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  • Public defence: 2017-04-25 10:15 K3, Kåkenhus, Norrköping
    Volkov, Anton
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Ionic and electronic transport in electrochemical and polymer based systems2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Electrochemical systems, which rely on coupled phenomena of the chemical change and electricity, have been utilized for development an interface between biological systems and conventional electronics.  The development and detailed understanding of the operation mechanism of such interfaces have a great importance to many fields within life science and conventional electronics. Conducting polymer materials are extensively used as a building block in various applications due to their ability to transduce chemical signal to electrical one and vice versa. The mechanism of the coupling between the mass and charge transfer in electrochemical systems, and particularly in conductive polymer based system, is highly complex and depends on various physical and chemical properties of the materials composing the system of interest.

    The aims of this thesis have been to study electrochemical systems including conductive polymer based systems and provide knowledge for future development of the devices, which can operate with both chemical and electrical signals. Within the thesis, we studied the operation mechanism of ion bipolar junction transistor (IBJT), which have been previously utilized to modulate delivery of charged molecules. We analysed the different operation modes of IBJT and transition between them on the basis of detailed concentration and potential profiles provided by the model.

    We also performed investigation of capacitive charging in conductive PEDOT:PSS polymer electrode. We demonstrated that capacitive charging of PEDOT:PSS electrode at the cyclic voltammetry, can be understood within a modified Nernst-Planck-Poisson formalism for two phase system in terms of the coupled ion-electron diffusion and migration without invoking the assumption of any redox reactions.

    Further, we studied electronic structure and optical properties of a self-doped p-type conducting polymer, which can polymerize itself along the stem of the plants. We performed ab initio calculations for this system in undoped, polaron and bipolaron electronic states. Comparison with experimental data confirmed the formation of undoped or bipolaron states in polymer film depending on applied biases.

    Finally, we performed simulation of the reduction-oxidation reaction at microband array electrodes. We showed that faradaic current density at microband array electrodes increases due to non-linear mass transport on the microscale compared to the corresponding macroscale systems.  The studied microband array electrode was used for developing a laccase-based microband biosensor. The biosensor revealed improved analytical performance, and was utilized for in situ phenol detection.

    List of papers
    1. Modeling of Charge Transport in Ion Bipolar Junction Transistors
    Open this publication in new window or tab >>Modeling of Charge Transport in Ion Bipolar Junction Transistors
    2014 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 30, no 23, 6999-7005 p.Article in journal (Refereed) Published
    Abstract [en]

    Spatiotemporal control of the complex chemical microenvironment is of great importance to many fields within life science. One way to facilitate such control is to construct delivery circuits, comprising arrays of dispensing outlets, for ions and charged biomolecules based on ionic transistors. This allows for addressability of ionic signals, which opens up for spatiotemporally controlled delivery in a highly complex manner. One class of ionic transistors, the ion bipolar junction transistors (IBJTs), is especially attractive for these applications because these transistors are functional at physiological conditions and have been employed to modulate the delivery of neurotransmitters to regulate signaling in neuronal cells. Further, the first integrated complementary ionic circuits were recently developed on the basis of these ionic transistors. However, a detailed understanding of the device physics of these transistors is still lacking and hampers further development of components and circuits. Here, we report on the modeling of IBJTs using Poissons and Nernst-Planck equations and the finite element method. A two-dimensional model of the device is employed that successfully reproduces the main characteristics of the measurement data. On the basis of the detailed concentration and potential profiles provided by the model, the different modes of operation of the transistor are analyzed as well as the transitions between the different modes. The model correctly predicts the measured threshold voltage, which is explained in terms of membrane potentials. All in all, the results provide the basis for a detailed understanding of IBJT operation. This new knowledge is employed to discuss potential improvements of ion bipolar junction transistors in terms of miniaturization and device parameters.

    Place, publisher, year, edition, pages
    American Chemical Society (ACS), 2014
    National Category
    Electrical Engineering, Electronic Engineering, Information Engineering Physical Sciences
    Identifiers
    urn:nbn:se:liu:diva-109131 (URN)10.1021/la404296g (DOI)000337644200044 ()24854432 (PubMedID)
    Available from: 2014-08-13 Created: 2014-08-11 Last updated: 2017-03-17Bibliographically approved
    2. In vivo polymerization and manufacturing of wires and supercapacitors in plants
    Open this publication in new window or tab >>In vivo polymerization and manufacturing of wires and supercapacitors in plants
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    2017 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 11, 2807-2812 p.Article in journal (Refereed) Published
    Abstract [en]

    Electronic plants, e-Plants, are an organic bioelectronic platform that allows electronic interfacing with plants. Recently we have demonstrated plants with augmented electronic functionality. Using the vascular system and organs of a plant, we manufactured organic electronic devices and circuits in vivo, leveraging the internal structure and physiology of the plant as the template, and an integral part of the devices. However, this electronic functionality was only achieved in localized regions, whereas new electronic materials that could be distributed to every part of the plant would provide versatility in device and circuit fabrication and create possibilities for new device concepts. Here we report the synthesis of such a conjugated oligomer that can be distributed and form longer oligomers and polymer in every part of the xylem vascular tissue of a Rosa floribunda cutting, forming long-range conducting wires. The plant’s structure acts as a physical template, whereas the plant’s biochemical response mechanism acts as the catalyst for polymerization. In addition, the oligomer can cross through the veins and enter the apoplastic space in the leaves. Finally, using the plant’s natural architecture we manufacture supercapacitors along the stem. Our results are preludes to autonomous energy systems integrated within plants and distribute interconnected sensor-actuator systems for plant control and optimization

    Place, publisher, year, edition, pages
    National Academy of Sciences, 2017
    National Category
    Plant Biotechnology Condensed Matter Physics Textile, Rubber and Polymeric Materials Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-135492 (URN)10.1073/pnas.1616456114 (DOI)000396094200029 ()
    Note

    Funding agencies: Knut and Alice Wallenberg Foundation Scholar Grant [KAW 2012.0302]; Linkoping University; Onnesjo Foundation; Wenner-Gren Foundations; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkping University [SFO-Mat-

    Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2017-04-03Bibliographically approved
    3. Total phenol analysis of weakly supported water using a laccase-based microband biosensor.
    Open this publication in new window or tab >>Total phenol analysis of weakly supported water using a laccase-based microband biosensor.
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    2016 (English)In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 907, 45-53 p.Article in journal (Refereed) Published
    Abstract [en]

    The monitoring of phenolic compounds in wastewaters in a simple manner is of great importance for environmental control. Here, a novel screen printed laccase-based microband array for in situ, total phenol estimation in wastewaters and for water quality monitoring without additional sample pre-treatment is presented. Numerical simulations using the finite element method were utilized for the characterization of micro-scale graphite electrodes. Anodization followed by covalent modification was used for the electrode functionalization with laccase. The functionalization efficiency and the electrochemical performance in direct and catechol-mediated oxygen reduction were studied at the microband laccase electrodes and compared with macro-scale electrode structures. The reduction of the dimensions of the enzyme biosensor, when used under optimized conditions, led to a significant improvement in its analytical characteristics. The elaborated microsensor showed fast responses towards catechol additions to tap water – a weakly supported medium – characterized by a linear range from 0.2 to 10 μM, a sensitivity of 1.35 ± 0.4 A M−1 cm−2 and a dynamic range up to 43 μM. This enhanced laccase-based microsensor was used for water quality monitoring and its performance for total phenol analysis of wastewater samples from different stages of the cleaning process was compared to a standard method.

    Place, publisher, year, edition, pages
    Elsevier, 2016
    Keyword
    Laccase; microelectrode; microband; electrochemical modeling; total phenol analysis; wastewater
    National Category
    Analytical Chemistry
    Identifiers
    urn:nbn:se:liu:diva-123677 (URN)10.1016/j.aca.2015.12.006 (DOI)000368422900005 ()
    Note

    Funding agencies: Swedish research council Formas [245-2010-1062]; research centre Security Link [VINNOVA 2009-00966]; Norrkopings fond for Forskning och Utveckling; VINNOVA

    Available from: 2016-01-07 Created: 2016-01-07 Last updated: 2017-03-17Bibliographically approved
  • Public defence: 2017-04-27 10:15 Plank, Fysikhuset, Linköping
    Ajjan Godoy, Fátima Nadia
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Biohybrid Polymer Electrodes for Renewable Energy Storage2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Daily and seasonally fluctuating energy supply and demand requires adequate energy storage solutions. In recent years electrochemical supercapacitors have attracted considerable attention due to their ability to both store and deliver electrical energy efficiently. Our efforts are focused on developing and optimizing sustainable organic electrode materials for supercapacitors based on renewable bioorganic materials, offering a cheap, environmentally friendly and scalable alternative to store energy. In particular, we are using the second most abundant biopolymer in nature, lignin (Lig), which is an insulating material. However, when used in combination with electroactive and conducting polymers such as polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT), the biohybrid electrodes PPy/Lig and PEDOT/Lig display significantly enhanced energy storage performance as compared to the pristine conducting polymers without the lignin. Redox cyclic voltammetry and galvanostatic charge/discharge measurements indicate that the enhanced performance is due to the additional pseudocapacitance generated by the quinone moieties in lignin. Moreover, a conjugated redoxpolymer poly(aminoanthraquinone) PAAQ, with intrinsic quinone functions and excellentstability, has been combined with lignin and PEDOT resulting in a trihybrid bioelectrode. PEDOT compensates the low conductivity of PAAQ and provides electrical pathways to the quinone groups. The electrochemically generated quinones undergo a two electron, two protonredox process within the biohybrid electrodes as revealed by FTIR spectroelectrochemistry.These remarkable features reveal the exciting potential of a full organic energy storage device with long cycle life. Therefore, supercapacitor devices were designed in symmetric or asymmetric two electrode configuration. The best electrochemical performance was achieved by the asymmetric supercapacitor based on PEDOT+Lignin/PAAQ as the positive electrode and PEDOT/PAAQ as the negative electrode. This device exhibits superior electrochemical performance and outstanding stability after 10000 charge/discharge cycles due to the synergistic effect of the two electrodes. Finally, we have characterized the response of this supercapacitor device when charged with the intermittent power supply from an organic photovoltaic module. We have designed charging/discharging conditions such that reserve power was available in the storage device at all times. This work has resulted in an inexpensive fully organic system witht he dual function of energy conversion and storage.

    List of papers
    1. Biopolymer hybrid electrodes for scalable electricity storage
    Open this publication in new window or tab >>Biopolymer hybrid electrodes for scalable electricity storage
    2016 (English)In: Materials Horizons, ISSN 2051-6347, E-ISSN 2051-6355, Vol. 3, no 3, 174-185 p.Article, review/survey (Refereed) Published
    Abstract [en]

    Powering the future, while maintaining a cleaner environment and a strong socioeconomic growth, is going to be one of the biggest challenges faced by mankind in the 21st century. The first step in overcoming the challenge for a sustainable future is to use energy more efficiently so that the demand for fossil fuels can be reduced drastically. The second step is a transition from the use of fossil fuels to renewable energy sources. In this sense, organic electrode materials are becoming increasingly attractive compared to inorganic electrode materials which have reached a plateau regarding performance and have severe drawbacks in terms of cost, safety and environmental friendliness. Using organic composites based on conducting polymers, such as polypyrrole, and abundant, cheap and naturally occurring biopolymers rich in quinones, such as lignin, has recently emerged as an interesting alternative. These materials, which exhibit electronic and ionic conductivity, provide challenging opportunities in the development of new charge storage materials. This review presents an overview of recent developments in organic biopolymer composite electrodes as renewable electroactive materials towards sustainable, cheap and scalable energy storage devices.

    Place, publisher, year, edition, pages
    ROYAL SOC CHEMISTRY, 2016
    National Category
    Other Environmental Engineering
    Identifiers
    urn:nbn:se:liu:diva-128741 (URN)10.1039/c5mh00261c (DOI)000375296600002 ()
    Note

    Funding Agencies|Knut and Alice Wallenberg Foundation; Wallenberg Scholar grant

    Available from: 2016-05-31 Created: 2016-05-30 Last updated: 2017-03-31
    2. Spectroelectrochemical investigation of redox states in a polypyrrole/lignin composite electrode material
    Open this publication in new window or tab >>Spectroelectrochemical investigation of redox states in a polypyrrole/lignin composite electrode material
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    2015 (English)In: Journal of Materials Chemistry A, ISSN 2050-7488, Vol. 3, no 24, 12927-12937 p.Article in journal (Refereed) Published
    Abstract [en]

    We report spectroelectrochemical studies to investigate the charge storage mechanism of composite polypyrrole/lignin electrodes. Renewable bioorganic electrode materials were produced by electropolymerization of pyrrole in the presence of a water-soluble lignin derivative acting as a dopant. The resulting composite exhibited enhanced charge storage abilities due to a lignin-based faradaic process, which was expressed after repeated electrochemical redox of the material. The in situ FTIR spectroelectrochemistry results show the formation of quinone groups, and reversible oxidation-reduction of these groups during charge-discharge experiments in the electrode materials. The most significant IR bands include carbonyl absorption near 1705 cm(-1), which is attributed to the creation of quinone moieties during oxidation, and absorption at 1045 cm(-1) which is due to hydroquinone moieties.

