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  • 1.
    Abate Waktola, Ebba Abate
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. EPHI, Ethiopia.
    Blomgran, Robert
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Lerm, Maria
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Belayneh, Meseret
    Univ Addis Abeba, Ethiopia.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Stendahl, Olle
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Schön, Thomas
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Kalmar County Hospital, Kalmar, Sweden.
    Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 3126Article in journal (Refereed)
    Abstract [en]

    Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study.

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  • 2.
    Abbey-Lee, Robin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Uhrig, Emily
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Southern Oregon Univ, OR 97520 USA.
    Garnham, Laura
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Lundgren, Kristoffer
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Child, Sarah
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Univ Manchester, England.
    Lovlie, Hanne
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Experimental manipulation of monoamine levels alters personality in crickets2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 16211Article in journal (Refereed)
    Abstract [en]

    Animal personality has been described in a range of species with ecological and evolutionary consequences. Factors shaping and maintaining variation in personality are not fully understood, but monoaminergic systems are consistently linked to personality variation. We experimentally explored how personality was influenced by alterations in two key monoamine systems: dopamine and serotonin. This was done using ropinirole and fluoxetine, two common human pharmaceuticals. Using the Mediterranean field cricket (Gryllus bimaculatus), we focused on the personality traits activity, exploration, and aggression, with confirmed repeatability in our study. Dopamine manipulations explained little variation in the personality traits investigated, while serotonin manipulation reduced both activity and aggression. Due to limited previous research, we created a dose-response curve for ropinirole, ranging from concentrations measured in surface waters to human therapeutic doses. No ropinirole dose level strongly influenced cricket personality, suggesting our results did not come from a dose mismatch. Our results indicate that the serotonergic system explains more variation in personality than manipulations of the dopaminergic system. Additionally, they suggest that monoamine systems differ across taxa, and confirm the importance of the mode of action of pharmaceuticals in determining their effects on behaviour.

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  • 3.
    Abdalla, Hassan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Complex Materials and Devices. Linköping University, Faculty of Science & Engineering.
    van de Ruit, Kevin
    Eindhoven University of Technology, Netherlands.
    Kemerink, Martijn
    Linköping University, Department of Physics, Chemistry and Biology, Complex Materials and Devices. Linköping University, Faculty of Science & Engineering. Eindhoven University of Technology, Netherlands.
    Effective Temperature and Universal Conductivity Scaling in Organic Semiconductors2015In: Scientific Reports, E-ISSN 2045-2322, Vol. 5, article id 16870Article in journal (Refereed)
    Abstract [en]

    We investigate the scalability of the temperature-and electric field-dependence of the conductivity of disordered organic semiconductors to universal curves by two different but commonly employed methods; by so-called universal scaling and by using the effective temperature concept. Experimentally both scaling methods were found to be equally applicable to the out-of-plane charge transport in PEDOT: PSS thin films of various compositions. Both methods are shown to be equivalent in terms of functional dependence and to have identical limiting behavior. The experimentally observed scaling behavior can be reproduced by a numerical nearest-neighbor hopping model, accounting for the Coulomb interaction, the high charge carrier concentration and the energetic disorder. The underlying physics can be captured in a simple empirical model, describing the effective temperature of the charge carrier distribution as the outcome of a heat balance between Joule heating and (effective) temperature-dependent energy loss to the lattice.

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  • 4.
    Abdollahi Sani, Negar
    et al.
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Wang, Xin
    Acreo Swedish ICT AB, Sweden.
    Granberg, Hjalmar
    INNVENTIA AB, Sweden.
    Andersson Ersman, Peter
    Acreo Swedish ICT AB, Sweden.
    Crispin, Xavier
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Dyreklev, Peter
    Acreo Swedish ICT AB, Sweden.
    Engquist, Isak
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Gustafsson, Göran
    Acreo Swedish ICT AB, Sweden.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Flexible Lamination-Fabricated Ultra-High Frequency Diodes Based on Self-Supporting Semiconducting Composite Film of Silicon Micro-Particles and Nano-Fibrillated Cellulose2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, no 28921Article in journal (Refereed)
    Abstract [en]

    Low cost and flexible devices such as wearable electronics, e-labels and distributed sensors will make the future "internet of things" viable. To power and communicate with such systems, high frequency rectifiers are crucial components. We present a simple method to manufacture flexible diodes, operating at GHz frequencies, based on self-adhesive composite films of silicon micro-particles (Si-mu Ps) and glycerol dispersed in nanofibrillated cellulose (NFC). NFC, Si-mu Ps and glycerol are mixed in a water suspension, forming a self-supporting nanocellulose-silicon composite film after drying. This film is cut and laminated between a flexible pre-patterned Al bottom electrode and a conductive Ni-coated carbon tape top contact. A Schottky junction is established between the Al electrode and the Si-mu Ps. The resulting flexible diodes show current levels on the order of mA for an area of 2 mm(2), a current rectification ratio up to 4 x 10(3) between 1 and 2 V bias and a cut-off frequency of 1.8 GHz. Energy harvesting experiments have been demonstrated using resistors as the load at 900 MHz and 1.8 GHz. The diode stack can be delaminated away from the Al electrode and then later on be transferred and reconfigured to another substrate. This provides us with reconfigurable GHz-operating diode circuits.

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  • 5.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Increased nutrient availability in dense breast tissue of postmenopausal women in vivo2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 42733Article in journal (Refereed)
    Abstract [en]

    Metabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included. Microdialysis was performed for the in vivo sampling of amino acids (AAs), analyzed by ultra-high performance liquid chromatography with tandem mass spectroscopy, glucose, lactate and vascular endothelial growth factor (VEGF) in breast tissues and, as a control, in abdominal subcutaneous (s.c.) fat. We found that dense breast tissue exhibited significantly increased levels of 20 proteinogenic AAs and that 18 of these AAs correlated significantly with VEGF. No differences were found in the s.c. fat, except for one AA, suggesting tissue-specific alterations in the breast. Glucose and lactate were unaltered. Our findings provide novel insights into the biology of dense breast tissue that may be explored for breast cancer prevention strategies.

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  • 6.
    Abramavicius, V.
    et al.
    Vilnius University, Lithuania; Centre Phys Science and Technology, Lithuania.
    Pranculis, V.
    Centre Phys Science and Technology, Lithuania.
    Melianas, Armantas
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Gulbinas, V.
    Centre Phys Science and Technology, Lithuania.
    Abramavicius, D.
    Vilnius University, Lithuania.
    Role of coherence and delocalization in photo-induced electron transfer at organic interfaces2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, no 32914Article in journal (Refereed)
    Abstract [en]

    Photo-induced charge transfer at molecular heterojunctions has gained particular interest due to the development of organic solar cells (OSC) based on blends of electron donating and accepting materials. While charge transfer between donor and acceptor molecules can be described by Marcus theory, additional carrier delocalization and coherent propagation might play the dominant role. Here, we describe ultrafast charge separation at the interface of a conjugated polymer and an aggregate of the fullerene derivative PCBM using the stochastic Schrodinger equation (SSE) and reveal the complex time evolution of electron transfer, mediated by electronic coherence and delocalization. By fitting the model to ultrafast charge separation experiments, we estimate the extent of electron delocalization and establish the transition from coherent electron propagation to incoherent hopping. Our results indicate that even a relatively weak coupling between PCBM molecules is sufficient to facilitate electron delocalization and efficient charge separation at organic interfaces.

