| 83161. |
- Thuresson, Ann-Charlotte, 1964-
(författare)
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Regulation of Mammalian Poly(A) Polymerase Activity
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Poly(A) polymerase (PAP) is the enzyme catalyzing the synthesis of the adenine tail to the 3’-end of mRNA. This A-tail is present on the majority of the primary RNA transcripts of protein-coding genes, and is important for mRNA stability, export to the cytoplasm and translation. Therefore, PAP is a key regulator of eukaryotic gene expression. This thesis describes the heterogeneity of PAP and the functional significance of multiple isoforms of PAP.PAP exists in many different isoforms generated by three different mechanisms, gene duplication, alternative mRNA processing and post-translational modification. In HeLa cell extracts three different forms of PAP being 90, 100 and 106 kDa in size have been detected, where the 106 kDa isoform is a phosphorylated version of the 100 kDa species. It is shown that the N-terminal region of PAP contains a region required for catalysis, while the C-terminal end is important for the interaction with the cleavage and polyadenylation specificity factor (CPSF). Interestingly, it was found that also the extreme N-terminal end is important for the interaction with CPSF. This region is post-translationally modified by phosphorylation. Five alternatively spliced forms of PAP mRNAs are encoded by the PAPOLA gene while one unique species is encoded by the PAPOLG gene. The analysis showed that the exact structure of the alternatively spliced C-terminal end of PAP played an important role for catalytic efficiency. Thus, the C-terminal end contains a region important for modulating the catalytic efficiency of PAP.Aminoglycoside antibiotics inhibit PAP activity, most likely by displacement of catalytically important divalent metal ions. Data shows that different aminoglycosides inhibit PAP activity by different mechanisms suggesting that the binding sites for the different aminoglycosides do not completely overlap. It is concluded that aminoglycosides interfere with enzymes important for housekeeping functions in mammalian cell, which may explain some of the toxic side effects caused by aminoglycoside antibiotics in clinical practice.
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| 83162. |
- Thuresson, Axel
(författare)
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Swelling and Microstructure of Nanoplatelet Systems
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many clay minerals consist of charged nanoplatelets that swell in an aqueous solution. The swelling and the microstructure depend on the type of clay mineral but are also dependent on, for example, the ionic composition and the temperature of the solution. The synthetic clay mineral Laponite and the natural clay mineral montmorillonite have been studied experimentally and theoretically. The swelling has been studied by swelling pressure measurements in a test cell and the microstructure has been studied by small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). Theoretically, Metropolis Monte Carlo (MC) simulations and molecular dynamics (MD) simulations were used to study the electrostatic interactions between the platelets and an adsorbing polymer was also included. Coarse-grained models have been used to represent the platelets, the ions, and the polymers. This thesis can be divided into three parts:In the first part, the tactoid formation (platelets aggregating face-to-face with an equidistant separation) and the microstructure of negatively charged platelets were investigated by simulations. Tactoid formation was promoted by increasing the platelet surface charge density, the platelet size, the ion valency, and the salt concentration. With enough added salt, an isodesmic model was suggested that gives a monotonically decaying distribution of aggregation numbers.In the second part, the tactoid formation and the microstructure were investigated with respect to the platelet size for flocculated Laponite and montmorillonite at elevated salt concentrations, with and without the addition of the polymer polyethylene glycol (PEG). The smaller Laponite platelets give rise to a more disordered microstructure compared to the larger montmorillonite platelets. The number of platelets per tactoid increased with the addition of PEG. The simulations suggested that the role of the salt is to screen the repulsive interactions between the platelets, and the role of the polymer is to bridge between the platelets.In the third part, the temperature response of Na/Ca montmorillonite was investigated. It was found that the swelling pressure increased with increased temperature if sodium is the dominating counterion whereas the opposite was found if calcium is the dominating counterion. The simulations predicted this behavior and it was shown that the results could be explained by a single equation.
