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Coming dissertations at TekNat

  • Solid-state nanopores : fabrication and applications

    Author: Shuangshuang Zeng
    Publication date: 2020-01-31 10:13

    Nanopores are of great interest in study of DNA sequencing, protein profiling and power generation. Among them, solid-state nanopores show obvious advantages over their biological counterparts in terms of high chemical stability and reusability as well as compatibility with the existing CMOS fabrication techniques. Nanopore sensing is most frequently based on measuring ionic current through a nanopore while applying a voltage across it. When an analyte passes through the pore, the ionic current temporarily changes, providing information of the analyte such as its size, shape and surface charge. Although many magnificent reports on using solid-state nanopores have appeared in the literature, several challenges still remain for their wider applications, which include improvement of fabrication reproducibility for mass production of ultra-small nanopores and minimization of measurement instability as well as control of translocation speed and reduction of background noise. This thesis work explores different techniques to achieve robust and high throughput fabrication of sub-10 nm nanopores for different applications.

    The thesis starts with presenting various fabrication...

  • Too close for comfort : The role of Contact-Dependent growth Inhibition (CDI) in interbacterial competition and cooperation

    Author: Marcus Wäneskog
    Publication date: 2020-01-31 06:21

    Contact-Dependent growth inhibition (CDI) was discovered in 2005 in the E. coli isolate EC93. Since then our knowledge of CDI systems and their impact on bacterial communities have increased exponentially. Yet many biological aspects of CDI systems are still unknown and their impact on complex microbial communities have only just begun to be studied. CDI systems require the function of three proteins; CdiBAI. The outer-membrane transport protein, CdiB, allows for the transportation of the toxin delivery protein CdiA to the cell surface of an inhibitor cell. Through a contact- and receptor-dependent interaction with a target cell the toxic C-terminal domain of CdiA is cleaved off and delivered into the target cell were it mediates a growth arrest. Different CdiA-CT domains encodes for diverse toxic activities, such as nucleases and membrane ionophore toxins. Each unique CdiA-CT toxin has a cognate immunity protein (CdiI) that binds and neutralize against its toxic activity, thus preventing a possible self-inhibition.

    In this thesis I have studied the effect of CDI system(s) on both single cell and population level, within both intra- and interspecies bacterial...

  • Fiber Floer cohomology and conormal stops

    Author: Johan Asplund
    Publication date: 2020-01-30 09:10
  • New Paradigms in GPCR Drug Discovery : Structure Prediction and Design of Ligands with Tailored Properties

    Author: Mariama Jaiteh
    Publication date: 2020-01-24 08:43

    G protein-coupled receptors (GPCRs) constitute a large superfamily of membrane proteins with key roles in cellular signaling. Upon activation by a ligand, GPCRs transduce signals from the extracellular to the intracellular environment. GPCRs are important drug targets and are associated with diseases such as central nervous system (CNS) disorders, cardiovascular diseases, cancer, and diabetes. Currently, 34% of FDA-approved drugs mediate their effects via modulation of GPCRs. Research during the past decades has resulted in a deeper understanding of GPCR structure and function. Moreover, recent breakthroughs in structural biology allowed the determination of several atomic resolution GPCR structures. New paradigms in GPCR pharmacology have also emerged that can lead to improved drugs. Together, these advances provide new avenues for structure-based drug discovery. The work in this thesis focused on how the large amount of structural data gathered over the last decades can be used to model GPCR targets for which no experimental structures are available, and the use of structure-based virtual screening (SBVS) campaigns to identify ligands with tailored pharmacological properties...

  • Characterization of conjugated protease inhibitors

    Author: Erika Billinger
    Publication date: 2020-01-23 09:03

    The overall theme of this thesis is a step by step approach for the design and characterization of conjugated protease inhibitors. This involves both a new assay method for protease activity and protease inhibition (paper I), a study of the stoichiometry for protease inhibitor interaction (paper II), design of inhibitory peptides (paper IV) and the construction of inhibitor conjugates (paper III & IV).

    (I) A model based primarily on erosion in gelatin for protease activity and inhibition studies was designed. The model was also extended to a separate protective layer covering the layer containing the target substrate. A good correlation between protease concentration and rate of erosion was observed. Similarly, increased concentration of inhibitors gave a systematic decrease in the erosion rate. Kinetic analyses of a two-layer model with substrate in the bottom layer displayed a strict dependence of both inhibitor concentration and thickness of the top “protective” layer.

    (II) The binding stoichiometry between pancreatic proteases and a serine...

  • Bound to the past: Historical contingency in aquatic microbial metacommunities

    Author: Máté Vass
    Publication date: 2020-01-16 12:24

    The composition of ecological communities differs due to a combination of different processes, which includes selection by local environmental conditions, dispersal from the regional species pool and random events. Additionally, historical processes such as past dispersal events may leave their imprint on communities as well, resulting in historically contingent communities. However, in most ecological studies the existence and the effect of historical processes remained hidden, even though they could be important predictors of contemporary variations in ecological communities.