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  • 7.
    Afzali, Maryam
    et al.
    Cardiff Univ, Wales; Univ Leeds, England.
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Özarslan, Evren
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jones, Derek K.
    Cardiff Univ, Wales.
    Computing the orientational-average of diffusion-weighted MRI signals: a comparison of different techniques2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 14345Article in journal (Refereed)
    Abstract [en]

    Numerous applications in diffusion MRI involve computing the orientationally-averaged diffusion-weighted signal. Most approaches implicitly assume, for a given b-value, that the gradient sampling vectors are uniformly distributed on a sphere (or shell), computing the orientationally-averaged signal through simple arithmetic averaging. One challenge with this approach is that not all acquisition schemes have gradient sampling vectors distributed over perfect spheres. To ameliorate this challenge, alternative averaging methods include: weighted signal averaging; spherical harmonic representation of the signal in each shell; and using Mean Apparent Propagator MRI (MAP-MRI) to derive a three-dimensional signal representation and estimate its isotropic part. Here, these different methods are simulated and compared under different signal-to-noise (SNR) realizations. With sufficiently dense sampling points (61 orientations per shell), and isotropically-distributed sampling vectors, all averaging methods give comparable results, (MAP-MRI-based estimates give slightly higher accuracy, albeit with slightly elevated bias as b-value increases). As the SNR and number of data points per shell are reduced, MAP-MRI-based approaches give significantly higher accuracy compared with the other methods. We also apply these approaches to in vivo data where the results are broadly consistent with our simulations. A statistical analysis of the simulated data shows that the orientationally-averaged signals at each b-value are largely Gaussian distributed.

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  • 8.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Brain size is reduced by selectionfor tameness in Red Junglefowl–correlated effects in vital organs2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 3306Article in journal (Refereed)
    Abstract [en]

    During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

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  • 9.
    Aguilar-Calvo, Patricia
    et al.
    University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA.
    Xiao, Xiangzhu
    Case Western Reserve University, OH 44116 USA.
    Bett, Cyrus
    University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA; US FDA, MD USA.
    Erana, Hasier
    CIC bioGUNE, Spain.
    Soldau, Katrin
    University of Calif San Diego, CA 92093 USA.
    Castilla, Joaquin
    University of Calif San Diego, CA 92093 USA; CIC bioGUNE, Spain; Ikerbasque, Spain.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Surewicz, Witold K.
    Case Western Reserve University, OH 44116 USA.
    Sigurdson, Christina J.
    University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA; University of Calif Davis, CA 95616 USA.
    Post-translational modifications in PrP expand the conformational diversity of prions in vivo2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 43295Article in journal (Refereed)
    Abstract [en]

    Misfolded prion protein aggregates (PrPSc) show remarkable structural diversity and are associated with highly variable disease phenotypes. Similarly, other proteins, including amyloid-beta, tau, alpha-synuclein, and serum amyloid A, misfold into distinct conformers linked to different clinical diseases through poorly understood mechanisms. Here we use mice expressing glycophosphatidylinositol (GPI)anchorless prion protein, PrPC, together with hydrogen-deuterium exchange coupled with mass spectrometry (HXMS) and a battery of biochemical and biophysical tools to investigate how posttranslational modifications impact the aggregated prion protein properties and disease phenotype. Four GPI-anchorless prion strains caused a nearly identical clinical and pathological disease phenotype, yet maintained their structural diversity in the anchorless state. HXMS studies revealed that GPIanchorless PrPSc is characterized by substantially higher protection against hydrogen/deuterium exchange in the C-terminal region near the N-glycan sites, suggesting this region had become more ordered in the anchorless state. For one strain, passage of GPI-anchorless prions into wild type mice led to the emergence of a novel strain with a unique biochemical and phenotypic signature. For the new strain, histidine hydrogen-deuterium mass spectrometry revealed altered packing arrangements of beta-sheets that encompass residues 139 and 186 of PrPSc. These findings show how variation in posttranslational modifications may explain the emergence of new protein conformations in vivo and also provide a basis for understanding how the misfolded protein structure impacts the disease.

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  • 10.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK 99508 USA.
    Bonnedahl, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Sweden.
    Hernandez, Jorge
    Uppsala Univ, Sweden.
    Olsen, Bjorn
    Uppsala Univ, Sweden.
    Ramey, Andrew M.
    US Geol Survey, AK 99508 USA.
    Acquisition and dissemination of cephalosporin-resistant E.coli in migratory birds sampled at an Alaska landfill as inferred through genomic analysis2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 7361Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in bacterial pathogens threatens global health, though the spread of AMR bacteria and AMR genes between humans, animals, and the environment is still largely unknown. Here, we investigated the role of wild birds in the epidemiology of AMR Escherichia coli. Using next-generation sequencing, we characterized cephalosporin-resistant E. coli cultured from sympatric gulls and bald eagles inhabiting a landfill habitat in Alaska to identify genetic determinants conferring AMR, explore potential transmission pathways of AMR bacteria and genes at this site, and investigate how their genetic diversity compares to isolates reported in other taxa. We found genetically diverse E. coli isolates with sequence types previously associated with human infections and resistance genes of clinical importance, including blaCTX-M and blaCMY. Identical resistance profiles were observed in genetically unrelated E. coli isolates from both gulls and bald eagles. Conversely, isolates with indistinguishable core-genomes were found to have different resistance profiles. Our findings support complex epidemiological interactions including bacterial strain sharing between gulls and bald eagles and horizontal gene transfer among E. coli harboured by birds. Results suggest that landfills may serve as a source for AMR acquisition and/or maintenance, including bacterial sequence types and AMR genes relevant to human health.

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  • 11.
    Akram, Usman
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Quttineh, Nils-Hassan
    Linköping University, Department of Mathematics, Applied Mathematics. Linköping University, Faculty of Science & Engineering.
    Wennergren, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Tonderski, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Metson, Genevieve
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering. Linköping University, Centre for Climate Science and Policy Research, CSPR.
    Author Correction: Enhancing nutrient recycling from excreta to meet crop nutrient needs in Sweden - a spatial analysis2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 361Article in journal (Other academic)
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  • 12.
    Akram, Usman
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Quttineh, Nils-Hassan
    Linköping University, Department of Mathematics, Optimization. Linköping University, Faculty of Science & Engineering.
    Wennergren, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Tonderski, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Metson, Genevieve
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Enhancing nutrient recycling from excreta to meet crop nutrient needs in Sweden - a spatial analysis2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 10264Article in journal (Refereed)
    Abstract [en]

    Increased recycling of nutrient-rich organic waste to meet crop nutrient needs is an essential component of a more sustainable food system. However, agricultural specialization continues to pose a significant challenge to balancing crop nutrient needs and the nutrient supply from animal manure and human excreta locally. For Sweden, this study found that recycling all excreta (in 2007) could meet up to 75% of crop nitrogen and 81% of phosphorus needs, but that this would exceed crop potassium needs by 51%. Recycling excreta within municipalities could meet 63% of crop P nutrient needs, but large regional differences and imbalances need to be corrected to avoid over or under fertilizing. Over 50% of the total nitrogen and phosphorus in excreta is contained in just 40% of municipalities, and those have a surplus of excreta nutrients compared to crop needs. Reallocation of surpluses (nationally optimized for phosphorus) towards deficit municipalities, would cost 192 million USD (for 24 079 km of truck travel). This is 3.7 times more than the total NPK fertilizer value being transported. These results indicate that Sweden could reduce its dependence on synthetic fertilizers through investments in excreta recycling, but this would likely require valuing also other recycling benefits.