    Place, publisher, year, edition, pages
    ROYAL SOC CHEMISTRY, 2015
    National Category
    Materials Chemistry
    Identifiers
    urn:nbn:se:liu:diva-120069 (URN)10.1039/c5ta00788g (DOI)000356022800044 ()
    Note

    Funding Agencies|Knut and Alice Wallenberg foundation; Marie Curie network Renaissance; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]

    Available from: 2015-07-06 Created: 2015-07-06 Last updated: 2017-03-31
    3. High performance PEDOT/lignin biopolymer composites for electrochemical supercapacitors
    Open this publication in new window or tab >>High performance PEDOT/lignin biopolymer composites for electrochemical supercapacitors
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    2016 (English)In: Journal of Materials Chemistry A, ISSN 2050-7488, Vol. 4, no 5, 1838-1847 p.Article in journal (Refereed) Published
    Abstract [en]

    Developing sustainable organic electrode materials for energy storage applications is an urgent task. We present a promising candidate based on the use of lignin, the second most abundant biopolymer in nature. This polymer is combined with a conducting polymer, where lignin as a polyanion can behave both as a dopant and surfactant. The synthesis of PEDOT/Lig biocomposites by both oxidative chemical and electrochemical polymerization of EDOT in the presence of lignin sulfonate is presented. The characterization of PEDOT/Lig was performed by UV-Vis-NIR spectroscopy, FTIR infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, cyclic voltammetry and galvanostatic charge-discharge. PEDOT doped with lignin doubles the specific capacitance (170.4 F g(-1)) compared to reference PEDOT electrodes (80.4 F g(-1)). The enhanced energy storage performance is a consequence of the additional pseudocapacitance generated by the quinone moieties in lignin, which give rise to faradaic reactions. Furthermore PEDOT/Lig is a highly stable biocomposite, retaining about 83% of its electroactivity after 1000 charge/discharge cycles. These results illustrate that the redox doping strategy is a facile and straightforward approach to improve the electroactive performance of PEDOT.

    Place, publisher, year, edition, pages
    ROYAL SOC CHEMISTRY, 2016
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:liu:diva-125323 (URN)10.1039/c5ta10096h (DOI)000368839200035 ()
    Note

    Funding Agencies|Power Papers project from the Knut and Alice Wallenberg foundation; Wallenberg Scholar grant from the Knut and Alice Wallenberg foundation; Marie Curie network Renaissance (NA); European Research Council by Starting Grant Innovative Polymers for Energy Storage (iPes) [306250]; Basque Government

    Available from: 2016-02-23 Created: 2016-02-19 Last updated: 2017-03-31
  • Public defence: 2017-04-28 10:15 Planck, Fysikhuset, Linköping
    Mosyagin, Igor
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    Development and applications of theoretical algorithms for simulations of materials at extreme conditions2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Materials at extreme conditions exhibit properties that differ substantially from ambient conditions. High pressure and high temperature expose anharmonic, non-linear behavior, and can provoke phase transitions among other effects. Experimental setups to study that sort of effects are typically costly and experiments themselves are laborious. It is common to apply theoretical techniques in order to provide a road-map for experimental research. In this thesis I cover computational algorithms based on first-principles calculations for high-temperature and high-pressure conditions. The two thoroughly described algorithms are: 1) the free energy studies using temperature-dependent effective potential method (TDEP), and 2) a higher-order elastic constants calculation procedure. The algorithms are described in an easy to follow manner with motivation for every step covered.

    The Free energy calculation algorithm is demonstrated with applications to hexagonal close-packed Iron at the conditions close to the inner Earth Core’s. The algorithm of elastic constants calculation is demonstrated with application to Molybdenum, Tantalum, and Niobium. Other projects included in the thesis are the study of effects of van der Waals corrections on the graphite and diamond equations of state.

    List of papers
    1. Highly Efficient Free Energy Calculations of the Fe Equation of State Using Temperature-Dependent Effective Potential Method
    Open this publication in new window or tab >>Highly Efficient Free Energy Calculations of the Fe Equation of State Using Temperature-Dependent Effective Potential Method
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    2016 (English)In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 120, no 43, 8761-8768 p.Article in journal (Refereed) Published
    Abstract [en]

    Free energy calculations at finite temperature based on ab initio molecular dynamics (AIMD) simulations have become possible, but they are still highly computationally demanding. Besides, achieving simultaneously high accuracy of the calculated results and efficiency of the computational algorithm is still a challenge. In this work we describe an efficient algorithm to determine accurate free energies of solids in simulations using the recently proposed temperature-dependent effective potential method (TDEP). We provide a detailed analysis of numerical approximations employed in the TDEP algorithm. We show that for a model system considered in this work, hcp Fe, the obtained thermal equation of state at 2000 K is in excellent agreement with the results of standard calculations within the quasiharmonic approximation.

    Place, publisher, year, edition, pages
    American Chemical Society (ACS), 2016
    National Category
    Theoretical Chemistry
    Identifiers
    urn:nbn:se:liu:diva-132993 (URN)10.1021/acs.jpca.6b08633 (DOI)000387198600028 ()27700093 (PubMedID)
    Note

    Funding Agencies|Swedish Foundation for Strategic Research (SSF) program SRL [10-0026]; Swedish Research Council (VR) [2015-04391, 2014-4750, 637-2013-7296]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]; Ministry of Education and Science of the Russian Federation [14.Y26.31.0005]; PRACE-2IP project [FP7 RI-283493]

    Available from: 2016-12-09 Created: 2016-12-07 Last updated: 2017-04-24Bibliographically approved
    2. Theoretical description of pressure-induced phase transitions: a case study of Ti-V alloys
    Open this publication in new window or tab >>Theoretical description of pressure-induced phase transitions: a case study of Ti-V alloys
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    2015 (English)In: High Pressure Research, ISSN 0895-7959, Vol. 35, no 1, 42-48 p.Article in journal (Refereed) Published
    Abstract [en]

    We discuss theoretical description of pressure-induced phase transitions by means of first-principles calculations in the framework of density functional theory. We illustrate applications of theoretical tools that allow one to take into account configurational and vibrational disorders, considering Ti-V alloys as a model system. The universality of the first-principles theory allows us to apply it in studies of different phenomena that occur in the Ti-V system upon compression. Besides the transitions between different crystal structures, we discuss isostructural transitions in bcc Ti-V alloys. Moreover, we present arguments for possible electronic transitions in this system, which may explain peculiar behaviour of elastic properties of V upon compression.

    Place, publisher, year, edition, pages
    Taylor andamp; Francis: STM, Behavioural Science and Public Health Titles, 2015
    Keyword
    phase stability; first-principles calculations; Ti-V alloys; high pressure
    National Category
    Physical Sciences
    Identifiers
    urn:nbn:se:liu:diva-114586 (URN)10.1080/08957959.2014.992896 (DOI)000348672100007 ()
    Note

    Funding Agencies|Ministry of Education and Science of the Russian Federation [14.Y26.31.0005]; SSF [SRL 10-0026]; Russian Foundation for Basic Researches [13-02-00606a]; Tomsk State University Academic D.I. Mendeleev Fund Program; Program of Fundamental Research of State Academies of Sciences

    Available from: 2015-02-27 Created: 2015-02-26 Last updated: 2017-04-10
    3. Finite Temperature, Magnetic, and Many-Body Effects in Ab Initio Simulations of Alloy Thermodynamics
    Open this publication in new window or tab >>Finite Temperature, Magnetic, and Many-Body Effects in Ab Initio Simulations of Alloy Thermodynamics
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    2013 (English)In: TMS2013 Supplemental Proceedings, John Wiley & Sons, 2013, 617-626 p.Chapter in book (Refereed)
    Abstract [en]

    Ab initio electronic structure theory is known as a useful tool for prediction of materials properties. However, majority of simulations still deal with calculations in the framework of density functional theory with local or semi-local functionals carried out at zero temperature. We present new methodological solution.s, which go beyond this approach and explicitly take finite temperature, magnetic, and many-body effects into account. Considering Ti-based alloys, we discuss !imitations of the quasiharmonic approximation for the treatment of lattice vibrations, and present an accurate and easily extendable method to calculate free ,energies of strongly anharmonic solids. We underline the necessity to going beyond the state-of-the-art techniques for the determination of effective cluster interactions in systems exhibiting mctal-to-insulator transition, and describe a unified cluster expansion approach developed for this class of materials. Finally, we outline a first-principles method, disordered local moments molecular dynamics, for calculations of thermodynamic properties of magnetic alloys, like Cr1-x,.AlxN, in their high-temperature paramagnetic state. Our results unambiguously demonstrate importance of finite temperature effects in theoretical calculations ofthermodynamic properties ofmaterials.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2013
    Keyword
    Alloy thermodynamics, Ti alloys, (Ti-Al)N, (Cr-Al)N
    National Category
    Condensed Matter Physics Theoretical Chemistry Inorganic Chemistry Metallurgy and Metallic Materials
    Identifiers
    urn:nbn:se:liu:diva-136443 (URN)10.1002/9781118663547.ch77 (DOI)9781118605813 (ISBN)9781118663547 (ISBN)
    Available from: 2017-04-10 Created: 2017-04-10 Last updated: 2017-04-21Bibliographically approved
  • Public defence: 2017-04-28 13:15 Visionen, B-huset, Linköping
    Orlof, Anna
    Linköping University, Department of Mathematics, Mathematics and Applied Mathematics. Linköping University, Faculty of Science & Engineering.
    Quantum scattering and interaction in graphene structures2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Since its isolation in 2004, that resulted in the Nobel Prize award in 2010, graphene has been the object of an intense interest, due to its novel physics and possible applications in electronic devices. Graphene has many properties that differ it from usual semiconductors, for example its low-energy electrons behave like massless particles. To exploit the full potential of this material, one first needs to investigate its fundamental properties that depend on shape, number of layers, defects and interaction. The goal of this thesis is to perform such an investigation.

    In paper I, we study electronic transport in monolayer and bilayer graphene nanoribbons with single and many short-range defects, focusing on the role of the edge termination (zigzag vs armchair). Within the discrete tight-binding model, we perform an-alytical analysis of the scattering on a single defect and combine it with the numerical calculations based on the Recursive Green's Function technique for many defects. We find that conductivity of zigzag nanoribbons is practically insensitive to defects situated close to the edges. In contrast, armchair nanoribbons are strongly affected by such defects, even in small concentration. When the concentration of the defects increases, the difference between different edge terminations disappears. This behaviour is related to the effective boundary condition at the edges, which respectively does not and does couple valleys for zigzag and armchair ribbons. We also study the Fano resonances.

    In the second paper we consider electron-electron interaction in graphene quantum dots defined by external electrostatic potential and a high magnetic field. The interaction is introduced on the semi-classical level within the Thomas Fermi approximation and results in compressible strips, visible in the potential profile. We numerically solve the Dirac equation for our quantum dot and demonstrate that compressible strips lead to the appearance of plateaus in the electron energies as a function of the magnetic field. This analysis is complemented by the last paper (VI) covering a general error estimation of eigenvalues for unbounded linear operators, which can be used for the energy spectrum of the quantum dot considered in paper II. We show that an error estimate for the approximate eigenvalues can be obtained by evaluating the residual for an approximate eigenpair. The interpolation scheme is selected in such a way that the residual can be evaluated analytically.

    In the papers III, IV and V, we focus on the scattering on ultra-low long-range potentials in graphene nanoribbons. Within the continuous Dirac model, we perform analytical analysis and show that, considering scattering of not only the propagating modes but also a few extended modes, we can predict the appearance of the trapped mode with an energy eigenvalue close to one of the thresholds in the continuous spectrum. We prove that trapped modes do not appear outside the threshold, provided the potential is sufficiently small. The approach to the problem is different for zigzag vs armchair nanoribbons as the related systems are non-elliptic and elliptic respectively; however the resulting condition for the existence of the trapped mode is analogous in both cases.

    List of papers
    1. Effect of zigzag and armchair edges on the electronic transport in single-layer and bilayer graphene nanoribbons with defects
    Open this publication in new window or tab >>Effect of zigzag and armchair edges on the electronic transport in single-layer and bilayer graphene nanoribbons with defects
    2013 (English)In: Physical Review B. Condensed Matter and Materials Physics, ISSN 1098-0121, E-ISSN 1550-235X, Vol. 88, no 12Article in journal (Refereed) Published
    Abstract [en]

    We study electronic transport in monolayer and bilayer graphene with single and many short-range defects focusing on the role of edge termination (zigzag versus armchair). Within the tight-binding approximation, we derive analytical expressions for the transmission amplitude in monolayer graphene nanoribbons with a single short-range defect. The analytical calculations are complemented by exact numerical transport calculations for monolayer and bilayer graphene nanoribbons with a single and many short-range defects and edge disorder. We find that for the case of the zigzag edge termination, both monolayer and bilayer nanoribbons in a single- and few-mode regime remain practically insensitive to defects situated close to the edges. In contrast, the transmission of both armchair monolayer and bilayer nanoribbons is strongly affected by even a small edge defect concentration. This behavior is related to the effective boundary condition at the edges, which, respectively, does not and does couple valleys for zigzag and armchair nanoribbons. In the many-mode regime and for sufficiently high defect concentration, the difference of the transmission between armchair and zigzag nanoribbons diminishes. We also study resonant features (Fano resonances) in monolayer and bilayer nanoribbons in a single-mode regime with a short-range defect. We discuss in detail how an interplay between the defect's position at different sublattices in the ribbons, the defect's distance to the edge, and the structure of the extended states in ribbons with different edge termination influence the width and the energy of Fano resonances.

