Coming dissertations at Uppsala university
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Imprints on the gut microbiome : A study of sleep apnea, physical activity, and antibiotic use
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539738
Growing evidence has highlighted the importance of the gut microbiome for human health. However, detailed investigations on how specific host factors influence the gut microbiome are lacking. The research in this thesis examined the relationship of obstructive sleep apnea (OSA), physical activity, and antibiotic use with the gut microbiome. The studies in this thesis used gut microbiome data from deep fecal shotgun metagenomics in large population-based cohorts.
Study I used the baseline data of 3,570 individuals aged 50-65 from the Swedish CArdioPulmonary bioImage Study (SCAPIS). OSA was assessed with respiratory polygraphy. We identified 128 microbiome species associated with the number of oxygen desaturation events per hour of sleep or the percentage of sleep time in hypoxia. For instance, more severe hypoxia during sleep was associated with higher abundance of Collinsela aerofaciens and Blautia obeum. Additionally, C. aerofaciens was also associated with increased systolic blood pressure.
Study II used baseline data from 8,416 SCAPIS participants who had valid accelerometer-derived physical activity data. The distribution of awake time in sedentary behavior or physical activity of different intensities was associated with the abundance of 651 gut microbiome species. For example, longer time in moderate-intensity physical activity and shorter time in sedentary behavior were associated with higher abundance of Prevotella copri and Faecalibacterium prausnitzii and lower abundance of Escherichia coli and [Ruminococcus] torques.
Study III investigated the association between antibiotic use in the past eight years and the gut microbiome in 15,131 participants from SCAPIS, the Swedish Infrastructure for Medical Population-based Life-course and Environmental Research (SIMPLER), and the Malmö Offspring Study (MOS). Antibiotic use 4–8 years and 1–4 years earlier was associated with lower gut microbiome alpha diversity after adjustment for more recent use, sociodemographics, lifestyle, and comorbidities. Most of the species-level associations were found for the antibiotics clindamycin, fluoroquinolones, and flucloxacillin.
Study IV assessed the causal effect of physical activity on the gut microbiome using a two-sample Mendelian randomization (MR) analysis based on summary statistics from genome-wide association studies. We found evidence of a positive effect of moderate-to-vigorous intensity physical activity (MVPA) on gut microbiome alpha diversity. Using a multivariable MR analysis, we found that MVPA had a positive on alpha diversity independent of BMI, smoking, education, or liking of a low-calorie diet.
This thesis has applied diverse epidemiology and statistical methods to rigorously investigate host factor associations with the gut microbiome. Altogether, it underlines the tight host-microbiome connection through detailed analyses of OSA, physical activity, and antibiotic use with the gut microbiome.
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Electrohydrodynamic printing of supercapacitors
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540019
This thesis presents research towards fully printed supercapacitor cells in a stacked electrode configuration. A supercapacitor is an energy storage device similar to a battery, but with higher power density and lower energy density. This, together with a long cycle life, make supercapacitors a suitable device for fast charging and discharging in the range of seconds. Printing of supercapacitors could be useful to implement energy storage in microsystems, small electronic devices.
The core components of a supercapacitor are two electrodes of a conductive material with a high surface area, a separator or gap between the two electrodes, and an electrolyte. Bulk-manufactured supercapacitors use a stacked electrode configuration, but printed supercapacitors typically place the electrodes side-by-side, with both electrodes printed on the same surface. This is due to challenges when printing the different materials on top of each other.
The electrohydrodynamic processes of electrospinning and electrospraying have been developed into printing methods at suitable resolutions for printing of supercapacitor cells of a few cm2. Porous electrodes are printed using electrospraying of graphene oxide. These electrodes are deoxygenated after or during printing using ascorbic acid (vitamin C) and/or alkaline electrolyte to achieve sufficient electrical conductivity and energy storage performance. The electrochemical characteristics of deoxygenated graphene oxide electrodes is measured using cyclic voltammetry, galvanostatic cycling, and electrical impedance spectroscopy. The graphene electrodes, both printed and coated, have good energy and power densities for electrical double layer supercapacitors of these materials. Development of high-resolution electrospinning has been used to print solid separators that soak in the electrolyte while preventing the printed electrodes from short-circuiting. Current collectors and electrolyte have also been printed or dripped using electrohydrodynamic processes. By combining these four methods, stacked electrode supercapacitor cells are fully printed and chemically treated directly in the printing setup. This configuration of electrodes increases the electrode size compared with the side-by-side electrode configuration, which is limited to half the size of the full supercapacitor cell.
The thesis is focused on developing the printing methods as well as the material and electrochemical characterization. The microstructures of the printed materials are viewed and measured using scanning electron microscopy. The graphene oxide deoxygenation is measured using Raman spectroscopy and energy dispersive X-ray spectroscopy. The work of this thesis provides new strategies for printed graphene supercapacitors, in graphene oxide treatments, printing methods, and electrode configuration. The strategies have been developed to enable robust printing in air, without extra post-printing steps.
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On-chip sensing
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540189
With Organ-on-chip (OoC) systems being developed for the last 15 years, they have started to establish themselves as the more in-vivo like alternative to standard cell-culturing methods. With their ability to replicate mechanical and chemical stimulus more accurately, they are promised to improve research predictions and start reducing animal testing. Their more in-vivo like features although come with more settings to be adjusted, more dynamic behaviour, and more complexity in the results. Most of the OoCs produce only very little sample volume compared to the effort of running them, which makes it more difficult to track their status with conventional measurement techniques. Therefore, this thesis is focused on integrating and improving sensing methods for OoC applications. An in-line cytokine detection chip was built, using bead-based immunoassays and acoustic trapping to reduce the necessary sample volume by 97% to 1.5 µl, while reducing the assay time by 80% to 35 min and retaining a detection limit of 1.2 ng/ml. The internal temperature profile of acoustofluidic devices was characterised using integrated thin-film resistive temperature devices, with sensitivities <10mK. One chip was built to compare internal measurements to external measurements, allowing the cytokine detection chip to operate within safe margins at high acoustic energies and without the need to integrate its own temperature sensor. Another chip was built to measure the temperature gradient in an acoustophoresis channel to provide validation data for streaming simulations at high acoustic powers, with the thought to optimise the sample exposure of the cytokine detection chip. Lastly, a flexible thin-film electrode fabrication based on polyimide tape was developed to integrate electrodes into OoCs, the method was demonstrated by integrating multiple electrodes in a gut-on-chip model and performing impedance spectroscopies to determine the TEER value of the cell layer.