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  • 13.
    Alene Asres, Georgies
    et al.
    University of Oulu, Finland.
    Dombovari, Aron
    University of Oulu, Finland.
    Sipola, Teemu
    University of Oulu, Finland.
    Puskas, Robert
    University of Szeged, Hungary.
    Kukovecz, Akos
    University of Szeged, Hungary; MTA SZTE Lendulet Porous Nanocomposites Research Grp, Hungary.
    Konya, Zoltan
    University of Szeged, Hungary; MTA SZTE React Kinet and Surface Chemistry Research Grp, Hungary.
    Popov, Alexey
    University of Oulu, Finland.
    Lin, Jhih-Fong
    University of Oulu, Finland.
    Lorite, Gabriela S.
    University of Oulu, Finland.
    Mohl, Melinda
    University of Oulu, Finland.
    Toth, Geza
    University of Oulu, Finland.
    Lloyd Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, Faculty of Science & Engineering. University of Oulu, Finland.
    Kordas, Krisztian
    University of Oulu, Finland.
    A novel WS2 nanowire-nanoflake hybrid material synthesized from WO3 nanowires in sulfur vapor2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, no 25610Article in journal (Refereed)
    Abstract [en]

    In this work, WS2 nanowire-nanoflake hybrids are synthesized by the sulfurization of hydrothermally grown WO3 nanowires. The influence of temperature on the formation of products is optimized to grow WS2 nanowires covered with nanoflakes. Current-voltage and resistance-temperature measurements carried out on random networks of the nanostructures show nonlinear characteristics and negative temperature coefficient of resistance indicating that the hybrids are of semiconducting nature. Bottom gated field effect transistor structures based on random networks of the hybrids show only minor modulation of the channel conductance upon applied gate voltage, which indicates poor electrical transport between the nanowires in the random films. On the other hand, the photo response of channel current holds promise for cost-efficient solution process fabrication of photodetector devices working in the visible spectral range.

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  • 14.
    Alexander-Webber, J. A.
    et al.
    University of Oxford, England; University of Cambridge, England.
    Huang, J.
    University of Oxford, England.
    Maude, D. K.
    CNRS UGA UPS INSA, France.
    Janssen, T. J. B. M.
    National Phys Lab, England.
    Tzalenchuk, A.
    National Phys Lab, England; Royal Holloway University of London, England.
    Antonov, V.
    Royal Holloway University of London, England.
    Yager, T.
    Chalmers, Sweden.
    Lara-Avila, S.
    Chalmers, Sweden.
    Kubatkin, S.
    Chalmers, Sweden.
    Yakimova, Rositsa
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    Nicholas, R. J.
    University of Oxford, England.
    Giant quantum Hall plateaus generated by charge transfer in epitaxial graphene2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, no 30296Article in journal (Refereed)
    Abstract [en]

    Epitaxial graphene has proven itself to be the best candidate for quantum electrical resistance standards due to its wide quantum Hall plateaus with exceptionally high breakdown currents. However one key underlying mechanism, a magnetic field dependent charge transfer process, is yet to be fully understood. Here we report measurements of the quantum Hall effect in epitaxial graphene showing the widest quantum Hall plateau observed to date extending over 50 T, attributed to an almost linear increase in carrier density with magnetic field. This behaviour is strong evidence for field dependent charge transfer from charge reservoirs with exceptionally high densities of states in close proximity to the graphene. Using a realistic framework of broadened Landau levels we model the densities of donor states and predict the field dependence of charge transfer in excellent agreement with experimental results, thus providing a guide towards engineering epitaxial graphene for applications such as quantum metrology.

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  • 15.
    Ali, Abshir A.
    et al.
    East Africa Univ, Somalia.
    Aalto, Mikko
    Bosaso Gen Hosp, Somalia.
    Jonasson, Jon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Osman, Abdimajid
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Genome-wide analyses disclose the distinctive HLA architecture and the pharmacogenetic landscape of the Somali population2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 5652Article in journal (Refereed)
    Abstract [en]

    African populations are underrepresented in medical genomics studies. For the Somali population, there is virtually no information on genomic markers with significance to precision medicine. Here, we analyzed nearly 900,000 genomic markers in samples collected from 95 unrelated individuals in the North Eastern Somalia. ADMIXTURE program for estimation of individual ancestries revealed a homogenous Somali population. Principal component analysis with PLINK software showed approximately 60% East African and 40% West Eurasian genes in the Somali population, with a close relation to the Cushitic and Semitic speaking Ethiopian populations. We report the unique features of human leukocyte antigens (HLA) in the Somali population, which seem to differentiate from all other neighboring regions compared. Current study identified high prevalence of the diabetes type 1 (T1D) predisposing HLA DR-DQ haplotypes in Somalia. This finding may explain the increased T1D risk observed among Somali children. In addition, ethnic Somalis were found to host the highest frequencies observed thus far for several pharmacogenetic variants, including UGT1A4*2. In conclusion, we report that the Somali population displays genetic traits of significance to health and disease. The Somali dataset is publicly available and will add more information to the few genomic datasets available for African populations.

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  • 16.
    Alizadeh, Javad
    et al.
    University of Manitoba, Canada.
    Zeki, Amir A.
    Centre Comparat Resp Biol and Med, CA USA.
    Mirzaei, Nima
    University of Manitoba, Canada.
    Tewary, Sandipan
    University of Manitoba, Canada.
    Rezaei Moghadam, Adel
    University of Manitoba, Canada; University of Manitoba, Canada.
    Glogowska, Aleksandra
    University of Manitoba, Canada.
    Nagakannan, Pandian
    University of Manitoba, Canada.
    Eftekharpour, Eftekhar
    University of Manitoba, Canada.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Gordon, Joseph W.
    University of Manitoba, Canada; University of Manitoba, Canada; University of Manitoba, Canada.
    Xu, Fred. Y.
    University of Manitoba, Canada; University of Manitoba, Canada.
    Field, Jared T.
    University of Manitoba, Canada.
    Yoneda, Ken Y.
    Centre Comparat Resp Biol and Med, CA USA.
    Kenyon, Nicholas J.
    Centre Comparat Resp Biol and Med, CA USA.
    Hashemi, Mohammad
    Zehedan University of Medical Science, Iran.
    Hatch, Grant M.
    University of Manitoba, Canada; University of Manitoba, Canada.
    Hombach-Klonisch, Sabine
    University of Manitoba, Canada.
    Klonisch, Thomas
    University of Manitoba, Canada.
    Ghavami, Saeid
    University of Manitoba, Canada; University of Manitoba, Canada; Shiraz University of Medical Science, Iran.
    Mevalonate Cascade Inhibition by Simvastatin Induces the Intrinsic Apoptosis Pathway via Depletion of Isoprenoids in Tumor Cells2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 44841Article in journal (Refereed)
    Abstract [en]

    The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway. In all cancer cell types tested, simvastatin-induced cell death was not rescued by cholesterol, but was dependent on GGPP-and FPP-depletion. We confirmed that simvastatin caused the translocation of the small Rho GTPases RhoA, Cdc42, and Rac1/2/3 from cell membranes to the cytosol in U251 (glioblastoma), A549 (lung adenocarcinoma) and MDA-MB231( breast cancer). Simvastatin-induced Rho-GTP loading significantly increased in U251 cells which were reversed with MEV, FPP, GGPP. In contrast, simvastatin did not change Rho-GTP loading in A549 and MDA-MB-231. Inhibition of geranylgeranyltransferase I by GGTi-298, but not farnesyltransferase by FTi-277, induced significant cell death in U251, A549, and MDA-MB-231. These results indicate that MEV cascade inhibition by simvastatin induced the intrinsic apoptosis pathway via inhibition of Rho family prenylation and depletion of GGPP, in a variety of different human cancer cell lines.