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| 83163. |
- Thuresson, Britt
(författare)
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Studies on the Polymorphism and Transcriptional Regulation of the ABO and P1PK Histo-blood Group Genes
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antigens of the clinically important ABO and P1PK blood group systems are carbohydrate structures. Thus the underlying genes do not encode antigens directly but glycosyltransferases that add specific sugar molecules to selected precursor chains. The aim of this study was to investigate the transcriptional regulation of ABO and A4GALT, with an emphasis on interindividual differences. The up-and downstream regions of the major ABO alleles were sequenced to identify allele-specific motifs. Transcript levels were evaluated in both peripheral blood and bone marrow samples. Considerable allelic variation was observed between the common ABO alleles although this did not appear to influence transcript levels. Strikingly, however transcripts from the two major A alleles, A1 and A2 were undetectable in peripheral blood while, B/O transcripts were readily found. Consequently all alleles were transcribed in bone marrow cells undergoing erythroid culture. In a second study, a novel ABO hybrid allele with an anomalous enhancer region was characterized in a A1Bweak sample. Contrary to current beliefs, the number minisatellite 43-bp elements in the enhancer region did not correlate with ABO transcript levels in these two studies. A4GALT gene transcripts were measured in P1 and P2 phenotypes samples. Regarding transcript levels and RBC surface antigen expression. Through the discovery of a novel A4GALT transcript containing a previously unrecognized and polymorphic A4GALT exon, the long-suspected link between the P1 and Pk antigens was established. A P1/P2 polymorphism was confirmed useful for genotyping in >200 donors. The P2 allele was shown to lower A4GALT transcript levels as well as P1 and Pk antigen expression. Accordingly P1/P2 zygosity appears to explain the well-known but poorly understood variability in P1 strength on erythrocytes. Based on these studies, the Pk antigen has now joined P1 in the former P blood group system, appropriately re-designated P1PK. In summary, these studies of ABO and A4GALT transcriptional have resulted in significant discoveries towards increased understanding of two clinically important blood group systems. The mechanisms underlying 1) the apparent absence of A transcripts in peripheral blood, and 2) how the P2-specific polymorphism down-regulates A4GALT transcripts remains to be explained.
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| 83164. |
- Thuresson, Daniel, 1974
(författare)
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Thermomechanics of block brakes
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Friction in sliding contacts plays an important role in tribology. Applications can be found in many engineering fields such as braking of vehicles in which friction brakes are by far the most common. Thus, an understanding of the mechanisms involved in friction brakes has become more important as the demands on brakes increase. Today, the braking systems used are acknowledged to have problems related to thermal loading. From a theoretical as well as experimental perspective, little is actually known about the location, magnitude and distribution of pressure and temperature between sliding bodies. This is especially true when considering high energy sliding contacts, which can be found in brakes and clutches. This thesis concerns the temperature and pressure distribution between two sliding bodies. Investigations of how various parameters influence contact pressure and temperature have been carried out. An instability phenomenon known as thermoelastic instability, which is frequently observed in experiments, was found to be the main driving force in terms of excessive pressure and temperature. Thermoelastic instability on the friction material appears as moving contact points, caused by the interaction between wear and thermal expansion. A two-dimensional finite element model and a pin model were used to calculate interface pressure and temperature. These models can handle temperature dependent variables, such as the friction and wear coefficients. The models and methods employed in the present thesis were chosen in order to illuminate essential aspects of a braking system and, coupled with numerical results, to quantify the effects of different materials properties. A less complex pin model of a brake was employed to reduce the computational effort, which is practical when simulating several minutes of high speed braking or if the brake model forms a part of a larger simulation model. Temperature measurements in a full-scale block brake test rig were also performed, in order to investigate block temperature and to verify the mathematical models. Both measurements and simulations show an unstable temperature distribution under the studied conditions. Comparison with experiments and the finite element model revealed that the pin model may be an alternative to more complex models for studying aspects of sliding contact, in particular contact pressure, temperature and thermoelastic instability.
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| 83165. |
- Thuresson, Hanna, 1972-
(författare)
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Yngre barns meningsskapande om läsande och skrivande i förskolans literacypraktik
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the youngest (one- to -three-year-old) preschool children's literacy meaning making practices in preschool. Preschool is the first formal educational setting that children attend, and preschool teachers' actions, teaching, and choice of materials and places for reading and writing activities affect the ways in which children make meaning of literacy. The research focuses on preschool as a specific educational and cultural context and on children’s interaction with their peers and the literacy tools used. The aim of the study is to contribute to the understanding of preschool as an educational as well as a cultural practice for young children by studying how they make meaning of literacy.The theoretical framework for this study is based on a social approach to literacy, drawing from Multimodality and New Literacy Studies. Observations of literacy practices were documented by camera and fieldnotes. The observations took place in four different preschool settings and focused on one- to three-year-old children’s actions.The study identifies eight different meaning making methods in children’s use of different social, material, and bodily resources. These different meaning making methods that children use lead to the conclusion that the norms of literacy in the literacy practices clearly shape children’s literacy meaning making. Despite the children’s relatively minimal experiences of literacy in educational settings they already make meaning of how, where, and with what material literacy is enacted. An important finding for educational settings, therefore, is that literacy is not only a skill, but also a way of learning how to handle objects in different places and to move your body in the setting. Second, children’s meaning making of literacy also contains aspects of breaking with the norms that surround meaning making of literacy. Children challenge and question the literacy habits entailed in educational literacy practices.