    Place, publisher, year, edition, pages
    American Physical Society, 2013
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-98145 (URN)10.1103/PhysRevB.88.125409 (DOI)000323944800009 ()
    Note

    Funding Agencies|Swedish Institute||

    Available from: 2013-09-30 Created: 2013-09-30 Last updated: 2017-03-27
    2. Electron-electron interactions in graphene field-induced quantum dots in a high magnetic field
    Open this publication in new window or tab >>Electron-electron interactions in graphene field-induced quantum dots in a high magnetic field
    2015 (English)In: Physical Review B. Condensed Matter and Materials Physics, ISSN 1098-0121, E-ISSN 1550-235X, Vol. 92, no 7, 075431- p.Article in journal (Refereed) Published
    Abstract [en]

    We study the effect of electron-electron interaction in graphene quantum dots defined by an external electrostatic potential and a high magnetic field. To account for the electron-electron interaction, we use the Thomas-Fermi approximation and find that electron screening causes the formation of compressible strips in the potential profile and the electron density. We numerically solve the Dirac equations describing the electron dynamics in quantum dots, and we demonstrate that compressible strips lead to the appearance of plateaus in the electron energies as a function of the magnetic field. Finally, we discuss how our predictions can be observed using the Kelvin probe force microscope measurements.

    Place, publisher, year, edition, pages
    American Physical Society, 2015
    National Category
    Mathematics Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:liu:diva-121107 (URN)10.1103/PhysRevB.92.075431 (DOI)000359859900004 ()
    Note

    Funding Agencies|Danish National Research Foundation [DNRF58]

    Available from: 2015-09-07 Created: 2015-09-07 Last updated: 2017-03-27
    3. Trapped modes supported by localized potentials in the zigzag graphene ribbon
    Open this publication in new window or tab >>Trapped modes supported by localized potentials in the zigzag graphene ribbon
    2016 (English)In: Comptes rendus. Mathematique, ISSN 1631-073X, E-ISSN 1778-3569, Vol. 354, no 1, 63-67 p.Article in journal (Refereed) Published
    Abstract [en]

    Localized potentials in the Dirac equation for the electron dynamics in a zigzag graphene ribbon are constructed to support trapped modes while the corresponding eigenvalues are embedded into the continuous spectrum. (C) 2015 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.

    Place, publisher, year, edition, pages
    ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2016
    National Category
    Mathematics
    Identifiers
    urn:nbn:se:liu:diva-127590 (URN)10.1016/j.crrna.2015.10.007 (DOI)000373518100011 ()
    Note

    Funding Agencies|Linkoping University; Russian Foundation of Basic Research [15-01-02175]

    Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2017-03-27
    4. Error Estimation for Eigenvalues of Unbounded Linear Operators and an Application to Energy Levels in Graphene Quantum Dots
    Open this publication in new window or tab >>Error Estimation for Eigenvalues of Unbounded Linear Operators and an Application to Energy Levels in Graphene Quantum Dots
    2017 (English)In: Numerical Functional Analysis and Optimization, ISSN 0163-0563, E-ISSN 1532-2467, Vol. 38, no 3, 293-305 p.Article in journal (Refereed) Published
    Abstract [en]

    The eigenvalue problem for linear differential operators is important since eigenvalues correspond to the possible energy levels of a physical system. It is also important to have good estimates of the error in the computed eigenvalues. In this work, we use spline interpolation to construct approximate eigenfunctions of a linear operator using the corresponding eigenvectors of a discretized approximation of the operator. We show that an error estimate for the approximate eigenvalues can be obtained by evaluating the residual for an approximate eigenpair. The interpolation scheme is selected in such a way that the residual can be evaluated analytically. To demonstrate that the method gives useful error bounds, we apply it to a problem originating from the study of graphene quantum dots where the goal was to investigate the change in the spectrum from incorporating electron–electron interactions in the potential.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2017
    Keyword
    Energy levels, error estimation, graphene, linear operator, quantum dot, spectrum
    National Category
    Computational Mathematics Mathematical Analysis
    Identifiers
    urn:nbn:se:liu:diva-135540 (URN)10.1080/01630563.2017.1279176 (DOI)000396822500002 ()
    Available from: 2017-03-22 Created: 2017-03-22 Last updated: 2017-04-11
  • Public defence: 2017-04-28 13:15 TEMCAS, T-huset, Linköping
    Hallberg, Mathilda
    Linköping University, Department of Thematic Studies, Department of Child Studies. Linköping University, Faculty of Arts and Sciences.
    Barn till beskådan: Familj, välfärdsstat och nation i fototävlingar och fotoböcker 1930-19442017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This dissertation focusses on the culture of visual display during the 1930s and 1940s, more specifically photo contests and photo books based on photographs of children. The overall purpose of this investigation has been to study how photo contests and photo books have been a part of the negotiation of the organization of welfare for children and the family. It examines how the family, the welfare state and the nation were constructed by means of representations of children, the messages that were thus established, and the political visions that were communicated. Analyses of images and texts show that photo contests and photo books presented a unified message which said that more and better children were needed, but also how photo contests and photo books communicated disparate visions of how this goal should be reached. The study highlights how useful representations of children were in the construction of welfare. They had the potential to communicate both different visions and a shared vision of the welfare society.

  • Public defence: 2017-05-04 09:00 Belladonna, Hus 511, Linköping
    Chenna Narendra, Sudeep
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Systemic and local regulation of experimental arthritis by IFN-α, dendritic cells and uridine2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, we have studied the immunological processes of joint inflammation that may be targets for future treatment of patients with arthritis. We focus on the immune-modulating properties of interferon-α (IFN-α) and uridine in experimental arthritis. The nucleoside uridine, which is regarded a safe treatment has anti-inflammatory properties notably by inhibiting tumor necrosis factor (TNF) release. Because the inflamed synovium in rheumatoid arthritis (RA) is characterised by pathogenic TNF-production, uridine could potentially be away to ameliorate arthritis. Systemic administration of uridine had no effect on antigeninduced arthritis (AIA), which is a T-cell dependent model where animals are immunized twice (sensitization) with bovine serum albumin (mBSA), before local triggering of arthritis by intra-articular antigen (mBSA) re-challenge. In contrast, intra-articular administration of uridine clearly down modulated development of AIA in a dose dependent manner and inhibited the expression of synovial adhesion molecules, influx of inflammatory leukocytes and synovial expression of TNF and interleukin 6, but did not affect systemic levels of proinflammatory cytokines or antigen-specific T-cell responses. Local administration of uridine may thus be a viable therapeutic option for treatment of arthritis in the future.

    Viral double-stranded deoxyribonucleic acid (dsRNA), a common nucleic acid found in most viruses, can be found in the joints of RA patients and local deposition of such viral dsRNA induces arthritis by activating IFN-α. Here we show that arthritis induced by dsRNA can be mediated by IFN-producing dendritic cells in the joint and this may thus explain why viral infections are sometimes associated with arthritis.

    Earlier, to study the effect of dsRNA and IFN-α in an arthritis model, that like RA, is dependent on adaptive immunity, dsRNA and IFN-α were administered individually during the development of AIA. Both molecules clearly protected against AIA in a type I IFN receptor-dependent manner but were only effective if administered in the sensitization phase of AIA. Here we show that the anti-inflammatory effect of IFN-α is critically dependent on signalling via transforming growth factor β (TGF-β) and the enzymatic activity of indoleamine 2,3 dioxygenase 1 (IDO). The IDO enzyme is produced by plasmacytoid DC and this cell type was critically required both during antigen sensitization and in the arthritis phase of AIA for the protective effect of IFN-α against AIA. In contrast, TGF-β and the enzymatic activity of IDO were only required during sensitization, which indicate that they are involved in initial steps of tolerogenic antigen sensitization. In this scenario, IFN- α first activates the enzymatic activity of IDO in pDC, which converts Tryptophan to Kynurenine, which thereafter activates TGF-β. Common for IDO-expressing pDC, Kyn and TGF-β is their ability to induce development of regulatory T cells (Tregs). We found that Tregs were crucial for IFN-α-mediated protection against AIA, but only in the arthritis phase. In line with this, adoptive transfer of Tregs isolated from IFN-α treated mice to recipient animals in the arthritis phase clearly protected against AIA. The numbers of Tregs were not significantly altered by IFN-α but IFN-α increased the suppressive capacity of Tregs against antigen-induced proliferation. This enhanced suppressive activity of Tregs in the arthritis phase was dependent on the earlier activated enzyme IDO1 during the sensitization phase of AIA. Thus, presence of IFN-α at the time of antigen sensitization activates the enzymatic activity of IDO, which generates Tregs with enhanced suppressive capacity that upon antigen re-challenge prevents inflammation. We have thus identified one example of how immune tolerance can be developed, that may be a future way to combat autoimmunity.

    List of papers
    1. Local but Not Systemic Administration of Uridine Prevents Development of Antigen-Induced Arthritis
    Open this publication in new window or tab >>Local but Not Systemic Administration of Uridine Prevents Development of Antigen-Induced Arthritis
    2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, e0141863- p.Article in journal (Refereed) Published
    Abstract [en]

    Objective Uridine has earlier been show to down modulate inflammation in models of lung inflammation. The aim of this study was to evaluate the anti-inflammatory effect of uridine in arthritis. Methods Arthritis was induced by intra-articular injection of mBSA in the knee of NMRI mice preimmunized with mBSA. Uridine was either administered locally by direct injection into the knee joint or systemically. Systemic treatment included repeated injections or implantation of a pellet continuously releasing uridine during the entire experimental procedure. Anti-mBSA specific immune responses were determined by ELISA and cell proliferation and serum cytokine levels were determined by Luminex. Immunohistochemistry was used to identify cells, study expression of cytokines and adhesion molecules in the joint. Results Local administration of 25-100 mg/kg uridine at the time of arthritis onset clearly prevented development of joint inflammation. In contrast, systemic administration of uridine (max 1.5 mg uridine per day) did not prevent development of arthritis. Protection against arthritis by local administration of uridine did not affect the anti-mBSA specific immune response and did not prevent the rise in serum levels of pro-inflammatory cytokines associated with the triggering of arthritis. In contrast, local uridine treatment efficiently inhibited synovial expression of ICAM-1 and CD18, local cytokine production and recruitment of leukocytes to the synovium. Conclusion Local, but not systemic administration of uridine efficiently prevented development of antigen- induced arthritis. The protective effect did not involve alteration of systemic immunity to mBSA but clearly involved inhibition of synovial expression of adhesion molecules, decreased TNF and IL-6 production and prevention of leukocyte extravasation. Further, uridine is a small, inexpensive molecule and may thus be a new therapeutic option to treat joint inflammation in RA.

    Place, publisher, year, edition, pages
    PUBLIC LIBRARY SCIENCE, 2015
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-123070 (URN)10.1371/journal.pone.0141863 (DOI)000363920300089 ()26512984 (PubMedID)
    Note

    Funding Agencies|Vetenskapsradet-Grant [521-2011-3095]; Reumatikerforbundet Grant [155261]; County Council of Ostergotland, Sweden; Linkoping University

    Available from: 2015-12-04 Created: 2015-12-03 Last updated: 2017-03-31
    2. IDO1 and TGF-beta Mediate Protective Effects of IFN-alpha in Antigen-Induced Arthritis
    Open this publication in new window or tab >>IDO1 and TGF-beta Mediate Protective Effects of IFN-alpha in Antigen-Induced Arthritis
    Show others...
    2016 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 197, no 8, 3142-3151 p.Article in journal (Refereed) Published
    Abstract [en]

    IFN-alpha prevents Ag-induced arthritis (AIA), and in this study we investigated the role of IDO1 and TGF-beta signaling for this anti-inflammatory property of IFN-alpha. Arthritis was induced by methylated BSA (mBSA) in mBSA-sensitized wild-type (WT), Ido1(-/-), or Ifnar(-/-) mice, treated or not with IFN-alpha or the IDO1 product kynurenine (Kyn). Enzymatic IDO1 activity, TGF-beta, and plasmacytoid dendritic cells (pDC) were neutralized by 1-methyltryptophan and Abs against TGF-beta and pDC, respectively. IDO1 expression was determined by RT-PCR, Western blot, and FACS, and enzymatic activity by HPLC. Proliferation was measured by H-3-thymidine incorporation and TGF-beta by RT-PCR and ELISA. WT but not Ido1(-/-) mice were protected from AIA by IFN-alpha, and Kyn, the main IDO1 product, also prevented AIA, both in WTand Ifnar(-/-) mice. Protective treatment with IFN-alpha increased the expression of IDO1 in pDC during AIA, and Ab-mediated depletion of pDC, either during mBSA sensitization or after triggering of arthritis, completely abrogated the protective effect of IFN-alpha. IFN-alpha treatment also increased the enzymatic IDO1 activity (Kyn/tryptophan ratio), which in turn activated production of TGF-beta. Neutralization of enzymatic IDO1 activity or TGF-beta signaling blocked the protective effect of IFN-alpha against AIA, but only during sensitization and not after triggering of arthritis. Likewise, inhibition of the IDO1 enzymatic activity in the sensitization phase, but not after triggering of arthritis, subdued the IFN-alpha-induced inhibition of mBSA-induced proliferation. In conclusion, presence of IFN-alpha at Ag sensitization activates an IDO1/TGF-beta-dependent anti-inflammatory program that upon antigenic rechallenge prevents inflammation via pDC.

