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  • Pettersson, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Information Systems.
    Nyrén, Nils
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Information Systems.
    Hur får vi e-lärande att fungera?: En litteraturstudie med fokus på faktorer som främjar universitetsstudenters användande av e-lärande2020Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    A large number of studies have been carried out in recent years to investigate the success factors in elearning. Based on the large number of studies, an opportunity to conduct a literature review to compile the information was identified. The chosen method for the study is a literature review based on 22 scientific articles. Based on the identified literature, two theories have been central, the Technology Acceptance Model and the Unified Theory of User Acceptance and Use of Technology. The literature is not completely unanimous on the success factors that are most critical for getting students to use elearning. Overall, two success factors from each model were identified: Perceived Usefulness and Perceived Ease of Use from TAM and Performance Expectancy and Effort Expectancy from UTAUT. The articles indicate that the success factors look different depending on how different generations view and use modern technology, as well as cultural differences.

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  • Norell, Jesper
    et al.
    Stockholm Univ, AlbaNova Univ Ctr, Dept Phys, SE-10691 Stockholm, Sweden.
    Odelius, Michael
    Stockholm Univ, AlbaNova Univ Ctr, Dept Phys, SE-10691 Stockholm, Sweden.
    Vacher, Morgane
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Theoretical Chemistry. Univ Nantes, CNRS, Lab CEISAM, UMR 6230, F-44300 Nantes, France.
    Ultrafast dynamics of photo-excited 2-thiopyridone: Theoretical insights into triplet state population and proton transfer pathways2020In: STRUCTURAL DYNAMICS-US, ISSN 2329-7778, Vol. 7, no 2, article id 024101Article in journal (Refereed)
    Abstract [en]

    Ultrafast non-adiabatic dynamics of the small heteroaromatic compound 2-thiopyridone has been studied with surface hopping simulations based on multi-configurational quantum chemistry. Initial excitation of the bright S-2(pi,pi*) state is found to promptly relax to S-1(n, pi*) through in-plane motion. The subsequent dynamics are oppositely driven by out-of-plane motion, which results in both complex population transfers among all the available states and intersystem crossing predominantly through the "El-Sayed forbidden" S-1(n, pi*) to T-2(n, pi*) channel, through significant mixing of electronic excitation characters. Despite this complexity, the femto- to picosecond triplet population, expected from several spectroscopic measurements, is well described as a simple exponential decay of the singlet state manifold. No proton transfer is found in the reported trajectories, but two mechanisms for its possible mediation in previously reported experiments are proposed based on the observed structural dynamics: (i) ultrafast intra-molecular transfer driven by the initially coherent in-plane motion and (ii) inter-molecular solvent-mediated transfer driven by the out-of-plane modes that dominate the later motion.

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  • Pérez-Penichet, Carlos
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computer Architecture and Computer Communication. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Computer Systems.
    Seamless Integration of Battery-Free Communications in Commodity Wireless Networks2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ubiquitous sensing applications have countless potential benefits to society. However, batteries have long been an obstacle to their full development. Harvesting energy from the environment is a promising alternative to battery power, but traditional radio transceivers consume too much for most harvesters.  This work is motivated by backscatter communications, a technique that reduces the energy that devices spend exchanging data by up to three orders of magnitude relative to regular radios.  This reduction enables sensing devices that operate indefinitely without having to replace batteries; instead they leverage energy harvesting.  My goal is to enable the seamless integration of battery-free devices with widespread low-power commodity networks such as Bluetooth or ZigBee/IEEE 802.15.4.  Making this integration seamless is critical for the broad adoption of the new class of devices.

    At a high level, my dissertation outlines a series of challenges to the seamless integration of the new devices with regular low-power networks.  We then propose ways to address these challenges, and demonstrate how we could integrate ultra-low-power battery-free devices with regular networks, while avoiding hardware modifications and minimizing any disruption that the addition may cause to existing and co-located communication devices.

    This work advances the state of the art by: First, demonstrating how to augment an existing sensor network with new sensors without any hardware modification to the pre-existing hardware. The existing network provides the unmodulated carrier that the battery-free nodes need to communicate. Second, we demonstrate a radio receiver that, if implemented in silicon, can directly receive low-power commodity wireless signals when assisted by an unmodulated carrier, and with a power consumption of a few hundred microwatts. The receiver makes battery-free devices directly compatible with regular networks. We introduce simulation models and a first-of-its-kind tool to simulate battery-free communications that integrate with regular networks. Finally, we demonstrate how to efficiently provide unmodulated carrier support for battery-free devices in the previous scenarios without unnecessarily spending energy and spectrum and without undue disturbance to co-located devices.

    List of papers
    1. Augmenting IoT networks with backscatter-enabled passive sensor tags
    Open this publication in new window or tab >>Augmenting IoT networks with backscatter-enabled passive sensor tags
    2016 (English)In: Proceedings of the 3rd Workshop on Hot Topics in Wireless, 2016, p. 23-27Conference paper, Published paper (Refereed)
    Abstract [en]

    The sensing modalities available in an Internet-of-Things (IoT) network are usually fixed before deployment, when the operator selects a suitable IoT platform. Retrofitting a deployment with additional sensors can be cumbersome, because it requires either modifying the deployed hardware or adding new devices that then have to be maintained. In this paper, we present our vision and work towards passive sensor tags: battery-free devices that allow to augment existing IoT deployments with additional sensing capabilities without the need to modify the existing deployment. Our passive sensor tags use backscatter transmissions to communicate with the deployed network. Crucially, they do this in a way that is compatible with the deployed network's radio protocol, and without the need for additional infrastructure. We present an FPGA-based prototype of a passive sensor tag that can communicate with unmodified 802.15.4 IoT devices. Our initial experiments with the prototype support the feasibility of our approach. We also lay out the next steps towards fully realizing the vision of passive sensor tags.

    Keywords
    Backscatter communication, Internet of Things, Wireless
    National Category
    Communication Systems
    Identifiers
    urn:nbn:se:uu:diva-306898 (URN)10.1145/2980115.2980132 (DOI)978-1-4503-4251-3 (ISBN)
    Conference
    3rd Workshop on Hot Topics in Wireless, HotWireless. October 3-7, 2016. New York
    Available from: 2016-11-04 Created: 2016-11-04 Last updated: 2020-04-01Bibliographically approved
    2. Battery-free 802.15. 4 Receiver
    Open this publication in new window or tab >>Battery-free 802.15. 4 Receiver
    2018 (English)In: 17th ACM/IEEE International Conference on Information Processing in Sensor Networks (IPSN), IEEE, 2018Conference paper, Published paper (Refereed)
    Abstract [en]

    We present the architecture of an 802.15.4 receiver that, for the first time, operates at a few hundred microwatts, enabling new battery-free applications. To reach the required micro-power consumption, the architecture diverges from that of commodity receivers in two important ways. First, it offloads the power-hungry local oscillator to an external device, much like backscatter transmitters do. Second, we avoid the energy cost of demodulating a phase-modulated signal by treating 802.15.4 as a frequency-modulated one, which allows us to receive with a simple passive detector and an energy-efficient thresholding circuit. We describe a prototype that can receive 802.15.4 frames with a power consumption of 361 μW. Our receiver prototype achieves sufficient communication range to integrate with deployed wireless sensor networks (WSNs). We illustrate this integration by pairing the prototype with an 802.15.4 backscatter transmitter and integrating it with unmodified 802.15.4 sensor nodes running the TSCH and Glossy protocols.

    Place, publisher, year, edition, pages
    IEEE, 2018
    Keywords
    Battery free, Backscatter, receiver, 802.15.4, Zigbee, sensor networks, passive radio, wireless
    National Category
    Computer Engineering
    Identifiers
    urn:nbn:se:uu:diva-366929 (URN)10.1109/IPSN.2018.00045 (DOI)000449016500037 ()978-1-5386-5298-5 (ISBN)
    Conference
    17th ACM/IEEE International Conference on Information Processing in Sensor Networks, Porto, Portugal, 11-13 April, 2018.
    Funder
    Swedish Research Council, 2017-045989Knowledge Foundation, 20140319
    Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2020-04-01Bibliographically approved
    3. Modelling Battery-free Communications for the Cooja Simulator
    Open this publication in new window or tab >>Modelling Battery-free Communications for the Cooja Simulator
    2019 (English)In: Proceedings of the 2019 International Conference on Embedded Wireless Systems and Networks, 2019, p. 47-58Conference paper, Published paper (Refereed)
    Abstract [en]

    Recent progress on backscatter communications enable devices that, assisted by an unmodulated carrier, receive and transmit standard wireless protocols such as IEEE 802.15.4 with sub-milliwatt power consumption. This paradigm, that we call carrier-assisted communications, enables batteryfree devices due to its reduced power consumption. To develop at scale, and integrate seamlessly into networks of unmodified conventional nodes, we need novel protocols at the MAC layer and above that can coordinate the carrier generators with receivers and transmitters while maintaining energy and spectral efficiency. A highly effective tool to develop such protocols is a network simulator. We introduce models for the communication range, energy consumption and other characteristics of carrier-assisted links based on parameters gathered from real-world experiments. We implement the models in Cooja, a well-known simulator, creating the first carrier-assisted communications framework to simulate interoperable battery-free devices alongside conventional sensor nodes. We illustrate how such a tool can offer valuable insights in the development and evaluation of efficient protocols for carrier-assisted communications.

    National Category
    Communication Systems
    Identifiers
    urn:nbn:se:uu:diva-407784 (URN)978-0-9949886-3-8 (ISBN)
    Conference
    EWSN '19, Beijing, China, February 25-27, 2019
    Available from: 2020-03-28 Created: 2020-03-28 Last updated: 2020-04-01Bibliographically approved
    4. TagAlong: Efficient Integration of Battery-free Sensor Tags in Standard Wireless Networks
    Open this publication in new window or tab >>TagAlong: Efficient Integration of Battery-free Sensor Tags in Standard Wireless Networks
    2020 (English)In: Proceedings of the 19th ACM/IEEE International Conference on Information Processing in Sensor Networks, 2020Conference paper, Published paper (Refereed)
    Abstract [en]

    New battery-free sensor tags that interoperate with unmodified standard IoT devices can extend a sensor network's capabilities in a scalable and cost-effective manner. The tags achieve battery-free operation through backscatter-related techniques, while the standard IoT devices can provide the necessary unmodulated carrier, avoiding additional dedicated infrastructure. However, this approach presents multiple challenges: It requires coordination between nodes transmitting, receiving and generating carrier, adds extra latency and energy consumption to already constrained devices, and increases interference and contention in shared spectrum. We present TagAlong, a medium access mechanism for interoperable sensor tags that, besides coordinating, optimizes the use of carrier generators, minimizing the disruption caused to the operation of the regular nodes.We accomplish this by parallelizing communications with battery-free tags when possible, sharing carriers for multiple tags concurrently and synchronizing communications with tags that share carrier generators. We demonstrate the feasibility of TagAlong in a testbed deployment. In our evaluation we find that it can reduce the duration of the tags' schedule by 60% while improving the energy and spectrum usage by 30% when compared to sequential interrogation with no difference in reliability.

    National Category
    Communication Systems
    Identifiers
    urn:nbn:se:uu:diva-407785 (URN)10.1109/IPSN48710.2020.00020 (DOI)
    Conference
    IPSN '20
    Available from: 2020-03-28 Created: 2020-03-28 Last updated: 2020-04-01Bibliographically approved
    5. A Fast Carrier Scheduling Algorithm for Battery-free Sensor Tags in Commodity Wireless Networks
    Open this publication in new window or tab >>A Fast Carrier Scheduling Algorithm for Battery-free Sensor Tags in Commodity Wireless Networks
    2020 (English)Conference paper, Published paper (Refereed)
    Abstract [en]

    New battery-free sensor tags that interoperate with unmodified standard IoT devices and protocols can extend a sensor network’s capabilities in a scalable and cost-effective manner. The tags achieve battery-free operation through backscatter-related techniques, while the standard IoT devices avoid additional dedicated infrastructure by providing the unmodulated carrier that tags need to communicate. However, this approach requires coordination between devices transmitting, receiving and generating carrier, adds extra latency and energy consumption to already constrained devices, and increases interference and contention in the shared spectrum. We present a scheduling mechanism that optimizes the use of carrier generators, minimizing any disruptions to the regular nodes. We employ timeslots to coordinate the unmodulated carrier while minimizing latency, energy consumption and overhead radio emissions. We propose an efficient scheduling algorithm that parallelizes communications with battery-free tags when possible and shares carriers among multiple tags concurrently. In our evaluation we demonstrate the feasibility and reliability of our approach in testbed experiments. We find that we can significantly reduce the excess latency and energy consumption caused by the addition of sensor tags when compared to sequential interrogation. We show that the gains tend to improve with the network size and that our solution is close to optimal on average.

    National Category
    Communication Systems
    Identifiers
    urn:nbn:se:uu:diva-407786 (URN)
    Conference
    INFOCOM 2020, June 13-19, 2020, Las Vegas, Nevada
    Available from: 2020-03-28 Created: 2020-03-28 Last updated: 2020-04-01Bibliographically approved
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  • Jespers, Willem
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Free energy calculations of G protein-coupled receptor modulation: New methods and applications2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    G protein-coupled receptors (GPCRs) are membrane proteins that transduce the signals of extracellular ligands, such as hormones, neurotransmitters and metabolites, through an intracellular response via G proteins. They are abundant in human physiology and approximately 34% of the marketed drugs target a GPCR. Upon activation, the receptor undergoes conformational changes to accommodate the binding of the G protein. Our insights in the structural determinants of ligand binding and receptor activation have increased tremendously over the past decade. This has largely been a cause of the growing amount of experimentally determined structures, which provide crucial insights in ligand binding mechanisms. However, in a typical drug design project it is unlikely that such structures can be generated for all ligands. In those cases, computationally derived models of the protein-ligand complex can be generated. Rigorous free energy calculations such as the free energy perturbation (FEP) method, can subsequently provide the missing link between those structures and experimental ligand binding data, and provide further insights in the binding mechanism.

    In this thesis, two workflows are presented to calculate free energies of binding for ligands to wildtype (QligFEP) and mutant (QresFEP) receptors. Both methods were tested on a set of solvation free energies of sidechain mimics. QligFEP was furthermore applied on three protein-ligand binding datasets, including pair comparisons between topologically unrelated molecules (scaffold hopping). QresFEP was used to calculate protein-ligand binding affinities to mutants of the neuropeptide Y1, and to predicte the effect of receptor modifications on the thermal stability of T4 lysozyme.

    The remainder of this work focussed on the application of these protocols in the design, synthesis and molecular pharmacology of ligands for the family of adenosine receptor (ARs). These receptors, involved in many physiological processes such as promotion of sleep (caffeine is a well-known inhibitor), have recently been pursued as drug targets in immuno-oncology. QligFEP was used in the design of novel series of antagonists for the A3AR and A2BAR. QresFEP was used to study ligand binding to the A1AR and in a multidisciplinary approach to characterize binding to the orphan receptor GPR139. Both approaches were combined to design a series of A2AAR antagonist, and to propose a binding mode later confirmed by new crystal structures. Finally, a new application of FEP is introduced based on conformational equilibria between the active and inactive A2AAR, to elucidate the regulation mechanism of receptor activation by ligands and receptor mutations.

