599 research outputs found

    ENGINEERING HIGH-RESOLUTION EXPERIMENTAL AND COMPUTATIONAL PIPELINES TO CHARACTERIZE HUMAN GASTROINTESTINAL TISSUES IN HEALTH AND DISEASE

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    In recent decades, new high-resolution technologies have transformed how scientists study complex cellular processes and the mechanisms responsible for maintaining homeostasis and the emergence and progression of gastrointestinal (GI) disease. These advances have paved the way for the use of primary human cells in experimental models which together can mimic specific aspects of the GI tract such as compartmentalized stem-cell zones, gradients of growth factors, and shear stress from fluid flow. The work presented in this dissertation has focused on integrating high-resolution bioinformatics with novel experimental models of the GI epithelium systems to describe the complexity of human pathophysiology of the human small intestines, colon, and stomach in homeostasis and disease. Here, I used three novel microphysiological systems and developed four computational pipelines to describe comprehensive gene expression patterns of the GI epithelium in various states of health and disease. First, I used single cell RNAseq (scRNAseq) to establish the transcriptomic landscape of the entire epithelium of the small intestine and colon from three human donors, describing cell-type specific gene expression patterns in high resolution. Second, I used single cell and bulk RNAseq to model intestinal absorption of fatty acids and show that fatty acid oxidation is a critical regulator of the flux of long- and medium-chain fatty acids across the epithelium. Third, I use bulk RNAseq and a machine learning model to describe how inflammatory cytokines can regulate proliferation of intestinal stem cells in an experimental model of inflammatory hypoxia. Finally, I developed a high throughput platform that can associate phenotype to gene expression in clonal organoids, providing unprecedented resolution into the relationship between comprehensive gene expression patterns and their accompanying phenotypic effects. Through these studies, I have demonstrated how the integration of computational and experimental approaches can measurably advance our understanding of human GI physiology.Doctor of Philosoph

    Production and characterisation of dipolar Bose–Einstein condensates

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    Remarkable progress in the field of ultracold atoms has enabled the study of a great variety of topics in many-body quantum mechanics. The precise control of key parameters, such as interactions, temperature, density, internal and external degrees of freedom, dimensionality and the trapping geometry makes them a powerful and flexible experimental platform. The ability to create degenerate samples of atoms which feature long-range and anisotropic dipole–dipole interactions besides the more conventional short-range and isotropic contact interactions drew considerable attention, enabling the creation of quantum droplets and a supersolid phase. This thesis reports on experimental and theoretical progress in investigating dipolar many-body quantum systems. We present an overview of our experimental apparatus and the techniques used for obtaining a Bose–Einstein condensate (BEC) of erbium. We then discuss our experimental sequence for producing a quantum degenerate gas, creating a quasi-pure BEC with 2.2 x 10^5 atoms. To optimise the production of erbium BECs, we explore density- and temperature-dependent losses in 166Er and identify six previously unreported resonant loss features. Finally, to enable studies of density-dependent phenomena, we present a theoretical investigation of dipolar condensates in box-like traps, where we explore stability and how one can use it to replicate properties of an infinite, homogeneous system to study dipolar physics. We found that traps with hard walls trigger roton-like density oscillations even if the bulk of the system is far from the roton regime, so smoother potentials are better suited to recreate homogeneous conditions. This sets the ground for future experiments, where the atoms will be loaded into a box trap to enable studies of systems which are tightly trapped in one direction but homogeneous in the other two

    Advances in Micro- and Nanomechanics

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    This book focuses on recent advances in both theoretical and experimental studies of material behaviour at the micro- and nano-scales. Special attention is given to experimental studies of nanofilms, nanoparticles and nanocomposites as well as tooth defects. Various experimental techniques were used. Magneto- and thermoelastic coupling were considered, as were nonlocal models of thin structures

    Abstracts of the 1st GeoDays, 14th–17th March 2023, Helsinki, Finland

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    Non peer reviewe

    Serial sectioning block-face imaging of post-mortem human brain

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    No current imaging technology can directly and without significant distortion visualize the defining microscopic features of the human brain. Ex vivo histological techniques yield exquisite planar images, but the cutting, mounting and staining they require induce slice-specific distortions, introducing cross-slice differences that prohibit true 3D analysis. Clearing techniques have proven difficult to apply to large blocks of human tissue and cause dramatic distortions as well. Thus, we have only a poor understanding of human brain structures that occur at a scale of 1–100 μm, in which neurons are organized into functional cohorts. To date, mesoscopic features which are critical components of this spatial context, have only been quantified in studies of 2D histologic images acquired in a small number of subjects and/or over a small region of the brain, typically in the coronal orientation, implying that features that are oblique or orthogonal to the coronal plane are difficult to properly analyze. A serial sectioning optical coherence tomography (OCT) imaging infrastructure will be developed and utilized to obtain images of cyto- and myelo-architectural features and microvasculature network of post-mortem human brain tissue. Our imaging infrastructure integrates vibratome with imaging head along with pre and post processing algorithms to construct volumetric OCT images of cubic centimeters of brain tissue blocks. Imaging is performed on tissue block-face prior to sectioning, which preserves the 3D information. Serial sections cut from the block can be subsequently treated with multiplexed histological staining of multiple molecular markers that will facilitate cellular classification or imaged with high-resolution transmission birefringence microscope. The successful completion of this imaging infrastructure enables the automated reconstruction of undistorted volume of human tissue brain blocks and permits studying the pathological alternations arising from diseases. Specifically, the mesoscopic and microscopic pathological alternations, as well as the optical properties and cortical morphological alternations of the dorsolateral prefrontal cortical region of two difference neurodegeneration diseases, Chronic Traumatic Encephalopathy (CTE) and Alzheimer’s Disease (AD), were evaluated using this imaging infrastructure
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