Publikationer från Uppsala Universitet
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Numerical Simulation of Polymer Flow Dynamics in Cable Extrusion Processes
No full textThe quality of the insulation in a HV cable is largely determined in the extrusion process and more needs to be understood about the behavior of polymer melt within the extrusion die. This master thesis aims to increase the knowledge of how to properly simulate the polymer flow pattern and thermal build up within the extrusion die. The main part of the work is to recreate a simulation model made in 1998 by ABB, and improve the model based on literature recommendations. The model is implemented in Ansys Fluent Material Processing with the same boundary conditions as presented in the legacy report, with very similar results. Realistic wall slip conditions, material properties and thermal boundary condition for the conductor are then added separately. The largest improvements come from including wall slip, since undesired local effects highlighted as important in the legacy report are drastically lowered in the more realistic case. Changing the material properties and thermal condition appears to mostly affect the viscosity and for the latter case of course also the thermal buildup close to the conductor. Further, there were several aspects that could not be simulated in the study, but due to their potential importance they are still analyzed
Elevated levels of aquaporin-4-containing extracellular vesicles in cerebrospinal fluid of patients with bipolar disorder
No full textObjectives: To examine a hypothetical dysfunction of the brain water channels in bipolar disorder by analyzing aquaporin-4 (AQP4) exposing extracellular vesicles (EVs) in cerebrospinal fluid (CSF) from individuals with bipolar disorder types 1 and 2, and healthy controls. Methods: We analyzed exposure of AQP4 EVs to three different epitopes-the N-and C-terminals, and the epitope containing amino acids 273-291-in CSF by flow cytometry in 24 individuals with bipolar disorder (type 1, n = 20; type 2, n = 4) and in 14 healthy controls. Results: We observed significantly higher levels of EVs expressing AQP4 in the CSF from individuals with bipolar disorder compared with healthy controls. Specifically, the mean +/- SD concentration of AQP4 + EVs per mu l CSF for the N-terminal epitope was 346 +/- 22 in patients with bipolar disorder type 1, 386 +/- 78 in those with bipolar disorder type 2, compared with 39 +/- 6.9 in the healthy control group (P < 0.0001). For AQP4+ EVs targeting the C-terminal epitope, the corresponding values were 350 +/- 22 for bipolar disorder type 1, 374 +/- 46 for bipolar disorder type 2, and 36 +/- 6.3 for healthy controls. Similarly, EVs expressing AQP4+ epitopes containing amino acids 273-291 showed concentrations of 344 +/- 17 in bipolar disorder type 1, 398 +/- 63 in bipolar disorder type 2, and 38 +/- 6.4 in the control group (P < 0.0001). Conclusion: Our findings revealed significantly more EVs expressing the three AQP4 epitopes in patients with bipolar disorder compared with healthy controls. This suggests a dysregulated expression of AQP4, implicating a potential disruption in brain water homeostasis as a contributing pathogenic mechanism in bipolar disorder
Controls on organic matter decomposition across ecosystems
No full textOrganic matter (OM) comprises all living organisms and their remains and its decomposition is a fundamental process in the global carbon cycle, influencing the proportion of OM that either accumulates as a long-term sink or is mineralized into greenhouse gases released into the atmosphere. Understanding how microbes break down OM is essential for predicting carbon dynamics under global change. The controls on OM decomposition have been summarized in two major groups: those related to the inherent chemical properties of OM and the various environmental parameters that influence its decomposability. While previous studies often focused on drivers within one ecosystem, this thesis adopts a cross-system approach to identify universal mechanistic controls on OM biodegradability across terrestrial and aquatic environments. Another central focus is to estimate the range of the respiratory quotient (RQ), defined as the molar ratio of CO2 produced to O2 consumed during microbial degradation of OM, and to explore what regulates its variability. This thesis aims to fill these knowledge gaps through five studies that combine literature synthesis, methodological development for measuring CO2 and O2 in various environmental samples, and controlled incubation experiments. The findings show that RQ varies substantially across ecosystems, with the commonly assumed value of 1 potentially introducing over 50% uncertainty to carbon flux estimates. Measuring RQ with membrane inlet mass spectrometry (MIMS), identified as the most versatile and reproducible method, revealed that RQ reflects microbial metabolic efficiency, which is influenced by both substrate availability and ecosystem properties. Furthermore, the experimental studies demonstrate that OM energy density and Gibbs free energy of formation (ΔGf) are strong and consistent predictors of decomposition rates across systems. In peat that has been subject to permafrost thaw, OM potential decomposition was limited at depth and mainly constrained by its inherent energetic and thermodynamic properties, rather than by post-thaw ecological conditions. Overall, these findings highlight the importance of considering energetic and thermodynamic properties when examining OM reactivity across various environments. By connecting RQ with the microbial metabolic capacity and estimating its global range, this thesis also aims to contribute to improved predictions of organic carbon mineralization in a changing world
Motion Planning and Control – Ackermann Robots : Path Finding and Trajectory Tracking with Nonlinear Dynamics