    List of papers
    1. QligFEP: an automated workflow for small molecule free energy calculations in Q
    Open this publication in new window or tab >>QligFEP: an automated workflow for small molecule free energy calculations in Q
    2019 (English)In: Journal of Cheminformatics, ISSN 1758-2946, E-ISSN 1758-2946, Vol. 11, article id 26Article in journal (Refereed) Published
    Abstract [en]

    The process of ligand binding to a biological target can be represented as the equilibrium between the relevant solvated and bound states of the ligand. This which is the basis of structure-based, rigorous methods such as the estimation of relative binding affinities by free energy perturbation (FEP). Despite the growing capacity of computing power and the development of more accurate force fields, a high throughput application of FEP is currently hampered due to the need, in the current schemes, of an expert user definition of the alchemical transformations between molecules in the series explored. Here, we present QligFEP, a solution to this problem using an automated workflow for FEP calculations based on a dual topology approach. In this scheme, the starting poses of each of the two ligands, for which the relative affinity is to be calculated, are explicitly present in the MD simulations associated with the (dual topology) FEP transformation, making the perturbation pathway between the two ligands univocal. We show that this generalized method can be applied to accurately estimate solvation free energies for amino acid sidechain mimics, as well as the binding affinity shifts due to the chemical changes typical of lead optimization processes. This is illustrated in a number of protein systems extracted from other FEP studies in the literature: inhibitors of CDK2 kinase and a series of A(2A) adenosine G protein-coupled receptor antagonists, where the results obtained with QligFEP are in excellent agreement with experimental data. In addition, our protocol allows for scaffold hopping perturbations to identify the binding affinities between different core scaffolds, which we illustrate with a series of Chk1 kinase inhibitors. QligFEP is implemented in the open-source MD package Q, and works with the most common family of force fields: OPLS, CHARMM and AMBER.

    Place, publisher, year, edition, pages
    BMC, 2019
    Keywords
    Free energy perturbation (FEP), Molecular dynamics (MD), Ligand binding, Application programming interface (API), Dual topology
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-382389 (URN)10.1186/s13321-019-0348-5 (DOI)000463589200001 ()30941533 (PubMedID)
    Funder
    Swedish Research CouncileSSENCE - An eScience Collaboration
    Available from: 2019-04-26 Created: 2019-04-26 Last updated: 2020-03-30Bibliographically approved
    2. QresFEP: An Automated Protocol for Free Energy Calculations of Protein Mutations in Q
    Open this publication in new window or tab >>QresFEP: An Automated Protocol for Free Energy Calculations of Protein Mutations in Q
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    2019 (English)In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 15, no 10, p. 5461-5473Article in journal (Refereed) Published
    Abstract [en]

    Predicting the effect of single-point mutations on protein stability or protein-ligand binding is a major challenge in computational biology. Free energy calculations constitute the most rigorous approach to this problem, though the estimation of converged values for amino acid mutations remains challenging. To overcome this limitation, we developed tailored protocols to calculate free energy shifts associated with single-point mutations. We herein describe the QresFEP protocol, which includes an extension of our recent protocols to cover all amino acids mutations, based on the latest versions of the OPLS-AA force field. QresFEP is implemented in an application programming interface framework and the graphic interface QGui, for the molecular dynamics software Q. The complete protocol is benchmarked in several model systems, optimizing a number of sampling parameters and the implementation of Zwanzig's exponential formula and Bennet's acceptance ratio methods. QresFEP shows an excellent performance on estimating the hydration free energies of amino acid side-chain mimics, including their charged analogues. We also examined its performance on a protein-ligand binding problem of pharmaceutical relevance, the antagonism of neuropeptide Y1 G protein-coupled receptor. Here, the calculations show very good agreement with the experimental effect of 16 mutations on the binding of antagonists BIBP3226, in line with our recent applications in this field. Finally, the characterization of 43 mutations of T4-lysozyme reveals the capacity of our protocol to assess variations of the thermal stability of proteins, achieving a similar performance to alternative free energy perturbation (FEP) approaches. In summary, QresFEP is a robust, versatile, and user-friendly computational FEP protocol to examine biochemical effects of single-point mutations with high accuracy.

    National Category
    Bioinformatics (Computational Biology)
    Identifiers
    urn:nbn:se:uu:diva-395642 (URN)10.1021/acs.jctc.9b00538 (DOI)000489678700026 ()31436990 (PubMedID)
    Funder
    The Research Council of Norway, 262695 274858Swedish Research CouncilKnut and Alice Wallenberg FoundationeSSENCE - An eScience Collaboration
    Available from: 2019-10-22 Created: 2019-10-22 Last updated: 2020-03-30Bibliographically approved
    3. Free energy calculations for protein-ligand binding prediction
    Open this publication in new window or tab >>Free energy calculations for protein-ligand binding prediction
    2020 (English)In: Protein-Ligand Interactions and Drug Design, Springer Nature, 2020Chapter in book (Other academic)
    Place, publisher, year, edition, pages
    Springer Nature, 2020
    National Category
    Bioinformatics (Computational Biology)
    Identifiers
    urn:nbn:se:uu:diva-407846 (URN)
    Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2020-05-20
    4. Structural Mapping of Adenosine Receptor Mutations: Ligand Binding and Signaling Mechanisms
    Open this publication in new window or tab >>Structural Mapping of Adenosine Receptor Mutations: Ligand Binding and Signaling Mechanisms
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    2018 (English)In: TIPS - Trends in Pharmacological Sciences, ISSN 0165-6147, E-ISSN 1873-3735, Vol. 39, no 1, p. 75-89Article, review/survey (Refereed) Published
    Abstract [en]

    The four adenosine receptors (ARs), A(1), A(2A), A(2B), and A(3), constitute a subfamily of G protein-coupled receptors (GPCRs) with exceptional foundations for structure-based ligand design. The vast amount of mutagenesis data, accumulated in the literature since the 1990s, has been recently supplemented with structural information, currently consisting of several inactive and active structures of the A(2A) and inactive conformations of the A(1) ARs. We provide the first integrated view of the pharmacological, biochemical, and structural data available for this receptor family, by mapping onto the relevant crystal structures all site-directed mutagenesis data, curated and deposited at the GPCR database (available through http://www.gpcrdb.org). This analysis provides novel insights into ligand binding, allosteric modulation, and signaling of the AR family.

    National Category
    Pharmacology and Toxicology Structural Biology
    Identifiers
    urn:nbn:se:uu:diva-347706 (URN)10.1016/j.tips.2017.11.001 (DOI)000418597900006 ()29203139 (PubMedID)
    Funder
    Swedish Research Council, 521-2014-2118European Regional Development Fund (ERDF)German Research Foundation (DFG), FOR2372
    Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2020-03-30Bibliographically approved
    5. Effect of Nitrogen Atom Substitution in A(3) Adenosine Receptor Binding: N-(4,6-Diarylpyridin-2-yl)acetamides as Potent and Selective Antagonists
    Open this publication in new window or tab >>Effect of Nitrogen Atom Substitution in A(3) Adenosine Receptor Binding: N-(4,6-Diarylpyridin-2-yl)acetamides as Potent and Selective Antagonists
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    2017 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 60, no 17, p. 7502-7511Article in journal (Refereed) Published
    Abstract [en]

    We report the first family of 2-acetamidopyridines as potent and selective A, adenosine receptor (AR) antagonists. The computer -assisted design was focused on the bioisosteric replacement of the N1 atom by a CH group in a previous series of diarylpyrimidines. Some of the generated 2-acetamidopyridines elicit an antagonistic effect with excellent affinity (K-j < 10 nM) and outstanding selectivity profiles, providing an alternative and simpler chemical scaffold to the parent series of diarylpyrimidines. In addition, using molecular dynamics and free energy perturbation simulations, we elucidate the effect of the second nitrogen of the parent diarylpyrimidines, which is revealed as a stabilizer of a water network in the binding site. The discovery of 2,6-diaryl-2-acetamidopyridines represents a step forward in the search of chemically simple, potent, and selective antagonists for the hA(3)AR, and exemplifies the benefits of a joint theoretical- experimental approach to identify novel hA(3)AR antagonists through succinct and efficient synthetic methodologies.

    Place, publisher, year, edition, pages
    American Chemical Society (ACS), 2017
    National Category
    Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:uu:diva-336483 (URN)10.1021/acs.jmedchem.7b00860 (DOI)000411171700020 ()28792759 (PubMedID)
    Available from: 2017-12-14 Created: 2017-12-14 Last updated: 2020-03-30Bibliographically approved
    6. 3,4-Dihydropyrimidin-2(1H)-ones as Antagonists of the Human A2B Adenosine Receptor: SAR Studies, Enantiospecific Recognition and Evidences of Antimetastatic Effect
    Open this publication in new window or tab >>3,4-Dihydropyrimidin-2(1H)-ones as Antagonists of the Human A2B Adenosine Receptor: SAR Studies, Enantiospecific Recognition and Evidences of Antimetastatic Effect
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    (English)In: Article in journal (Refereed) Submitted
    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-407849 (URN)
    Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2020-04-06
    7. Trifluorinated Pyrimidine-Based A(2B) Antagonists: Optimization and Evidence of Stereospecific Recognition
    Open this publication in new window or tab >>Trifluorinated Pyrimidine-Based A(2B) Antagonists: Optimization and Evidence of Stereospecific Recognition
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    2019 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 62, no 20, p. 9315-9330Article in journal (Refereed) Published
    Abstract [en]

    We report the identification of two subsets of fluorinated nonxanthine A(2B) adenosine receptor antagonists. The novel derivatives explore the effect of fluorination at different positions of two pyrimidine-based scaffolds. The most interesting ligands combine excellent hA(2B) affinity (K-i < 15 nM) and remarkable subtype selectivity. The results of functional cAMP experiments confirmed the antagonistic behavior of representative ligands. The compounds were designed on the basis of previous molecular models of the stereoselective binding of the parent scaffolds to the hA(2B) receptor, and we herein provide refinement of such models with the fluorinated compounds, which allows the explanation of the spurious effects of the fluorination at the different positions explored. These models are importantly confirmed by a synergistic study combining chiral HPLC, circular dichroism, diastereoselective synthesis, molecular modeling, and X-ray crystallography, providing experimental evidence toward the stereospecific interaction between optimized trifluorinated stereoisomers and the hA(2B) receptor.

    Place, publisher, year, edition, pages
    AMER CHEMICAL SOC, 2019
    National Category
    Medicinal Chemistry
    Identifiers
    urn:nbn:se:uu:diva-396965 (URN)10.1021/acs.jmedchem.9b01340 (DOI)000492801800027 ()31557025 (PubMedID)
    Funder
    Swedish Research CouncileSSENCE - An eScience Collaboration
    Available from: 2019-11-13 Created: 2019-11-13 Last updated: 2020-03-30Bibliographically approved
    8. The GPR139 reference agonists 1a and 7c, and tryptophan and phenylalanine share a common binding site
    Open this publication in new window or tab >>The GPR139 reference agonists 1a and 7c, and tryptophan and phenylalanine share a common binding site
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    2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1128Article in journal (Refereed) Published
    Abstract [en]

    GPR139 is an orphan G protein-coupled receptor expressed in the brain, in particular in the habenula, hypothalamus and striatum. It has therefore been suggested that GPR139 is a possible target for metabolic disorders and Parkinson's disease. Several surrogate agonist series have been published for GPR139. Two series published by Shi et al. and Dvorak et al. included agonists 1a and 7c respectively, with potencies in the ten-nanomolar range. Furthermore, Isberg et al. and Liu et al. have previously shown that tryptophan (Trp) and phenylalanine (Phe) can activate GPR139 in the hundred-micromolar range. In this study, we produced a mutagenesis-guided model of the GPR139 binding site to form a foundation for future structure-based ligand optimization. Receptor mutants studied in a Ca2+ assay demonstrated that residues F109(3x33), H187(5x43), W241(6x48) and N271(7x38), but not E108(3x32), are highly important for the activation of GPR139 as predicted by the receptor model. The initial ligand-receptor complex was optimized through free energy perturbation simulations, generating a refined GPR139 model in agreement with experimental data. In summary, the GPR139 reference surrogate agonists 1a and 7c, and the endogenous amino acids L-Trp and L-Phe share a common binding site, as demonstrated by mutagenesis, ligand docking and free energy calculations.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2017
    National Category
    Basic Medicine
    Identifiers
    urn:nbn:se:uu:diva-322726 (URN)10.1038/s41598-017-01049-z (DOI)000400104200017 ()28442765 (PubMedID)
    Funder
    Swedish Research Council
    Available from: 2017-05-29 Created: 2017-05-29 Last updated: 2020-03-30Bibliographically approved
    9. Structure-Based Design of Potent and Selective Ligands at the Four Adenosine Receptors
    Open this publication in new window or tab >>Structure-Based Design of Potent and Selective Ligands at the Four Adenosine Receptors
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    2017 (English)In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, no 11, article id 1945Article in journal (Refereed) Published
    Abstract [en]

    The four receptors that signal for adenosine, A(1), A(2A), A(2B) and A(3) ARs, belong to the superfamily of G protein-coupled receptors (GPCRs). They mediate a number of (patho)physiological functions and have attracted the interest of the biopharmaceutical sector for decades as potential drug targets. The many crystal structures of the A(2A), and lately the A(1) ARs, allow for the use of advanced computational, structure-based ligand design methodologies. Over the last decade, we have assessed the efficient synthesis of novel ligands specifically addressed to each of the four ARs. We herein review and update the results of this program with particular focus on molecular dynamics (MD) and free energy perturbation (FEP) protocols. The first in silico mutagenesis on the A(1)AR here reported allows understanding the specificity and high affinity of the xanthine-antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX). On the A(2A)AR, we demonstrate how FEP simulations can distinguish the conformational selectivity of a recent series of partial agonists. These novel results are complemented with the revision of the first series of enantiospecific antagonists on the A(2B)AR, and the use of FEP as a tool for bioisosteric design on the A(3)AR.