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  • 17.
    Alling, Björn
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Högberg, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Armiento, Rickard
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    Rosén, Johanna
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Hultman, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    A theoretical investigation of mixing thermodynamics, age-hardening potential, and electronic structure of ternary (M1-xMxB2)-M-1-B-2 alloys with AlB2 type structure2015In: Scientific Reports, E-ISSN 2045-2322, Vol. 5Article in journal (Refereed)
    Abstract [en]

    Transition metal diborides are ceramic materials with potential applications as hard protective thin films and electrical contact materials. We investigate the possibility to obtain age hardening through isostructural clustering, including spinodal decomposition, or ordering-induced precipitation in ternary diboride alloys. By means of first-principles mixing thermodynamics calculations, 45 ternary (M1-xMxB2)-M-1-B-2 alloys comprising (MB2)-B-i (M-i = Mg, Al, Sc, Y, Ti, Zr, Hf, V, Nb, Ta) with AlB2 type structure are studied. In particular Al1-xTixB2 is found to be of interest for coherent isostructural decomposition with a strong driving force for phase separation, while having almost concentration independent a and c lattice parameters. The results are explained by revealing the nature of the electronic structure in these alloys, and in particular, the origin of the pseudogap at E-F in TiB2, ZrB2, and HfB2.

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  • 18.
    Alshourbaji, Ibrahim
    et al.
    Univ Hertfordshire, England; Jazan Univ, Saudi Arabia.
    Helian, Na
    Univ Hertfordshire, England.
    Sun, Yi
    Univ Hertfordshire, England.
    Hussien, Abdelazim
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering. Fayoum Univ, Egypt.
    Abualigah, Laith
    Al Al Bayt Univ, Jordan; Lebanese Amer Univ, Lebanon; Al Ahliyya Amman Univ, Jordan; Middle East Univ, Jordan; Appl Sci Private Univ, Jordan; Univ Sains Malaysia, Malaysia; Sunway Univ, Malaysia.
    Elnaim, Bushra
    Prince Sattam Bin Abdulaziz Univ, Saudi Arabia.
    An efficient churn prediction model using gradient boosting machine and metaheuristic optimization2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 14441Article in journal (Refereed)
    Abstract [en]

    Customer churn remains a critical challenge in telecommunications, necessitating effective churn prediction (CP) methodologies. This paper introduces the Enhanced Gradient Boosting Model (EGBM), which uses a Support Vector Machine with a Radial Basis Function kernel (SVMRBF) as a base learner and exponential loss function to enhance the learning process of the GBM. The novel base learner significantly improves the initial classification performance of the traditional GBM and achieves enhanced performance in CP-EGBM after multiple boosting stages by utilizing state-of-the-art decision tree learners. Further, a modified version of Particle Swarm Optimization (PSO) using the consumption operator of the Artificial Ecosystem Optimization (AEO) method to prevent premature convergence of the PSO in the local optima is developed to tune the hyper-parameters of the CP-EGBM effectively. Seven open-source CP datasets are used to evaluate the performance of the developed CP-EGBM model using several quantitative evaluation metrics. The results showed that the CP-EGBM is significantly better than GBM and SVM models. Results are statistically validated using the Friedman ranking test. The proposed CP-EGBM is also compared with recently reported models in the literature. Comparative analysis with state-of-the-art models showcases CP-EGBMs promising improvements, making it a robust and effective solution for churn prediction in the telecommunications industry.

  • 19.
    Altimiras, Jordi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Lindgren, Isa
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Giraldo-Deck, Lina Maria
    University of Mayor San Andres, Bolivia.
    Matthei, Alberto
    Tinamou Chile SL, Chile.
    Garitano-Zavala, Alvaro
    University of Mayor San Andres, Bolivia.
    Aerobic performance in tinamous is limited by their small heart. A novel hypothesis in the evolution of avian flight2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 15964Article in journal (Refereed)
    Abstract [en]

    Some biomechanical studies from fossil specimens suggest that sustained flapping flight of birds could have appeared in their Mesozoic ancestors. We challenge this idea because a suitable musculoskeletal anatomy is not the only requirement for sustained flapping flight. We propose the "heart to fly" hypothesis that states that sustained flapping flight in modern birds required an enlargement of the heart for the aerobic performance of the flight muscles and test it experimentally by studying tinamous, the living birds with the smallest hearts. The small ventricular size of tinamous reduces cardiac output without limiting perfusion pressures, but when challenged to fly, the heart is unable to support aerobic metabolism (quick exhaustion, larger lactates and post-exercise oxygen consumption and compromised thermoregulation). At the same time, cardiac growth shows a crocodilian-like pattern and is correlated with differential gene expression in MAPK kinases. We integrate this physiological evidence in a new evolutionary scenario in which the ground-up, short and not sustained flapping flight displayed by tinamous represents an intermediate step in the evolution of the aerobic sustained flapping flight of modern birds.

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  • 20.
    Anacleto, Thuane Mendes
    et al.
    Univ Fed Rio de Janeiro, Brazil; Univ Fed Rio de Janeiro, Brazil.
    Kozlowsky-Suzuki, Betina
    Fed Univ State Rio De Janeiro, Brazil; Fed Univ State Rio De Janeiro, Brazil; Fed Univ State Rio De Janeiro, Brazil.
    Björn, Annika
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Solutions Research Center.
    Shakeri Yekta, Sepehr
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Solutions Research Center.
    Masuda, Laura Shizue Moriga
    Ch Mendes Inst Biodivers Conservat ICMBio, Brazil.
    de Oliveira, Vinicius Peruzzi
    Univ Fed Rio de Janeiro, Brazil.
    Enrich Prast, Alex
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Solutions Research Center. Univ Fed Rio de Janeiro, Brazil; Fed Univ Sao Paulo IMar UNIFESP, Brazil.
    Methane yield response to pretreatment is dependent on substrate chemical composition: a meta-analysis on anaerobic digestion systems2024In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 1240Article in journal (Refereed)
    Abstract [en]

    Proper pretreatment of organic residues prior to anaerobic digestion (AD) can maximize global biogas production from varying sources without increasing the amount of digestate, contributing to global decarbonization goals. However, the efficiency of pretreatments applied on varying organic streams is poorly assessed. Thus, we performed a meta-analysis on AD studies to evaluate the efficiencies of pretreatments with respect to biogas production measured as methane yield. Based on 1374 observations our analysis shows that pretreatment efficiency is dependent on substrate chemical dominance. Grouping substrates by chemical composition e.g., lignocellulosic-, protein- and lipid-rich dominance helps to highlight the appropriate choice of pretreatment that supports maximum substrate degradation and more efficient conversion to biogas. Methane yield can undergo an impactful increase compared to untreated controls if proper pretreatment of substrates of a given chemical dominance is applied. Non-significant or even adverse effects on AD are, however, observed when the substrate chemical dominance is disregarded.