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| 83166. |
- Thuresson, Kaj, 1971-
(författare)
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Occupational exposure to brominated flame retardants : With emphasis on polybrominated diphenyl ethers
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Brominated flame retardants (BFRs) are a diverse group of chemicals, which are used to slow down or inhibit the development of fires. BFRs are incorporated into a wide range of consumer products that are considered as potential fire hazards, such as TV-sets, household appliances, computers, and textiles. The production and use of BFRs is extensive and consists of mainly tetrabromobisphenol A (TBBPA), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecan (HBCD). BFRs in general, but in particular the PBDEs, have led to both scientific and public concern since they have been found to bioaccumulate in humans and wildlife. The general population is targeted by the PBDEs due to their applications and via the food web. Occupational exposure occurs not only during direct handling of BFRs, but also during handling, repair and dismantling of flame retarded goods.This thesis is aimed to assess occupational exposure to BFRs. It is mainly focused PBDEs and especially the PBDEs with high bromine content, such as decabromodiphenyl ether (BDE-209). The work has been accomplished by analysis of BFRs in indoor air at industries handling BFRs or flame retarded goods, and by analysis of blood drawn from workers with potential exposure to BFRs. A referent group, abattoir workers with no occupational exposure to PBDEs, was also investigated. Data from these cross-sectional investigations and from serum sampling during vacation in PBDE-exposed workers have been used for calculation of apparent halflives of hepta- to decaBDE in serum.The results clearly show that the workers were exposed to PBDEs when handling PBDE containing products or goods. The serum PBDE levels in computer technicians were found to correlate to the estimated cumulative work hours with computers. Exceptionally high concentrations of BDE-209, almost up to 300 pmol/g lipid weight (l.w.) were observed in serum from rubber workers manufacturing or handling rubber compound that was flame retarded with a technical mixture of decabromodiphenyl ether (DecaBDE). Elevated concentrations of PBDEs with eight or nine bromine substituents were also observed. In an electronics dismantling plant, where elevated levels of PBDEs previously had been observed, reduced serum levels of some, but not all PBDE congeners were observed after industrial hygiene improvements. Notably, it was observed that the BDE-209 concentrations in referents with no occupational exposure were similar to the concentrations of 2,2’,4,4’- tetrabromodiphenyl ether (BDE-47), often referred to as the most abundant PBDE congener in humans and wildlife. Additionally, PBDEs with high bromine content were found to have a fast rate of elimination or transformation in humans, based on serum analysis. BDE-209 had an apparent half-life in serum of only 15 days.The possibility of quantifying BFRs, such as PBDEs, in human serum at low levels of detection has been achieved by reducing the contamination of the samples and procedural blanks. Major efforts have been done to develop routines and clean up methodology to enable an almost contamination-free environment at the laboratory. The use of a clean room has decreased PBDE levels in the blanks to acceptable limits. The modifications of the original analytical method have made it possible to quantify almost all PBDE congeners of interest in one GC/MS run.Occupational and general background exposure of BFRs to humans will continue as long as these chemicals are a part of our daily life and present as environmental contaminants. The present scientific knowledge of the potential health risks of these BFRs still needs to be further developed. It should be stressed that health effects to PBDEs have not been assessed in this work. It is the author's wish that this thesis should add another piece of knowledge to the puzzle of BFRs and BFR exposure to humans and that these data will be used in future risk assessments of PBDEs in particular.
