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Coming dissertations at TekNat

  • Development of an analytic Beam Model with non-linear Space-Charge Forces and Envelope Stability Studies

    Author: Michael Holz
    Publication date: 2019-11-28 08:03

    Space-charge—the repelling force of same-charged particles—is a major challenge in the development and application of high-current linear accelerators like spallation sources or accumulator rings. Understanding the dynamical behavior of the beam in its presence is imperative to prevent beam loss and subsequent detrimental effects. There are several established methods to examine the beam’s behavior in the presence of space-charge. On one hand, there are fast, analytic methods describing the beam as a collective, thereby describing coherent beam envelope modes. An example of such a method is the widely used, so-called envelope equation. They have been extensively employed in the frame of modeling space-charge in high-current linear and circular accelerators. On the other hand, numerical methods resolve the dynamics of single particles that comprise the beam. These methods include the incoherent dynamics of single particles, but are therefore computationally expensive. The two approaches also reveal adichotomy in particle beam modeling in which the collective beam behavior is contrasted with that of individual particles. In order to complement the established methods, an analytic...

  • Quantifiers and Theories : A Lazy Approach

    Author: Peter Backeman
    Publication date: 2019-11-22 13:52

    In this thesis we study Automated Theorem Proving (ATP) as well as Satisfiability Modulo Theories (SMT) and present lazy strategies for improving reasoning within these areas. A lazy strategy works by simplifying a problem, and gradually refines the abstraction only when necessary. Often, a solution can be found without solving the full problem, saving valuable resources. We formulate our contributions within two key challenges in ATP and SMT: theory and quantifier reasoning.Many problems need first-order reasoning modulo a theory, i.e., reasoning where symbols in formulas are interpreted according to some background theory. In software verification, which often involves conditions over machine arithmetic, bit-vectors as well as floating-point numbers play an important role. Finding methods for how to reason with these theories in an efficient manner is therefore an important task. In this thesis we present a lazy method for handling bit-vector constraints as well as bit-vector interpolation, which improves performance and produces simpler interpolants. Moreover, a modular approximation framework is described, which allows for high-level description of lazy strategies...

  • Computational prediction of ligand binding in peptide G-protein coupled receptors

    Author: Silvana Vasile
    Publication date: 2019-11-21 09:03

    G-protein coupled receptors (GPCRs) are a superfamily of membrane receptors involved in a wide variety of biological processes, and their malfunction is associated with many diseases. Consequently, GPCRs are targeted by one-third of the drugs on the market, and constitute the focus of active public and private research in the search of more effective drugs. The GPCR families that are activated by endogenous peptides are particularly challenging for the drug design process, which in this case contemplates peptides, peptidomimetics and small molecules, as selective activators (agonists) or blockers (antagonists) of the particular receptor subtype of interest. This process benefits of a detailed understanding of how known ligands bind to the receptors. Homology modelling, molecular dynamics (MD) and free energy perturbation (FEP) are computational methods used to predict binding modes and binding affinities. In this thesis, these techniques are applied (and even further developed) in combination with novel experimental data provided by our collaborators, in order to elucidate the molecular determinants of endogenous peptide ligands, analogues and mimetics to two families of...

  • Image and Data Analysis for Biomedical Quantitative Microscopy

    Author: Damian J. Matuszewski
    Publication date: 2019-11-20 08:29

    This thesis presents automatic image and data analysis methods to facilitate and improve microscopy-based research and diagnosis. New technologies and computational tools are necessary for handling the ever-growing amounts of data produced in life science. The thesis presents methods developed in three projects with different biomedical applications.

    In the first project, we analyzed a large high-content screen aimed at enabling personalized medicine for glioblastoma patients. We focused on capturing drug-induced cell-cycle disruption in fluorescence microscopy images of cancer cell cultures. Our main objectives were to identify drugs affecting the cell-cycle and to increase the understanding of different drugs’ mechanisms of action.  Here we present tools for automatic cell-cycle analysis and identification of drugs of interest and their effective doses.

    In the second project, we developed a feature descriptor for image matching. Image matching is a central pre-processing step in many applications. For example, when two or more images must be matched and registered to create a larger field of view or to analyze differences and changes over time. Our descriptor is...

  • Development of titanium-copper alloys for dental applications

    Author: Lee Fowler
    Publication date: 2019-11-18 12:53

    Titanium alloys find wide application in the medical implants industry, which includes areas of orthopaedic and dental implants. The reason for the popularity of the material is high mechanical strength, low density, and reported growth of bone onto the material, as well as corrosion resistance. Despite the general success of titanium materials, a drawback is that it is vulnerable to bacterial colonization, which can cause implant failure through inflammatory diseases. Peri-implantitis is one such disease, which can lead to irreversible bone loss and subsequently implant instability.

    This thesis focuses on the use of copper (Cu) as an antibacterial element in titanium alloys, where the purpose is designing inherently antibacterial materials.

    With an understanding that copper can reduce bacterial populations by ion release of Cu into solutions, as well as by direct contact of bacteria with Cu surfaces: studies on the effect of Cu ions on bacteria and cells were conducted, in addition to studies on Ti-Cux alloys.

    Varying Cu concentrations in solution were introduced to bacteria (Staphylococcus epidermidis) and cells (MC3T3 murine calvarial...

  • Effect of Macromolecular Crowding on Diffusive Processes

    Author: Zahedeh Bashardanesh
    Publication date: 2019-11-18 12:37

    Macromolecular crowding are innate to cellular environment. Understanding their effect on cellular components and processes is essential. This is often neglected in dilute experimental setup both in vitro and in silico.