    Place, publisher, year, edition, pages
    AMER ASSOC IMMUNOLOGISTS, 2016
    National Category
    Immunology in the medical area
    Identifiers
    urn:nbn:se:liu:diva-133121 (URN)10.4049/jimmunol.1502125 (DOI)000387965100018 ()27647832 (PubMedID)
    Available from: 2016-12-12 Created: 2016-12-09 Last updated: 2017-04-24
    3. Dendritic cells activated by double-stranded RNA induce arthritis via autocrine type I IFN signaling.
    Open this publication in new window or tab >>Dendritic cells activated by double-stranded RNA induce arthritis via autocrine type I IFN signaling.
    2014 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 95, no 4, 661-666 p.Article in journal (Refereed) Published
    Abstract [en]

    Viral dsRNA can be found at the site of inflammation in RA patients, and intra-articular injection of dsRNA induces arthritis by activating type I IFN signaling in mice. Further, DCs, a major source of IFN-α, can be found in the synovium of RA patients. We therefore determined the occurrence of DCs in dsRNA-induced arthritis and their ability to induce arthritis. Here, we show, by immunohistochemistry, that cells expressing the pan-DC marker CD11c and the pDC marker 120G8 are present in the inflamed synovium in dsRNA-induced arthritis. Flt3L-generated and splenic DCs preactivated with dsRNA before intra-articular injection, but not mock-stimulated cells, clearly induced arthritis. Induction of arthritis was dependent on type I IFN signaling in the donor DCs, whereas IFNAR expression in the recipient was not required. Sorting of the Flt3L-DC population into cDCs (CD11c(+), PDCA-1(-)) and pDCs (CD11c(+), PDCA-1(+)) revealed that both subtypes were arthritogenic and produced type I IFN if treated with dsRNA. Taken together, these results demonstrate that viral nucleic acids can elicit arthritis by activating type I IFN signaling in DCs. Once triggered, autocrine type I IFN signaling in dsRNA-activated DCs is sufficient to propagate arthritis.

    Place, publisher, year, edition, pages
    Society for Leukocyte Biology, 2014
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-102370 (URN)10.1189/jlb.0613320 (DOI)000335346300011 ()24304616 (PubMedID)
    Available from: 2013-12-09 Created: 2013-12-09 Last updated: 2017-03-31
  • Public defence: 2017-05-05 09:00 Hugo Theorell-salen, Linköping
    Venetsanos, Dimitrios
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Improving management of STEMI patients treated with primary PCI: Pharmacotherapy, renal function estimation and gender perspective2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focused on the acute management of patients with ST-segment elevation myocardial infarction (STEMI) in an effort to provide information that may improve outcome. The aim was to evaluate the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in STEMI patients during primary PCI. Furthermore, to provide pharmacodynamic data of novel ways of ticagrelor administration compared to standard tivcagrelor. Additionally, to identify subgroups of patients, such as women who may derive greater benefit from specific antithrombotic strategies due to their risk/benefit profile. Finally, to evaluate current formulas for estimation of renal function in the acute phase of STEMI.

    In Paper I, all STEMI patients in Sweden between 2008 and 2014, treated with primary PCI and UFH or bivalirudin were included in our analysis. Of the total population of 23 800 patients, 8 783 (36.9%) were included in the UFH group and 15 017 (63.1%) in the bivalirudin group. Concomitant GPI administration was 68.5% in the UFH arm compared to 3.5% in the bivalirudin arm (p<0.01).The adjusted incidence of 30-day mortality was not significant different between the two groups (UFH vs bivalirudin, adjusted HR 0.94; 95% CI 0.82 -1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between the two groups. In contrast, patients treated with UFH had a significantly higher incidence of major in-hospital bleeding (adjusted OR 1.62; 95%CI 1.30 -2.03).

    In Paper II pharmacodynamic data of chewed or crushed ticagrelor compared to standard ticagrelor loading dose (LD) was assessed in 99 patients with stable angina. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60 minutes after LD. High Residual platelet reactivity (HRPR) was defined as > 208 P2Y12 reaction units (PRU). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60 minutes. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20 minutes whereas no difference was observed at 60 minutes. At 20 minutes, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01).

    In Paper III we presented a pre-specified gender analysis of the ATLANTIC trial including 1 862 STEMI patients that were randomly assigned to pre-hospital versus in-hospital administration of 180mg ticagrelor. Women were older and had higher TIMI risk score. Women had a 3-fold higher risk for all-cause mortality compared to men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 – 5.51). However, after adjustment for baseline characteristics, the difference was lesser and no longer significant (HR 1.98, 95% CI 0.97 – 4.04). Female gender was not an independent predictor of risk for bleeding after multivariable adjustments (BARC type 3-5 HR 1.52, 95% CI 0.74-3.09). There was no interaction between gender and efficacy or safety of randomised treatment.

    In Paper IV, forty patients with PCI- treated STEMI were included between November 2011 and February 2013. We validated the performance of the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rGCystC) equations for estimation of GFR against measured GFR (mGFR) during the index hospitalisation for STEMI.

    MDRD-IDMS and CKD-EPI demonstrated a good performance to estimate GFR with accuracy within 30% (P30) 82.5% vs 82.5%, respectively. CKD was best classified by CKD-EPI (Kappa 0.83). CG showed the worst performance with the lowest P30. The rG-CystC equation had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03).

    Conclusions – In STEMI patients treated with primary PCI, bivalirudin should be preferred in patient at high risk for bleeding. With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared with standard integral tablets. In STEMI patients, fast and potent platelet inhibition with chewed ticagrelor may reduce the risk of early stent thrombosis and patients treated with a less aggressive antithrombotic strategy, such as UFH or bivalirudin monotherapy, may derive a greater benefit. Although gender differences in adverse outcomes could mainly be explained by older age and clustering of comorbidities in women, a bleedreduction strategy in women with high risk characteristics is warranted in order to improve their outcome. Regardless the choice of antithrombotic strategy, dose adjustment of drugs cleared by kidneys based on GFR estimation is of crucial importance. MDRD and CKD-EPI should be the formulas used for estimation of GFR in STEMI patients

    List of papers
    1. Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets: The inhibition of platelet aggregation after administration of three different ticagrelor formulations (IPAAD-Tica) study, a randomised controlled trial.
    Open this publication in new window or tab >>Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets: The inhibition of platelet aggregation after administration of three different ticagrelor formulations (IPAAD-Tica) study, a randomised controlled trial.
    2017 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 149, 88-94 p.Article in journal (Refereed) Published
    Abstract [en]

    AIMS: To provide pharmacodynamic data of crushed and chewed ticagrelor tablets, in comparison with standard integral tablets.

    METHODS: Ninety nine patients with stable angina were randomly assigned, in a 3:1:1 fashion, to one of the following 180mg ticagrelor loading dose (LD) formulations: A) Integral B) Crushed or C) Chewed tablets. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60min after LD. High residual platelet reactivity (HRPR) was defined as >208 P2Y12 reaction units (PRU).

    RESULTS: There was no significant difference in PRU values at baseline. PRU 20min after LD were 237 (182-295), 112 (53-238) and 84 (29-129) and 60min after LD, 56 (15-150), 51 (18-85) and 9 (7-34) in integral, crushed and chewed ticagrelor LD, respectively (p<0.01 for both). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60min. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20min whereas no difference was observed at 60min. At 20min, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01).

    CONCLUSION: With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared to standard integral tablets. We also show that administration of chewed tablets is feasible and provides faster inhibition than either crushed or integral tablets.

    CLINICAL TRIAL REGISTRATION: European Clinical Trial Database (EudraCT number 2014-002227-96).

    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-133985 (URN)10.1016/j.thromres.2016.10.013 (DOI)000391287300016 ()27773347 (PubMedID)
    Note

    Funding agencies: AstraZeneca

    Available from: 2017-01-17 Created: 2017-01-17 Last updated: 2017-04-19
    2. Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR
    Open this publication in new window or tab >>Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR
    Show others...
    2015 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 9, 1-8 p., e007835Article in journal (Refereed) Published
    Abstract [en]

    Objectives: To validate the performance of the most commonly used formulas for estimation of glomerular filtration rate (GFR) against measured GFR during the index hospitalisation for ST-elevation myocardial infarction (STEMI). Setting: Single centre, methodological study. Participants: 40 patients with percutaneous coronary intervention-treated STEMI were included between November 2011 and February 2013. Patients on dialysis, cardiogenic shock or known allergy to iodine were excluded. Outcome measures: Creatinine and cystatin C were determined at admission and before discharge in 40 patients with STEMI. Clearance of iohexol was measured (mGFR) before discharge. We evaluated and compared the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rG-CystC) with GFR regarding correlation, bias, precision and accuracy (P30). Agreement between eGFR and mGFR to discriminate CKD was assessed by Cohens. statistics. Results: MDRD-IDMS and CKD-EPI demonstrated good performance to estimate GFR (correlation 0.78 vs 0.81%, bias -1.3% vs 1.5%, precision 17.9 vs 17.1 mL/min 1.73 m(2) and P30 82.5% vs 82.5% for MDRD-IDMS vs CKD-EPI). CKD was best classified by CKD-EPI (. 0.83). CG showed the worst performance (correlation 0.73%, bias -1% to 3%, precision 22.5 mL/min 1.73 m(2) and P30 75%). The rG-CystC formula had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03). At arrival, CKD-EPI and rG-CystC had almost perfect agreement in CKD classification (kappa=0.87), whereas at discharge agreement was substantially lower (kappa=0.59) and showed a significant discrepancy in CKD classification (p=0.02). Median cystatin C concentration increased by 19%. Conclusions: In acute STEMI, CKD-EPI showed the best CKD-classification ability followed by MDRD-IDMS, whereas CG performed the worst. STEMI altered the performance of the cystatin C equation during the acute phase, suggesting that other factors might be involved in the rise of cystatin C.

    Place, publisher, year, edition, pages
    BMJ PUBLISHING GROUP, 2015
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-122794 (URN)10.1136/bmjopen-2015-007835 (DOI)000363484000021 ()26399570 (PubMedID)
    Available from: 2015-11-23 Created: 2015-11-23 Last updated: 2017-04-19
  • Public defence: 2017-05-12 13:15 K1, Kåkenhus, Norrköping
    Elfström Pettersson, Katarina
    Linköping University, Department of Social and Welfare Studies, Learning, Aesthetics, Natural science. Linköping University, Faculty of Educational Sciences.
    Production and Products of Preschool Documentation: Entanglements of children, things, and templates2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The objective of the present study is to produce knowledge about how children, things, documents, computers, teachers, templates and other entities take part in and produce documentation in preschool systematic quality development work. The thesis asks questions about how and what is produced as quality in preschool documentation. Through a posthumanist agential realist approach, the study engages empirically in video recordings of preschool documentation practices from one Swedish preschool, and in documentation from four other Swedish preschools.

    The results, presented in four articles, show that documentation practice is complex and entangled with a variety of entities, human and non-human, and spaces and time. The study shows how children’s participation in production of documentation does not depend on which documentation method is used. In the study, objects such as computers, images and coloured labels, together with teachers’ attitudes and agendas, have an impact on the way that children are involved in producing documentation. The results also show that the products of documentation, intra-acting with a local template, with past and present preschool traditions and policies, produce rather than represent certain elements of quality such as teachers’ actions, children’s interests and thematic work. The thesis produces knowledge about how the focus of preschool documentation shifts away from individual children and towards teachers’ activities, and creates possibilities for what preschool practices and quality may become.

    List of papers
    1. Children's participation in preschool documentation practices
    Open this publication in new window or tab >>Children's participation in preschool documentation practices
    2015 (English)In: Childhood, ISSN 0907-5682, E-ISSN 1461-7013, Vol. 22, no 2, 231-247 p.Article in journal (Refereed) Published
    Abstract [en]

    The Swedish preschool curriculum not only prescribes documentation and quality assessment, it also requires children’s participation in the documentation process, although it offers no directions on how the documenting should be done, which can leave teachers unsure of how to do it. This study differs from research that presents pedagogical documentation as a way of enabling children’s participation in preschool in that it explores children’s participation in producing different forms of documentation in a Swedish preschool – and it finds that such participation is complex. The findings imply that, whether documentation is activity-integrated or retrospective, different forms of participation are possible.