No full textThis thesis is about the development of a complete framework for path planning and automatic motion control for an ackermann steered robot. The purpose of the thesis was to let a robot automatically navigate its way through an obstacle course, from a given start position to a set goal, whilst adhering to the robot's physical constraints and dynamics. The work was divided into three main parts: path finding, trajectory planning, and motion control. For path finding, we build an algorithm based on Steven M. LaValle's Rapidly Exploring Trees (RRT), which sequentially generates a tree like structure made up of nodes. The algorithm was chosen based on its reliability and ability to navigate difficult environments without the need to first discretize the world space. Two different methods to track the generated path were implemented: a waypoint method, and a polynomial fit function method. Both methods were tested using the same control system which we also developed. The control system was made by linearizing the robot's ackermann dynamics, which made it possible to use a PID-like control strategy where positional error, error in velocity and error in acceleration could be used to calculate appropriate values for the control signals, jerk and rateof steering angle. The entire framework was simulated using MATLAB, although it was never realized on a real world robot. The results were good. Both methods were able to produce reliable and consistent collision avoidance and satisfactory trajectory tracking. Upon testing it became apparent that the waypoint method was best suited for labyrinth-like obstacle courses, and the polynomial fit function method was best suited for more open environments. Even though the simulation results were good, there is still further development required beforeany real world application can be made, such as testing the framework on a real robot, and implementing more features which take physical constraints into account, such as sensor noise.
Pre-clinical safety and efficacy evaluation of Helicobacter Pylori neutrophil-activating protein (NAP)-armed CAR-T cells targeting B cell lymphomas
No full textCD19 CAR-T cell therapy shows striking results in treating B cell malignancies. However, approximately two-thirds of the lymphoma patients eventually relapse, with about one-third displaying CD19-negative tumors at relapse. Our previous study showed that CAR-T cells armed with the Helicobacterpylori neutrophil-activating protein (NAP), CAR(NAP)-T cells, can trigger a bystander immune response and eliminate CAR-target-antigen-negative tumor cells. Here, we report the development of CD20-targeted CAR-T cells (CAR20-T cells), with the targeting moiety from rituximab, and the safety and efficacy of NAP-armed CAR-T cells. CAR20-T cells displayed efficient and specific cytotoxic potential against multiple human B cell lymphoma cell lines in vitro. In addition, primary mantle cell lymphoma cells, isolated from a patient who relapsed after rituximab treatment, can also be eliminated by CAR20-T cells. CAR20(NAP)-T cells delayed tumor growth and prolonged survival of mice with lymphoma. No obvious histopathological alteration in major organs were observed in mice treated with CAR(NAP)-T cells. Further, no excessive cytokine release or immune cell activation was observed when human blood from healthy volunteers was exposed to recombinant NAP protein in an ex vivo blood loop assay, suggesting a safe therapeutic profile for NAP. Taken together, these results warrant the clinical investigation of CAR20(NAP)-T cells.De två första författarna delar förstaförfattarskapet.De två sista författarna delar sistaförfattarskapet.</p
On the regularity of systems of dispersive partial differential equations
No full textWe extend and improve a regularity result that shows polynomial growth in time of solutions of certain systems of partial differential equations that model dispersive equations interacting with a general class of multilinear operators. This is done by a general multilinearisation method that extends estimates on linear oscillatory integral operators to the case of multilinear operators
Svenska som andraspråk i två nationella kontexter : En komparativ studie om målgruppen i ämnet svenska som andraspråk i Sverige respektive i Finland
No full textSvenska som andraspråk är ett relativt nytt ämne som undervisas både i Sverige och Finland. Ämnet är detsamma, men sammanhanget där det undervisas är olika. I det här didaktiska examsarbetet ligger fokus på att beskriva SVA i dessa två nationella kontexter, i relation till de elever som ämnet är avsett för. Materialet har hämtats från ländernas språkpolitiska styrdokument (Skolverket och Utbildningsstyrelsen) samt genom att få en inblick med hjälp av enkätstudie (f 10, fem SVA-lärare i Finland och fem i Sverige) om hur ämnets undervisning, elevgrupper och lärarnas uppfattning om ämnet i relation till styrdokumenten ser ut i skolorna. Resultaten presenteras i stapeldiagram, tabeller samt med hjälp av citat. Båda ländernas styrdokument och lärarnas svar har sedan analyserats med hjälp av komparativ innehållsanalys. Resultaten och analysen tyder att ämnet karaktäriseras på ett liknande sätt i styrdokumenten, men när det gäller elever utgår Skolverket från ett tydligare resursperspektiv medan Utbildningsstyrelsen betraktar flerspråkighet ur ett starkare bristperspektiv. Enkäterna indikerar att elevgrupperna är relativt jämbördiga i de skolor där ämnet undervisas, men att antalet SVA-elever är något mindre i Finland. Det finns skillnader i hur ämnet organiseras, exempelvis utifrån elevgruppers sammansättning och tillgång till läromedel. Dessa skillnader kan förstås i ljuset av ländernas olika historik och politik kring mångkulturalism. För att undervisningen ska bli likvärdig och ändamålsenlig krävs ett stärkt, systematiskt och flexibelt arbete att möta heterogena elevgrupper i båda länderna.