  • 21.
    Andersson, Anna-Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Blanka
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lorell, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Raffetseder, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, no 28171Article in journal (Refereed)
    Abstract [en]

    To survive and replicate in macrophages Mycobacterium tuberculosis (Mtb) has developed strategies to subvert host defence mechanisms, including autophagy. Autophagy induction has the potential to clear Mtb, but little is known about its effect during controlled tuberculosis and HIV co-infection. Mammalian target of rapamycin complex1 (mTORC1) inhibitors were used to induce autophagy in human macrophages pre-infected with HIV-1(BaL) and infected with a low dose of Mtb (co-infected), or single Mtb infected (single infected). The controlled Mtb infection was disrupted upon mTOR inhibition resulting in increased Mtb replication in a dose-dependent manner which was more pronounced during co-infection. The increased Mtb replication could be explained by the marked reduction in phagosome acidification upon mTOR inhibition. Autophagy stimulation targeting mTORC1 clearly induced a basal autophagy with flux that was unlinked to the subcellular environment of the Mtb vacuoles, which showed a concurrent suppression in acidification and maturation/flux. Overall our findings indicate that mTOR inhibition during Mtb or HIV/Mtb co-infection interferes with phagosomal maturation, thereby supporting mycobacterial growth during low-dose and controlled infection. Therefore pharmacological induction of autophagy through targeting of the canonical mTORC1-pathway should be handled with caution during controlled tuberculosis, since this could have serious consequences for patients with HIV/Mtb co-infection.

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  • 22.
    Andersson White, Pär
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Faresjö, Tomas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Low maternal education increases the risk of Type 1 Diabetes, but not other autoimmune diseases: a mediating role of childhood BMI and exposure to serious life events2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1Article in journal (Refereed)
    Abstract [en]

    The objective of this paper was to investigate if socioeconomic status (SES), measured by maternal education and household income, influenced the risk of developing autoimmune disease (Type 1 Diabetes, Celiac disease, Juvenile Idiopathic Arthritis, Crohns disease, Ulcerative colitis, and autoimmune thyroid disease), or age at diagnosis, and to analyse pathways between SES and autoimmune disease. We used data from the All Babies in Southeast Sweden (ABIS) study, a population-based prospective birth cohort, which included children born 1997-1999. Diagnoses of autoimmune disease was collected from the Swedish National Patient Register Dec 2020. In 16,365 individuals, low maternal education, but not household income, was associated with increased risk of Type 1 Diabetes; middle education RR 1.54, 95% CI 1.06, 2.23; P 0.02, low education RR 1.81, 95% CI 1.04, 3.18; P 0.04. Maternal education and household income was not associated with any other autoimmune disease and did not influence the age at diagnosis. Part of the increased risk of Type 1 Diabetes by lower maternal education was mediated by the indirect pathway of higher BMI and higher risk of Serious Life Events (SLE) at 5 years of age. The risk of developing Type 1 Diabetes associated to low maternal education might be reduced by decreasing BMI and SLE during childhood.

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  • 23.
    Armgarth, Astrid
    et al.
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering. RISE Res Inst Sweden AB, Sweden.
    Pantzare, Sandra
    RISE Res Inst Sweden AB, Sweden.
    Arven, Patrik
    J2 Holding AB, Sweden.
    Lassnig, Roman
    RISE Res Inst Sweden AB, Sweden.
    Jinno, Hiroaki
    RIKEN, Japan; Univ Tokyo, Japan.
    Gabrielsson, Erik
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Kifle, Yonatan Habteslassie
    Linköping University, Department of Electrical Engineering, Integrated Circuits and Systems. Linköping University, Faculty of Science & Engineering.
    Cherian, Dennis
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Arbring Sjöström, Theresia
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Berthou, Gautier
    Res Inst Sweden AB, Sweden.
    Dowling, Jim
    Res Inst Sweden AB, Sweden; KTH Royal Inst Technol, Sweden.
    Someya, Takao
    RIKEN, Japan; Univ Tokyo, Japan.
    Wikner, Jacob
    Linköping University, Department of Electrical Engineering, Integrated Circuits and Systems. Linköping University, Faculty of Science & Engineering.
    Gustafsson, Göran
    RISE Res Inst Sweden AB, Sweden.
    Simon, Daniel
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    A digital nervous system aiming toward personalized IoT healthcare2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 7757Article in journal (Refereed)
    Abstract [en]

    Body area networks (BANs), cloud computing, and machine learning are platforms that can potentially enable advanced healthcare outside the hospital. By applying distributed sensors and drug delivery devices on/in our body and connecting to such communication and decision-making technology, a system for remote diagnostics and therapy is achieved with additional autoregulation capabilities. Challenges with such autarchic on-body healthcare schemes relate to integrity and safety, and interfacing and transduction of electronic signals into biochemical signals, and vice versa. Here, we report a BAN, comprising flexible on-body organic bioelectronic sensors and actuators utilizing two parallel pathways for communication and decision-making. Data, recorded from strain sensors detecting body motion, are both securely transferred to the cloud for machine learning and improved decision-making, and sent through the body using a secure body-coupled communication protocol to auto-actuate delivery of neurotransmitters, all within seconds. We conclude that both highly stable and accurate sensing-from multiple sensors-are needed to enable robust decision making and limit the frequency of retraining. The holistic platform resembles the self-regulatory properties of the nervous system, i.e., the ability to sense, communicate, decide, and react accordingly, thus operating as a digital nervous system.

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  • 24.
    Aronsson, Christopher
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Dånmark, Staffan
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Zhou, Feng
    Nanyang Technology University, Singapore.
    Öberg, Per
    Linköping University, Department of Electrical Engineering, Vehicular Systems. Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Su, Haibin
    Nanyang Technology University, Singapore.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties2015In: Scientific Reports, E-ISSN 2045-2322, Vol. 5, no 14063Article in journal (Refereed)
    Abstract [en]

    Coiled coils with defined assembly properties and dissociation constants are highly attractive components in synthetic biology and for fabrication of peptide-based hybrid nanomaterials and nanostructures. Complex assemblies based on multiple different peptides typically require orthogonal peptides obtained by negative design. Negative design does not necessarily exclude formation of undesired species and may eventually compromise the stability of the desired coiled coils. This work describe a set of four promiscuous 28-residue de novo designed peptides that heterodimerize and fold into parallel coiled coils. The peptides are non-orthogonal and can form four different heterodimers albeit with large differences in affinities. The peptides display dissociation constants for dimerization spanning from the micromolar to the picomolar range. The significant differences in affinities for dimerization make the peptides prone to thermodynamic social self-sorting as shown by thermal unfolding and fluorescence experiments, and confirmed by simulations. The peptides self-sort with high fidelity to form the two coiled coils with the highest and lowest affinities for heterodimerization. The possibility to exploit self-sorting of mutually complementary peptides could hence be a viable approach to guide the assembly of higher order architectures and a powerful strategy for fabrication of dynamic and tuneable nanostructured materials.