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| 83167. |
- Thuresson, Krister
(författare)
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Solution properties of a hydrophobically modified polymer
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The influence of hydrophobic modification on solution properties of water-soluble polymers in the semi-dilute regime have been studied. The nonionic ethyl(hydroxyethyl)cellulose (EHEC) and its hydrophobically modified analogue (HM-EHEC) are used as model substances. Interactions between the polymer molecules in solution and a third component are investigated, and in particular the influence of the surfactant sodium dodecylsulfate (SDS). The polymer/SDS complex formation is investigated by using several techniques (phase behaviour, rheology, calorimetry, DS- sensitive electrode, NMR, and light scattering and fluorescence techniques). This combination of methods gives thermodynamic information on the complex formation, as well as information about the dynamics of the polymer/surfactant complex. In a binary, semi-dilute, HM-EHEC solution the hydrophobic tails associate in clusters with an average of ten tails. These 'pre-formed' micelles act as nucleation sites for other molecules that contain hydrophobic moieties. The number of mixed micelles, and the strengths of the inter polymeric bonds which they give rise to, control both microscopic properties (as chain motions) and macroscopic behaviour (as rheology and phase behaviour). Experimental phase studies with hexanol as a third component were compared with model calculations in a modified Flory-Huggins approach. By assuming that hydrophobic modification causes enhanced association with the polymer semi-quantitative agreement was found. The associative phase separation that is usually observed in mixtures of two oppositely charged polyelectrolytes is effectively prevented by hydrophobic modification of both polyelectrolytes; a highly viscous phase is formed.
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| 83168. |
- Thuresson, Martin, 1977
(författare)
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Compression Techniques for Improved Bandwidth and Static Code Size in Computer Systems
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Technological improvements in integrated circuits have for a longtime allowed the performance of computer chips to growexponentially, allowing for more and more advancedsystems. Unfortunately, the I/O-pins connecting the processorcore/cores with memory and other devices have not seen the samerate of improvement. In this thesis I study the opportunities andchallenges with using compression to help solve some of thechallenges that have emerged. These include reducing thebandwidth needed and the static code size.The first part of the thesis addresses data-link compression. Bystudying the data transferred between the last-level cache andmain memory, several types of localities that can be used tocompress the data are identified. Current state-of-the-artcompression techniques are analyzed in the context of thiscategorization. Using this categorization, I show that it ispossible to combine techniques that work on different types oflocality into a more efficient compression algorithm. Moreover, Ishow how stateful compression schemes can be implemented inmulti-node systems.This thesis also considers efficient program representation. Inmost programs, identical sequences of instructions often appearin several places, making dictionary based compression anefficient scheme for reducing the static code size. In thisthesis I propose a new, more flexible scheme in which similarsequences of instructions can be represented by the samedictionary entry and executed with low hardware overhead.Finally, a code compression scheme targeting wide instructionformats is presented. The scheme is based on dynamic look-uptables, which allow the compiler to adapt the compression todifferent phases of the application. Also presented is amethodology for dimensioning the decompression engine and analgorithm for generating compressed programs that dynamicallymanage the look-up tables with little run-time performanceoverhead. The compression scheme is evaluated using FlexCore, anarchitecture with exposed datapath control, and shown toefficiently reduce the control-bits of the instruction word bymore than 50%.
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| 83169. |
- Thuresson, Markus, 1994-
(författare)
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Ext-algebras of standard modules over quasi-hereditary algebras
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the representation theory of a particular class of finite-dimensional algebras, called quasi-hereditary algebras. In particular, it considers two subclasses of quasi-hereditary algebras: dual extension algebras and hereditary algebras. It consists of three papers.Paper I describes the Ext-algebra of standard modules over the dual extension algebra of two arbitrary directed algebras up to isomorphism of graded associative algebras. This Ext-algebra carries the natural structure of an A-infinity algebra, and under certain technical assumptions, we provide explicit formulae for its A-infinity structure in terms of the directed algebras used to construct the dual extension algebra.Paper II classifies all (basic) generalized tilting modules and all full exceptional sequences of a certain family of quasi-hereditary algebras, which are examples of the dual extension algebras studied in Paper I. This is achieved by constructing a combinatorial model for the poset of self-orthogonal indecomposable modules with standard filtration, where the order relation arises from extensions of positive degree.Paper III describes the quiver and relations of the Ext-algebra of standard modules over the path algebra of a uniformly oriented linear quiver. For a deconcatenation of a quiver at a sink or a source, we describe the Ext-algebra of standard modules over the path algebra of the quiver in terms of that over the path algebras of the parts of the deconcatenation. Moreover, we characterize the deconcatenations for which the path algebra of the quiver admits a regular exact Borel subalgebra in the sense of König. We apply these results to determine a necessary and sufficient condition for the path algebra of a linear quiver of arbitrary orientation to admit a regular exact Borel subalgebra.