    Place, publisher, year, edition, pages
    MDPI AG, 2017
    Keywords
    free energy perturbation (FEP), G protein-coupled receptors (GPCRs), molecular dynamics (MD) simulations, structure-based drug design (SBDD)
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-344330 (URN)10.3390/molecules22111945 (DOI)000416528400145 ()
    Funder
    Swedish Research Council, 521-2014-2118eSSENCE - An eScience CollaborationEuropean Regional Development Fund (ERDF)
    Available from: 2018-03-08 Created: 2018-03-08 Last updated: 2020-03-30Bibliographically approved
    10. X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists
    Open this publication in new window or tab >>X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Bioinformatics (Computational Biology)
    Identifiers
    urn:nbn:se:uu:diva-407854 (URN)
    Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2020-03-30
    11. Predicting conformational selectivity in a prototypical GPCR
    Open this publication in new window or tab >>Predicting conformational selectivity in a prototypical GPCR
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Bioinformatics (Computational Biology)
    Identifiers
    urn:nbn:se:uu:diva-407855 (URN)
    Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2020-03-30
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  • Varenius, Malin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Applied Mathematics and Statistics.
    Using Hidden Markov Models to Beat OMXS302020Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • Patetsos Wikström, Maria
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Tjänstemannaansvar i kommunal verksamhet: en utredning om betydelsen av en utvidgning av tjänsteansvaret och huruvida kommunfullmäktige bör omfattas av det straffrättsliga ansvaret2020Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • Fredman, David
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Storlek, form och mönster: Om svenska domstolars bevisvärdering av sakkunniga vid blodbildsanalys2020Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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    Storlek, form och mönster
  • Hemmingsson, Isak
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics.
    Det är kul om det går bra!: En kvalitativ intervjustudie om matematik-elevers motivation2020Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • Ament-Velásquez, Sandra Lorena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Drivers of evolutionary change in Podospora anserina2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Genomic diversity is shaped by a myriad of forces acting in different directions. Some genes work in concert with the interests of the organism, often shaped by natural selection, while others follow their own interests. The latter genes are considered “selfish”, behaving either neutrally to the host, or causing it harm. In this thesis, I focused on genes that have substantial fitness effects on the fungus Podospora anserina and relatives, but whose effects are very contrasting. In Papers I and II, I explored the evolution of a particular type of selfish genetic elements that cause meiotic drive. Meiotic drivers manipulate the outcome of meiosis to achieve overrepresentation in the progeny, thus increasing their likelihood of invading and propagating in a population. In P. anserina there are multiple meiotic drivers but their genetic basis was previously unknown. In Paper I, we demonstrated that drive is caused by members of the Spok gene family. We discovered two new Spok genes, Spok3 and Spok4, which locate in different chromosomes in different strains. In Paper II, we showed that Spok3 and Spok4 are found on a gigantic (up to 247 Kb long) variant of Enterprise, a Crypton-like transposable element. Enterprise likely mobilize through the action of a putative tyrosine-recombinase that we call Kirc. When carrying the Spoks, this element has double selfish properties: transposition and meiotic drive. In addition, we found that homologs of the Spoks (Paper I) and of Kirc (Paper II) are widespread in fungi but their phylogenies are discordant with that of the species, suggesting that they have undergone horizontal gene transfer. In Papers III and IV, I turned the focus into genes that have an adaptive function. In fungi, the het genes control conspecific self/non-self recognition. Such genes are expected to evolve under frequency-dependent balancing selection. In Paper III, we found evidence of balancing selection acting on some het genes across the P. anserina species complex. Unexpectedly, we also discovered that het genes of the HNWD gene family are duplicated in a transposon-like manner, broadening our understanding of their potential fitness effects. Finally, in Paper IV we show how het genes with pleiotropic effects on sexual recognition lead to the evolution of strong reproductive isolation, and hence speciation. Overall, the results of my thesis highlight the functional intersection between mobile selfish genetic elements and other genes, either selfish or adaptive, and their effects on genome architecture and population structure.

    List of papers
    1. Combinations of Spok genes create multiple meiotic drivers in Podospora
    Open this publication in new window or tab >>Combinations of Spok genes create multiple meiotic drivers in Podospora
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    2019 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 8, article id e46454Article in journal (Refereed) Published
    Abstract [en]

    Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the Spok gene family underlies the Psks. The combination of Spok genes at different chromosomal locations defines the spore killer types and creates a killing hierarchy within a population. We identify two novel Spok homologs located within a large (74-167 kbp) region (the Spok block) that resides in different chromosomal locations in different strains. We confirm that the SPOK protein performs both killing and resistance functions and show that these activities are dependent on distinct domains, a predicted nuclease and kinase domain. Genomic and phylogenetic analyses across ascomycetes suggest that the Spok genes disperse through cross-species transfer, and evolve by duplication and diversification within lineages.

    Place, publisher, year, edition, pages
    ELIFE SCIENCES PUBLICATIONS LTD, 2019
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-391362 (URN)10.7554/eLife.46454 (DOI)000477678700001 ()31347500 (PubMedID)
    Funder
    EU, Horizon 2020, ERC-2014-CoGSwedish Research Council
    Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2020-03-28Bibliographically approved
    2. The Enterprise: A massive transposon carrying Spok meiotic drive genes
    Open this publication in new window or tab >>The Enterprise: A massive transposon carrying Spok meiotic drive genes
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The genomes of eukaryotes are full of parasitic sequences known as transposable elements (TEs). Most TEs studied to date are relatively small (50 — 12000 bp), but can contribute to very large proportions of genomes. Here we report the discovery of a giant tyrosine-recombinase-mobilized DNA transposon, Enterprise, from the model fungus Podospora anserina. Previously, we described a large genomic feature called the Spok block which is notable due to the presence of meiotic drive genes of the Spok gene family. The Spok block ranges from 110 kb to 247 kb and can be present in at least four different genomic locations within P. anserina, despite what is an otherwise highly conserved genome structure. We have determined that the reason for its varying positions is that the Spok block is not only capable of meiotic drive, but is also capable of transposition. More precisely, the Spok block represents a unique case where the Enterprise has captured the Spoks, thereby parasitizing a resident genomic parasite to become a genomic hyperparasite. Furthermore, we demonstrate that Enterprise (without the Spoks) is found in other fungal lineages, where it can be as large as 70 kb. Lastly, we provide experimental evidence that the Spok block is deleterious, with detrimental effects on spore production in strains which carry it. In contrast to the selfish role of the Enterprise in P. anserina, we speculate that the mobility of the Enterprise may also play an adaptive role in many other fungi, through the horizontal transfer of metabolic genes. This union of meiotic drivers and a transposon has created a selfish element of impressive size in Podospora, challenging our perception of how TEs influence genome evolution and broadening the horizons in terms of what the upper limit of transposition may be.

    Keywords
    Spok, Podospora, Transposable elements, Enterprise, meiotic drive, Fungi, spore killing
    National Category
    Evolutionary Biology
    Research subject
    Biology with specialization in Evolutionary Genetics
    Identifiers
    urn:nbn:se:uu:diva-406885 (URN)10.1101/2020.03.25.007153 (DOI)
    Available from: 2020-03-27 Created: 2020-03-27 Last updated: 2020-03-28
    3. The evolution of the allorecognition gene repertoire in the Podospora anserina species complex
    Open this publication in new window or tab >>The evolution of the allorecognition gene repertoire in the Podospora anserina species complex
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Across the Tree of Life, self/non-self recognition is typically achieved through highly polymorphic loci under balancing selection. In fungi, vegetative conspecific recognition, or allorecognition, is defined by the compatibility interactions between loci known as het genes. In this study we explore the evolution of the het genes in the model fungus Podospora anserina and its closest relatives (the Podospora anserina species complex). First, we used chromosome-level genome assemblies to resolve their phylogenetic relationships. We found that the species in the complex are well defined but diversified recently and rapidly, leading to high degrees of conflict at deep branches of the phylogeny. Unlike typical orthologous genes from the complex, some allorecognition genes (het-z and het-s) show trans-species polymorphism, a hallmark of long-term balancing selection. By contrast, the het genes belonging to the HNWD family exhibit a high turn-over, with losses and duplications happening often. In particular, the species P. pseudocomata has a considerable increase of HNWD genes. Unexpectedly, we show that the HNWD paralogs have clean defined boundaries flanked by a target site duplication (TSD), implicating a DNA transposon-like mechanism in the genesis of new duplicates. Overall, our data highlights the diversity of evolutionary histories behind individual self/non-self recognition genes at short evolutionary timescales.

    Keywords
    Podospora, Allorecognition, heterokaryon incompatibility, vegetative incompatibility, balancing selection, Transposable elements, NLRs
    National Category
    Evolutionary Biology
    Research subject
    Biology with specialization in Evolutionary Genetics
    Identifiers
    urn:nbn:se:uu:diva-406881 (URN)
    Available from: 2020-03-27 Created: 2020-03-27 Last updated: 2020-03-28
    4. Allorecognition genes drive reproductive isolation in Podospora anserina
    Open this publication in new window or tab >>Allorecognition genes drive reproductive isolation in Podospora anserina
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Allorecognition, the capacity to recognize self from conspecific non-self, is likely to influence the evolution of reproductive isolation. Pre- and post-zygotic reproductive barriers can result from an overlap between the genetic basis of sexual (in)compatibility and that of the recognition of non-self. In the model fungus Podospora anserina, the loci controlling vegetative incompatibility, or het genes, are associated with various degrees of sexual incompatibilities, including female sterility, hybrid inviability, and meiotic drive. Here, we use genomic data of a natural population to explore the effects of pleiotropic allorecognition genes on reproductive isolation and genetic differentiation. We show that the het genes in P. anserina display strong signatures of balancing selection, as expected from allorecognition loci, amongst a genomewide context of extremely low genetic diversity. We determine that mating success correlates to the identity of the locus het-v, which we characterize through positional and complementation cloning, as well as site-directed mutagenesis. The epistatic interaction of het-v alleles with the unlinked het-r gene defines the boundaries of two mating groups. We confirmed a significant deficit of recombinant genotypes in the wild, demonstrating the lack of current mixing despite substrate and temporal co-occurrence. Lastly, we use individual-based simulations to show how the interaction between selfing rates, balancing selection, and pre- and postzygotic barriers can result in maintenance of reproductively isolated groups in sympatry. We conclude that the het-r/v system not only contributes to speciation, but it directly defines reproductively isolated groups by equating vegetative recognition with sexual compatibility.

    Keywords
    Podospora, Genetics, Speciation, Reproductive isolation, allorecognition, heterokaryon incompatibility genes, vegetative incompatibility, balancing selection, selfing
    National Category
    Evolutionary Biology
    Research subject
    Biology with specialization in Systematics; Biology with specialization in Systematics; Biology with specialization in Evolutionary Genetics
    Identifiers
    urn:nbn:se:uu:diva-406878 (URN)
    Available from: 2020-03-27 Created: 2020-03-27 Last updated: 2020-03-29
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  • Larsson, Susanna C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Nobels Vag 13, SE-17177 Stockholm, Sweden.
    Bäck, Magnus
    Karolinska Inst, Ctr Mol Med, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Heart & Vasc Theme, Div Valvular & Coronary Dis, Stockholm, Sweden.
    Rees, Jessica M. B.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England;Univ Edinburgh, Inst Populat Hlth Sci & Informat, Edinburgh Clin Trials Unit, Edinburgh, Midlothian, Scotland.
    Mason, Amy M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Burgess, Stephen
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England;Univ Cambridge, MRC Biostat Unit, Cambridge, England.
    Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: a Mendelian randomization study2020In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 41, no 2, p. 221-226Article in journal (Refereed)
    Abstract [en]

    Aims: The causal role of adiposity for several cardiovascular diseases (CVDs) is unclear. Our primary aim was to apply the Mendelian randomization design to investigate the associations of body mass index (BMI) with 13 CVDs and arterial hypertension. We also assessed the roles of fat mass and fat-free mass on the same outcomes.

    Methods and results: Single-nucleotide polymorphisms associated with BMI and fat mass and fat-free mass indices were used as instru- and results mental variables to estimate the associations with the cardiovascular conditions among 367 703 UK Biobank participants. After correcting for multiple testing, genetically predicted BMI was significantly positively associated with eight outcomes, including and with decreasing magnitude of association: aortic valve stenosis, heart failure, deep vein thrombosis, arterial hypertension, peripheral artery disease, coronary artery disease, atrial fibrillation, and pulmonary embolism. The odds ratio (OR) per 1 kg/m(2) increase in BMI ranged from 1.06 [95% confidence interval (CI) 1.02-1.11; P=2.6 x 10(-3)] for pulmonary embolism to 1.13 (95% CI 1.05-1.21; P=1.2 x 10(-3)) for aortic valve stenosis. There was suggestive evidence of positive associations of genetically predicted fat mass index with nine outcomes (P < 0.05). The strongest magnitude of association was with aortic valve stenosis (OR per 1 kg/m(2) increase in fat mass index 1.46, 95% CI 1.13-1.88; P=3.9 x 10(-3)). There was suggestive evidence of inverse associations of fat-free mass index with atrial fibrillation, ischaemic stroke, and abdominal aortic aneurysm.

    Conclusion: This study provides evidence that higher BMI and particularly fat mass index are associated with increased risk of aortic valve stenosis and most other cardiovascular conditions.

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  • Gao, Ming
    et al.
    Guangxi Med Univ, Guangxi Engn Ctr Biomed Mat Tissue & Organ Regene, Affiliated Hosp 1, Nanning 530021, Peoples R China;Guangxi Med Univ, Guangxi Collaborat Innovat Ctr Biomed, Affiliated Hosp 1, Nanning 530021, Peoples R China.
    Yang, Yifeng
    Guangxi Med Univ, Guangxi Engn Ctr Biomed Mat Tissue & Organ Regene, Affiliated Hosp 1, Nanning 530021, Peoples R China;Guangxi Med Univ, Guangxi Collaborat Innovat Ctr Biomed, Affiliated Hosp 1, Nanning 530021, Peoples R China.
    Bergfelt, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Huang, Lanli
    Guangxi Med Univ, Pharmaceut Coll, Nanning 530021, Peoples R China.
    Zheng, Li
    Guangxi Med Univ, Guangxi Engn Ctr Biomed Mat Tissue & Organ Regene, Affiliated Hosp 1, Nanning 530021, Peoples R China;Guangxi Med Univ, Guangxi Collaborat Innovat Ctr Biomed, Affiliated Hosp 1, Nanning 530021, Peoples R China.
    Melander Bowden, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Self-assembly of cholesterol end-capped polymer micelles for controlled drug delivery2020In: Journal of Nanobiotechnology, ISSN 1477-3155, E-ISSN 1477-3155, Vol. 18, article id 13Article in journal (Refereed)
    Abstract [en]

    Background: During the past few decades, drug delivery system (DDS) has attracted many interests because it could enhance the therapeutic effects of drugs and reduce their side effects. The advent of nanotechnology has promoted the development of nanosized DDSs, which could promote drug cellular uptake as well as prolong the half-life in blood circulation. Novel polymer micelles formed by self-assembly of amphiphilic polymers in aqueous solution have emerged as meaningful nanosystems for controlled drug release due to the reversible destabilization of hydrophobic domains under different conditions.

    Results: The amphiphilic polymers presented here were composed of cholesterol groups end capped and poly (poly (ethylene glycol) methyl ether methacrylate) (poly (OEGMA)) as tailed segments by the synthesis of cholesterol-based initiator, followed by atom transfer radical polymerization (ATRP) with OEGMA monomer. FT-IR and NMR confirmed the successfully synthesis of products including initiator and polymers as well as the Mw of the polymers were from 33,233 to 89,088 g/mol and their corresponding PDI were from 1.25 to 1.55 by GPC. The average diameter of assembled polymer micelles was in hundreds nanometers demonstrated by DLS, AFM and SEM. The behavior of the amphiphilic polymers as micelles was investigated using pyrene probing to explore their critical micelle concentration (CMC) ranging from 2.53 x 10(-4) to 4.33 x 10(-4) mg/ml, decided by the balance between cholesterol and poly (OEGMA). Besides, the CMC of amphiphilic polymers, the quercetin (QC) feeding ratio and polarity of solvents determined the QC loading ratio maximized reaching 29.2% certified by UV spectrum, together with the corresponding size and stability changes by DLS and Zeta potential, and thermodynamic changes by TGA and DSC. More significantly, cholesterol end-capped polymer micelles were used as nanosized systems for controlled drug release, not only alleviated the cytotoxicity of QC from 8.6 to 49.9% live cells and also achieved the QC release in control under different conditions, such as the presence of cyclodextrin (CD) and change of pH in aqueous solution.