    In this thesis I have dealt with challenges in biomolecular simulations at two levels of modeling, Brownian Dynamics (BD) and Molecular Dynamics (MD).

    Conventional BD simulations become inefficient since most of the computational time is spent propagating the particles towards each other before any reaction takes place. Event-driven algorithms have proven to be several orders of magnitude faster than conventional BD algorithms. However, the presence of diffusion-limited reactions in biochemical networks lead to multiple rebindings in case of a reversible reaction which deteriorates the efficiency of these types of algorithms. In this thesis, I modeled a reversible reaction coupled with diffusion in order to incorporate multiple rebindings. I implemented a Green's Function Reaction Dynamics (GFRD) algorithm by using the analytical solution of the reversible reaction diffusion equation. I show that the algorithm performance is independent of the number...

  • The response in native wildlife to an invading pathogen: Swedish amphibians and Batrachochytrium dendrobatidis

    Author: Sara Meurling
    Publication date: 2019-11-15 13:11

    Emerging infectious diseases are causing mortality and declines in wildlife populations globally. My thesis aims to get as clear a picture as possible of the effect the invasive chytrid fungus Batrachochytrium dendrobatidis has on the Swedish amphibian community.

    In Paper I I performed a large-scale survey testing for the presence of Bd in three regions in Sweden (Southern, Central and Northern). I sampled 1917 amphibians from 101 localities and found that Bd was widespread in southern and central Sweden, occurring in all nine investigated species and in 45.5 % of the sampled sites with an overall prevalence of 13.8%. I found a positive correlation between the temperature at spawning for each species and species prevalence. Species that require higher temperatures for egg-laying are distributed in the southern parts of the country, which led to a higher prevalence in the southern region.

    In Paper II, I investigated which local environmental factors in breeding habitats, landscape structure and amphibian community affect the occurrence and prevalence of Bd among breeding sites in southern Sweden....

  • Engineered Alcohol Dehydrogenases for Stereoselective Chemical Transformations

    Author: Thilak Reddy Enugala
    Publication date: 2019-11-15 12:41

    Enzymes are biomolecules built from amino acids and catalyze the chemical transformations in a cell. Enzymes are by nature stereoselective, biodegradable, environmentally friendly, and can perform catalysis in aqueous solutions and at ambient temperatures. Due to these advantages the use of enzymes as biocatalysts for chemical transformations has emerged as an attractive “greener” alternative to conventional chemical synthesis strategies. And, if naturally occurring enzymes cannot carry out the desired chemical transformations, the functional properties of enzymes can be modified by directed evolution or protein engineering techniques. Since enzymes are genetically encoded they can be optimized for desired traits such as substrate selectivity or improved catalytic efficiency. Considering these advantages and also keeping the synthetic and industrial application in mind, we have employed alcohol dehydrogenase-A (ADH-A) from Rhodococcus ruber DSM 44541 as a study object in engineering for new catalytic properties. ADH-A tolerates water miscible organic solvents, accepts a relatively wide range of aromatic sec-alcohols/ketones as substrates and is therefore a...

  • Insights into wear and deformation of alternative binder hardmetals

    Author: Lisa Toller-Nordström
    Publication date: 2019-11-14 07:56

    This work presents new insights into how hardmetals with alternative binders as well as cobalt based references react to wear and deformation. The main focus has been on hardmetals for steel turning, but also on studying certain fundamental properties of the new binder materials.

    Cobalt has traditionally been the most common binder phase for tungsten carbide grains in hardmetals, but recent insights into the carcinogenicity of cobalt powder has led to a need to research alternatives. In this work hardmetals with binder phases consisting of alloys of iron and nickel or iron, nickel and cobalt have been studied.

    Coated hardmetal inserts used until end of tool life in steel turning have been evaluated with respect to the plastic deformation and coating adhesion. It was found that grain boundary sliding of tungsten carbide/tungsten carbide grain boundaries is an important deformation mechanism during dry face turning, concluded based on an increased number of binder phase lamellae in tungsten carbide/tungsten carbide grain boundaries in the deformed microstructure.  The lamellae were found to have a preferred orientation, coinciding with the expected flow of material...

  • Probing Ligand Binding Mechanisms in Insulin-Regulated Aminopeptidases : Computational analysis and free energy calculations of binding modes

    Author: Sudarsana Reddy Vanga
    Publication date: 2019-11-13 13:23

    In recent years insulin-regulated aminopeptidase (IRAP) has emerged as a new therapeutic target for the treatment of Alzheimer’s disease and other memory-related disorders. So far, many potent and specific IRAP inhibitors had been disclosed, including peptides, peptidomimetics, and low-molecular-weight sulfonamides. In this thesis, various computational approaches such as docking, molecular dynamics (MD), linear interaction energy (LIE), and free energy perturbations (FEP) are used to understand the molecular basis for the binding of these inhibitors to the IRAP.

    By applying MD and LIE, the binding mode of Ang IV and the critical role of its N-terminal tripeptide in the binding to IRAP were described. The stark difference in the binding properties of two stereoisomers of a peptidomimetic inhibitor, HA08 and HA09, was determined using MD simulations and LIE binding affinity estimations. With the help of the FEP method, we discriminate the most probable, between two alternative binding poses for the sulfonamide family of compounds. The binding modes of the HFI family of compounds (competitive inhibitors), and spiro-oxindole compounds (allosteric, uncompetitive inhibitors)...