    Place, publisher, year, edition, pages
    Sage Publications, 2015
    Keyword
    Childhood, children’s participation, children’s rights, pedagogical documentation, preschool practice
    National Category
    Pedagogical Work
    Identifiers
    urn:nbn:se:liu:diva-105830 (URN)10.1177/0907568213513480 (DOI)000353984500007 ()2-s2.0-84930347007 (ScopusID)
    Funder
    Swedish Research Council, 729-2010-200
    Available from: 2014-04-09 Created: 2014-04-09 Last updated: 2017-04-21Bibliographically approved
    2. Sticky Dots and Lion Adventures Playing a Part in Preschool Documentation Practices
    Open this publication in new window or tab >>Sticky Dots and Lion Adventures Playing a Part in Preschool Documentation Practices
    2015 (English)In: International Journal of Early Childhood, ISSN 0020-7187, E-ISSN 1878-4658, Vol. 47, no 3, 443-460 p.Article in journal (Other academic) Published
    Abstract [en]

    This article is based on a study of Swedish preschool documentation practices. The 2010 revised version of the Swedish preschool curriculum emphasizes documentation as an important practice. The Swedish preschool curriculum also emphasizes children’s participation in documentation and evaluation. The main reason for this can be found in the very first words of the curriculum: ‘Democracy forms the foundation of the preschool’ (Swedish National Agency of Education, 2011, p. 3). This is connected to children’s right to make their voices heard in all matters affecting them according to UNCRC. However, the curriculum does not give any guidelines on how to carry out this practice. A quality audit by the Swedish Schools Inspectorate in 2011 found that preschool teachers were uncertain about how to document (Skolinspektionen, 2011). This, and a lack of knowledge about documentation, sometimes impedes teachers’ documentation practices in the preschools (Palmer, 2012). With the term documentation practices I refer to all events connected to making and using documentations in the preschool; these include, for example, taking photographs, writing captions, printing documents, looking at and talking about photos, and discussing events depicted in photos or drawings. In documentation practices different kinds of artefacts or devices are present and used (e.g., cameras, computers, printers, pencils, and paper) or produced (e.g, printed photos, texts, and drawings). Through methods that are shaped by an agential realist construct, the main objective of this article is to explore how different kinds of material agents, such as computers, photos, teachers and children, can intra-act (Barad, 2007) in the production of children’s participation in preschool documentation practices. The reason for using the term intra-act rather than interact is that, in Barad’s terms, the world is not seen as consisting of separate entities, which the word interaction implies. Instead entities (which could be human or non-human) are temporarily separated or produced through intra-action; ‘relations do not follow relata, but the other way around’ (Barad, 2007, pp. 136-137). This means that entities are not themselves agential, but become agential through intra-action, and that there is no way of determining, in advance, that any of them are active agents. Agency is also not situated within entities, but is rather produced through intra-action, suggesting that also material objects can become active.

    What is documented in Swedish preschools can vary considerably, from activities and/or achievements of individual children to activities that encompass the whole preschool. Documentation can be done for different reasons, such as showing parents what their children have been doing,  assessing individual children or evaluating preschool quality as a whole, and it can also be used as a tool for developing the preschool practice (Vallberg-Roth, 2012). There are thus different aims, from documenting in order to be able to remember and evaluate or assess to documenting in order to make way for and develop new activities (Swedish National Agency of Education, 2011).

    Place, publisher, year, edition, pages
    Springer Netherlands, 2015
    Keyword
    Early childhood education, Children’s participation, Pedagogical documentation, Preschool practice, Childhood
    National Category
    Pedagogical Work
    Identifiers
    urn:nbn:se:liu:diva-112873 (URN)10.1007/s13158-015-0146-9 (DOI)
    Note

    On the day of the defence date the status of this article was Manuscript.

    Available from: 2014-12-18 Created: 2014-12-18 Last updated: 2017-04-21Bibliographically approved
    3. Teachers’ actions and children’s interests: Quality becomings in preschool documentation
    Open this publication in new window or tab >>Teachers’ actions and children’s interests: Quality becomings in preschool documentation
    2017 (English)In: Nordisk Barnehageforskning, ISSN 1890-9167, E-ISSN 1890-9167, Vol. 14, no 2, 1-17 p.Article in journal (Refereed) Published
    Abstract [en]

    High quality is considered to be important for children’s development and learning in early childhood education. Swedish preschool teachers are required to systematically develop their practice and support children’s learning, using documentation and taking children’s interests into account. From a posthumanist perspective, preschool documentation, models and templates could be seen as actively producing certain elements of quality.  Reading  documentation from eight Swedish preschool groups diffractively through different texts, such as the national curriculum, supportive texts and research, this article discusses how teachers’ actions and children’s interests are produced as important quality aspects in one of these groups.

    Place, publisher, year, edition, pages
    Høgskolen i Oslo og Akershus, 2017
    Keyword
    Documentation, Early childhood education, Posthumanism, Preschool quality
    National Category
    Pedagogical Work Pedagogy Didactics Learning Specific Languages
    Identifiers
    urn:nbn:se:liu:diva-136693 (URN)10.7577/nbf.1756 (DOI)
    Available from: 2017-04-21 Created: 2017-04-21 Last updated: 2017-04-21Bibliographically approved
  • Public defence: 2017-05-19 09:00 Belladonnan, Linköping
    Spreco, Armin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Epidemiological and statistical basis for detection and prediction of influenza epidemics2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A large number of emerging infectious diseases (including influenza epidemics) has been identified during the last century. The emergence and re-emergence of infectious diseases have a negative impact on global health. Influenza epidemics alone cause between 3 and 5 million cases of severe illness annually, and between 250,000 and 500,000 deaths. In addition to the human suffering, influenza epidemics also impose heavy demands on the health care system. For example, hospitals and intensive care units have limited excess capacity during infectious diseases epidemics. Therefore, it is important that increased influenza activity is noticed early at local levels to allow time to adjust primary care and hospital resources that are already under pressure. Algorithms for the detection and prediction of influenza epidemics are essential components to achieve this.

    Although a large number of studies have reported algorithms for detection or prediction of influenza epidemics, outputs that fulfil standard criteria for operational readiness are seldom produced. Furthermore, in the light of the rapidly growing availability of “Big Data” from both diagnostic and prediagnostic (syndromic) data sources in health care and public health settings, a new generation of epidemiologic and statistical methods, using several data sources, is desired for reliable analyses and modeling.

    The rationale for this thesis was to inform the planning of local response measures and adjustments to health care capacity during influenza epidemics. The overall aim was to develop a method for detection and prediction of influenza epidemics. Before developing the method, three preparatory studies were performed. In the first of these studies, the associations (in terms of correlation) between diagnostic and pre-diagnostic data sources were examined, with the aim of investigating the potential of these sources for use in influenza surveillance systems. In the second study, a literature study of detection and prediction algorithms used in the field of influenza surveillance was performed. In the third study, the algorithms found in the previous study were compared in a prospective evaluation study. In the fourth study, a method for nowcasting of influenza activity was developed using electronically available data for real-time surveillance in local settings followed by retrospective application on the same data. This method includes three functions: detection of the start of the epidemic at the local level and predictions of the peak timing and the peak intensity. In the fifth and final study, the nowcasting method was evaluated by prospective application on authentic data from Östergötland County, Sweden.

    In the first study, correlations with large effect sizes between diagnostic and pre-diagnostic data were found, indicating that pre-diagnostic data sources have potential for use in influenza surveillance systems. However, it was concluded that further longitudinal research incorporating prospective evaluations is required before these sources can be used for this purpose. In the second study, a meta-narrative review approach was used in which two narratives for reporting prospective evaluation of influenza detection and prediction algorithms were identified: the biodefence informatics narrative and the health policy research narrative. As a result of the promising performances of one detection algorithm and one prediction algorithm in the third study, it was concluded that both further evaluation research and research on methods for nowcasting of influenza activity were warranted. In the fourth study, the performance of the nowcasting method was promising when applied on retrospective data but it was concluded that thorough prospective evaluations are necessary before recommending the method for broader use. In the fifth study, the performance of the nowcasting method was promising when prospectively applied on authentic data, implying that the method has potential for routine use. In future studies, the validity of the nowcasting method must be investigated by application and further evaluation in multiple local settings, including large urbanizations.

    List of papers
    1. Performance of eHealth data sources in local influenza surveillance: a 5-year open cohort study
    Open this publication in new window or tab >>Performance of eHealth data sources in local influenza surveillance: a 5-year open cohort study
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    2014 (English)In: Journal of Medical Internet Research, ISSN 1438-8871, Vol. 16, no 4, e116- p.Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: There is abundant global interest in using syndromic data from population-wide health information systems--referred to as eHealth resources--to improve infectious disease surveillance. Recently, the necessity for these systems to achieve two potentially conflicting requirements has been emphasized. First, they must be evidence-based; second, they must be adjusted for the diversity of populations, lifestyles, and environments.

    OBJECTIVE: The primary objective was to examine correlations between data from Google Flu Trends (GFT), computer-supported telenursing centers, health service websites, and influenza case rates during seasonal and pandemic influenza outbreaks. The secondary objective was to investigate associations between eHealth data, media coverage, and the interaction between circulating influenza strain(s) and the age-related population immunity.

    METHODS: An open cohort design was used for a five-year study in a Swedish county (population 427,000). Syndromic eHealth data were collected from GFT, telenursing call centers, and local health service website visits at page level. Data on mass media coverage of influenza was collected from the major regional newspaper. The performance of eHealth data in surveillance was measured by correlation effect size and time lag to clinically diagnosed influenza cases.

    RESULTS: Local media coverage data and influenza case rates showed correlations with large effect sizes only for the influenza A (A) pH1N1 outbreak in 2009 (r=.74, 95% CI .42-.90; P<.001) and the severe seasonal A H3N2 outbreak in 2011-2012 (r=.79, 95% CI .42-.93; P=.001), with media coverage preceding case rates with one week. Correlations between GFT and influenza case data showed large effect sizes for all outbreaks, the largest being the seasonal A H3N2 outbreak in 2008-2009 (r=.96, 95% CI .88-.99; P<.001). The preceding time lag decreased from two weeks during the first outbreaks to one week from the 2009 A pH1N1 pandemic. Telenursing data and influenza case data showed correlations with large effect sizes for all outbreaks after the seasonal B and A H1 outbreak in 2007-2008, with a time lag decreasing from two weeks for the seasonal A H3N2 outbreak in 2008-2009 (r=.95, 95% CI .82-.98; P<.001) to none for the A p H1N1 outbreak in 2009 (r=.84, 95% CI .62-.94; P<.001). Large effect sizes were also observed between website visits and influenza case data.

    CONCLUSIONS: Correlations between the eHealth data and influenza case rates in a Swedish county showed large effect sizes throughout a five-year period, while the time lag between signals in eHealth data and influenza rates changed. Further research is needed on analytic methods for adjusting eHealth surveillance systems to shifts in media coverage and to variations in age-group related immunity between virus strains. The results can be used to inform the development of alert-generating eHealth surveillance systems that can be subject for prospective evaluations in routine public health practice.

    Place, publisher, year, edition, pages
    Journal of Medical Internet Research, 2014
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-106758 (URN)10.2196/jmir.3099 (DOI)000336501600017 ()24776527 (PubMedID)
    Available from: 2014-05-21 Created: 2014-05-21 Last updated: 2017-04-19Bibliographically approved
    2. Algorithms for detecting and predicting influenza outbreaks: metanarrative review of prospective evaluations
    Open this publication in new window or tab >>Algorithms for detecting and predicting influenza outbreaks: metanarrative review of prospective evaluations
    2016 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 5, e010683- p.Article, review/survey (Refereed) Published
    Abstract [en]

    Objectives Reliable monitoring of influenza seasons and pandemic outbreaks is essential for response planning, but compilations of reports on detection and prediction algorithm performance in influenza control practice are largely missing. The aim of this study is to perform a metanarrative review of prospective evaluations of influenza outbreak detection and prediction algorithms restricted settings where authentic surveillance data have been used. Design The study was performed as a metanarrative review. An electronic literature search was performed, papers selected and qualitative and semiquantitative content analyses were conducted. For data extraction and interpretations, researcher triangulation was used for quality assurance. Results Eight prospective evaluations were found that used authentic surveillance data: three studies evaluating detection and five studies evaluating prediction. The methodological perspectives and experiences from the evaluations were found to have been reported in narrative formats representing biodefence informatics and health policy research, respectively. The biodefence informatics narrative having an emphasis on verification of technically and mathematically sound algorithms constituted a large part of the reporting. Four evaluations were reported as health policy research narratives, thus formulated in a manner that allows the results to qualify as policy evidence. Conclusions Awareness of the narrative format in which results are reported is essential when interpreting algorithm evaluations from an infectious disease control practice perspective.

    Place, publisher, year, edition, pages
    BMJ PUBLISHING GROUP, 2016
    Keyword
    influenza; detection algorithms; prediction algorithms; evaluation; meta-narrative review
    National Category
    Health Care Service and Management, Health Policy and Services and Health Economy
    Identifiers
    urn:nbn:se:liu:diva-130311 (URN)10.1136/bmjopen-2015-010683 (DOI)000378414700068 ()27154479 (PubMedID)
    Note

    Funding Agencies|Swedish Civil Contingencies Agency [2010-2788]; Swedish Science Council [2008-5252]

    Available from: 2016-07-31 Created: 2016-07-28 Last updated: 2017-04-19
  • Public defence: 2017-05-19 10:15 Planck, Fysikhuset, Linköping
    Melianas, Armantas
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Non-Equilibrium Charge Motion in Organic Solar Cells2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Organic photovoltaic (OPV) devices based on semiconducting polymers and small molecules allow for a low cost alternative to inorganic solar cells. Recent developments show power conversion efficiencies as high as 10-12%, highlighting the potential of this technology. Nevertheless, further improvements are necessary to achieve commercialization.

    To a large extent the performance of these devices is dictated by their ability to extract the photo-generated charge, which is related to the charge carrier mobility. Various time-resolved and steady-state techniques are available to probe the charge carrier mobility in OPVs but often lead to different mobility values for one and the same system. Despite such conflicting observations it is generally assumed that charge transport in OPV devices can be described by well-defined charge carrier mobilities, typically obtained using a single steady-state technique. This thesis shows that the relevance of such well-defined mobilities for the charge separation and extraction processes is very limited.