    Conclusions: The results observed in this study offered a strong foundation for the design of favorable polymer micelles as nanosized systems for controlled drug release, and the molecular weight adjustable amphiphilic polymer micelles held potential for use as controlled drug release system in practical application.

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  • Tossavainen, E.
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Cardiol, S-90185 Umea, Sweden.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Henein, M. Y.
    Umea Univ, Dept Publ Hlth & Clin Med, Cardiol, S-90185 Umea, Sweden.
    Lundqvist, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wiklund, U.
    Umea Univ, Dept Radiat Sci, Biomed Engn, Umea, Sweden.
    Lindqvist, P.
    Umea Univ, Dept Surg & Perioperat Sci, Clin Physiol, Umea, Sweden.
    Passive leg-lifting in heart failure patients predicts exercise-induced rise in left ventricular filling pressures2020In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 109, no 4, p. 498-507Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to assess PCWP with passive leg-lifting (PLL) and exercise, in two groups of patients presenting with normal left ventricular ejection fraction (LVEF); one group with elevated NT-proBNP (eBNP), and one with normal NT-proBNP (nBNP) plasma concentration.

    Methods and results: Fifty-one patients with eBNP (NT-proBNP >= 125 ng/l) and LVEF > 50%, were investigated and compared with 34 patients with nBNP (NT-proBNP < 125 ng/l) and LVEF > 50%. Both groups underwent right heart catheterization (RHC) at rest, PLL and exercise. From RHC, mean pulmonary arterial pressure (mPAP), cardiac output (CO), and PCWP were measured. All nBNP patients had PCWP < 15 mmHg at rest, and a PCWP of < 25 mmHg with PLL and during exercise. Patients with eBNP had higher (p < 0.01) resting mPAP, PCWP, and mPAP/CO. These values increased with exercise; however, CO increased less in comparison with nBNP patients (p = 0.001). 20% of patients with eBNP had a PCWP > 15 mmHg at rest, this percentage increased to 47% with PLL and 41% had a PCWP > 25 mmHg during exercise. Of those with PCWP > 25 mmHg during exercise, 91% had a PCWP > 15 mmHg with PLL. A PCWP > 15 mmHg on PLL had a 91% sensitivity and 92% specificity in predicting exercise-induced PCWP of > 25 mmHg.

    Conclusion: In patients presenting with eBNP, PLL can predict which patients will develop elevated PCWP with exercise. These findings highlight the role of stress assessment.

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  • Cross, Ellen
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Media and Communication Studies.
    Det dolda sociala spelet: En kvalitativ studie om digitala handlingar på Instagram2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of the study is to analyze how 18 year old Instagram users experience the strategic social interaction, which can be seen as a digital interaction online while using Instagram application. The main focus was to se how it affects and influences social life outside the digital sphere.   

    The study consists of two focus groups with a total of eight young secondary upper school students. This method worked out with reality-based scenarios based on Instagram, which we in our study refer to as “cases”. With the case the young students discussed their thoughts, opinions and ideas. In addition to the focus groups, the study was supplemented with two interviews. A total of three theories were used to analyze the material; Pierre Bourdieu's Habitus and social capital, Jay Blumer and Denis McQuails Uses and Gratification and Anja Hirdman's perspectives on gender in society and in digital media. 

    The result showed that 18 years old users tend to strategically use different combinations at the platform Instagram to influence their social life - the social room, a sphere that involves people in the real life (meetings). The fact that young people are affected both positively and negatively was also evident. Instagram can be seen as an interconnection tool but also a source of inspiration where you can escape your reality. However, all participants were aware that those who exist on the platform are exaggerated and far from reality. 

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  • Hellman, Jörgen
    University of Gothenburg.
    Witnessing Anthropological Journeys, and the Returns: A Report from the 2019 Vega Symposium2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 191-194Article in journal (Other academic)
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  • Friberg, Torbjörn
    Malmö University.
    Harmonization and Ethnographic Critique in the Context of Innovation Politics2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 175-190Article in journal (Refereed)
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  • Dahl, Gudrun
    Stockholm University.
    About the Moralities of the Commons in the East African Cattle Economy2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 159-173Article in journal (Refereed)
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  • Hagberg, Sten
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Cultural Anthropology and Ethnology.
    The Rise and Fall of a Political Party: Handling Political Failure in Municipal Elections in Burkina Faso2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 141-156Article in journal (Refereed)
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  • Jennische, Ulrik
    Stockholm University.
    Divisive Democracy, Urban Trade, and Small-Small Politics in Northern Ghana2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 125-140Article in journal (Refereed)
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  • Ekoluoma, Mari-Elina
    Stockholm University.
    Local Politics in Controlling Commercial Sex in a Philippine Municipality2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 111-124Article in journal (Refereed)
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  • Balasubramaniam, Madhura
    et al.
    Indian Institute of Technology, Madras.
    Gupta, Sonika
    Indian Institute of Technology, Madras.
    From Refuge to Rights: Majnu ka Tilla Tibetan Colony in New Delhi2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 95-110Article in journal (Refereed)
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  • Hagberg, Sten
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Cultural Anthropology and Ethnology.
    Koné, Bintou
    Institut des Sciendes Humaines, Mali.
    Diaspora-Driven Development and Dispute: Home-Area Associations and Municipal Politics in Mali2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 81-93Article in journal (Refereed)
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  • Körling, Gabriella
    et al.
    Stockholm University.
    Moussa Ibrahima, Hassane
    LASDEL.
    “Tout a été loti!”: Decentralisation, Land Speculation and Urban Expansion in Niamey, Niger2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 67-79Article in journal (Refereed)
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  • Baral, Anna
    Århus University.
    “Like the Chicken and the Egg”: Market Vendors and the Dilemmas of Neoliberal Urban Planning in Re-Centralised Kampala (Uganda)2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 51-66Article in journal (Refereed)
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  • Widmark, Charlotta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Cultural Anthropology and Ethnology.
    Political Gender Dilemmas of Conflict and Complementarity in Bolivia: Quotas, Resistance and Parallelism2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, Vol. 2, no 1-2, p. 33-49Article in journal (Refereed)
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  • Antlöv, Hans
    FHI 360, Jakarta.
    Community Development and the Third Wave of Decentralisation in Indonesia: The Politics of the 2014 Village Law2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, ISSN 2003-1173, Vol. 2, no 1-2, p. 17-31Article in journal (Refereed)
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  • Hagberg, Sten
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Cultural Anthropology and Ethnology.
    Introduction: Comparative Municipal Ethnographies2019In: kritisk etnografi: Swedish Journal of Anthropology, ISSN 2003-1173, ISSN 2003-1173, Vol. 2, no 1-2, p. 9-15Article in journal (Refereed)
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  • O'Rourke Brogan, Roisín
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    AGN Candidates for High Energy Neutrino Emission in IceCube2020Independent thesis Advanced level (degree of Master (Two Years)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Since the construction of the IceCube Neutrino Observatory was completed in 2010, many amazing discoveries have been made in the field of neutrino physics. Recently a neutrino event has been linked to an blazar-type active galactic nucleus source, bringing us one step closer to understanding the production of high-energy extragalactic neutrinos and ushering in a new era of multimessenger astronomy. This was found by linking the neutrino event to one of the Fermi Collaboration’s gamma ray sources which had a blazar counterpart. The quest to link other neutrino events to AGN (active galactic nuclei) sources through collaboration with the Fermi Large Area Telescope has turned up some interesting candidates. The fact that some of these potential sources are not blazars is curious and, although unconfirmed as neutrino sources, these objects merit further investigation due to their unusual nature.

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  • Holmsved, Love
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Electrical Engineering, Electricity.
    Kartläggning och modellering av tjänster levererade av elnätsanslutna energilager2020Independent thesis Basic level (Higher Education Diploma (Fine Arts)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This study has examined what services grid-connected energy storage systems can provide to the electricity grid in Sweden. In particular, energy storages in the form of batteries have been examined. This has been done by studying existing literature and current installations of grid-connected batteries. A total of 13 different services were identified: arbitrage, capacity firming, curtailment minimization, electric supply capacity, black start, frequency regulation, voltage support, transmission and distribution congestion relief, reduced transmission grid costs, increase of self consumption, end-consumer power quality, time-of-use bill management and backup power. Furthermore, a grid-connected battery storage system that will be installed by Vattenfall was modelled and simulated in this paper. The results showed that the battery storage system can mitigate congestion in the transmission grid, as well as providing the grid with frequency regulation. This can generate a revenue of 3 million SEK annually.

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  • Lutnaes, Carl
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Electrical Engineering, Signals and Systems.
    Beamforming in 5G mm-wave radionetworks: Importance of frequency multiplexing for users in urban macro environments2020Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    5G brings a few key technological improvements compared to previous generations in telecommunications. These include, but are not limited to, greater speeds, increased capacity and lower latency. These improvements are in part due to using high band frequencies, where increased capacity is found. By advancements in various technologies, mobile broadband traffic has become increasingly chatty, i.e. more small packets are being sent. From a capacity standpoint this characteristic poses a challenge for early 5G millimeter-wave advanced antenna systems. This thesis investigates if network performance of 5G millimetre-wave systems can be improved by increasing the utilisation of the bandwidth by using adaptive beamforming. Two adaptive codebook approaches are proposed; a single- beam and a multi-beam approach. The simulations are performed in an outdoor urban macro scenario. The results show that for a small packet scenario with good coverage the ability to frequency multiplex users is important for good network performance.

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    Lutnaes, C. (2020). Beamforming in 5G mm-wave radio networks: importance of frequency multiplexing for users in urban macro environments
  • Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Åberg, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Neuhaus, Dominique
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Ferguson, Stephen J.
    Öhman, Caroline
    Helgason, Benedikt
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Mechanical behaviour of composite calcium phosphate-titanium cranial implants: Effects of loading rate and design2020In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 104, article id 103701Article in journal (Refereed)
    Abstract [en]

    Cranial implants are used to repair bone defects following neurosurgery or trauma. At present, there is a lack of data on their mechanical response, particularly in impact loading. The aim of the present study was to assess the mechanical response of a recently developed composite calcium phosphate-titanium (CaP-Ti) implant at quasi-static and impact loading rates. Two different designs were tested, referred to as Design 1 (D1) and Design 2 (D2). The titanium structures in the implant specimens were additively manufactured by a powder-bed fusion process and subsequently embedded in a self-setting CaP material. D1 was conceptually representative of the clinically used implants. In D2, the titanium structure was simplified in terms of geometry in order to facilitate the manufacturing. The mechanical response of the implants was evaluated in quasi-static compression, and in impact using a drop-tower. Similar peak loads were obtained for the two designs, at the two loading rates: 808 ± 29 N and 852 ± 34 for D1, and 840 ± 40 N and 814 ± 13 for D2. A strain rate dependency was demonstrated for both designs, with a higher stiffness in the impact test. Furthermore, the titanium in the implant fractured in the quasi-static test (to failure) but not in the impact test (to 5.75 J) for D1. For D2, the displacement at peak load was significantly lower in the impact test than in the quasi-static test. The main difference between the designs was seen in the quasi-static test results where the deformation zones, i.e. notches in the titanium structure between the CaP tiles, in D1 likely resulted in a localization of the deformation, compared to in D2 (which did not have deformation zones). In the impact test, the only significant difference between the designs was a higher maximum displacement of D2 than of D1. In comparison with other reported mechanical tests on osteoconductive ceramic-based cranial implants, the CaP-Ti implant demonstrates the highest reported strength in quasi-static compression. In conclusion, the titanium structure seems to make the CaP-Ti implant capable of cerebral protection in impact situations like the one tested in this study.

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  • Matti, Salam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Behandlas analgetikainducerad huvudvärk bäst medavbrytande av analgetikabehandling?2020Independent thesis Advanced level (degree of Master (Two Years)), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Introduktion: Överanvändning av all analgetika både som monoterapi eller i kombination är ofta associerad med utveckling av en sekundär huvudvärk även kallad läkemedelsinducerad huvudvärk(MOH). Huvudvärk i sig kan behandlas på egenhand och smärtstillande läkemedel köps receptfritt. Analgetikaanvändning, missbruk och överanvändning representerar större hälsoproblem förknippade med flera negativa hälsokonsekvenser som läkemedelsinducerad huvudvärk, högre blodtryck och hjärt- och kärlsjukdomar. MOH definieras som en kronisk huvudvärksstörning vilket innebär en huvudvärk som förekommer under mer än 15 dagar per månad under mer än tre månader i sträck i kombination med en överanvändning av analgetika definierat som analgetikaintag under mer än 15 dagar i månaden under minst tre månader

    Metod: En systematisk litteratursökning utfördes i databaserna PubMed och CINAHL. Relevanta studietyper var randomiserade studier, systematiska översikter och kohortstudier. Studierna relevans- och kvalitetsgranskades med hjälp av granskningsmallar från Statens beredning för medicinsk och social utvärdering.

    Syfte: Syftet med projektet var att undersöka vilka evidens det finns för behandling av MOH med hjälp av olika tilläggsbehandlingar jämfört med att bara sätta ut analgetikan.

    Resultat: 10 studier inkluderades i projektet. Det framkom att tilläggsbehandlingar med prednisolon, celecoxib, botulinumtoxin och paracetamol inte ger stora fördelar jämfört med att sätta ut det överanvända läkemedlet. Tilläggsbehandlingar gav främst en minskning av biverkningar vid MOH när man sätter ut analgetikan. Istället var utbildning av patienter och motivering en stor bidragande faktor till att få patienter att avsluta sin överanvändning och därmed bota sin MOH. Utbildning gjorde att patienter minskade sina huvudvärksdagar per månad samt antal medicinerings dagar per månad utan att få tilläggsbehandling.

    Slutsats:Slutsatsen som kan dras av studien är att de tilläggsbehandlingar som har provats under dessa studier inte ger en tydlig förbättring av MOH utan bara symtom lindring och att enbart få patienten att förstå sjukdomen kan vara det sättet man bör gå tillväga för att bota MOH.