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  • 25.
    Arshamian, Artin
    et al.
    Karolinska Institute, Sweden; Radboud University of Nijmegen, Netherlands; Radboud University of Nijmegen, Netherlands; Stockholm University, Sweden.
    Laska, Matthias
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Gordon, Amy R.
    Karolinska Institute, Sweden; Monell Chemistry Senses Centre, PA 19104 USA.
    Norberg, Matilda
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Lahger, Christian
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Porada, Danja K.
    Karolinska Institute, Sweden.
    Jelvez Serra, Nadia
    Lund University, Sweden.
    Johansson, Emilia
    Karolinska Institute, Sweden.
    Schaefer, Martin
    Karolinska Institute, Sweden.
    Amundin, Mats
    Kolmarden Wildlife Pk, Sweden.
    Melin, Harald
    Karolinska Institute, Sweden.
    Olsson, Andreas
    Karolinska Institute, Sweden.
    Olsson, Mats J.
    Karolinska Institute, Sweden.
    Stensmyr, Marcus
    Lund University, Sweden.
    Lundstrom, Johan N.
    Karolinska Institute, Sweden; Monell Chemistry Senses Centre, PA 19104 USA; University of Penn, PA 19104 USA.
    A mammalian blood odor component serves as an approach-avoidance cue across phylum border - from flies to humans2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 13635Article in journal (Refereed)
    Abstract [en]

    Chemosignals are used by predators to localize prey and by prey to avoid predators. These cues vary between species, but the odor of blood seems to be an exception and suggests the presence of an evolutionarily conserved chemosensory cue within the blood odor mixture. A blood odor component, E2D, has been shown to trigger approach responses identical to those triggered by the full blood odor in mammalian carnivores and as such, is a key candidate as a food/alarm cue in blood. Using a multidisciplinary approach, we demonstrate that E2D holds the dual function of affecting both approach and avoidance behavior in a predator-prey predicted manner. E2D evokes approach responses in two taxonomically distant blood-seeking predators, Stable fly and Wolf, while evoking avoidance responses in the prey species Mouse. We extend this by demonstrating that this chemical cue is preserved in humans as well; E2D induces postural avoidance, increases physiological arousal, and enhances visual perception of affective stimuli. This is the first demonstration of a single chemical cue with the dual function of guiding both approach and avoidance in a predator-prey predicted manner across taxonomically distant species, as well as the first known chemosignal that affects both human and non-human animals alike.

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  • 26.
    Asadi, Mehdi
    et al.
    Tarbiat Modares Univ, Iran.
    Poursalim, Fatemeh
    Shiraz Univ Med Sci, Iran.
    Loni, Mohammad
    Malardalen Univ, Sweden.
    Daneshtalab, Masoud
    Malardalen Univ, Sweden.
    Sjodin, Mikael
    Malardalen Univ, Sweden.
    Gharehbaghi, Arash
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Accurate detection of paroxysmal atrial fibrillation with certified-GAN and neural architecture search2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 11378Article in journal (Refereed)
    Abstract [en]

    This paper presents a novel machine learning framework for detecting PxAF, a pathological characteristic of electrocardiogram (ECG) that can lead to fatal conditions such as heart attack. To enhance the learning process, the framework involves a generative adversarial network (GAN) along with a neural architecture search (NAS) in the data preparation and classifier optimization phases. The GAN is innovatively invoked to overcome the class imbalance of the training data by producing the synthetic ECG for PxAF class in a certified manner. The effect of the certified GAN is statistically validated. Instead of using a general-purpose classifier, the NAS automatically designs a highly accurate convolutional neural network architecture customized for the PxAF classification task. Experimental results show that the accuracy of the proposed framework exhibits a high value of 99.0% which not only enhances state-of-the-art by up to 5.1%, but also improves the classification performance of the two widely-accepted baseline methods, ResNet-18, and Auto-Sklearn, by 2.2% and 6.1%.

  • 27.
    Ashaduzzaman, Md.
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering. UCS, Institute Adv Mat, Teknikringen 4A,Mjardevi Science Pk, SE-58330 Linkoping, Sweden.
    Deshpande, Swapneel R.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering. UCS, Institute Adv Mat, Teknikringen 4A,Mjardevi Science Pk, SE-58330 Linkoping, Sweden.
    Arul Murugan, N.
    Royal Institute Technology, Sweden.
    Kumar Mishra, Yogendra
    University of Kiel, Germany.
    Turner, Anthony
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Tiwari, Ashutosh
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering. UCS, Institute Adv Mat, Teknikringen 4A,Mjardevi Science Pk, SE-58330 Linkoping, Sweden; Vinoba Bhave Research Institute, India.
    On/off-switchable LSPR nano-immunoassay for troponin-T2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 44027Article in journal (Refereed)
    Abstract [en]

    Regeneration of immunosensors is a longstanding challenge. We have developed a re-usable troponin-T (TnT) immunoassay based on localised surface plasmon resonance (LSPR) at gold nanorods (GNR). Thermosensitive poly(N-isopropylacrylamide) (PNIPAAM) was functionalised with anti-TnT to control the affinity interaction with TnT. The LSPR was extremely sensitive to the dielectric constant of the surrounding medium as modulated by antigen binding after 20 min incubation at 37 degrees C. Computational modelling incorporating molecular docking, molecular dynamics and free energy calculations was used to elucidate the interactions between the various subsystems namely, IgG-antibody (c. f., anti-TnT), PNIPAAM and/or TnT. This study demonstrates a remarkable temperature dependent immuno-interaction due to changes in the PNIPAAM secondary structures, i.e., globular and coil, at above or below the lower critical solution temperature (LCST). A series of concentrations of TnT were measured by correlating the lambda(LSPR) shift with relative changes in extinction intensity at the distinct plasmonic maximum (i. e., 832 nm). The magnitude of the red shift in lambda(LSPR) was nearly linear with increasing concentration of TnT, over the range 7.6 x 10(-15) to 9.1 x 10(-4) g/mL. The LSPR based nano-immunoassay could be simply regenerated by switching the polymer conformation and creating a gradient of microenvironments between the two states with a modest change in temperature.

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  • 28.
    Asutay, Erkin
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Chalmers, Sweden.
    Västfjäll, Daniel
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Decis Research, OR USA.
    Auditory attentional selection is biased by reward cues2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 36989Article in journal (Refereed)
    Abstract [en]

    Auditory attention theories suggest that humans are able to decompose the complex acoustic input into separate auditory streams, which then compete for attentional resources. How this attentional competition is influenced by motivational salience of sounds is, however, not well-understood. Here, we investigated whether a positive motivational value associated with sounds could bias the attentional selection in an auditory detection task. Participants went through a reward-learning period, where correct attentional selection of one stimulus (CS+) lead to higher rewards compared to another stimulus (CS-). We assessed the impact of reward-learning by comparing perceptual sensitivity before and after the learning period, when CS+ and CS-were presented as distractors for a different target. Performance decreased after reward-learning when CS+ was a distractor, while it increased when CS- was a distractor. Thus, the findings show that sounds that were associated with high rewards captures attention involuntarily. Additionally, when successful inhibition of a particular sound (CS-) was associated with high rewards then it became easier to ignore it. The current findings have important implications for the understanding of the organizing principles of auditory perception and provide, for the first time, clear behavioral evidence for reward-dependent attentional learning in the auditory domain in humans.