Unveiling Antibiotic Phototransformation Products in Surface Water: Structural Elucidation, (Eco)toxicological Risks, and Resistance-Related Implications
No full textAntibiotics have tremendously improved the treatment of bacterial infections, but their widespread use has raised environmental concerns and contributed to the rapid growth of antibiotic-resistant bacteria. Once released into the aquatic environment, antibiotics can undergo various degradation processes, such as photodegradation, forming phototransformation products (TPs) with largely unknown ecotoxicological effects and the potential to contribute to the development of resistance. This study investigated the phototransformation of four widely used antibiotics clindamycin, metronidazole, meropenem, and sulfamethoxazole, in surface water. Using liquid chromatography coupled to high-resolution mass spectrometry, eight novel photo TPs were identified with high confidence: CLI1–5 (clindamycin), MRO1–3(meropenem), and the reference compounds MET1 (metronidazole) and SMX1(sulfamethoxazole). Elucidated transformation pathways included dehydrogenation, β-lactamring opening, atom rearrangement, and acetylation. The potential of clindamycin photo TPs to induce antibiotic resistance was also examined through genetic analysis of resistance-related genes, which was determined in a real environmental community in surface water. No significant upregulation of integrons, mobile genetic elements, or resistance genes was observed, suggesting a limited influence under the tested conditions. To assess potential ecological risks, the acute and chronic toxicity of the identified TPs was predicted in silico using TRIDENT and VEGA. Most photo TPs showed reduced toxic potential compared to their parent compounds, except MET1, which demonstrated increased toxicity across multiple trophic levels. Clindamycin and sulfamethoxazole TPs showed heightened sensitivity in invertebrates, while meropenem TPs appeared to pose the lowest ecological hazard. None of the TPs were predicted to be bioaccumulative or bind to endocrine nuclear receptors. Given the environmental occurrence of these antibiotics and their rapid photodegradation, further research is warranted to assess the environmental fate, stability, and long-term ecological impact of their photo TPs. In particular, MET1 and clindamycin´s TPs should be prioritised for future monitoring and risk assessment due to their higher predicted toxicity
Investigation of nanocomposite formation in TiSiN coatings using atom probe tomography
No full textOwing to their superior mechanical properties, TiSiN nanocomposite coatings are known as excellent protective layers for cutting tools. In the present study, isotopic substitution of N is applied to investigate the nanostructure of TiSiN coatings with varying Si contents using atom probe tomography (APT). TiSiN coatings containing ∼2, 5, and 10 at% Si were sputter-deposited using 15N-enriched nitrogen. The APT results show that Si enriches at assumed grain boundaries forming an amorphous phase for all investigated coatings. This result is corroborated by complementary performed high resolution scanning transmission electron microscopy investigations. Further, no Si-free regions could be observed by APT, evidencing that for all coatings Si is also incorporated into a Ti1-xSixN solid solution. In addition, also no Ti-free regions are present, indicating that the amorphous phase can be assigned as a-SiaTibNc. With increasing the overall Si content from ∼2 to 10 at% the Si incorporated into the solid solution increases from ∼2 to ∼9 at%, while the Si-enrichment in the amorphous phase fraction is rather constant at ∼4 to 6 at%. The highest hardness of 38.5 ± 1.4 GPa, as determined by nanoindentation, was obtained for the coating containing ∼5 at% Si. This study demonstrates that isotopic substitution of nitrogen is a suitable tool to study the nanocomposite structure of TiSiN coatings in unprecedented detail
Acquisition of neural crest promoted thyroid evolution from chordate endostyle
No full textThe endostyle is an endodermal organ unique to nonvertebrate chordates except for lamprey larvae, where it serves as forerunner to the adult thyroid. Here, we examine whether the acquisition of neural crest in the vertebrate lineage played a role in the elaboration of the endostyle. CM-DiI lineage tracing reveals a neural crest contribution to the endostyle, and CRISPR-Cas9 mutagenesis of key neural crest genes causes endostyle defects including formation of a single rather than bilobed structure. RNA sequencing reveals gene profiles characteristic of embryonic neural crest cells and Schwann cell precursors in the developing endostyle. Contrasting with the prevailing view that the endostyle is an endoderm-derived organ, we propose that the acquisition of the neural crest played a critical step in promoting thyroid evolution from chordate endostyle