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  • Åberg, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Civil and Industrial Engineering, Civil Engineering and Built Environment.
    Fälting, Lars
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economic History.
    Förekomst av lärstilar hos studenter på Uppsala universitets tre vetenskapsområden: en strukturell analys2019Report (Other academic)
    Abstract [sv]

    Utgångspunkten i det här projektet är att undervisningsformer används i olika stor utsträckning inom olika vetenskapsdiscipliner samt att det finns skillnader i hur studenter föredrar att lära sig. Frågan vi ställer oss är om det finns ett tydligt samband mellan undervisningsform och inlärningspreferens, samt om det i så fall skulle kunna användas vid utformning av undervisning. Med hjälp av en enkätstudie baserad på en etablerad men även kritiserad teori om förekomst av lärstilar, kartläggs lärstilsprofiler hos studenter vid Uppsala universitets tre vetenskapsområden. Resultaten visar på skillnader i hur studenter uppfattar att de bäst lär sig, samt skillnader i förekomst av lärstilar hos studenter vid olika vetenskapsområden. Men resultaten visar också på svårigheter med att identifiera tydliga lärstilsprofiler. Det på ett sätt som styrker kritiken mot idén om att inlärningspreferenser är statiska och går att kategorisera på det sätt som teorin gör gällande. Vi anser därför att det är problematiskt att utgå från lärstilskonceptet vid utformning av undervisning.

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  • Munkhammar, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Civil and Industrial Engineering, Civil Engineering and Built Environment.
    Enhancing creative and critical thinking with open problems in engineering sciences: an example from solar energy2020Report (Other academic)
    Abstract [en]

    The use of open problems in engineering sciences is analysed from a case study perspective for a solar energy course with open problems in a computer lab and a written exam. The open problems are evaluated from the perspective of creative and critical thinking, and a set of guidelines for design of open ended questions is made.

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  • Marattukalam, Jithin J.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Pacheco, Victor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
    Karlsson, Dennis
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
    Riekehr, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
    Lindwall, Johan
    Forsberg, Fredrik
    Jansson, Ulf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
    Sahlberg, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
    Hjörvarsson, Björgvin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics. Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Development of process parameters for selective laser melting of a Zr-based bulk metallic glass2020In: Additive Manufacturing, ISSN 2214-8604, Vol. 33, article id 101124Article in journal (Refereed)
    Abstract [en]

    Parameters for selective laser melting of Zr59.3Cu28.8Al10.4Nb1.5 (trade name AMZ4), allowing crack-free bulk metallic glass with low porosity, have been developed. The phase formation was found to be strongly influenced by the heating power of the laser. X-ray amorphous samples were obtained with laser power at and below 75 W. The as-processed bulk metallic glass was found to devitrify by a two-stage crystallization process within which the presence of oxygen was concluded to play an essential role. At laser powers above 75 W, the observed crystallites were found to be a cubic phase (Cu2Zr4O). The hardness and Young’s modulus in the as-processed samples was found to increase marginally with increased fraction of the crystalline phase.

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  • af Geijerstam, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Folkeryd, Jenny
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Utveckling av metaspråk för tidigt skolskrivande2020In: Grænsegængere og grænsedragninger i nordiska modersmålsfag / [ed] N. Elf, T. Høegh, K. Kabel, E. Krogh, A. Piekut, & H. Rørbech, Odense: Syddansk Universitetsforlag, 2020, p. 277-295Chapter in book (Refereed)
    Abstract [sv]

    I kapitlet undersöks och diskuteras metaspråkets roll för att lärare ska kunna diskutera elevers texter, och i förlängningen kunna skapa goda förutsättningar för alla elevers utveckling av olika typer av skrivande. Lärares samtal om informativa texter skrivna i tidiga skolår undersöktes. Samtalen fördes före och efter en fortbildning om språkliga resurser för att uttrycka, fördjupa och skapa ett sammanhängande innehåll samt för att skapa en relation till en läsare. Den största skillnaden mellan lärarnas samtal före och efter fortbildningen fanns i samtal om hur texterna relaterar till en läsare, där en stor ökning av den metaspråkliga repertoaren syntes. I avslutande textdiskussioner utvecklar lärare också de metaspråkliga begreppen i högre grad genom exemplifieringar och förklaringar i relation till den text som kommenteras, vilket tyder på att metaspråket börjar systematiseras.

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  • Adlarson, Patrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Augustyniak, W.
    Natl Ctr Nucl Res, Dept Nucl Phys, Ul Pasteura 7, PL-02093 Warsaw, Poland..
    Bardan, W.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Bashkanov, M.
    Univ Edinburgh, Sch Phys & Astron, James Clerk Maxwell Bldg,Peter Guthrie Tait Rd, Edinburgh EH9 3FD, Midlothian, Scotland..
    Bass, S. D.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland.;Kitzbuhel Ctr Phys, Kitzbuhel, Austria..
    Berlowski, M.
    Natl Ctr Nucl Res, High Energy Phys Dept, Ul Pasteura 7, PL-02093 Warsaw, Poland..
    Bondar, A.
    RAS, Budker Inst Nucl Phys SB, 11 Akad Lavrentieva Prospect, Novosibirsk 630090, Russia.;Novosibirsk State Univ, 2 Pirogova Str, Novosibirsk 630090, Russia..
    Buescher, M.
    Forschungszentrum Julich, PGI 6 Elektron Eigenschaften, Peter Grunberg Inst, D-52425 Julich, Germany.;Heinrich Heine Univ Dusseldorf, Inst Laser & Plasmaphys, Univ Str 1, D-40225 Dusseldorf, Germany..
    Calén, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Ciepal, I.
    Polish Acad Sci, Henryk Niewodniczanski Inst Nucl Phys, 152 Radzikowskiego St, PL-31342 Krakow, Poland..
    Clement, H.
    Eberhard Karls Univ Tubingen, Phys Inst, Morgenstelle 14, D-72076 Tubingen, Germany.;Univ Tubingen, Phys Inst, Kepler Ctr Astro & Teilchenphys, Morgenstelle 14, D-72076 Tubingen, Germany..
    Czerwinski, E.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Engels, R.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Erven, A.
    Forschungszentrum Julich, Zentralinst Engn Elekt & Analyt, D-52425 Julich, Germany..
    Erven, W.
    Forschungszentrum Julich, Zentralinst Engn Elekt & Analyt, D-52425 Julich, Germany..
    Eyrich, W.
    Friedrich Alexander Univ Erlangen Nurnberg, Phys Inst, Erwin Rommel Str 1, D-91058 Erlangen, Germany..
    Fedorets, P.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany.;Natl Res Ctr Kurchatov Inst, Inst Theoret & Expt Phys, 25 Bolshaya Cheremushkinskaya, Moscow 117218, Russia..
    Foehl, K.
    Justus Liebig Univ Giessen, Phys Inst 2, Heinrich Buff Ring 16, D-35392 Giessen, Germany..
    Fransson, Kjell
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Goldenbaum, F.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Goswami, A.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany.;Indian Inst Technol Indore, Dept Phys, Khandwa Rd, Indore 453552, Madhya Pradesh, India..
    Grigoryev, K.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics. Natl Res Ctr Kurchatov Inst, Petersburg Nucl Phys Inst, High Energy Phys Dept, 1 Mkr Orlova Roshcha, Gatchina 188300, Russia..
    Heijkenskjöld, Lena
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics. Johannes Gutenberg Univ Mainz, Inst Kernphys, Johann Joachim Becher Weg 45, D-55128 Mainz, Germany..
    Hejny, V.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Hirenzaki, S.
    Nara Womens Univ, Dept Phys, Nara 6308506, Japan..
    Jarczyk, L.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Johansson, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Kamys, B.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Kelkar, N. G.
    Univ Los Andes, Dept Fis, Cra 1E,18A-10, Bogota, Colombia..
    Kemmerling, G.
    Forschungszentrum Julich, Zentralinst Engn Elekt & Analyt, D-52425 Julich, Germany.;Forschungszentrum Julich, JCNS, D-52425 Julich, Germany..
    Khreptak, A.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Kirillov, D. A.
    Joint Inst Nucl Phys, Veksler & Baldin Lab High Energiy Phys, Dubna 141980, Russia..
    Kistryn, S.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Kleines, H.
    Forschungszentrum Julich, Zentralinst Engn Elekt & Analyt, D-52425 Julich, Germany.;Forschungszentrum Julich, JCNS, D-52425 Julich, Germany..
    Klos, B.
    Univ Silesia, August Chelkowski Inst Phys, Uniwersytecka 4, PL-40007 Katowice, Poland..
    Krzemien, W.
    Natl Ctr Nucl Res, High Energy Phys Div, PL-05400 Otwock, Poland..
    Kulessa, P.
    Polish Acad Sci, Henryk Niewodniczanski Inst Nucl Phys, 152 Radzikowskiego St, PL-31342 Krakow, Poland..
    Kupsc, Andrzej
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics. Natl Ctr Nucl Res, High Energy Phys Dept, Ul Pasteura 7, PL-02093 Warsaw, Poland..
    Lalwani, K.
    Malaviya Natl Inst Technol Jaipur, Dept Phys, JLN Marg, Jaipur 302017, Rajasthan, India..
    Lersch, D.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany.;Florida State Univ, Dept Phys, 77 Chieftan Way, Tallahassee, FL 32306 USA..
    Lorentz, B.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Magiera, A.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Maier, R.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany.;Forschungszentrum Julich, JARA FAME, Julich Aachen Res Alliance, D-52425 Julich, Germany.;Rhein Westfal TH Aachen, D-52056 Aachen, Germany..
    Marciniewski, Pawel
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Marianski, B.
    Natl Ctr Nucl Res, Dept Nucl Phys, Ul Pasteura 7, PL-02093 Warsaw, Poland..
    Morsch, H. -P
    Moskal, P.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Ohm, H.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Parol, W.
    Polish Acad Sci, Henryk Niewodniczanski Inst Nucl Phys, 152 Radzikowskiego St, PL-31342 Krakow, Poland..
    del Rio, E. Perez
    Eberhard Karls Univ Tubingen, Phys Inst, Morgenstelle 14, D-72076 Tubingen, Germany.;Univ Tubingen, Phys Inst, Kepler Ctr Astro & Teilchenphys, Morgenstelle 14, D-72076 Tubingen, Germany.;INFN, Lab Nazl Frascati, Via E Fermi 40, I-00044 Frascati, Roma, Italy..
    Piskunov, N. M.
    Joint Inst Nucl Phys, Veksler & Baldin Lab High Energiy Phys, Dubna 141980, Russia..
    Prasuhn, D.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Pszczel, Damian
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics. Natl Ctr Nucl Res, High Energy Phys Dept, Ul Pasteura 7, PL-02093 Warsaw, Poland..
    Pysz, K.
    Polish Acad Sci, Henryk Niewodniczanski Inst Nucl Phys, 152 Radzikowskiego St, PL-31342 Krakow, Poland..
    Ritman, J.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany.;Forschungszentrum Julich, JARA FAME, Julich Aachen Res Alliance, D-52425 Julich, Germany.;Rhein Westfal TH Aachen, D-52056 Aachen, Germany.;Ruhr Univ Bochum, Inst Expt Phys 1, Univ Str 150, D-44780 Bochum, Germany..
    Roy, A.
    Indian Inst Technol Indore, Dept Phys, Khandwa Rd, Indore 453552, Madhya Pradesh, India..
    Rundel, O.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Sawant, S.
    Indian Inst Technol, Dept Phys, Mumbai 400076, Maharashtra, India..
    Schadmand, S.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Schatti-Ozerianska, I.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Sefzick, T.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Serdyuk, V.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Shwartz, B.
    RAS, Budker Inst Nucl Phys SB, 11 Akad Lavrentieva Prospect, Novosibirsk 630090, Russia.;Novosibirsk State Univ, 2 Pirogova Str, Novosibirsk 630090, Russia..
    Skorodko, T.
    Eberhard Karls Univ Tubingen, Phys Inst, Morgenstelle 14, D-72076 Tubingen, Germany.;Univ Tubingen, Phys Inst, Kepler Ctr Astro & Teilchenphys, Morgenstelle 14, D-72076 Tubingen, Germany.;Tomsk State Univ, Dept Phys, 36 Lenina Ave, Tomsk 634050, Russia..
    Skurzok, M.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland.;INFN, Lab Nazl Frascati, Via E Fermi 40, I-00044 Frascati, Roma, Italy..
    Smyrski, J.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Sopov, V.
    Natl Res Ctr Kurchatov Inst, Inst Theoret & Expt Phys, 25 Bolshaya Cheremushkinskaya, Moscow 117218, Russia..
    Stassen, R.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Stepaniak, J.
    Natl Ctr Nucl Res, High Energy Phys Dept, Ul Pasteura 7, PL-02093 Warsaw, Poland..
    Stephan, E.
    Univ Silesia, August Chelkowski Inst Phys, Uniwersytecka 4, PL-40007 Katowice, Poland..
    Sterzenbach, G.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Stockhorst, H.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany..
    Stroeher, H.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany.;Forschungszentrum Julich, JARA FAME, Julich Aachen Res Alliance, D-52425 Julich, Germany.;Rhein Westfal TH Aachen, D-52056 Aachen, Germany..
    Szczurek, A.
    Polish Acad Sci, Henryk Niewodniczanski Inst Nucl Phys, 152 Radzikowskiego St, PL-31342 Krakow, Poland..
    Trzcinski, A.
    Natl Ctr Nucl Res, Dept Nucl Phys, Ul Pasteura 7, PL-02093 Warsaw, Poland..
    Wolke, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Wronska, A.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Wuestner, P.
    Forschungszentrum Julich, Zentralinst Engn Elekt & Analyt, D-52425 Julich, Germany..
    Yamamoto, A.
    High Energy Accelerator Res Org KEK, Tsukuba, Ibaraki 3050801, Japan..
    Zabierowski, J.
    Natl Ctr Nucl Res, Dept Astrophys, PL-90950 Lodz, Poland..
    Zielinski, M. J.
    Jagiellonian Univ, Inst Phys, Prof Stanislawa Lojasiewicza 11, PL-30348 Krakow, Poland..
    Zlomanczuk, Jozef
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Zupranski, P.
    Natl Ctr Nucl Res, Dept Nucl Phys, Ul Pasteura 7, PL-02093 Warsaw, Poland..
    Zurek, M.
    Forschungszentrum Julich, Inst Kernphys, D-52425 Julich, Germany.;Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA..
    Search for η mesic 3He with the WASA-at-COSY facility in the pd -> 3He2γ and pd -> 3He6γ  reaction2020In: Physics Letters B, ISSN 0370-2693, E-ISSN 1873-2445, Vol. 802, article id 135205Article in journal (Refereed)
    Abstract [en]

    We report on the experimental search for the bound state of an eta meson and He-3 nucleus performed using the WASA-at-COSY detector setup. In order to search for the eta-mesic nucleus decay, the pd -> (3)He2(gamma) and pd -> (3)He6 gamma channels have been analysed. These reactions manifest the direct decay of the ti meson bound in a He-3 nucleus. This non-mesonic decay channel has been considered for the first time. When taking into account only statistical errors, the obtained excitation functions reveal a slight indication for a possible bound state signal corresponding to a He-3-eta nucleus width Gamma above 20 MeV and binding energy B-s between 0 and 15 MeV. However, the determined cross sections are consistent with zero in the range of the systematic uncertainty. Therefore, as final result we estimate only the upper limit for the cross section of the eta-mesic He-3 nucleus formation followed by the eta meson decay which varies between 2 nb and 15 nb depending on possible bound state parameters.