    This thesis focuses on how historical processes could influence aquatic microbial metacommunities by investigating when and where history matters, and which factors may regulate historical contingency.

    Using null model approaches, evidence for historical contingency was found in natural ecosystems, more specifically rock pool metacommunities, and appeared to be more likely to influence bacterial than microeukaryotic communities.

    The thesis further used an outdoor mesocosm experiment to test how ecosystem-sized induced differences in environmental fluctuations influenced community...

  • Towards atomically resolved magnetic measurements in the transmission electron microscope : A study of structure and magnetic moments in thin films

    Author: Hasan Ali
    Publication date: 2020-01-15 09:09

    The magnetic properties of thin metallic films are significantly different from the bulk properties due to the presence of interfaces. The properties shown by such thin films are influenced by the atomic level structure of the films and the interfaces. Transmission electron microscope (TEM) has the potential to analyse the structure and the magnetic properties of such systems with atomic resolution. In this work, the TEM is employed to characterize the structure of the Fe/V and Fe/Ni multilayers and the technique of electron magnetic circular dichroism (EMCD) is developed to obtain the quantitative magnetic measurements with high spatial resolution.

    From TEM analysis of short period Fe/V  multilayers, a coherent superlattice structure is found. In short period Fe/Ni multilayer samples with different repeat frequency, only the TEM technique could verify the existence of the multilayer structure in the thinnest layers. The methods of scanning TEM imaging and electron energy loss spectroscopy (EELS) results were used and refined to determine interdiffusion at the interfaces. The confirmation of the multilayer structure helped to explain the saturation magnetization of these...

  • Computational Modeling of the Structure, Function and Dynamics of Biomolecular Systems

    Author: Yashraj Kulkarni
    Publication date: 2020-01-14 10:38

    Proteins are a structurally diverse and functionally versatile class of biomolecules. They perform a variety of life-sustaining biological processes with utmost efficiency. A profound understanding of protein function requires knowledge of its structure. Experimentally determined protein structures can serve as a starting point for computer simulations in order to study their dynamic behavior at a molecular level. In this thesis, computational methods have been used to understand structure-function relationships in two classes of proteins - intrinsically disordered proteins (IDP) and enzymes.

    Misfolding and subsequent aggregation of the amyloid beta (Aβ) peptide, an IDP, is associated with the progression of Alzheimer’s disease. Besides enriching our understanding of structural dynamics, computational studies on a medically relevant IDP such as Aβ can potentially guide therapeutic development. In the present work, binding interactions of the monomeric form of this peptide with biologically relevant molecular species such as divalent metal ions (Zn2+, Cu2+, Mn2+) and amphiphilic surfactants were characterized using long timescale molecular dynamics (MD) simulations. Among...

  • Atomic Scale Modelling in Photoelectrocatalysis : Towards the Development of Efficient Materials for Solar Fuel Production

    Author: Giane B. Damas
    Publication date: 2020-01-10 12:10

    Using sunlight to produce valuable chemicals has been pointed out as an interesting alternative to deal with the well-known environmental problem related to the use of fossil fuels for energy generation. Thus, it is crucial for this field the development of novel photocatalysts that could drive the uphill reactions with high efficiency while presenting low price and toxicity. In this context, conjugated polymers with a donor-acceptor architecture have shown good photoactivity for the hydrogen evolution reaction (HER) due to their advantageous properties, including a broad UV-Vis absorption spectrum and thermodynamic driving force to carry out the charge transfer processes. In this thesis, a series of fluorene- and benzothiadiazole-based polymers are evaluated by means of ab initio methods as potential candidates for photocatalytic HER. A set of small-molecules with well-defined molecular weight have also been considered for this application. In general, tailoring a chemical unit has enabled an improvement of the absorption capacity in benzo(triazole-thiadiazole)-based polymers and cyclopentadithiophene-based polymers, with a higher impact exhibited upon acceptor tailoring. On...

  • High Power Radio Frequency Solid-State Amplifiers and Combiners for Particle Accelerators : From module to system design approach

    Author: Long Hoang
    Publication date: 2019-12-20 13:13

    The rise of Big Science projects brings issues related to the energy consumption and the associated environmental impacts of such large-scale facilities. Therefore, environmentally-sustainable developments are undertaken towards the adoption of energy savings and improved energy-efficient approaches. The advent of the superconducting (SC) radio frequency (RF) accelerating cavity is bringing answers to these issues. Such superconducting RF (SRF) cavity is made of niobium that allows much higher accelerating gradients with a minimization of the energy consumption. The SC RF technology is increasingly used in many modern particle accelerators, including: the European Spallation Source (ESS), the X-ray Free Electron Laser (XFEL), the Linac Coherent Light Source (LCLS)-II and the proposed International Linear Collider (ILC).

    The innovation of solid state PA technology pushes limits regarding packaging, efficiency, frequency capability, thermal stability, making them more attractive than other well-established alternative technologies, such as vacuum tube technology in mid-range power applications. Through the investigations of designs and techniques, this research goal of the...