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Coming dissertations at Uppsala university

  • Micropatterning of hyaluronic acid hydrogels for in vitro models Author: Ana María Porras Hernández Link: Publication date: 2022-05-19 14:34

    The human body consist of a vast number of cells, and jointly, the cells, form tissues and organs. The cells interact and respond to their local microenvironment. The cellular microenvironment consists of a highly hydrated and compliant extracellular matrix, neighboring cells and circulating biochemical factors; and jointly, provide chemical and physical cues that regulate cell behaviour However, these cues are often not present in traditional in vitro models, where cells experience a stiff and unstructured environment. 

    An approach to better mimic the in vivo microenvironment in vitro is to use hydrogels. Hydrogels are soft and highly hydrated polymers based on materials naturally found in the extracellular matrix of various tissues. Furthermore, these materials can be chemically functionalized to control the physical, chemical, and mechanical properties of the hydrogels. These functionalities can also be used to prepare micrometre sized cell adhesive regions, or micropatterns, on the hydrogel substrate. The micropatterns guide the cell shape and permit the study of the cell response to these changes in shape and function, which has been observed in e.g., endothelial cells from various origins. 

    Taken all together, the aim of this work was to develop a hydrogel-based cell culture substrate that permits the control of the spatial adhesion of brain endothelial cells in order to study the morphological effects on these cells and contribute to the understanding of the function of brain endothelial cells in health and disease. 

    This thesis demonstrates the functionalization of hyaluronic acid, a naturally occurring extracellular matrix polymer, to prepare photocrosslinkable hydrogels. Then, through photolithography, micropatterns of cell adhesive peptides were prepared on these hydrogels. Brain microvascular endothelial cells, a highly specialized type of endothelial cells, adhered to the micropatterns, and the effect on their alignment and cell chirality depending on the micropatterned sized was studied. Furthermore, changes in their alignment were also observed when exposed to different glucose concentration.

  • Image-based multi-omics data integration : Exploring whole-body PET/MRI, -omics data and body composition Author: Robin Visvanathar Link: Publication date: 2022-05-19 14:11

    Advanced body composition analysis with whole-body imaging could uncover novel associations between regional tissue composition and metabolic disease. Imiomics is an automated image analysis framework that enables large-scale integration of magnetic resonance imaging (MRI) data and orthogonal technologies such as metabolomics and genomics for the detailed study of body composition. The Imiomics method is based on spatial normalisation to attain voxel-to-voxel correspondence in large cohorts of volumetric MR images. The spatially normalised data is then further used to generate voxel-wise statistical inference volumes for analysis. In this thesis, Imiomics was integrated with metabolomics for the first time, providing a detailed map of the relationship between the metabolome and regional body composition in T2D. Furthermore, Imiomics was integrated with genomics for the first time, exposing detailed associations between single nucleotide polymorphisms (SNPs) and sex-stratified body composition. A rapid and intuitive visual framework was developed for the analysis of volumetric Imiomics maps, and further applied to study the relationship between body composition and clinical variables in T2D. Whole-body positron emission tomography (PET)/MR was used to study detailed insulin-stimulated glucose metabolism and its associations with tissue volume and tissue fat fraction. This thesis has contributed to the field of advanced body composition research, primarily through the integration of Imiomics with additional -omics platforms.

  • In the Image of Loss : A new perspective on the works of Johan Huizinga (1872–1945) Author: Thor Rydin Link: Publication date: 2022-05-19 13:08

    "I no longer understand it, and I no longer care for it," Johan Huizinga, Professor of General History at Leiden University, said about his own field to his undoubtedly perplexed students at the opening of the academic year in 1919. The Great War had shocked him to the bone: states, traditions, norms and communities that until only recently had seemed part of life’s unquestionable fabric had been torn apart – and though Huizinga did not know at the time, more experiences of loss and upheaval were soon to follow. Other than he announced in 1919, however, Huizinga continued to "care" for and write history after the war; or rather, "history" became a way of "caring" for himself and others in times of rupture. Today, Huizinga is commonly ranked among the most eminent cultural historians of his century.

    This dissertation examines through the lens of Huizinga’s work how "experiences of loss" mediated not only a different angle on particular historical periods but renegotiated the meaning and purpose of "history" just before and during the interwar period. Against the background of loss, "history" became a way of life to Huizinga – a way of organizing thoughts and passions in unsteady times. By making this argument, this dissertation makes two claims: one historical, the other historiographical. Historically, it offers a new and original perspective on an iconic and celebrated historian and his times. Historiographically, it produces a case in point for an "experiential" approach to authors, and historians in particular, writing in times of great uncertainty.