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  • 29.
    Asutay, Erkin
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Västfjäll, Daniel
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Decis Research, OR 97401 USA.
    Exposure to arousal-inducing sounds facilitates visual search2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 10363Article in journal (Refereed)
    Abstract [en]

    Exposure to affective stimuli could enhance perception and facilitate attention via increasing alertness, vigilance, and by decreasing attentional thresholds. However, evidence on the impact of affective sounds on perception and attention is scant. Here, a novel aspect of affective facilitation of attention is studied: whether arousal induced by task-irrelevant auditory stimuli could modulate attention in a visual search. In two experiments, participants performed a visual search task with and without auditory-cues that preceded the search. Participants were faster in locating high-salient targets compared to low-salient targets. Critically, search times and search slopes decreased with increasing auditory-induced arousal while searching for low-salient targets. Taken together, these findings suggest that arousal induced by sounds can facilitate attention in a subsequent visual search. This novel finding provides support for the alerting function of the auditory system by showing an auditory-phasic alerting effect in visual attention. The results also indicate that stimulus arousal modulates the alerting effect. Attention and perception are our everyday tools to navigate our surrounding world and the current findings showing that affective sounds could influence visual attention provide evidence that we make use of affective information during perceptual processing.

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  • 30.
    Asutay, Erkin
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Västfjäll, Daniel
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Decis Res, OR USA.
    The continuous and changing impact of affect on risky decision-making2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 10613Article in journal (Refereed)
    Abstract [en]

    Affective experience has an important role in decision-making with recent theories suggesting a modulatory role of affect in ongoing subjective value computations. However, it is unclear how varying expectations and uncertainty dynamically influence affective experience and how dynamic representation of affect modulates risky choices. Using hierarchical Bayesian modeling on data from a risky choice task (N = 101), we find that the temporal integration of recently encountered choice parameters (expected value, uncertainty, and prediction errors) shapes affective experience and impacts subsequent choice behavior. Specifically, self-reported arousal prior to choice was associated with increased loss aversion, risk aversion, and choice consistency. Taken together, these findings provide clear behavioral evidence for continuous affective modulation of subjective value computations during risky decision-making.

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  • 31.
    Azharuddin, Mohammad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology.
    Dhara, Ashis Kumar
    Natl Inst Technol Durgapur, India.
    Jain, Mayur Vilas
    Lund Univ, Sweden.
    D´arcy, Padraig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Slater, Nigel K. H.
    Univ Cambridge, England.
    Patra, Hirak Kumar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Univ Cambridge, England.
    Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 20066Article in journal (Refereed)
    Abstract [en]

    One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-imensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.

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  • 32.
    Aziz, Mubashir
    et al.
    Islamia Univ Bahawalpur, Pakistan.
    Ejaz, Syeda Abida
    Islamia Univ Bahawalpur, Pakistan.
    Tamam, Nissren
    Princess Nourah Bint Abdulrahman Univ, Saudi Arabia.
    Siddique, Farhan
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering. Royal Inst Med Sci RIMS, Pakistan.
    Riaz, Naheed
    Islamia Univ Bahawalpur, Pakistan.
    Qais, Faizan Abul
    Aligarh Muslim Univ, India.
    Chtita, Samir
    Hassan II Univ Casablanca, Morocco.
    Iqbal, Jamshed
    COMSATS Univ Islamabad, Pakistan.
    Identification of potent inhibitors of NEK7 protein using a comprehensive computational approach2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 6404Article in journal (Refereed)
    Abstract [en]

    NIMA related Kinases (NEK7) plays an important role in spindle assembly and mitotic division of the cell. Over expression of NEK7 leads to the progression of different cancers and associated malignancies. It is becoming the next wave of targets for the development of selective and potent anti-cancerous agents. The current study is the first comprehensive computational approach to identify potent inhibitors of NEK7 protein. For this purpose, previously identified anti-inflammatory compound i.e., Phenylcarbamoylpiperidine-1,2,4-triazole amide derivatives by our own group were selected for their anti-cancer potential via detailed Computational studies. Initially, the density functional theory (DFT) calculations were carried out using Gaussian 09 software which provided information about the compounds stability and reactivity. Furthermore, Autodock suite and Molecular Operating Environment (MOE) softwares were used to dock the ligand database into the active pocket of the NEK7 protein. Both software performances were compared in terms of sampling power and scoring power. During the analysis, Autodock results were found to be more reproducible, implying that this software outperforms the MOE. The majority of the compounds, including M7, and M12 showed excellent binding energies and formed stable protein-ligand complexes with docking scores of - 29.66 kJ/mol and - 31.38 kJ/mol, respectively. The results were validated by molecular dynamics simulation studies where the stability and conformational transformation of the best protein-ligand complex were justified on the basis of RMSD and RMSF trajectory analysis. The drug likeness properties and toxicity profile of all compounds were determined by ADMETlab 2.0. Furthermore, the anticancer potential of the potent compounds were confirmed by cell viability (MTT) assay. This study suggested that selected compounds can be further investigated at molecular level and evaluated for cancer treatment and associated malignancies.

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  • 33.
    Babu Moparthi, Satish
    et al.
    Aix Marseille University, France.
    Carlsson, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Vincentelli, Renaud
    University of Aix Marseille, France.
    Jonsson, Bengt-Harald
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Wenger, Jerome
    Aix Marseille University, France.
    Differential conformational modulations of MreB folding upon interactions with GroEL/ES and TRiC chaperonin components2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, no 28386Article in journal (Refereed)
    Abstract [en]

    Here, we study and compare the mechanisms of action of the GroEL/GroES and the TRiC chaperonin systems on MreB client protein variants extracted from E. coli. MreB is a homologue to actin in prokaryotes. Single-molecule fluorescence correlation spectroscopy (FCS) and time-resolved fluorescence polarization anisotropy report the binding interaction of folding MreB with GroEL, GroES and TRiC. Fluorescence resonance energy transfer (FRET) measurements on MreB variants quantified molecular distance changes occurring during conformational rearrangements within folding MreB bound to chaperonins. We observed that the MreB structure is rearranged by a binding-induced expansion mechanism in TRiC, GroEL and GroES. These results are quantitatively comparable to the structural rearrangements found during the interaction of beta-actin with GroEL and TRiC, indicating that the mechanism of chaperonins is conserved during evolution. The chaperonin-bound MreB is also significantly compacted after addition of AMP-PNP for both the GroEL/ES and TRiC systems. Most importantly, our results showed that GroES may act as an unfoldase by inducing a dramatic initial expansion of MreB (even more than for GroEL) implicating a role for MreB folding, allowing us to suggest a delivery mechanism for GroES to GroEL in prokaryotes.