    Although different transient techniques probe different time scales after photogeneration, they are mutually consistent as they probe the same physical mechanism governing charge motion – gradual thermalization of the photo-generated carriers in the disorder broadened density of states (DOS). The photo-generated carriers gradually lose their excess energy during transport to the extracting electrodes, but not immediately. Typically not all excess energy is dissipated as the photo-generated carriers tend to be extracted from the OPV device before reaching quasi-equilibrium.

    Carrier motion is governed by thermalization, leading to a time-dependent carrier mobility that is significantly higher than the steady-state mobility. This picture is confirmed by several transient techniques: Time-resolved Terahertz Spectroscopy (TRTS), Time-resolved Microwave Conductance (TRMC) combined with Transient Absorption (TA), electrical extraction of photo-induced charges (photo-CELIV). The connection between transient and steady-state mobility measurements (space-charge limited conductivity, SCLC) is described. Unification of transient opto-electric techniques to probe charge motion in OPVs is presented.

    Using transient experiments the distribution of extraction times of photo-generated charges in an operating OPV device has been determined and found to be strongly dispersive, spanning several decades in time. In view of the strong dispersion in extraction times the relevance of even a well-defined time-dependent mean mobility is limited.

    In OPVs a continuous ‘percolating’ donor network is often considered necessary for efficient hole extraction, whereas if the network is discontinuous, hole transport is thought to deteriorate significantly, limiting device performance. Here, it is shown that even highly diluted donor sites (5.7-10 %) in a buckminsterfullerene (C60) matrix enable reasonably efficient hole transport. Using transient measurements it is demonstrated that hole transport between isolated donor sites can occur by long-range hole tunneling (over distances of ~4 nm) through several C60 molecules – even a discontinuous donor network enables hole transport

    List of papers
    1. Unified Study of Recombination in Polymer:Fullerene Solar Cells Using Transient Absorption and Charge-Extraction Measurements
    Open this publication in new window or tab >>Unified Study of Recombination in Polymer:Fullerene Solar Cells Using Transient Absorption and Charge-Extraction Measurements
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    2013 (English)In: Journal of Physical Chemistry Letters, ISSN 1948-7185, Vol. 4, no 12, 2069-2072 p.Article in journal (Refereed) Published
    Abstract [en]

    Recombination in the well-performing bulk heterojunction solar cell blend between the conjugated polymer TQ-1 and the substituted fullerene PCBM has been investigated with pump-probe transient absorption and charge extraction of photo-generated carriers (photo-CELIV). Both methods are shown to generate identical and overlapping data under appropriate experimental conditions. The dominant type of recombination is bimolecular with a rate constant of 7 x 10(-12) cm(-3) s(-1). This recombination rate is shown to be fully consistent with solar cell performance. Deviations from an ideal bimolecular recombination process, in this material system only observable at high pump fluences, are explained with a time-dependent charge-carrier mobility, and the implications of such a behavior for device development are discussed.

    Place, publisher, year, edition, pages
    American Chemical Society, 2013
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-95964 (URN)10.1021/jz4009745 (DOI)000320979400014 ()
    Note

    Funding Agencies|Swedish Research Council||Swedish Energy Agency (STEM)||Knut and Alice Wallenberg Foundation||ERC (VISCHEM)|226136|Wallenberg Scholar grant from the Knut and Alice Wallenberg Foundation||

    Available from: 2013-08-19 Created: 2013-08-12 Last updated: 2017-04-20
    2. Dispersion-Dominated Photocurrent in Polymer:Fullerene Solar Cells
    Open this publication in new window or tab >>Dispersion-Dominated Photocurrent in Polymer:Fullerene Solar Cells
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    2014 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 24, no 28, 4507-4514 p.Article in journal (Refereed) Published
    Abstract [en]

    Organic bulk heterojunction solar cells are often regarded as near-equilibrium devices, whose kinetics are set by well-defined charge carrier mobilities, and relaxation in the density of states is commonly ignored or included purely phenomenologically. Here, the motion of photocreated charges is studied experimentally with picosecond time resolution by a combination of time-resolved optical probing of electric field and photocurrent measurements, and the data are used to define parameters for kinetic Monte Carlo modelling. The results show that charge carrier motion in a prototypical polymer:fullerene solar cell under operational conditions is orders of magnitude faster than would be expected on the basis of corresponding near-equilibrium mobilities, and is extremely dispersive. There is no unique mobility. The distribution of extraction times of photocreated charges in operating organic solar cells can be experimentally determined from the charge collection transients measured under pulsed excitation. Finally, a remarkable distribution of the photocurrent over energy is found, in which the most relaxed charge carriers in fact counteract the net photocurrent.

    Place, publisher, year, edition, pages
    Weinheim, Germany: Wiley-VCH Verlagsgesellschaft, 2014
    Keyword
    solar cell; organic solar cell; dispersion; photocurrent; charge carrier relaxation; Monte Carlo simulations
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:liu:diva-108324 (URN)10.1002/adfm.201400404 (DOI)000339713900015 ()
    Note

    Funding agencies|Swedish Science Council (VR); Swedish Energy Agency; Knut and Alice Wallenberg foundation; European Social Fund under Global Grant measure

    Available from: 2014-06-26 Created: 2014-06-26 Last updated: 2017-04-20Bibliographically approved
    3. Photo-generated carriers lose energy during extraction from polymer-fullerene solar cells
    Open this publication in new window or tab >>Photo-generated carriers lose energy during extraction from polymer-fullerene solar cells
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    2015 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, no 8778Article in journal (Refereed) Published
    Abstract [en]

    In photovoltaic devices, the photo-generated charge carriers are typically assumed to be in thermal equilibrium with the lattice. In conventional materials, this assumption is experimentally justified as carrier thermalization completes before any significant carrier transport has occurred. Here, we demonstrate by unifying time-resolved optical and electrical experiments and Monte Carlo simulations over an exceptionally wide dynamic range that in the case of organic photovoltaic devices, this assumption is invalid. As the photo-generated carriers are transported to the electrodes, a substantial amount of their energy is lost by continuous thermalization in the disorder broadened density of states. Since thermalization occurs downward in energy, carrier motion is boosted by this process, leading to a time-dependent carrier mobility as confirmed by direct experiments. We identify the time and distance scales relevant for carrier extraction and show that the photo-generated carriers are extracted from the operating device before reaching thermal equilibrium.

    Place, publisher, year, edition, pages
    Nature Publishing Group, 2015
    National Category
    Biological Sciences Physical Sciences
    Identifiers
    urn:nbn:se:liu:diva-123824 (URN)10.1038/ncomms9778 (DOI)000366294700004 ()26537357 (PubMedID)
    Note

    Funding Agencies|Swedish Science Council and Energimyndigheten; Knut and Alice Wallenberg foundation; Deutsche Forschungsgemeinschaft [SPP1355]

    Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2017-04-20
    4. Photogenerated Carrier Mobility Significantly Exceeds Injected Carrier Mobility in Organic Solar Cells
    Open this publication in new window or tab >>Photogenerated Carrier Mobility Significantly Exceeds Injected Carrier Mobility in Organic Solar Cells
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    2017 (English)In: Advanced Energy Materials, ISSN 1614-6840Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    Charge transport in organic photovoltaic (OPV) devices is often characterized by space-charge limited currents (SCLC). However, this technique only probes the transport of charges residing at quasi-equilibrium energies in the disorder-broadened density of states (DOS). In contrast, in an operating OPV device the photogenerated carriers are typically created at higher energies in the DOS, followed by slow thermalization. Here, by ultrafast time-resolved experiments and simulations it is shown that in disordered polymer/fullerene and polymer/polymer OPVs, the mobility of photogenerated carriers significantly exceeds that of injected carriers probed by SCLC. Time-resolved charge transport in a polymer/polymer OPV device is measured with exceptionally high (picosecond) time resolution. The essential physics that SCLC fails to capture is that of photo­generated carrier thermalization, which boosts carrier mobility. It is predicted that only for materials with a sufficiently low energetic disorder, thermalization effects on carrier transport can be neglected. For a typical device thickness of 100 nm, the limiting energetic disorder is σ ≈71 (56) meV for maximum-power point (short-circuit) conditions, depending on the error one is willing to accept. As in typical OPV materials the disorder is usually larger, the results question the validity of the SCLC method to describe operating OPVs.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2017
    Keyword
    charge carrier relaxation, charge carrier transport, organic photovoltaics, space-charge limited currents (SCLC), time-dependent mobility
    National Category
    Condensed Matter Physics Chemical Process Engineering Atom and Molecular Physics and Optics Physical Chemistry
    Identifiers
    urn:nbn:se:liu:diva-135770 (URN)10.1002/aenm.201602143 (DOI)
    Note

    1602143

    Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2017-04-21Bibliographically approved
  • Public defence: 2017-05-19 13:00 Berzeliussalen, Linköping
    Nord, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Levodopa pharmacokinetics -from stomach to brain: A study on patients with Parkinson’s disease2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients.

    In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment.

    To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery.

    List of papers
    1. Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
    Open this publication in new window or tab >>Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
    2017 (English)In: Advances in Parkinsons Disease, ISSN 2169-9712, Vol. 06, no 01Article in journal (Refereed) Published
    Abstract [en]

    Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.

    Place, publisher, year, edition, pages
    Scientific Research Publishing, 2017
    National Category
    Neurology Gastroenterology and Hepatology Anesthesiology and Intensive Care Surgery Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-136685 (URN)10.4236/apd.2017.61001 (DOI)
    Available from: 2017-04-20 Created: 2017-04-20 Last updated: 2017-04-20
    2. The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF
    Open this publication in new window or tab >>The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF
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    2010 (English)In: MOVEMENT DISORDERS, ISSN 0885-3185, Vol. 25, no 3, 363-367 p.Article in journal (Refereed) Published
    Abstract [en]

    Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa. shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day I; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg bid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given alone and in combination with carbidopa. The C-max of levodopa in both CSF and blood increased significantly. Additional entacapone to levodopa therapy gives an increase of C-max in CSF and in blood. The increase is more evident when entacapone is combined with carbidopa.

    Place, publisher, year, edition, pages
    John Wiley and Sons, Ltd, 2010
    Keyword
    Parkinsons Disease, levodopa, continuous infusion, COMT
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54855 (URN)10.1002/mds.22613 (DOI)000276136900016 ()
    Available from: 2010-04-16 Created: 2010-04-16 Last updated: 2017-04-20
    3. Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease
    Open this publication in new window or tab >>Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease
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    2014 (English)In: Neurology and Clinical Neuroscience, ISSN 2049-4173, Vol. 2, no 5, 149-155 p.Article in journal (Refereed) Published
    Abstract [en]

    Background The mechanism by which deep brain stimulation of the nucleus subthalamicus improves Parkinson’s disease symptoms remains unclear. In a previous perioperative study, we showed that there might be alterations of neurotransmitter levels in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus. Aim In this study, we examined whether deep brain stimulation of the nucleus subthalamicus and levodopa infusion interact and affect the levels of neurotransmitters. Methods Five patients with advanced Parkinson’s disease took part in the study. During subthalamic nucleus surgery, microdialysis catheters were inserted bilaterally in the globus pallidum interna and unilaterally in the right putamen. A study protocol was set up and was followed for 3 days. Levodopa infusion with and without concomitant bilateral deep brain stimulation of the nucleus subthalamicus was also carried out. Results The putaminal dopamine levels increased during deep brain stimulation of the nucleus subthalamicus. In addition, an increase of gamma amino buturic acid concentrations in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus and during levodopa infusion was found. Conclusions These findings provide evidence that the subthalamic nucleus has a direct action on the substantia nigra pars compacta, and that deep brain stimulation of the nucleus subthalamicus might indirectly release putaminal dopamine. There is also evidence that deep brain stimulation of the nucleus subthalamicus interferes with levodopa therapy resulting in higher levels of levodopa in the brain, explaining why it is possible to decrease levodopa medication after deep brain stimulation surgery.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2014
    Keyword
    deep brain stimulation, levodopa, microdialysis, neurotransmitters, Parkinson
    National Category
    Medical Bioscience Medical Biotechnology Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-113590 (URN)10.1111/ncn3.109 (DOI)
    Available from: 2015-01-23 Created: 2015-01-23 Last updated: 2017-04-20Bibliographically approved
  • Public defence: 2017-05-19 13:15 K2, Kåkenhus, Norrköping
    Harling, Martin
    Linköping University, Department of Social and Welfare Studies, Learning, Aesthetics, Natural science. Linköping University, Faculty of Educational Sciences.
    Välja vara: En studie om gymnasieval, mässor och kampen om framtiden2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The thesis explores and analyzes in four empirical articles how student subjects are constructed in everyday school life and what role market principles play in these constructions. In particular, it focuses on the logics that constitute upper secondary school choice practices, and how these are legitimized, interpreted and challenged. The results show that upper secondary school choice practices divide the present and the future of the students as the choice between an explicit utopia and an implied dystopia. Here, the students themselves are made responsible for their success or failure in realizing the utopia that is staged in school choice practices. This division generally appears to the actors as natural and apolitical, which in turn legitimizes its effects in terms of exclusion, inequality and segregation, often on the basis of social class. Furthermore, the market-driven school discourses construct and divide the students as if they were commodities of different value. The notion of fantasmatic logics can explain how students are gripped by market-driven discourses and how they handle contradictory conditions. For instance, it explains how, for students, school choice means they can transform and become who they want to be, while at the same time they can also become more of what they already are, by choosing to be who they are. Students, however, problematize and destabilize dominant market logics in the school in all examined contexts, which in the thesis is analyzed in terms of penetrations and destabilizations of how schools and education are linked to the market logics. By penetrating the presupposed neutrality of secondary school choice practice, the students expose how the market orientation of education in general and the staging of school fairs in particular appear to be in schools’, rather than students’, interest.

