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- Drobin, Kimi
(författare)
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Antibody-based bead arrays for high-throughput protein profiling in human plasma and serum
- 2018
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Affinity-based proteomics utilizes affinity binders to detect target proteins in a large-scale manner. This thesis describes a high-throughput method, which enables the search for biomarker candidates in human plasma and serum. A highly multiplexed antibody-based suspension bead array is created by coupling antibodies generated in the Human Protein Atlas project to color-coded beads. The beads are combined for parallel analysis of up to 384 analytes in patient and control samples. This provides data to compare protein levels from the different groups.In paper I osteoporosis patients are compared to healthy individuals to find disease-linked proteins. An untargeted discovery screening was conducted using 4608 antibodies in 16 cases and 6 controls. This revealed 72 unique proteins, which appeared differentially abundant. A validation screening of 91 cases and 89 controls confirmed that the protein autocrine motility factor receptor (AMFR) is decreased in the osteoporosis patients.Paper II investigates the risk proteome of inflammatory bowel disease (IBD). Antibodies targeting 209 proteins corresponding to 163 IBD genetic risk loci were selected. To find proteins related to IBD or its subgroups, sera from 49 patients with Crohn’s disease, 51 with ulcerative colitis and 50 matched controls were analyzed. From these targeted assays, the known inflammation-related marker serum amyloid protein A (SAA) was shown to be elevated in the IBD cases. In addition, the protein laccase (multi-copper oxidoreductase) domain containing 1 (LACC1) was found to be decreased in the IBD subjects.In conclusion, assays using affinity-based bead arrays were developed and applied to screen human plasma and serum samples in two disease contexts. Untargeted and targeted screening strategies were applied to discover disease-associated proteins. Upon further validation, these potential biomarker candidates could be valuable in future disease studies.
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| 2. |
- Ek, Patrik, 1980-
(författare)
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Mass Spectrometry with Electrospray Ionization from an Adjustable Gap
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis the fabrication and analytical evaluation of two new electrospray emitters utilized for mass spectrometry analysis is presented. The emitters are based on a new concept, where the spray orifice can be varied in size. The thesis is based on two papers. All present-day nanoelectrospray emitters have fixed dimensions. The range of the applicable flow rate for such an emitter is therefore rather limited and exchange of emitters may be necessary from one experiment to another. Optimization of the signal of the analyte ions is also limited to adjustments of the applied voltage or the distance between the emitter and the mass spectrometer inlet. Furthermore, clogging can occur in emitters with fixed dimensions of narrow orifice sizes. In this thesis, electrospray emitters with a variable size of the spray orifice are proposed. An open gap between two thin substrates is filled with sample solution via a liquid bridge from a capillary. Electrospray is generated at the end point of the gap, which can be varied in width. In Paper I, electrospray emitters fabricated in polyethylene terephthalate have been evaluated. Triangular tips are manually cut from the polymer film. The tips are mounted to form a gap between the edges of the tips. The gap wall surfaces are subjected to a hydrophilic surface treatment to increase the wetting of the gap walls. In Paper II, silicon electrospray chips with high precision are fabricated and evaluated. A thin beam, elevated from the bulk silicon chip is fabricated by means of deep reactive ion etching. The top surfaces of the beams of two chips act as a sample conduit when mounted in the electrospray setup. An anisotropic etching step with KOH of the intersecting <100> crystal planes results in a very sharp spray point. The emitters were given a hydrophobic surface treatment except for the hydrophilic gap walls. For both emitter designs, the gap width has been adjusted during the experiments without any interruption of the electrospray. For a continuously applied peptide mixture, a shift towards higher charge states and increased signal to noise ratios could be observed when decreasing the gap width. The limit of detection has been investigated and the silicon chips have been interfaced with capillary electrophoresis.
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| 3. |
- Norell, Daniel, 1973-
(författare)
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Taming the Erratic : Representation and materialization in post-digital architectural design
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates materialization and representation in contemporary architectural design practice. Due to cultural and technological shifts, the act of design is no longer squarely located in the abstract realms of drawings or digital geometries. Computer aided manufacturing, simulation and scanning offer new design opportunities that are located in the transfer between representation and material. This has given rise to a post-digital model of practice and thought, in which ‘real’ and discrete chunks of matter are incorporated at the earliest stages of design.The thesis is practice-based, and spans in scope from design to technology to theory. The design work included explores materialization and representation from a particular point of view. In addition, it suggests a methodological approach to design, and explores the theoretical implications in this approach. These implications are addressed in two connected research questions: How can material processes, whether real or simulated, turn transfers between geometry and materialized objects into productive design opportunities? And how might material simulation alter the ways in which representations are conceptualized and used by architects? In parallel with practice-based work, the thesis suggests a theoretical framework for current issues of representation and materialization in architecture. This framework draws from the recent history of the digital turn in architecture as well as from recent design research work and theory in a post-digital turn.This thesis makes contributions in three main areas. Through the design work Erratic, it makes a visceral case for how the use of material simulation might open up new ways of harnessing material agency. It positions simulation in the field of architecture in-between established polarities such as geometry vs. matter, virtual vs. real and drawing vs. mock-up. It discusses the conceptual difference between design based on geometry and design based on discrete pieces of material. Finally, it proposes that form in architecture increasingly can be conceptualized as ‘chunks,’ as opposed to reduced descriptions of geometry.
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