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| 83170. |
- Thuresson, Marcus
(författare)
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On neck load among helicopter pilots : effects of head worn equipment, whole body vibration and neck position
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Helicopter pilots complain of pain originating from the neck region. The causes are still basically unknown, but the ergonomic situation when flying a helicopter, with unfavorable load caused by static neck and body positions, whole-body vibration and heavy head-worn equipment, has been suggested as a risk factor. Aim: The aim of the work reported in this thesis was to quantify the effects of external loads on helicopter pilots necks, and to evaluate different methods for measuring neck load. Methods: Thirty-nine Swedish military helicopter pilots participated in the five studies. The effects of different neck and body positions, head-worn equipment and vertical whole-body vibration were evaluated concerning neck muscle activity, induced mechanical load and seat-to-head transmissibility. Surface electromyograms (EMG) were recorded from upper and lower dorsal neck muscles, the sternocleidomastoid, and the upper trapezius. The induced load on the lower cervical spine was calculated using a sagittal, static, biomechanical model, and vibration transmissibility was calculated as the ratio of recordings from helmet-mounted accelerometers and vertical vibration acceleration measured at the seat. The neck and body positions evaluated were: neutral, neck flexion 20° (for muscle activity, induced load and transmissibility), neck rotation 30° (EMG), and trunk inclination 20° (EMG). The head-worn equipment evaluated was: helmet alone, helmet and night vision goggles (NVG), and helmet, NVG and counterweight (all evaluated using EMG, induced load and transmissibility). Vibration was evaluated at different frequencies (2.5-30 Hz) and magnitudes (0.5, 1, and 2 m/s 2) using EMG and transmissibility. For the reliability testing of a neck fatigue protocol, the pilots performed isometric contractions in neck flexion and extension for 45 s, sustaining a force representing 75 % of maximum strength in a seated position. Subjective fatigue was rated using the Borg CR-10 scale. The test was repeated twice the first day and then two additional times with one-week intervals. Variables analyzed were the slope of the median frequency change, the normalized slope, and the ratings after 15, 30 and 45 s; and also the initial median frequency (IMDF). The intra-class correlation (ICC) and the measurement error (S w), intra- and inter-day were calculated. Results: Dorsal neck muscle activity increased by 3-4 % of maximum voluntary electrical activation (MVE) as a cause of neck rotation, 2-3 % of neck flexion, and 1.5-2.5 % of trunk inclination. The use of NVG increased muscle activity in upper neck by 0.5-1.5 % and in lower neck by about 0.5 %. Results with added counterweight were about the same as with NVG. Muscle activity increased by about 0.5-1 % MVE as a function of vibration at frequencies around 4-5 Hz, with the higher levels when the neck was flexed. Muscle activity was also affected by vibration magnitude, where lower-neck-muscle and trapezius activity increased at the highest vibration level at frequencies around 4-5 Hz. The induced load was also affected by both neck flexion and NVG. The load at 20° flexion increased by about 8 % of maximum voluntary contraction (MVC) compared to neutral and by about 3 % MVC when adding NVG compared to using helmet only. The load decreased somewhat when a counterweight was added. The transmissibility peak in a vertical direction was highest when the head was in neutral position and the fore-and-aft transmissibility peak was highest when the head was flexed. There were no effects of head-worn equipment concerning vertical transmissibility, but the fore-and-aft transmissibility peak level was lower with NVG. Different magnitudes of vibration gave only minor effects on transmissibility. The best reliability for the slope was found for the 45 s intra-day analysis, taking all measurements into account (ICC 0.65-0.83). Reliability after 30 s was poorer but still acceptable (ICC 0.52-0.71). For the subjective ratings, the highest reliability was found after 30 s inter-day (ICC 0.86-0.88). IMDF showed generally high reliability for the intra-day analyses (ICC 0.63-0.80). Conclusion: All three proposed risk factors caused measurable changes in muscle activity, induced load and seat-to-head transmissibility. Of the three, neck and body position caused the highest response. EMG and seat-to-head transmissibility responded somewhat different as function of vibration indicating that effects of vibration should be measured using more then one outcome measure. The protocol for measuring neck muscle fatigue can be considered reliable for use in further research. Since performing a contraction of 75 % of maximum was quite strenuous, it is recommended that the protocol period be shortened to 30 s.
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