage in competency development. In the Saudi model, the Saudi Teaching Competencies Standard and awards are external factors as they include a preparatory period of intensive skills development. Teachers' experience from this informs the picture of Saudi teachers' training that is presented in the dissertation. Indeed, the trial participants stated that they mainly used self-directed learning for their competence development, drawing on internal motivation. One reason for this was that they felt that many of the skills development programs offered lacked timeliness and relevance. The studies on which the dissertation is based have been conducted in Saudi Arabia, but the results also provide insights into general challenges associated with regulating teachers' competence and the design of in-service training for teachers. The results clearly point out the importance of teachers' participation in the development of the profession in order for changes to be accepted and incorporated into their profession. Behavior change theories can be used to understand and predict how new regulations and pedagogical strategies will be received, and if they are likely to be accepted or rejected by teachers. These theories, therefore, constitute a useful tool in regulating teaching and the teaching profession.
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| 45. |
- Alhassan, Erwin, 1984-
(författare)
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Nuclear data uncertainty quantification and data assimilation for a lead-cooled fast reactor : Using integral experiments for improved accuracy
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- For the successful deployment of advanced nuclear systems and optimization of current reactor designs, high quality nuclear data are required. Before nuclear data can be used in applications they must first be evaluated, tested and validated against a set of integral experiments, and then converted into formats usable for applications. The evaluation process in the past was usually done by using differential experimental data which was then complemented with nuclear model calculations. This trend is fast changing due to the increase in computational power and tremendous improvements in nuclear reaction models over the last decade. Since these models have uncertain inputs, they are normally calibrated using experimental data. However, these experiments are themselves not exact. Therefore, the calculated quantities of model codes such as cross sections and angular distributions contain uncertainties. Since nuclear data are used in reactor transport codes as input for simulations, the output of transport codes contain uncertainties due to these data as well. Quantifying these uncertainties is important for setting safety margins; for providing confidence in the interpretation of results; and for deciding where additional efforts are needed to reduce these uncertainties. Also, regulatory bodies are now moving away from conservative evaluations to best estimate calculations that are accompanied by uncertainty evaluations.In this work, the Total Monte Carlo (TMC) method was applied to study the impact of nuclear data uncertainties from basic physics to macroscopic reactor parameters for the European Lead Cooled Training Reactor (ELECTRA). As part of the work, nuclear data uncertainties of actinides in the fuel, lead isotopes within the coolant, and some structural materials have been investigated. In the case of the lead coolant it was observed that the uncertainty in the keff and the coolant void worth (except in the case of 204Pb), were large, with the most significant contribution coming from 208Pb. New 208Pb and 206Pb random nuclear data libraries with realistic central values have been produced as part of this work. Also, a correlation based sensitivity method was used in this work, to determine parameter - cross section correlations for different isotopes and energy groups.Furthermore, an accept/reject method and a method of assigning file weights based on the likelihood function are proposed for uncertainty reduction using criticality benchmark experiments within the TMC method. It was observed from the study that a significant reduction in nuclear data uncertainty was obtained for some isotopes for ELECTRA after incorporating integral benchmark information. As a further objective of this thesis, a method for selecting benchmark for code validation for specific reactor applications was developed and applied to the ELECTRA reactor. Finally, a method for combining differential experiments and integral benchmark data for nuclear data adjustments is proposed and applied for the adjustment of neutron induced 208Pb nuclear data in the fast energy region.