    List of papers
    1. Examining "The Police": On Inclusion and "Investmentality" in Swedish Schooling
    Open this publication in new window or tab >>Examining "The Police": On Inclusion and "Investmentality" in Swedish Schooling
    2013 (English)In: European Education: Issues and Studies, ISSN 1056-4934, E-ISSN 1944-7086, Vol. 45, no 3, 51-66 p.Article in journal (Refereed) Published
    Abstract [en]

    In modern education, inequalities are assumed to be reduced by a redistribution of knowledge between the affluent and able on one side, and the poor and unable on the other. This article investigates ways in which the distribution of futures becomes naturalized in everyday school practices where equality is perceived as a goal rather than a starting point. The investigation draws on notions of governmentality and partition of the sensible, to analyze ethnographic material. The findings are thematized as discourses of inclusion and as "investmentality"—attitudes assumed and explained to the subjects involved.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2013
    National Category
    Pedagogy International Migration and Ethnic Relations Social Sciences Interdisciplinary
    Identifiers
    urn:nbn:se:liu:diva-136516 (URN)10.2753/EUE1056-4934450304 (DOI)
    Available from: 2017-04-18 Created: 2017-04-18 Last updated: 2017-04-18Bibliographically approved
    2. Pedagogik och Postpolitik
    Open this publication in new window or tab >>Pedagogik och Postpolitik
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    2015 (Swedish)In: Utbildning, makt och politik / [ed] Sverker Lindblad och Lisbeth Lundahl, Lund: Studentlitteratur, 2015, 195-217 p.Chapter in book (Other academic)
    Abstract [sv]

    Med vår pointillistiska ansats i form av ett antal studier får vi fram en bild av ett postpolitiskt landskap som kännetecknas av två faktorer. Den första är ett nät av aktörer – lokalt, nationellt och internationellt, exempelvis regeringen, OECD, Skolverket, McKinsey, Sveriges Kommuner och Landsting samt skolor och massmedia – som bygger på varandra i ett flöde av information och bedömningar av skolan och vad som behöver göras. Den andra är hierarkisering och konkurrens. Vad som räknas är rangordningar av länder, kommuner och skolor, vilka beskrivs genom jämförelser och har till uppgift att förbättra sina positioner eller att åtminstone inte falla nedåt. Inledningsvis pekade vi på kunskapsmätningarnas betydelse för regeringens tal om hur den svenska skolan hävdar sig, nationellt och internationellt. Den internationella konkurrensen i ekonomiskt hänseende har blivit en drivfjäder för utbildningspolitik över huvud taget (jfr Lindblad & Popkewitz, 2001; Lauder m.fl., 2006) och internationella jämförelser i form av provresultat har blivit viktiga mått på hur framgångsrikt ett land är därvidlag. Därför blir övernationella organisationer som OECD, med dess apparat för kunskapsmätningar, en viktig aktör i svensk utbildningspolitik. Och därför blir företag som McKinsey betydelsefulla, dels därför att de använder sådana mått, dels därför att de knyter dem till hur politiker och skolledare – återigen i internationellt ljus – kan hantera utbildningssystem och skolor på ett framgångsrikt sätt. Motsvarande kan sägas på nationell nivå om företag som ”Gymnasium.se”, som producerar bilder av möjliga bildningsgångar och sökmotorer för att finna vägarna dit. Vad som sker i en postpolitisk logik är att viktiga bedömningar överlåts till sådana aktörer, som befinner sig utanför skolväsendet som organisation. Och politiken kommer då också att i stor utsträckning handla om vad dessa aktörer hävdar beträffande kunskapsläge och skolorganisering. På motsvarande sätt kunde vi se hur instrument som SIRIS och SALSA, vilka tillkom för administrativa analyser, blev till verktyg för rangordning mellan kommuner och skolor. Sådana rangordningar har haft en rejäl genomslagskraft i massmedia och har använts för olika organisationers egna intressen. Jämförelser och rankingar har en inbyggd dramatik som är lättförstådd, slående och säljande. De fungerar som ett till synes objektivt underlag för kunden att informera sig om kvaliteten på skolorna som ingår i en skolmarknad i ett avreglerat och privatiserat skolväsende. Detta underlag är emellertid problematiskt då det vilar på tunna beskrivningar av skola, utbildning och kunskap vars relevans för rationellt handlande kan ifrågasättas. Detta bidrar till att talet om utbildning förändras så att fokus hamnar på jämförelser och hierarkier av olika slag i form av resultat på skolprov, betyg och positioner på rankinglistor. Utbildningspolitiska ambitioner reduceras då till att klättra på listorna eller att bibehålla positionerna. Och, som vår genomgång av massmedias rapportering visar, riktar kritiken mot makthavare in sig på dåliga listplaceringar för en skola eller ett land. Med denna logik beskrivs utbildningens mål och värde i termer av jämförelse och konkurrens. Detta gäller för såväl samhällen och utbildningssystem som skolor och elever. Vår analys av en gymnasiemässa kan belysa innebörden av postpolitiska tendenser på olika sätt. På en sådan mässa sker en översättning av skolor och elever till en ekonomi, bestående av företag som ska sälja sin vara och kunder som ska köpa varan ”utbildning” utifrån sina preferenser. Vi kan då notera hur skolorna opererar med sina varumärken och med anrop till olika kategorier av elever, för att eleverna i sin tur ska inse vilken kategori de tillhör och hur de på bästa sätt ska investera i sig själva för sin framtid. Vi kan också notera hur denna investeringslogik tycks forma elever och skolor som subjekt, som till exempel när framgångsrika elever görs till säljare av skolans varumärke (jfr Harling, 2013). Sammanfattningsvis vill vi med denna ”pointillistiska” analys peka på den bild som framträder när delarna formar en helhet. Vi menar att det är en postpolitisk bild av utbildning som växer fram, där avgörande och djupt politiska frågor om utbildningens mål och mening reducerats till teknikaliteter och till en sortering av elever byggd på ekonomisk logik. Vad vi presenterat är några nedslag och fortfarande återstår många frågor om denna omvandling att besvara.

    Place, publisher, year, edition, pages
    Lund: Studentlitteratur, 2015
    Keyword
    Utbildningspolitik, styrning, klassifikation, skoldifferentiering, post-politik, läroplansteori
    National Category
    Pedagogy Social Sciences Interdisciplinary
    Identifiers
    urn:nbn:se:liu:diva-136515 (URN)9789144076836 (ISBN)
    Available from: 2017-04-18 Created: 2017-04-18 Last updated: 2017-04-18Bibliographically approved
  • Public defence: 2017-05-23 13:15 Eken, Linköping
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    The Non-Invasive Liver Biopsy: Determining Hepatic Function in Diffuse and Focal LiverDisease2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development.

    Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level.

    Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies.

    The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI).

    The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis.

    Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function).

    In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.

    List of papers
    1. Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
    Open this publication in new window or tab >>Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
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    2013 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 23, no 1, 174-181 p.Article in journal (Refereed) Published
    Abstract [en]

    Objectives

    To apply dynamic contrast-enhanced (DCE) MRI on patients presenting with elevated liver enzymes without clinical signs of hepatic decompensation in order to quantitatively compare the hepatocyte-specific uptake of Gd-EOB-DTPA with histopathological fibrosis stage.

    Methods

    A total of 38 patients were prospectively examined using 1.5-T MRI. Data were acquired from regions of interest in the liver and spleen by using time series of single-breath-hold symmetrically sampled two-point Dixon 3D images (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). The signal intensity (SI) values were reconstructed using a phase-sensitive technique and normalised using multiscale adaptive normalising averaging (MANA). Liver-to-spleen contrast ratios (LSC_N) and the contrast uptake rate (KHep) were calculated. Liver biopsy was performed and classified according to the Batts and Ludwig system.

    Results

    Area under the receiver-operating characteristic curve (AUROC) values of 0.71, 0.80 and 0.78, respectively, were found for KHep, LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for KHep (borderline), LSC_N10 and LSC_N20.

    Conclusions

    Liver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and KHep will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.

    Place, publisher, year, edition, pages
    Springer, 2013
    Keyword
    Quantification, Gd-EOB-DTPA, Dynamic contrast-enhanced MRI, Pharmacokinetics, Liver
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-87242 (URN)10.1007/s00330-012-2583-2 (DOI)000312324500022 ()
    Projects
    NILB
    Note

    Funding Agencies|Swedish Research Council|VR/M 2007-2884|Medical Research Council of South-east Sweden|FORSS 12621|Linkoping University, Linkoping University Hospital Research Foundations||County Council of Ostergotland||

    Available from: 2013-01-14 Created: 2013-01-14 Last updated: 2017-04-19
    2. Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
    Open this publication in new window or tab >>Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
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    2014 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 4, 0095700- p.Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Diffuse liver disease (DLD), such as non-alcoholic fatty liver disease (NASH) and cirrhosis, is a rapidly growing problem throughout the Westernized world. Magnetic resonance imaging (MRI), based on uptake of the hepatocyte-specific contrast agent (CA) Gd-EOB-DTPA, is a promising non-invasive approach for diagnosing DLD. However, to fully utilize the potential of such dynamic measurements for clinical or research purposes, more advanced methods for data analysis are required. Methods: A mathematical model that can be used for such data-analysis was developed. Data was obtained from healthy human subjects using a clinical protocol with high spatial resolution. The model is based on ordinary differential equations and goes beyond local diffusion modeling, taking into account the complete system accessible to the CA. Results: The presented model can describe the data accurately, which was confirmed using chi-square statistics. Furthermore, the model is minimal and identifiable, meaning that all parameters were determined with small degree of uncertainty. The model was also validated using independent data. Conclusions: We have developed a novel approach for determining previously undescribed physiological hepatic parameters in humans, associated with CA transport across the liver. The method has a potential for assessing regional liver function in clinical examinations of patients that are suffering of DLD and compromised hepatic function.

    Place, publisher, year, edition, pages
    Public Library of Science, 2014
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-106962 (URN)10.1371/journal.pone.0095700 (DOI)000335226500139 ()
    Available from: 2014-06-04 Created: 2014-06-02 Last updated: 2017-04-19
    3. Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
    Open this publication in new window or tab >>Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
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    2017 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, StartPage-EndPage p.Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy (less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS), instead of collecting and analyzing liver biopsies to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF in measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (6 months or more) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereological point counts (SPCs). We correlated less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF findings with SPCs (r = 0.92; P less than.001). less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF results correlated with histopathology results (ρ = 0.87; P less than.001), and SPCs correlated with histopathology results (ρ = 0.88; P less than.001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values below 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve non-invasive detection of steatosis.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-136544 (URN)10.1053/j.gastro.2017.03.005 (DOI)
    Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2017-04-19Bibliographically approved
  • Public defence: 2017-05-24 10:00 Berzeliussalen, Linköping
    Ottosson, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Molecular Mechanisms of Resin Acids and Their Derivatives on the Opening of a Potassium Channel2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Voltage-gated ion channels play fundamental roles in excitable cells, such as neurons, where they enable electric signaling. Normally, this signaling is well controlled, but brain damage, alterations in the ionic composition of the extracellular solution, or dysfunctional ion channels can increase the electrical excitability thereby causing epilepsy. Voltage-gated ion channels are obvious targets for antiepileptic drugs, and, as a rule of thumb, excitability is dampened either by closing voltagegated sodium channels (Nav channels) or by opening voltage-gated potassium channels (Kv channels). For example, several classical antiepileptic drugs block the ion-conducting pore of Nav channels. Despite the large number of existing antiepileptic drugs, one third of the patients with epilepsy suffer from intractable or pharmacoresistant seizures.

    Our research group has earlier described how different polyunsaturated fatty acids (PUFAs) open a Kv channel by binding close to the voltage sensor and, from this position, electrostatically facilitate the movement of the voltage-sensor, thereby opening the channel. However, PUFAs affect a wide range of ion channels, making it difficult to use them as pharmaceutical drugs; it would be desirable to find smallmolecule compounds with an electrostatic, PUFA-like mechanism of action. The aim of the research leading to this thesis was to find, characterize, and refine drug candidates capable of electrostatically opening a Kv channel.

    The majority of the experiments were performed on the cloned Shaker Kv channel, expressed in oocytes from the frog Xenopus laevis, and the channel activity was explored with the two-electrode voltage-clamp technique. By systematically mutating the extracellular end of the channel’s voltage sensor, we constructed a highly PUFAsensitive channel, called the 3R channel. Such a channel is a useful tool in the search for electrostatic Kv-channel openers. We found that resin acids, naturally occurring in tree resins, act as electrostatic Shaker Kv channel openers. To explore the structure-activity relationship in detail, we synthesized 120 derivatives, whereof several were potent Shaker Kv channel openers. We mapped a common resin acidbinding site to a pocket formed by the voltage sensor, the channel’s third transmembrane segment, and the lipid membrane, a principally new binding site for small-molecule compounds. Further experiments showed that there are specific interactions between the compounds and the channel, suggesting promises for further drug development. Several of the most potent Shaker Kv channel openers also dampened the excitability in dorsal-root-ganglion neurons from mice, elucidating the pharmacological potency of these compounds. In conclusion, we have found that resin-acid derivatives are robust Kv-channel openers and potential drug candidates against diseases caused by hyperexcitability, such as epilepsy.

