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  • Presentation: 2018-05-04 10:00
    Drobin, Kimi
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Antibody-based bead arrays for high-throughput protein profiling in human plasma and serum2018Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    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.

  • Presentation: 2018-05-08 10:15 Q33, Stockholm
    Nguyen, Van-Dang
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST).
    High-Performance Finite Element Methods: with Application to Simulation of Diffusion MRI and Vertical Axis Wind Turbine2018Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The finite element methods (FEM) have been developed over decades, and together with the growth of computer engineering, they become more and more important in solving large-scale problems in science and industry. The objective of this thesis is to develop high-performance finite element methods (HP-FEM), with two main applications in mind: computational diffusion magnetic resonance imaging (MRI), and simulation of the turbulent flow past a vertical axis wind turbine (VAWT). In the first application, we develop an efficient high-performance finite element framework HP-PUFEM based on a partition of unity finite element method to solve the Bloch-Torrey equation in heterogeneous domains. The proposed framework overcomes the difficulties that the standard approaches have when imposing the microscopic heterogeneity of the biological tissues. We also propose artificial jump conditions at the external boundaries to approximate the pseudo-periodic boundary conditions which allows for the water exchange at the external boundaries for non-periodic meshes. The framework is of a high level simplicity and efficiency that well facilitates parallelization. It can be straightforwardly implemented in different FEM software packages and it is implemented in FEniCS for moderate-scale simulations and in FEniCS-HPC for the large-scale simulations. The framework is validated against reference solutions, and implementation shows a strong parallel scalability. Since such a high-performance simulation framework is still missing in the field, it can become a powerful tool to uncover diffusion in complex biological tissues. In the second application, we develop an ALE-DFS method which combines advanced techniques developed in recent years to simulate turbulence. We apply a General Galerkin (G2) method which is continuous piecewise linear in both time and space, to solve the Navier-Stokes equations for a rotating turbine in an Arbitrary Lagrangian-Eulerian (ALE) framework. This method is enhanced with dual-based a posterior error control and automated mesh adaptation. Turbulent boundary layers are modeled by a slip boundary condition to avoid a full resolution which is impossible even with the most powerful computers available today. The method is validated against experimental data of parked turbines with good agreements. The thesis presents contributions in the form of both numerical methods for high-performance computing frameworks and efficient, tested software, published open source as part of the FEniCS-HPC platform.

  • Presentation: 2018-05-08 12:30 B1, Stockholm
    Eriksson, Daniel
    KTH, School of Architecture and the Built Environment (ABE), Civil and Architectural Engineering, Concrete Structures.
    Numerical models for degradation of concrete in hydraulic structures due to long-term contact with water2018Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The durability of concrete is of major concern in all types of concrete structures where the combined effect of exposure conditions and the type and quality of the concrete material usually determines the rate of degradation. Furthermore, there are synergy effects between different deterioration mechanisms, which means that the combined rate of degradation is higher than the sum of the individual rates of each mechanism. Therefore, to accurately predict the residual service life of existing structures or when designing new structures, it is essential to consider all these aspects. This means that various chemical and physical processes, as well as how these interact, must be taken into account in models aiming to be used for service life predictions.

    This thesis presents the first part of a research project with the aim to investigate common deterioration mechanisms of concrete in hydraulic structures, and to improve the knowledge how these and other related phenomena can be described using mathematical models. The objective is also to study how different mechanisms interact and to find suitable approaches to account for these interactions in the models. To this end, a literature survey on commonly detected damage in hydraulic structures is presented. In addition, it also addresses in what types of and where in hydraulic structures the various damage types are usually observed. The mathematical models presented in this part of the project are focused on long-term water absorption in air-entrained concrete as well as on freezing of partially saturated air-entrained concrete. Both models are based on a multiphase description of concrete and poromechanics to describe the coupled hygro-thermo-mechanical behaviour. The thesis also presents some of the basic concepts of multiphase modelling of porous media, including discretization of the models using the finite element method (FEM). Furthermore, it covers the simplifications that are usually introduced in the general macroscopic balance equations for mass, energy and linear momentum when modelling cement-based materials.

    To verify the developed models and to show their capabilities, simulation results are compared with experimental data, in situ measurements and other simulations from the literature. The results indicate that both models perform well and can be used to predict long-term moisture conditions in hydraulic structures as well as freezing-induced strains in partially saturated air-entrained concrete, respectively. Even though no interactions with other deterioration mechanisms are included in the models, the development and use of these have given insights to which parameters that are important to consider in such extensions. Furthermore, based on the insights gained, the complexity of describing the full interactions between several mechanisms in mathematical models is also discussed. It is concluded that models aiming to be used for service life predictions of hydraulic structures in day-to-day engineering work need to be simplified. However, the type of advanced models presented in this thesis can serve as a basis to study which aspects and parameters that are essential to consider in simplified prediction models.