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  • Aaboud, M.
    et al.
    LPTPM, Oujda, Morocco;Univ Mohamed Premier, Fac Sci, Oujda, Morocco.
    Asimakopoulou, Eleni M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bergeås Kuutmann, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bokan, Petar
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Gradin, P. O. Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Isacson, Max
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Mårtensson, Mikael U. F.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Sales De Bruin, Pedro
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    CERN, Geneva, Switzerland.
    Z boson production in Pb+Pb collisions at √SNN=5.02 TeV measured by the ATLAS experiment2020In: Physics Letters B, ISSN 0370-2693, E-ISSN 1873-2445, Vol. 802, article id 135262Article in journal (Refereed)
    Abstract [en]

    The production yield of Z bosons is measured in the electron and muon decay channels in Pb+Pb collisions at /S-NN = 5.02 TeV with the ATLAS detector. Data from the 2015 LHC run corresponding to an integrated luminosity of 0.49 nb(-1) are used for the analysis. The Z boson yield, normalised by the total number of minimum-bias events and the mean nuclear thickness function, is measured as a function of dilepton rapidity and event centrality. The measurements in Pb+Pb collisions are compared with similar measurements made in proton-proton collisions at the same centre-of-mass energy. The nuclear modification factor is found to be consistent with unity for all centrality intervals. The results are compared with theoretical predictions obtained at next-to-leading order using nucleon and nuclear parton distribution functions. The normalised Z boson yields in Pb+Pb collisions lie 1-3a above the predictions. The nuclear modification factor measured as a function of rapidity agrees with unity and is consistent with a next-to-leading-order QCD calculation including the isospin effect. (C) 2020 The Author(s). Published by Elsevier B.V.

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  • Sayed, F.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering.
    Kotnana, Ganesh
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Solid State Physics.
    Barucca, G.
    Univ Politecn Marche, Dept SIMAU, Via Brecce Bianche, I-60131 Ancona, Italy.
    Muscas, G.
    Univ Cagliari, Dept Phys, Cittadella Univ Monserrato, SP 8 Km 0-700 Monserrato Sestu, I-09042 Monserrato, CA, Italy.
    Peddis, D.
    Univ Genoa, Dipartimento Chim & Chim Ind, Via Dodecaneso 31, I-16146 Genoa, Italy;Ist Struttura Mat CNR, Area Ric Romal, I-00015 Monterotondo, RM, Italy.
    Mathieu, Roland
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Solid State Physics.
    Sarkar, Tapati
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Solid State Physics.
    LaFeO3-CoFe2O4 bi-magnetic composite thin films prepared using an all-in-one synthesis technique2020In: Journal of Magnetism and Magnetic Materials, ISSN 0304-8853, E-ISSN 1873-4766, Vol. 503, article id 166622Article in journal (Refereed)
    Abstract [en]

    Bi-phasic composite films are generally grown as multilayers that result in layer-by-layer morphology with each layer having a distinct chemical composition. In this work, we report an all-in-one chemical synthesis technique combined with spin-coating to prepare single-layer bi-magnetic LaFeO3 (LFO)-CoFe2O4 (CFO) composite thin films with both phases co-existing in the same layer. The films have been characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM), and the magnetic properties have been probed using dc magnetometry at room and low temperature. The unique synthesis technique followed ensures homogeneity of the two phases on the nanoscale with grain sizes similar to 10 nm for CFO and few tens of nm for LFO, as observed from TEM images. XRD confirms the presence of only the desired LFO and CFO phases in the films without any undesired secondary phases. Magnetic hysteresis loops reveal a coercivity of similar to 0.2 T at room temperature that increases by nearly one order of magnitude at T = 5 K. The all-in-one synthesis technique reported here can be used to prepare different bi-phasic composites in the form of single-layer two-dimensional films as well as zero-dimensional nanoparticles by a suitable modification of the precursors, solvents, and chelating agents.

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  • Aad, G.
    et al.
    Aix Marseille Univ, IN2P3, CNRS, CPPM, Marseille, France.
    Asimakopoulou, Eleni M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bergeås Kuutmann, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bokan, Petar
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics. Georg August Univ Gottingen, Phys Inst 2, Gottingen, Germany.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellajosyula, Venugopal
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Isacson, Max
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Mårtensson, Mikael U. F.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    CERN, Geneva, Switzerland.
    Search for long-lived neutral particles produced in pp collisions at √s=13 TeV decaying into displaced hadronic jets in the ATLAS inner detector and muon spectrometer2020In: Physical Review D: covering particles, fields, gravitation, and cosmology, ISSN 2470-0010, E-ISSN 2470-0029, Vol. 101, no 5, article id 052013Article in journal (Refereed)
    Abstract [en]

    A search is presented for pair production of long-lived neutral particles using 33 fb(-1) off root s = 13 TcV proton-proton collision data, collected during 2016 by the ATLAS detector at the LHC. This search focuses on a topology in which one long-lived particle decays in the ATLAS inner detector and the other decays in the muon spectrometer. Special techniques are employed to reconstruct the displaced tracks and vertices in the inner detector and in the muon spectrometer. One event is observed that passes the full event selection, which is consistent with the estimated background. Limits are placed on scalar boson propagators with masses from 125 GeV to 1000 GeV decaying into pairs of long-lived hidden-sector scalars with masses from 8 GeV to 400 GeV. The limits placed on several low-mass scalars extend previous exclusion limits in the range of proper lifetimes c tau from 5 cm to 1 m.

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  • Aad, G.
    et al.
    Aix Marseille Univ, IN2P3, CNRS, CPPM, Marseille, France.
    Asimakopoulou, Eleni M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bergeås Kuutmann, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bokan, Petar
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics. Georg August Univ Gottingen, Phys Inst 2, Gottingen, Germany;Uppsala Univ, Dept Phys & Astron, Uppsala, Sweden.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellajosyula, Venugopal
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Isacson, Max
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Mårtensson, Mikael U. F.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    CERN, Geneva, Switzerland.
    Evidence for electroweak production of two jets in association with a Zγ pair in pp collisions at √S=13 TeV with the ATLAS detector2020In: Physics Letters B, ISSN 0370-2693, E-ISSN 1873-2445, Vol. 803, article id 135341Article in journal (Refereed)
    Abstract [en]

    Evidence for electroweak production of two jets in association with a Z gamma pair in root s = 13 TeV proton-proton collisions at the Large Hadron Collider is presented. The analysis uses data collected by the ATLAS detector in 2015 and 2016 that corresponds to an integrated luminosity of 36.1 fb(-1). Events that contain a Z boson candidate decaying leptonically into either e(+)e(-) or mu(+)mu(-), a photon, and two jets are selected. The electroweak component is measured with observed and expected significances of 4.1 standard deviations. The fiducial cross-section for electroweak production is measured to be sigma(Z gamma jj-Ew) = 7.8 +/- 2.0 fb, in good agreement with the Standard Model prediction.

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  • Bobev, Nikolay
    et al.
    Katholieke Univ Leuven, Inst Theoret Fys, Celestijnenlaan 200D, BE-3001 Leuven, Belgium.
    Bomans, Pieter
    Katholieke Univ Leuven, Inst Theoret Fys, Celestijnenlaan 200D, BE-3001 Leuven, Belgium.
    Gautason, Fridrik Freyr
    Katholieke Univ Leuven, Inst Theoret Fys, Celestijnenlaan 200D, BE-3001 Leuven, Belgium;Univ Iceland, Inst Sci, Dunhaga 3, IS-107 Reykjavik, Iceland.
    Minahan, Joseph A.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Theoretical Physics.
    Nedelin, Anton
    Technion, Dept Phys, IL-32000 Haifa, Israel.
    Supersymmetric Yang-Mills, spherical branes, and precision holography2020In: Journal of High Energy Physics (JHEP), ISSN 1126-6708, E-ISSN 1029-8479, no 3, article id 47Article in journal (Refereed)
    Abstract [en]

    Using supersymmetric localization we compute the free energy and BPS Wilson loop vacuum expectation values for planar maximally supersymmetric Yang-Mills theory on S-d in the strong coupling limit for 2 <= d < 6. The same calculation can also be performed in supergravity using the recently found spherical brane solutions. We find excellent agreement between the two sets of results. This constitutes a non-trivial precision test of holography in a non-conformal setting. The free energy of maximal SYM on S-6 diverges in the strong coupling limit which might signify the onset of little string theory. We show how this divergence can be regularized both in QFT and in supergravity. We also consider d = 7 with a small negative 't Hooft coupling and show that the free energy and Wilson loop vacuum expectation value agree with the results from supergravity after addressing some subtleties.

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  • Public defence: 2020-08-28 09:15 Häggsalen, Uppsala
    Johansson, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Core-hole Clock Spectroscopy Using Hard X-rays: Exciting States in Condensed Matter2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is about how electrons move from one place to another, that is charge transfer dynamics. Charge transfer dynamics is an important property governing chemical and physical changes that form the base for many applications such as electronics, optoelectronics and catalysis. The fundamental aspect is how charge transfer manifests in the constituent materials and their interfaces building up these devices. The basic method used is synchrotron radiation based electron spectroscopies.

    Using core-hole clock spectroscopy it is possible to study dynamic processes in the femtosecond and attosecond regimes - here we study the if the core-excited electron decays back into the core hole (local decays), or if the core excited electron have been tunneled away from the atomic site before the core-hole decays. Spectroscopically we can discern the two situations since one of the processes is photon energy dependent and one is not. Knowledge of the life-time of the core hole, and measuring the probability of the core-excited system decaying one way or the other makes it possible to calculate a charge transfer time. Using hard X-rays to create excited state with deep core-holes allow us to study high kinetic energy Auger electrons, also deep core-holes tend to be short lived, which gives access to short time-scales.

    Bulk crystals of 2D materials have been used as model systems here owing to their well-known properties. Using those it has been demonstrated that the regime of observable times using the mentioned method can be extended with an order of magnitude compared to previous studies. Our results present themselves on time-scales on par with the atomic unit of time. The highly selective nature of resonant X-ray excitations allows the anisotropic unoccupied electronic structure of bulk 2D crystals to be mapped out, here the example of SnS2 is presented. This shows that this is a direct probe of the unoccupied band structure.

    With core-hole clock spectroscopy the charge transfer time dependence on relative concentrations of blends between the low band-gap polymer PCPDTBT, with PCBM (functionalized fullerenes). This is a common prototypical system for organic photovoltaics. The charge transfer time decreases with increasing intermixing, up to a point where is starts getting slower, the same trend as the efficiency of solar cell devices made with the same mixing. The method employed here is chemically specific and probes the local surrounding energy landscape at the site of excitation – this is different from other techniques that utilize optical excitations which are non-local in character.

    The synthetization of bulk heterostructures and thin films, and the disentanglement of core-ionized states are also investigated using spectroscopic and scattering techniques.

    List of papers
    1. Resonant Auger Spectroscopy on Solid Xe on Cu and Au
    Open this publication in new window or tab >>Resonant Auger Spectroscopy on Solid Xe on Cu and Au
    (English)Manuscript (preprint) (Other academic)
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:uu:diva-407534 (URN)
    Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-26
    2. Gone in 23 Attoseconds: Charge Transfer in Resonantly Core Excited Black Phosphorous
    Open this publication in new window or tab >>Gone in 23 Attoseconds: Charge Transfer in Resonantly Core Excited Black Phosphorous
    (English)Manuscript (preprint) (Other academic)
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:uu:diva-407535 (URN)
    Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-26
    3. Interlayer Charge Transfer in Tin Disulphide: Orbital Anisotropy and Temporal Aspects
    Open this publication in new window or tab >>Interlayer Charge Transfer in Tin Disulphide: Orbital Anisotropy and Temporal Aspects
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:uu:diva-407536 (URN)
    Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-04-02
    4. Intralayer Charge Transfer Anisotropy in Black Phosphorus
    Open this publication in new window or tab >>Intralayer Charge Transfer Anisotropy in Black Phosphorus
    (English)Manuscript (preprint) (Other academic)
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:uu:diva-407537 (URN)
    Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-26
    5. Tailoring Ultra-fast Charge Transfer in MoS2
    Open this publication in new window or tab >>Tailoring Ultra-fast Charge Transfer in MoS2
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:uu:diva-407538 (URN)
    Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-26
    6. Femtosecond and Attosecond Electron-Transfer Dynamics in PCPDTBT: PCBM Bulk Heterojunctions
    Open this publication in new window or tab >>Femtosecond and Attosecond Electron-Transfer Dynamics in PCPDTBT: PCBM Bulk Heterojunctions
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    2018 (English)In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 122, no 24, p. 12605-12614Article in journal (Refereed) Published
    Abstract [en]

    Charge separation efficiency is a crucial parameter for photovoltaic devices-polymers consisting of alternating electron-rich and electron-deficient parts can achieve high such efficiencies, for instance, together with a fullerene electron acceptor. This offers a viable path toward solar cells with organic bulk heterojunctions. Here, we measured the charge-transfer times in the femtosecond and attosecond regimes via the decay of sulfur is X-ray core excited states (with the core-hole clock method) in blends of a low-band gap polymer {PCPDTBT [poly[2,6-(4,4-bis (2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-1/1 dithiophene)-alt-4,7- (2,1,3-benzothiadiazole)]]} consisting of a cyclopentadithiophene electron-rich part and a benzothiadiazole electron-deficient part. The constituting parts of the bulk heterojunction were varied by adding the fullerene derivative PCBM ([6,6]-phenyl-C-61-butyric acid methyl ester) (weight ratio of polymer/PCBM as 1:0, 1:1, 1:2, and 1:3). For low-energy excitations, the charge-transfer time varies to the largest extent for the thiophene donor part. The charge-transfer time in the 1:2 blend is reduced by 86% compared to that of pristine PCPDTBT. At higher energy excitations, the charge-transfer time does not vary with the chemical environment, as this regime is dominated by intramolecular conduction that yields ultrafast charge-transfer times for all blends, approaching 170 as. We thus demonstrate that the core-hole clock method applied to a series with changing composition can give information about local electron dynamics (with chemical specificity) at interfaces between the constituting parts the crucial part of a bulk heterojunction where the initial charge separation occurs.

    National Category
    Theoretical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-359439 (URN)10.1021/acs.jpcc.8b02453 (DOI)000436381600004 ()
    Available from: 2018-09-03 Created: 2018-09-03 Last updated: 2020-03-26Bibliographically approved
    7. Defect formation in graphene during low-energy ion bombardment
    Open this publication in new window or tab >>Defect formation in graphene during low-energy ion bombardment
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    2016 (English)In: APL Materials, ISSN 2166-532X, Vol. 4, no 4, article id 046104Article in journal, Letter (Refereed) Published
    Abstract [en]

    This letter reports on a systematic investigation of sputter induced damage in graphene caused by low energy Ar+ ion bombardment. The integral numbers of ions per area (dose) as well as their energies are varied in the range of a few eV's up to 200 eV. The defects in the graphene are correlated to the dose/energy and different mechanisms for the defect formation are presented. The energetic bombardment associated with the conventional sputter deposition process is typically in the investigated energy range. However, during sputter deposition on graphene, the energetic particle bombardment potentially disrupts the crystallinity and consequently deteriorates its properties. One purpose with the present study is therefore to demonstrate the limits and possibilities with sputter deposition of thin films on graphene and to identify energy levels necessary to obtain defect free graphene during the sputter deposition process. Another purpose is to disclose the fundamental mechanisms responsible for defect formation in graphene for the studied energy range.