    List of papers
    1. Drug-induced ion channel opening tuned by the voltage sensor charge profile
    Open this publication in new window or tab >>Drug-induced ion channel opening tuned by the voltage sensor charge profile
    2014 (English)In: The Journal of General Physiology, ISSN 0022-1295, Vol. 143, no 2, 173-182 p.Article in journal (Refereed) Published
    Abstract [en]

    Polyunsaturated fatty acids modulate the voltage dependence of several voltage-gated ion channels, thereby being potent modifiers of cellular excitability. Detailed knowledge of this molecular mechanism can be used in designing a new class of small-molecule compounds against hyperexcitability diseases. Here, we show that arginines on one side of the helical K-channel voltage sensor S4 increased the sensitivity to docosahexaenoic acid (DHA), whereas arginines on the opposing side decreased this sensitivity. Glutamates had opposite effects. In addition, a positively charged DHA-like molecule, arachidonyl amine, had opposite effects to the negatively charged DHA. This suggests that S4 rotates to open the channel and that DHA electrostatically affects this rotation. A channel with arginines in positions 356, 359, and 362 was extremely sensitive to DHA: 70 mu M DHA at pH 9.0 increased the current greater than500 times at negative voltages compared with wild type (WT). The small-molecule compound pimaric acid, a novel Shaker channel opener, opened the WT channel. The 356R/359R/362R channel drastically increased this effect, suggesting it to be instrumental in future drug screening.

    Place, publisher, year, edition, pages
    Rockefeller University Press, 2014
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-105035 (URN)10.1085/jgp.201311087 (DOI)000330628500006 ()
    Available from: 2014-03-06 Created: 2014-03-06 Last updated: 2017-04-20
    2. Resin-acid derivatives as potent electrostatic openers of voltage-gated K channels and suppressors of neuronal excitability
    Open this publication in new window or tab >>Resin-acid derivatives as potent electrostatic openers of voltage-gated K channels and suppressors of neuronal excitability
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    2015 (English)In: Scientific Reports, ISSN 2045-2322, Vol. 5, no 13278Article in journal (Refereed) Published
    Abstract [en]

    Voltage-gated ion channels generate cellular excitability, cause diseases when mutated, and act as drug targets in hyperexcitability diseases, such as epilepsy, cardiac arrhythmia and pain. Unfortunately, many patients do not satisfactorily respond to the present-day drugs. We found that the naturally occurring resin acid dehydroabietic acid (DHAA) is a potent opener of a voltage-gated K channel and thereby a potential suppressor of cellular excitability. DHAA acts via a non-traditional mechanism, by electrostatically activating the voltage-sensor domain, rather than directly targeting the ion-conducting pore domain. By systematic iterative modifications of DHAA we synthesized 71 derivatives and found 32 compounds more potent than DHAA. The most potent compound, Compound 77, is 240 times more efficient than DHAA in opening a K channel. This and other potent compounds reduced excitability in dorsal root ganglion neurons, suggesting that resin-acid derivatives can become the first members of a new family of drugs with the potential for treatment of hyperexcitability diseases.

    Place, publisher, year, edition, pages
    Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group, 2015
    National Category
    Clinical Medicine Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-121307 (URN)10.1038/srep13278 (DOI)000359905300001 ()26299574 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council; Swedish Brain Foundation; Swedish Heart-Lung Foundation; ALF; County Council of Ostergotland

    Available from: 2015-09-16 Created: 2015-09-14 Last updated: 2017-04-20Bibliographically approved
  • Public defence: 2017-05-31 10:15 Ada Lovelace (Visionen), Hus B, Ingång 25, Linköping
    Nielsen, Isak
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, Faculty of Science & Engineering.
    Structure Exploiting Numerical Algorithms for Optimal Control2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Efficient numerical algorithms for solving optimal control problems are important for commonly used advanced control strategies such as model predictive control (MPC), but can also be useful for advanced estimation techniques such as moving horizon estimation (MHE).

    In MPC the control input is computed by solving a constrained finite-time optimal control (CFTOC) problem on-line, and in MHE the estimated states are obtained by solving an optimization problem that often can be formulated as a CFTOC problem. Two common types of optimization methods for solving CFTOC problems are interior-point (IP) methods and active-set (AS) methods. In both IP and AS methods, the main computational effort is often the computation of the second-order search directions, which boils down to solving a sequence of systems of equations that correspond to unconstrained finite-time optimal control (UFTOC) problems. Hence, high-performing IP and AS methods for CFTOC problems rely on efficient numerical algorithms for solving UFTOC problems.

    When the solution to a CFTOC problem is computed using an AS type method, the system of equations that is solved in each iteration to compute the search direction is only changed by a low-rank modification between two AS iterations. In this thesis, it is shown how to exploit these structured modifications while still exploiting the UFTOC problem structure using the Riccati recursion. Furthermore, in the thesis direct (non-iterative) parallel algorithms for computing the solution to the search directions in both IP and AS methods are presented. These algorithms exploit, and retain, the sparse structure of the UFTOC problem such that no dense system of equations needs to be solved serially as in many other algorithms, and the proposed algorithms can be applied recursively to obtain logarithmic computational complexity growth in the prediction horizon length.  Another approach to solve linear MPC problems is to use multiparametric quadratic programming (mp-QP), where the corresponding CFTOC problem can be solved explicitly off-line. This is referred to as explicit MPC. One of the main limitations with mp-QP is the memory requirement for storing the parametric solution. In this thesis, an approach for decreasing the required memory is presented, with the aim of making mp-QP and explicit MPC more useful in practical applications such as embedded systems with limited memory resources. The proposed approach exploits the structure from the QP problem in the parametric solution to reduce the memory footprint for explicit MPC and general mp-QP solutions. The algorithm can be used directly in mp-QP solvers or as a post-processing step.

  • Public defence: 2017-06-16 13:15 ACAS, A-huset, Linköping
    Onufrey, Ksenia
    Linköping University, Department of Management and Engineering, Project Innovations and Entrepreneurship. Linköping University, Faculty of Science & Engineering.
    Enabled by the past: understanding endogenous innovation in mature industries2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mature industries have played and still play a crucial role in national and world economies. To survive and retain competitiveness, they need to innovate, as innovation is the driver of economics growth and industrial transformation. However, existing research does not provide sufficient explanation of how innovation in mature industries can be enabled based on resources and internal development logic of those industries, i.e. endogenously. Some previous studies focused on incremental innovation patterns, which led to an underestimation of innovation potential of mature industries. Other studies acknowledged a high innovation potential of mature industries, but failed to explain how, through what mechanisms, industry-endogenous logic can bring about major innovations.

    Therefore, the purpose of this thesis is to systematically address, explain and conceptualize endogenous industry- innovation and its driving mechanisms in mature industries. To achieve this purpose, three main issues are addressed. First, the thesis investigates and conceptualizes the notion of industry endogenous innovation mechanisms based on the path dependency theory. Second, the thesis addresses strategic choices and actions by established companies that are rooted in the industry endogenous mechanisms and result in highly innovative outcomes. Third, the thesis systematically analyses different aspects of radicalness of innovations resulting from industry endogenous mechanisms.

    The thesis represents a qualitative, embedded case study with two main industry cases, i.e. the global lighting industry and the Swedish pulp and paper industry. The lighting industry and its sub-cases in the form of specific lighting technologies have been studied via the analysis of patents of leading lighting manufacturers, archival and secondary data sources as well as interviews with different types of actors in the industry. The pulp and paper industry and its sub-cases in the form of innovation initiatives have been studied with the help of interviews with leading manufacturers and research institutes, as well the analysis of annual reports and secondary data sources. The outcomes of the study are presented in the form of the thesis cover paper and five appended papers.

    The results show that innovations of any magnitude can be endogenously developed in mature industries. At the industry level, endogenous innovation is driven by innovation mechanisms that can be conceptualized as reactive sequences and self-reinforcing mechanisms. At the level of individual companies, the exploitation strategy corresponds to the logic of endogenous innovation mechanisms by enabling highly innovative outcomes and building on a wide range of resources available in the industry. The endogenous character of innovation mechanisms imposes certain limitations on the radicalness of the outcomes in the form of trade-offs in terms of how many and what particular aspects can be radically new at once.

    With these results, the thesis contributes to a more balanced overall understanding of innovation potential of mature industries and allows shifting the focus of discussion from whether mature industries can develop radical innovation to when and under what conditions they can succeed in this process. The results of the thesis also suggest several recommendations for managers in established companies with regard to how they can they can take advantage of industry endogenous innovation mechanisms.

    List of papers
    1. Is one path enough? Multiple paths and path interaction as an extension of path dependency theory
    Open this publication in new window or tab >>Is one path enough? Multiple paths and path interaction as an extension of path dependency theory
    2014 (English)In: Industrial and Corporate Change, ISSN 0960-6491, E-ISSN 1464-3650, Vol. 23, no 5, 1261-1297 p.Article in journal (Refereed) Published
    Abstract [en]

    To explain the development of multi-technology companies and industries where several alternative technologies co-exist and interact over long periods, this article suggests an extension of path dependency theory by providing a conceptualization of the path notion that incorporates the theoretical possibility of multiple paths and path interaction. The conceptualization is applied to a patent study of three leading companies in the lighting industry: General Electric, Osram/Siemens, and Philips. The study shows technology development patterns that are characterized by strong persistence, both within each path and across the whole technology field. These results demonstrate that multiple technological paths can co-exist in companies and industries, characterized by simultaneous long-term presence of several technologies. In such cases, path interaction takes place both between co-existing paths and when new, radically different paths are created. Although further studies are needed to identify the underlying self-reinforcing mechanisms, there is a clear indication that technological path dependency is not restricted to unitary progression patterns, as implied by previous conceptualizations.

    Place, publisher, year, edition, pages
    Oxford University Press, 2014
    National Category
    Economics and Business Other Engineering and Technologies not elsewhere specified
    Identifiers
    urn:nbn:se:liu:diva-102614 (URN)10.1093/icc/dtt040 (DOI)000343321100005 ()
    Available from: 2013-12-17 Created: 2013-12-17 Last updated: 2017-03-27
    2. Endogenous sources of path generation in a path dependent industry
    Open this publication in new window or tab >>Endogenous sources of path generation in a path dependent industry
    2016 (English)In: Technology Analysis & Strategic Management, ISSN 0953-7325, E-ISSN 1465-3990Article in journal (Refereed) Published
    Abstract [en]

    This paper investigates and conceptualises industry endogenous sources of innovation in a context of path dependency. With an embedded case study of the mature multi-technology lighting industry, it considers two cases of technology generation (fluorescent lamps and light-emitting diodes) that have occurred under the dominance of established incandescent technology. The results demonstrate the existence of common driving forces (variety of performance criteria and variety of lighting applications) behind the development of the existing path and the generation of two new paths. Such common driving forces indicate the existence of a reactive sequence or a logical causal relationship between the existing and the new paths, which serve as an enabling mechanism in endogenous path generation.

    Keyword
    industry endogenous innovation, lighting industry, Path dependency, path generation, reactive sequences
    National Category
    Computer Science Other Engineering and Technologies not elsewhere specified Computer Systems Computer Engineering Information Systems, Social aspects
    Identifiers
    urn:nbn:se:liu:diva-136098 (URN)10.1080/09537325.2016.1268683 (DOI)
    Available from: 2017-03-27 Created: 2017-03-27 Last updated: 2017-04-03Bibliographically approved
    3. Self-reinforcing Mechanisms in a Multi-technology Industry: Understanding Sustained Technological Variety in a Context of Path Dependency
    Open this publication in new window or tab >>Self-reinforcing Mechanisms in a Multi-technology Industry: Understanding Sustained Technological Variety in a Context of Path Dependency
    2015 (English)In: Industry and Innovation, ISSN 1366-2716, E-ISSN 1469-8390, Vol. 22, no 6, 523-551 p.Article in journal (Refereed) Published
    Abstract [en]

    This paper studies self-reinforcing mechanisms in multi-technology industries, i.e. industries in which technological lock-in does not occur and several technologies continue to coexist. The purpose of this paper is to investigate what kind of self-reinforcing mechanisms can be present in such industries and explain how multiple paths can coexist and interact in a context of self-reinforcement and, ultimately, path dependency. Building on the empirical example of the lighting industry, the paper shows that all previously recognized types of self-reinforcing mechanisms can be present in a multi-technology industry. However, in addition to the path-internal positive feedbacks and cross-path negative externalities identified in single-path settings, multi-technology industries also experience positive cross-path externalities that create a symbiotic relationship between alternatives and allow for the reproduction of the same development pattern across technologies. Due to the existence of such non-negative technology interactions, multi-technology industries can be path dependent while still retaining technological variety.

    Place, publisher, year, edition, pages
    ROUTLEDGE JOURNALS, TAYLOR and FRANCIS LTD, 2015
    Keyword
    Self-reinforcing mechanisms; path dependency; multi-technology industries; lighting industry
    National Category
    Economics and Business
    Identifiers
    urn:nbn:se:liu:diva-123163 (URN)10.1080/13662716.2015.1100532 (DOI)000364722200004 ()
    Note

    Funding Agencies|Riksbankens Jubileumsfond via the KITE research program [M2006-0231]

    Available from: 2015-12-06 Created: 2015-12-04 Last updated: 2017-03-27