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| 46. |
- Ali, Hasan, 1985-
(författare)
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Towards atomically resolved magnetic measurements in the transmission electron microscope : A study of structure and magnetic moments in thin films
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The magnetic properties of thin metallic films are significantly different from the bulk properties due to the presence of interfaces. The properties shown by such thin films are influenced by the atomic level structure of the films and the interfaces. Transmission electron microscope (TEM) has the potential to analyse the structure and the magnetic properties of such systems with atomic resolution. In this work, the TEM is employed to characterize the structure of the Fe/V and Fe/Ni multilayers and the technique of electron magnetic circular dichroism (EMCD) is developed to obtain the quantitative magnetic measurements with high spatial resolution.From TEM analysis of short period Fe/V multilayers, a coherent superlattice structure is found. In short period Fe/Ni multilayer samples with different repeat frequency, only the TEM technique could verify the existence of the multilayer structure in the thinnest layers. The methods of scanning TEM imaging and electron energy loss spectroscopy (EELS) results were used and refined to determine interdiffusion at the interfaces. The confirmation of the multilayer structure helped to explain the saturation magnetization of these samples.Electron magnetic circular dichroism (EMCD) has the potential to quantitatively measure the magnetic moments of the materials with atomic resolution, but the technique presents several challenges. First, the EMCD measurements need to acquire two EELS spectra at two different scattering angles. These spectra are mostly acquired one after the other which makes it difficult to guaranty the identical experimental conditions and the spatial registration between the two acquisitions. We have developed a technique to simultaneously acquire the two angle-resolved EELS spectra in a single acquisition. This not only ensures the accuracy of the measurements but also improves the signal to noise ratio as compared to the previously used methods. The second important question is the effect of crystal orientations on the measured EMCD signals, considering the fact that the crystal orientation of a real crystal does not remain the same in the measured area. We developed the methodology to simultaneously acquire the EMCD signals and the local crystal orientations with high precision and experimentally showed that the crystal tilt significantly changes the magnetic signal. The third challenge is to obtain EMCD measurements with atomic resolution which is hampered by the need of high beam convergence angles. We further developed the simultaneous acquisition technique to obtain the quantitative EMCD measurements with beam convergence angles corresponding to atomic size electron probes.
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| 47. |
- Ali, Muhammad, 1990-
(författare)
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Identification of SLiMs: Mapping and characterizing motif-based protein interactions
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the last twenty years it has become evident that about 35-40% of amino acids in the proteome are in regions that have evolved to remain unstructured. These intrinsically disordered regions contain short linear motifs (SLiMs), which serve as docking sites for protein-protein interactions. SLiMs often mediate low-to-medium affinity interactions that are transient in their nature. The characteristics of SLiM-based interactions make them difficult to be captured using conventional approaches like affinity-purification coupled to mass spectrometry or yeast-two-hybrid. We therefore used and developed a dedicated method for large-scale screening of SLiM-based interactions termed proteomic peptide phage display (ProP-PD).Using ProP-PD, We identified large sets of ligands, for the binding pocket of shank1 PDZ domain, containing C-terminal or internal binding motifs and established the consensus motifs to be xTxL/F-COOH and xTxFx respectively. We further validated interactions using biophysical affinity determinations and pulldown experiments. Using X-ray crystallization, we uncovered that shank1 PDZ binds to internal xTxFx motifs using a binding mode similar to that for C-terminal peptides.Adding a level of complexity, we explored interactions of the multiple binding pocket containing FERM domains from four closely related proteins: ezrin, radixin, moesin and merlin. We found hundreds of FERM ligands, which contained binding motifs of at least four different classes. By combining docking simulations with experiments, we established ligands binding to different pockets, and uncovered a complex interplay between distinct pockets.We further developed an optimized version of a phage library that displays intrinsically disordered regions of the human proteome. We benchmarked the library using a set of protein domains and reported better recovery of known SLiM-based interactions. Furthermore, we highlighted the functional aspects of identified SLiMs, in the case of nuclear localization signals, found for binding to importin-subunit alpha-3. Finally, we validated predicted binding of SLiMs in the Sars-CoV-2 host receptor ACE2, which illustrates the importance of fundamental knowledge for SLiMs and their binding partners.This work, taken together, contributes with method development for expansion of motifs based interactomes and provide insights into the plastic yet selective nature of peptide binding proteins.