    National Category
    Materials Chemistry Nano Technology
    Identifiers
    urn:nbn:se:uu:diva-284702 (URN)10.1063/1.4945587 (DOI)000375846100007 ()
    Funder
    Knut and Alice Wallenberg Foundation, 2011.0082Swedish Research Council, 2014-5591 2014-6463
    Available from: 2016-04-19 Created: 2016-04-19 Last updated: 2020-03-26Bibliographically approved
    8. Minimizing sputter-induced damage during deposition of WS2 onto graphene
    Open this publication in new window or tab >>Minimizing sputter-induced damage during deposition of WS2 onto graphene
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    2017 (English)In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 110, no 9, article id 091601Article in journal (Refereed) Published
    Abstract [en]

    We demonstrate the sputter-deposition of WS2 onto a single-layer graphene film leaving the latter disorder-free. The sputtering process normally causes defects to the graphene lattice and adversely affects its properties. Sputtering of WS2 yields significant amounts of energetic particles, specifically negative S ions, and reflected neutral Ar, and it is therefore used as a model system in this work. The disorder-free sputtering is achieved by increasing the sputteringpressure of Ar thereby shifting the kinetic energy distribution towards lower energies for the impinging particle flux at the substrate. Raman spectroscopy is used to assess the amount of damage to the graphene film. Monte Carlo simulations of the sputteringprocess show that W is completely thermalized already at relatively low sputtering pressure, whereas Ar and S need a comparably higher pressure to thermalize so as to keep the graphene film intact. Apart from becoming completely amorphous at 2.3 mTorr, the graphene filmremains essentially disorder-free when the pressure is increased to 60 mTorr. The approach used here is generally applicable and readily extendable to sputter-deposition of other material combinations onto sensitive substrates. Moreover, it can be used without changing the geometry of an existing sputtering setup.

    National Category
    Other Physics Topics Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-316602 (URN)10.1063/1.4977709 (DOI)000397871600010 ()
    Available from: 2017-03-04 Created: 2017-03-04 Last updated: 2020-03-26Bibliographically approved
    9. Quantitative analysis of plasmon excitations in hard x-ray photoelectron spectra of bulk black phosphorus
    Open this publication in new window or tab >>Quantitative analysis of plasmon excitations in hard x-ray photoelectron spectra of bulk black phosphorus
    2020 (English)In: Applied Surface Science, ISSN 0169-4332, E-ISSN 1873-5584, Vol. 505, article id 144385Article in journal (Refereed) Published
    Abstract [en]

    Black phosphorus (BPh) is a layered material with strong in-plane anisotropy of its structural and electronic properties; in spite of the great potential of BPh for conceptually new devices in optoelectronics and plasmonics, its fundamental electronic excitations have not yet been fully elucidated. In order to discriminate collective (plasmons) and single-particle (inter band transitions) excitations, we investigate the energy-loss distribution of P 1s photoelectrons in hard X-ray photoelectron spectra of BPh over a wide energy range. The energy-loss function (ELF), averaged over the principal directions of the BPh crystal, has been retrieved by using a Fourier Transform analysis to eliminate multiple inelastic scattering events. At low loss energies (1-8 eV), weak unresolved energy loss peaks are well described by DFT calculated inter band transitions, showing some anisotropy in the dielectric function epsilon(omega, q) tensor of BPh. At high loss energies, the ELF is dominated by the collective excitation of valence electrons with a peak energy at 20.1 +/- 0.2 eV, and weak anisotropy is found in the DFT calculated Im(- 1/epsilon) tensor. The anomalously small peak energy (9.0 +/- 0.5 eV) of a weak surface plasmon resonance is attributed either to low surface electron density in the terminal phosphorene layer or to some anisotropic surface plasmon propagation.

    Keywords
    Black phosphorus, XPS, HAXPES, Energy loss, Plasmon
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:uu:diva-407533 (URN)10.1016/j.apsusc.2019.144385 (DOI)000510846500037 ()
    Funder
    Swedish Research Council, 2014-6463
    Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-04-01Bibliographically approved
    10. In Situ Formation of Ge Nanoparticles by Annealing of Al-Ge‑N ThinFilms Followed by HAXPES and XRD
    Open this publication in new window or tab >>In Situ Formation of Ge Nanoparticles by Annealing of Al-Ge‑N ThinFilms Followed by HAXPES and XRD
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    2019 (English)In: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 58, no 16, p. 11100-11109Article in journal (Refereed) Published
    Abstract [en]

    Ge nanoparticles embedded in thin films have attracted a lot of attention due to their promising optical and electronic properties that can be tuned by varying the particle size and choice of matrix material. In this study, Ge nanoparticle formation was investigated for Al-Ge-N based thin films by simultaneous measurements of HAXPES and grazing incidence XRD during in situ annealing in vacuum conditions. As-deposited Al-Ge-N thin films, synthesized by reactive dc magnetron sputtering, consisted of a nanocrystalline (Al1–xGex)Ny solid solution and an amorphous tissue phase of Ge3Ny. Upon annealing to 750 °C, elemental Ge was formed shown by both HAXPES and XRD measurements, and N2 gas was released as measured by a mass spectrometer. Postannealed ex situ analysis by SEM and TEM showed that the elemental Ge phase formed spherical nanoparticles on the surface of the film, with an average size of 210 nm. As the annealing temperature increased further to 850 °C, the Ge particles on the film surface evaporated, while the phase segregation of Ge still could be observed within the film. Thus, these results show the possibility for a controlled synthesis of Ge nanoparticles through annealing of Al-Ge-N thin films to produce materials suitable for use in electronic or optoelectronic devices.

    National Category
    Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-392698 (URN)10.1021/acs.inorgchem.9b01631 (DOI)000482173300075 ()31381309 (PubMedID)
    Funder
    Swedish Research Council, 2014-6463EU, FP7, Seventh Framework Programme, INCA 600398
    Available from: 2019-09-08 Created: 2019-09-08 Last updated: 2020-03-26Bibliographically approved
    11. Partially Reversible Photoinduced Chemical Changes in a Mixed-Ion Perovskite Material for Solar Cells
    Open this publication in new window or tab >>Partially Reversible Photoinduced Chemical Changes in a Mixed-Ion Perovskite Material for Solar Cells
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    2017 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, no 40, p. 34970-34978Article in journal (Refereed) Published
    Abstract [en]

    Metal halide perovskites have emerged as materials of high interest for solar energy-to-electricity conversion, and in particular, the use of mixed-ion structures has led to high power conversion efficiencies and improved stability. For this reason, it is important to develop means to obtain atomic level understanding of the photoinduced behavior of these materials including processes such as photoinduced phase separation and ion migration. In this paper, we implement a new methodology combining visible laser illumination of a mixed-ion perovskite ((FAP-bI(3))(0.85)(MAPbBr(3))(0.15)) with the element specificity and chemical sensitivity of core-level photoelectron spectroscopy. By carrying out measurements at a synchrotron beamline optimized for low X-ray fluxes, we are able to avoid sample changes due to X-ray illumination and are therefore able to monitor what sample changes are induced by visible illumination only. We find that laser illumination causes partially reversible chemistry in the surface region, including enrichment of bromide at the surface, which could be related to a phase separation into bromide- and iodide-rich phases. We also observe a partially reversible formation of metallic lead in the perovskite structure. These processes occur on the time scale of minutes during illumination. The presented methodology has a large potential for understanding light-induced chemistry in photoactive materials and could specifically be extended to systematically study the impact of morphology and composition on the photostability of metal halide perovskites.

    Place, publisher, year, edition, pages
    AMER CHEMICAL SOC, 2017
    Keywords
    photoelectron spectroscopy, laser illumination, lead halide perovskite, ion migration, phase separation, stability
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:uu:diva-340141 (URN)10.1021/acsami.7b10643 (DOI)000413131500043 ()28925263 (PubMedID)
    Funder
    EU, FP7, Seventh Framework Programme, 321319Swedish Research Council, 2014-6019Swedish Research Council, 2014-6463StandUpSwedish Foundation for Strategic Research , RMA15-0130
    Available from: 2018-01-26 Created: 2018-01-26 Last updated: 2020-03-26Bibliographically approved
    12. Auger- and Photoelectron Coincidences of Molecular O2 Adsorbed on Ag(111)
    Open this publication in new window or tab >>Auger- and Photoelectron Coincidences of Molecular O2 Adsorbed on Ag(111)
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Condensed Matter Physics
    Identifiers
    urn:nbn:se:uu:diva-407539 (URN)
    Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-26
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  • Calixto, Ana Rita
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Moreira, Catia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry. Uppsala Univ, Dept Chem BMC, S-75123 Uppsala, Sweden..
    Kamerlin, Shina Caroline Lynn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Recent Advances in Understanding Biological GTP Hydrolysis through Molecular Simulation2020In: ACS OMEGA, ISSN 2470-1343, Vol. 5, no 9, p. 4380-4385Article, review/survey (Refereed)
    Abstract [en]

    GTP hydrolysis is central to biology, being involved in regulating a wide range of cellular processes. However, the mechanisms by which GTPases hydrolyze this critical reaction remain controversial, with multiple mechanistic possibilities having been proposed based on analysis of experimental and computational data. In this mini-review, we discuss advances in our understanding of biological GTP hydrolysis based on recent computational studies and argue in favor of solvent-assisted hydrolysis as a conserved mechanism among GTPases. A concrete understanding of the fundamental mechanisms by which these enzymes facilitate GTP hydrolysis will have significant impact both for drug discovery efforts and for unraveling the role of oncogenic mutations.

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  • Nilsson, Per-Erik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Centre for Multidisciplinary Studies on Racism.
    Ekon från historien i den nya medieekologin2020In: Ikaros: Tidskrift om människan och vetenskapen, no 1, p. 4-6Article in journal (Other (popular science, discussion, etc.))
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  • Finlay, Roger D.
    et al.
    Swedish Univ Agr Sci, Uppsala BioCtr, Dept Forest Mycol & Plant Pathol, S-75007 Uppsala, Sweden..
    Mahmood, Shahid
    Swedish Univ Agr Sci, Uppsala BioCtr, Dept Forest Mycol & Plant Pathol, S-75007 Uppsala, Sweden..
    Rosenstock, Nicholas
    Lund Univ, Dept Biol, Box 117, S-22100 Lund, Sweden..
    Bolou-Bi, Emile B.
    Univ Felix Houphouet Boigny, UFR Sci Terre & Ressources Minieres, Dept Sci Sol, BP 582, Abidjan 22, Cote Ivoire..
    Kohler, Stephan J.
    Swedish Univ Agr Sci, Dept Aquat Sci & Assessment, Soil Water Environm Ctr, S-75007 Uppsala, Sweden..
    Fahad, Zaenab
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Swedish Univ Agr Sci, Uppsala BioCtr, Dept Forest Mycol & Plant Pathol, S-75007 Uppsala, Sweden.
    Rosling, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Wallander, Hakan
    Lund Univ, Dept Biol, Box 117, S-22100 Lund, Sweden..
    Belyazid, Salim
    Stockholm Univ, Dept Phys Geog, S-10691 Stockholm, Sweden..
    Bishop, Kevin
    Swedish Univ Agr Sci, Dept Aquat Sci & Assessment, Soil Water Environm Ctr, S-75007 Uppsala, Sweden..
    Lian, Bin
    Nanjing Normal Univ, Coll Marine Sci & Engn, Nanjing 210023, Peoples R China..
    Reviews and syntheses: Biological weathering and its consequences at different spatial levels - from nanoscale to global scale2020In: Biogeosciences, ISSN 1726-4170, E-ISSN 1726-4189, Vol. 17, no 6, p. 1507-1533Article, review/survey (Refereed)
    Abstract [en]

    Plant nutrients can be recycled through microbial decomposition of organic matter but replacement of base cations and phosphorus, lost through harvesting of biomass/biofuels or leaching, requires de novo supply of fresh nutrients released through weathering of soil parent material (minerals and rocks). Weathering involves physical and chemical processes that are modified by biological activity of plants, microorganisms and animals. This article reviews recent progress made in understanding biological processes contributing to weathering. A perspective of increasing spatial scale is adopted, examining the consequences of biological activity for weathering from nanoscale interactions, through in vitro and in planta microcosm and meso-cosm studies, to field experiments, and finally ecosystem and global level effects. The topics discussed include the physical alteration of minerals and mineral surfaces; the composition, amounts, chemical properties, and effects of plant and microbial secretions; and the role of carbon flow (including stabilisation and sequestration of C in organic and inorganic forms). Although the predominant focus is on the effects of fungi in forest ecosystems, the properties of biofilms, including bacterial interactions, are also discussed. The implications of these biological processes for modelling are discussed, and we attempt to identify some key questions and knowledge gaps, as well as experimental approaches and areas of research in which future studies are likely to yield useful results. A particular focus of this article is to improve the representation of the ways in which biological processes complement physical and chemical processes that mobilise mineral elements, making them available for plant uptake. This is necessary to produce better estimates of weathering that are required for sustainable management of forests in a post-fossil-fuel economy. While there are abundant examples of nanometre- and micrometre-scale physical interactions between microorganisms and different minerals, opinion appears to be divided with respect to the quantitative significance of these observations for overall weathering. Numerous in vitro experiments and microcosm studies involving plants and their associated microorganisms suggest that the allocation of plant-derived carbon, mineral dissolution and plant nutrient status are tightly coupled, but there is still disagreement about the extent to which these processes contribute to field-scale observations. Apart from providing dynamically responsive pathways for the allocation of plant-derived carbon to power dissolution of minerals, mycorrhizal mycelia provide conduits for the long-distance trans-portation of weathering products back to plants that are also quantitatively significant sinks for released nutrients. These mycelial pathways bridge heterogeneous substrates, reducing the influence of local variation in C : N ratios. The production of polysaccharide matrices by biofilms of interacting bacteria and/or fungi at interfaces with mineral surfaces and roots influences patterns of production of antibiotics and quorum sensing molecules, with concomitant effects on microbial community structure, and the qualitative and quantitative composition of mineral-solubilising compounds and weathering products. Patterns of carbon allocation and nutrient mobilisation from both organic and inorganic substrates have been studied at larger spatial and temporal scales, including both ecosystem and global levels, and there is a generally wider degree of acceptance of the "systemic" effects of microorganisms on patterns of nutrient mobilisation. Theories about the evolutionary development of weathering processes have been advanced but there is still a lack of information connecting processes at different spatial scales. Detailed studies of the liquid chemistry of local weathering sites at the micrometre scale, together with upscaling to soil-scale dissolution rates, are advocated, as well as new approaches involving stable isotopes.

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  • Vaisman, Alon
    et al.
    Univ Toronto, Toronto Gen Hosp, Div Infect Dis, 14EN 209,200 Elizabeth St, Toronto, ON M5G 2C4, Canada..
    Linder, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Lundin, Johan
    Karolinska Inst, Dept Global Publ Hlth, Stockholm, Sweden..
    Orchanian-Cheff, Ani
    Univ Hlth Network, Hlth Sci Lib, Toronto, ON, Canada..
    Coulibal, Jean T.
    Univ Felix Houphouet Boigny, Unite Format & Rech Biosci, Abidjan, Cote Ivoire..
    Ephraim, Richard K. D.
    Univ Cape Coast, Dept Med Lab Sci, Cape Coast, Ghana..
    Bogoch, Isaac I.
    Univ Toronto, Toronto Gen Hosp, Div Infect Dis, 14EN 209,200 Elizabeth St, Toronto, ON M5G 2C4, Canada..
    Artificial intelligence, diagnostic imaging and neglected tropical diseases: ethical implications2020In: Bulletin of the World Health Organization, ISSN 0042-9686, E-ISSN 1564-0604, Vol. 98, no 4, p. 288-289Article in journal (Other academic)
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  • Lohmann, Svenja
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Disparate Energy Scaling of Trajectory-Dependent Electronic Excitations for Slow Protons and He Ions2020In: Physical Review Letters, ISSN 0031-9007, E-ISSN 1079-7114, Vol. 124, article id 096601Article in journal (Refereed)
    Abstract [en]

    We have simultaneously measured angular distributions and electronic energy loss of helium ions and protons directly transmitted through self-supporting, single-crystalline silicon foils. We have compared the energy loss along channeled and random trajectories for incident ion energies between 50 and 200 keV. For all studied cases the energy loss in channeling geometry is found lower than in random geometry. In the case of protons, this difference increases with initial ion energy. This behavior can be explained by the increasing contribution of excitations of core electrons, which are more likely to happen at small impact parameters accessible only in random geometry. For helium ions we observe a reverse trend—a decrease of the difference between channeled and random energy loss for increasing ion energy. Because of the inefficiency of core-electron excitations even at small impact parameters at such low energies, another mechanism has to be the cause for the observed difference. We provide evidence that the observation originates from reionization events induced by close collisions of helium ions occurring only along random trajectories.

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  • Persson, Jelena
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Registrerade partners förmögenhetsförhållanden: Särskilt om relationens erkännande och tillämplig lag i svenskfranska förhållanden2020Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • Kjellin, Midori
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Klinisk Mikrobiologi och Vårdhygien.
    Study of Resistance in Hepatitis C Virus Prior to Treatment with Direct Acting Antivirals2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The rapid advancement of Hepatitis C (HCV) treatment presents a great challenge to clinicians in optimising therapy for their patients. Genotype (GT), efficacy, side-effects, drug combinations and treatment durations must be tailored to individual patients, considering comorbidities, degree of fibrosis, adherence and antiviral resistance.

    Resistance associated substitutions (RASs) may impair treatment response to direct-acting antiviral agents (DAA). Almost all patients who fail treatment acquire RASs that may persist for years. Even treatment-naïve patients can harbour naturally occurring RASs against currently approved DAAs, i.e. resistance at baseline. Prevalence of key NS3 and NS5A-RASs is relatively high (3-9%) at baseline for DAA-treatment-naïve GT1a and 3a patients with population sequencing at 20% cut-off in Sweden and Norway.

    The studies in this thesis comprise investigations on the prevalence and the effects of baseline RASs on treatment outcome in patients with HCV GT1 and GT3 receiving personalised treatment based on results from NS3 and NS5A resistance testing. We developed a pan-genotypic population sequencing method for detecting NS5A RASs (Paper I), which is certified and used in routine diagnostics at our laboratory together with our previously developed NS3 RAS sequencing method.  We acquired data on RAS prevalence and treatment outcome from the early DAA management and carried out a non-randomised, prospective real-life study seeking to examine the impact on treatment outcome in patients receiving treatment tailored to baseline resistance testing.

    The studies were carried out between 2011 and 2017, one retrospective study comprising patients in the Uppsala region (Paper II) and two prospective studies with patients in a multicentre study involving sites in both in Sweden and Norway (Paper III and IV).

    RAS prevalence data from the prospective studies was obtained from a total of 401 patients and was shown to be slightly lower than reported from previous studies. Still, although not statistically significant due to the low prevalence of RASs in the cohort, we could show that there was a trend toward tailoring treatment to baseline RAS testing has a favourable impact on treatment outcome over treatment according to standard recommendations, especially in patients with cirrhosis. The economical and best practise objectives were important factors to consider when treatment costs were high and adverse effects were challenging at the initiation of the studies.

    In summary, this doctoral thesis presents results from real-life studies that indicate that tailoring treatment based on baseline RAS-testing have beneficial impact on patients that are treatment experienced and/or patients with cirrhosis.

    List of papers
    1. Prevalence of polymorphisms with significant resistance to NS5A inhibitors in treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden
    Open this publication in new window or tab >>Prevalence of polymorphisms with significant resistance to NS5A inhibitors in treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden
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    2015 (English)In: INFECTIOUS DISEASES, ISSN 2374-4235, Vol. 47, no 8, p. 555-562Article in journal (Refereed) Published
    Abstract [en]

    Background: The future treatment of hepatitis C virus (HCV) infection will be combinations of direct-acting antivirals (DAAs) that not only target multiple viral targets, but are also effective against different HCV genotypes. Of the many drug targets in HCV, one promising target is the non-structural 5A protein (NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir, have shown potent efficacy. However, since HCV is known to have very high sequence diversity, development of resistance is a problem against but not limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and NS5B non-nucleoside inhibitors), when used in suboptimal combinations. Furthermore, it has been shown that natural resistance against DAAs is present in treatment-naive patients and such baseline resistance will potentially complicate future treatment strategies. Methods: A pan-genotypic population-sequencing method with degenerated primers targeting the NS5A region was developed. We have investigated the prevalence of baseline resistant variants in 127 treatment-naive patients of HCV genotypes 1a, 1b, 2b and 3a. Results: The method could successfully sequence more than 95% of genotype 1a, 1b and 3a samples. Interpretation of fold resistance data against the NS5A inhibitors was done with the help of earlier published phenotypic data. Baseline resistance variants associated with high resistance (1000-50000-fold) was found in three patients: Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient. Conclusion: Using this method, baseline resistance can be examined and the data could have a potential role in selecting the optimal and cost-efficient treatment for the patient.

    Keywords
    Hepatitis C virus, NS5A, prevalence, polymorphism, baseline resistance
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:uu:diva-259636 (URN)10.3109/23744235.2015.1028097 (DOI)000357738200007 ()25851241 (PubMedID)
    Note

    Funding: Uppsala-Orebro Regional Research Council, Selander Foundation

    Available from: 2015-08-21 Created: 2015-08-10 Last updated: 2020-03-26Bibliographically approved
    2. The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort
    Open this publication in new window or tab >>The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort
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    2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 50-56Article in journal (Refereed) Published
    Abstract [en]

    Background: The clinical experience with protease-inhibitor (PI) triple regimen appears disappointing regarding effect, side effects, high work load, and costs. This real-world study evaluates baseline and emerging resistance-associated substitutions (RASs) and their significance for treatment outcome.

    Method: Thirty-six genotype 1a/b patients treated according to Swedish recommendations during 2011-2013 with triple therapy including pegylated interferon and ribavirin in combination with a protease-inhibitor, either boceprevir (BOC) or telaprevir (TVR), were retrospectively evaluated. Frozen serum samples from the patients were tested for resistance with pan-genotypic population sequencing.

    Results: Overall, 56% (20/36) of the patients achieved sustained viral response (SVR). The SVR was comparable between BOC (64%; 9/14) and TVR (50%; 11/22) (p = 0.07), and the IL28B type non-CC (48%; 12/25) and CC (46%; 6/13) (p = 0.77). The SVR was higher in patients without cirrhosis (89.5%; 17/19) (p < 0.0005), in treatment-naive patients (70%; 14/20) (p = 0.02), and those with low viral load (<800,000 IU/mL) (66.7%; 8/12) (p < 0.0002), compared to those with cirrhosis (17.6%; 3/17), treatment-experienced (37.5%; 6/16), and high viral load (>800,000 IU/mL) (50%; 12/24).

    Conclusion: PI triple regimes were highly effective in treatment-naive patients without cirrhosis, but in this real-world cohort an inferior effect was evident in cirrhotic and treatment-experienced patients. Although tested on a limited sample, the baseline resistance testing seems to have no impact on prediction of therapy outcome. The reason could be that the baseline RASs T54S and V55A have relatively low resistance towards BOC and TVR. Emerging RASs, mainly R155K, with known high resistance to BOC and TVR were frequently found in non-responders.

    Place, publisher, year, edition, pages
    TAYLOR & FRANCIS LTD, 2018
    Keywords
    Boceprevir, hepatitis C, protease inhibitor, RAS, resistance association substitution, telaprevir
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:uu:diva-354543 (URN)10.1080/03009734.2018.1441928 (DOI)000428060300006 ()29536805 (PubMedID)
    Funder
    Erik, Karin och Gösta Selanders Foundation
    Available from: 2018-07-20 Created: 2018-07-20 Last updated: 2020-03-26Bibliographically approved
    3. Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014-2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy.
    Open this publication in new window or tab >>Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014-2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy.
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    2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 10-11, p. 1347-1353Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: Resistance-associated substitutions (RASs) may impair treatment response to direct-acting antivirals (DAA) in hepatitis C virus (HCV) treatment. We investigated the effects of baseline NS3-RASs (Q80K and R155K) and clinically relevant NS5A-RASs in patients with HCV genotype (GT) 1a infection on treatment outcome, with or without resistance-based DAA-treatment. This multi-center study was carried out between 2014 and 2016.

    PATIENTS/METHODS: Treatment in the intervention group (n = 92) was tailored to baseline resistance. Detection of NS3-RAS led to an NS5A-inhibitor-based regimen and detection of NS5A-RAS to a protease-inhibitor regimen. Patients without baseline RAS in the intervention group and all patients in the control group (n = 101) received recommended standard DAA-treatment.

    RESULTS: The sustained virologic response rates (SVR) in the intervention and control groups were 97.8% (90/92) and 93.1% (94/101), respectively (p = .174). A trend toward higher SVR-rate in cirrhotic patients (p = .058) was noticed in the intervention group compared to the control group with SVR-rates 97.5% (39/40) and 83.3% (35/42), respectively. All patients with baseline NS3 (Q80K/R155K) or NS5A-RASs in the intervention group achieved SVR with personalized resistance-based treatment. In the control group, five patients with Q80K or R155K at baseline were treated with simeprevir + sofosbuvir and treatment failed in two of them. Furthermore, one of three patients who failed ledipasvir + sofosbuvir treatment had NS5A-RASs at baseline.

    CONCLUSIONS: In line with the findings of the OPTIMIST-2 trial for Q80K and the EASL-guidelines 2016 for NS5A-RASs, baseline RASs appeared to have an impact on treatment outcome albeit a statistical significance was not observed in this low-prevalence population.

    Keywords
    Baseline resistance, NS5A, Q80K, hepatitis C virus, resistance-associated substitution, sustained virologic response
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:uu:diva-371722 (URN)10.1080/00365521.2018.1511824 (DOI)000457980900029 ()30394152 (PubMedID)
    Funder
    Erik, Karin och Gösta Selanders Foundation
    Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2020-03-26Bibliographically approved
    4. Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway
    Open this publication in new window or tab >>Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway
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    2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 8, p. 1042-1050Article in journal (Refereed) Published
    Abstract [en]

    Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5-10%) at baseline in direct-acting antiviral agents (DAA) treatment-naive genotype (GT) 3a patients when studied by the population-sequencing method (cut-off 20%). This RAS may impair HCV DAA treatment response, since it possesses a high fold in vitro resistance to daclatasvir (DCV) and velpatasvir (VEL) in GT 3. We investigated the effect of baseline Y93H in patients with GT 3a infection on treatment outcome, with or without resistance-based DAA-treatment during 2014-2017.

    Patients/Methods: Treatment in the intervention group (n = 130) was tailored to baseline resistance-findings by population-sequencing method. Detection of baseline Y93H above 20% prompted a prolonged treatment duration of NS5A-inhibitor and sofosbuvir (SOF) and/or addition of ribavirin (RBV). Patients without baseline Y93H in the intervention group and all patients in the control group (n = 78) received recommended standard DAA-treatment.

    Results: A higher sustained virologic response rate (SVR) in the intervention group was shown compared to the control group at 95.4% (124/130) and 88.5% (69/78), respectively (p = .06). All five patients with baseline Y93H in the intervention group achieved SVR with personalised treatment based on results from resistance testing; either with the addition of RBV or prolonged treatment duration (24w). In the control group, 2/4 patients with Y93H at baseline treated with ledipasvir/SOF/RBV or DCV/SOF without RBV, failed treatment.

    Conclusion: The results from this real-life study are in accordance with the findings of the randomised controlled trials in 2015 and the EASL-guidelines of 2016, thus, baseline Y93H impacts on DCV and VEL treatment outcome.

    Place, publisher, year, edition, pages
    TAYLOR & FRANCIS LTD, 2019
    Keywords
    Baseline resistance, hepatitis C virus, NS5A, resistance-associated substitution, sustained virologic response, Y93H
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:uu:diva-396109 (URN)10.1080/00365521.2019.1652846 (DOI)000481902500001 ()31424972 (PubMedID)
    Funder
    Erik, Karin och Gösta Selanders Foundation
    Available from: 2019-11-01 Created: 2019-11-01 Last updated: 2020-03-26Bibliographically approved
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  • Khajehdehi, Armin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    Skadestånd i gränsöverskridande brottmål: Internationellt privat- och processrättsliga frågor om domsrätt och lagval2020Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This master thesis illustrates and analyzes the various problems which might occur when dealing with questions of damages in cross-border criminal cases.

    In the Nordic legal systems the tradition is to join the private claim with the criminal case and handle them together in the criminal trial procedure. In Sweden the criminal case is decided under the Swedish Criminal Code (brottsbalken, SFS 1962:700) while the question of indemnity liability is decided under the Tort Liability Act (skadeståndslagen, SFS 1972:207) which is a part of the civil procedural law.

    In modern days Internet is often used as an aid to commit crimes. The Internet-related crimes have increased during the past decades. The perpetrator in one country can, by using Internet, commit crimes towards victims in other countries.

    Accordingly, I have analyzed the following questions: How should the courts’ international jurisdiction be decided when dealing with a private claim in a criminal case? Furthermore, which law is applicable when deciding the private claim? Other issues concern under what circumstances a court can separate the private claim from the criminal case.

    My analysis may shed some light on the needs of updating national regulations in these questions.

    Some of the issues this master thesis focuses on are that the Brussels Ibis Regulation and Rome II Regulation is treated as optional law instead of non-optional law. These instruments are to have priority as they originate in EU law.

    This master thesis shows that these issues must be dealt with in order to have confidence in the legal system and also to defend the rule of law such as legal security and foreseeability.

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