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| 48. |
- Alipour, Mehdi
(författare)
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Rethinking Dynamic Instruction Scheduling and Retirement for Efficient Microarchitectures
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Out-of-order execution is one of the main micro-architectural techniques used to improve the performance of both single- and multi-threaded processors. The application of such a processor varies from mobile devices to server computers. This technique achieves higher performance by finding independent instructions and hiding execution latency and uses the cycles which otherwise would be wasted or caused a CPU stall. To accomplish this, it uses scheduling resources including the ROB, IQ, LSQ and physical registers, to store and prioritize instructions.The pipeline of an out-of-order processor has three macro-stages: the front-end, the scheduler, and the back-end. The front-end fetches instructions, places them in the out-of-order resources, and analyzes them to prepare for their execution. The scheduler identifies which instructions are ready for execution and prioritizes them for scheduling. The back-end updates the processor state with the results of the oldest completed instructions, deallocates the resources and commits the instructions in the program order to maintain correct execution.Since out-of-order execution needs to be able to choose any available instructions for execution, its scheduling resources must have complex circuits for identifying and prioritizing instructions, which makes them very expansive, therefore, limited. Due to their cost, the scheduling resources are constrained in size. This limited size leads to two stall points respectively at the front-end and the back-end of the pipeline. The front-end can stall due to fully allocated resources and therefore no more new instructions can be placed in the scheduler. The back-end can stall due to the unfinished execution of an instruction at the head of the ROB which prevents other resources from being deallocated, preventing new instructions from being inserted into the pipeline.To address these two stalls, this thesis focuses on reducing the time instructions occupy the scheduling resources. Our front-end technique tackles IQ pressure while our back-end approach considers the rest of the resources. To reduce front-end stalls we reduce the pressure on the IQ for both storing (depth) and issuing (width) instructions by bypassing them to cheaper storage structures. To reduce back-end stalls, we explore how we can retire instructions earlier, and out-of-order, to reduce the pressure on the out-of-order resource.
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| 49. |
- Allalou, Amin, 1981-
(författare)
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Methods for 2D and 3D Quantitative Microscopy of Biological Samples
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New microscopy techniques are continuously developed, resulting in more rapid acquisition of large amounts of data. Manual analysis of such data is extremely time-consuming and many features are difficult to quantify without the aid of a computer. But with automated image analysis biologists can extract quantitative measurements and increases throughput significantly, which becomes particularly important in high-throughput screening (HTS). This thesis addresses automation of traditional analysis of cell data as well as automation of both image capture and analysis in zebrafish high-throughput screening. It is common in microscopy images to stain the nuclei in the cells, and to label the DNA and proteins in different ways. Padlock-probing and proximity ligation are highly specific detection methods that produce point-like signals within the cells. Accurate signal detection and segmentation is often a key step in analysis of these types of images. Cells in a sample will always show some degree of variation in DNA and protein expression and to quantify these variations each cell has to be analyzed individually. This thesis presents development and evaluation of single cell analysis on a range of different types of image data. In addition, we present a novel method for signal detection in three dimensions. HTS systems often use a combination of microscopy and image analysis to analyze cell-based samples. However, many diseases and biological pathways can be better studied in whole animals, particularly those that involve organ systems and multi-cellular interactions. The zebrafish is a widely-used vertebrate model of human organ function and development. Our collaborators have developed a high-throughput platform for cellular-resolution in vivo chemical and genetic screens on zebrafish larvae. This thesis presents improvements to the system, including accurate positioning of the fish which incorporates methods for detecting regions of interest, making the system fully automatic. Furthermore, the thesis describes a novel high-throughput tomography system for screening live zebrafish in both fluorescence and bright field microscopy. This 3D imaging approach combined with automatic quantification of morphological changes enables previously intractable high-throughput screening of vertebrate model organisms.
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| 50. |
- Allard, Erik, 1976-
(författare)
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Metabolic Studies with Liquid Separation Coupled to Mass Spectrometry
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Metabolism is the sum of all chemical processes with the purpose to maintain life, as well as enable reproduction, in a living organism. Through the study of metabolism, increased understanding of pharmacological mechanisms and diseases can be achieved. This thesis describes several ways of doing so, including targeted analysis of selected metabolites and investigations of systematic metabolic differences between selected groups through pattern recognition. A method for exploring metabolic patterns in urine samples after intake of coffee or tea was developed. The methodology was later used with the aim to find biomarkers for prostate cancer and urinary bladder cancer. Furthermore, a fully automated quantitative method was developed for concentration measurements of the double prodrug ximelagatran and its metabolites in pig liver. The method was then used to study the roll of active transporters in pig liver cells. Moreover, a fundamental study was conducted to investigate how monitoring of small, doubly charged analytes can improve the limit of detection and precision in a quantitative method. The techniques used for the experiments were liquid separation coupled to electrospray mass spectrometry. Extra efforts were made to make the separation and the ionization as compatible as possible to each other for increased quality of the collected data.
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