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  • 34.
    Badian, Reza A.
    et al.
    Oslo Univ Hosp, Norway.
    Utheim, Tor Paaske
    Oslo Univ Hosp, Norway; Sorlandet Hosp Arendal, Norway.
    Lagali, Neil
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Sensory Organs and Communication. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Sorlandet Hosp Arendal, Norway.
    Region of interest and directional analysis of subbasal nerves in wide-area corneal nerve plexus mosaics in type 2 diabetes mellitus2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 10802Article in journal (Refereed)
    Abstract [en]

    In vivo confocal microscopy (IVCM) imaging of the corneal subbasal nerve plexus (SBNP) is a clinical imaging modality gaining popularity for the diagnosis and follow-up of corneal neuropathy in various conditions such as diabetes mellitus. There remain, however, major limitations to the method, hindering its widespread clinical use. Finding the same exact area of the central cornea to standardize image acquisition is difficult without a reference point. Alternatively, creating wide-area mosaics of the SBNP is resource-intensive and has not yet been developed for routine clinical use. Here, we investigated whether IVCM analysis of the corneal SBNP in a predetermined, anatomically standardized region of interest (ROI) could be applied as an equivalent substitution for wide-area SBNP mosaic generation and analysis. Furthermore, we investigated nerve patterns outside the central corneal region for a possible relationship to type 2 diabetes mellitus status using a publicly available dataset. We found that corneal nerve fibre length density (CNFL) based on the ROI underestimated the mosaic-based CNFL by an average of 34% in 90% of cases (150 eyes), and did not exhibit a significant reduction with diabetes, as seen in the full SBNP. Outside the central cornea, nerve orientation differed depending on the anatomic region (left, central or right superior plexus, P<0.001). Moreover, in long-term type 2 diabetes mellitus (>= 10 years, 28 subjects), nerve density in the left superior sector of the SBNP was decreased (P<0.001) while that in the central superior SBNP increased (P=0.01) relative to 35 age-matched healthy subjects with normal glucose tolerance. These results indicate that subbasal nerve degeneration in type 2 diabetes mellitus can vary according to anatomic location, and regions with potential diagnostic value outside the central SBNP may warrant further investigation.

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  • 35.
    Bafekry, A.
    et al.
    Amirkabir Univ Technol, Iran; Univ Guilan, Iran.
    Naseri, M.
    Univ Calgary, Canada.
    Faraji, M.
    TOBB Univ Econ & Technol, Turkey.
    Fadlallah, M. M.
    Benha Univ, Egypt.
    Hoat, D. M.
    Duy Tan Univ, Vietnam; Duy Tan Univ, Vietnam.
    Jappor, H. R.
    Univ Babylon, Iraq.
    Ghergherehchi, M.
    Sungkyunkwan Univ, South Korea.
    Gogova-Petrova, Daniela
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    Afarideh, H.
    Amirkabir Univ Technol, Iran.
    Theoretical prediction of two-dimensional BC2X (X = N, P, As) monolayers: ab initio investigations2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 22269Article in journal (Refereed)
    Abstract [en]

    In this work, novel two-dimensional BC2X (X = N, P, As) monolayers with X atoms out of the B-C plane, are predicted by means of the density functional theory. The structural, electronic, optical, photocatalytic and thermoelectric properties of the BC2X monolayers have been investigated. Stability evaluation of the BC2X single-layers is carried out by phonon dispersion, ab-initio molecular dynamics (AIMD) simulation, elastic stability, and cohesive energies study. The mechanical properties reveal all monolayers considered are stable and have brittle nature. The band structure calculations using the HSE06 functional reveal that the BC2N, BC2P and BC2As are semiconducting monolayers with indirect bandgaps of 2.68 eV, 1.77 eV and 1.21 eV, respectively. The absorption spectra demonstrate large absorption coefficients of the BC2X monolayers in the ultraviolet range of electromagnetic spectrum. Furthermore, we disclose the BC2N and BC2P monolayers are potentially good candidates for photocatalytic water splitting. The electrical conductivity of BC2X is very small and slightly increases by raising the temperature. Electron doping may yield greater electric productivity of the studied monolayers than hole doping, as indicated by the larger power factor in the n-doped region compared to the p-type region. These results suggest that BC2X (X = N, P, As) monolayers represent a new promising class of 2DMs for electronic, optical and energy conversion systems.

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  • 36.
    Bagger-Sjoback, Dan
    et al.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Stromback, Karin
    Uppsala University, Sweden.
    Hultcrantz, Malou
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Papatziamos, Georgios
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Smeds, Henrik
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Danckwardt-Lilliestrom, Niklas
    Uppsala University, Sweden.
    Tideholm, Bo
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Johansson, Ann
    Karolinska University Hospital, Sweden.
    Hellstrom, Sten
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Hakizimana, Pierre
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Fridberger, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    High-frequency hearing, tinnitus, and patient satisfaction with stapedotomy: A randomized prospective study2015In: Scientific Reports, E-ISSN 2045-2322, Vol. 5, no 13341Article in journal (Refereed)
    Abstract [en]

    Otosclerosis is a common disorder that leads to conductive hearing loss. Most patients with otosclerosis also have tinnitus, and surgical treatment is known to improve hearing as well as tinnitus. Some patients however experience worsening of tinnitus after the operation, but there are no known factors that allow surgeons to predict who will be at risk. In this prospective observational study on 133 patients undergoing stapedotomy, we show that postoperative air conduction thresholds at very high stimulus frequencies predict improvement of tinnitus, as assessed with proportional odds logistic regression models. Young patients were significantly more likely to experience reduction of tinnitus and patients whose tinnitus became better were also more satisfied with the outcome of the operation. These findings have practical importance for patients and their surgeons. Young patients can be advised that surgery is likely to be beneficial for their tinnitus, but a less positive message should be conveyed to older patients.

  • 37.
    Balagula, Roman
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Jansson, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Yukimune, Mitsuki
    Ehime Univ, Japan.
    Stehr, Jan Eric
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Ishikawa, Fumitaro
    Ehime Univ, Japan.
    Chen, Weimin
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Buyanova, Irina
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Effects of thermal annealing on localization and strain in core/multishell GaAs/GaNAs/GaAs nanowires2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1Article in journal (Refereed)
    Abstract [en]

    Core/shell nanowire (NW) heterostructures based on III-V semiconductors and related alloys are attractive for optoelectronic and photonic applications owing to the ability to modify their electronic structure via bandgap and strain engineering. Post-growth thermal annealing of such NWs is often involved during device fabrication and can also be used to improve their optical and transport properties. However, effects of such annealing on alloy disorder and strain in core/shell NWs are not fully understood. In this work we investigate these effects in novel core/shell/shell GaAs/GaNAs/GaAs NWs grown by molecular beam epitaxy on (111) Si substrates. By employing polarization-resolved photoluminescence measurements, we show that annealing (i) improves overall alloy uniformity due to suppressed long-range fluctuations in the N composition; (ii) reduces local strain within N clusters acting as quantum dot emitters; and (iii) leads to partial relaxation of the global strain caused by the lattice mismatch between GaNAs and GaAs. Our results, therefore, underline applicability of such treatment for improving optical quality of NWs from highly-mismatched alloys. They also call for caution when using ex-situ annealing in strain-engineered NW heterostructures.

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  • 38.
    Barbe, Laure
    et al.
    Univ Nantes, France.
    Le Moullac-Vaidye, Beatrice
    Univ Nantes, France.
    Echasserieau, Klara
    Univ Nantes, France; Univ Nantes, France.
    Bernardeau, Karine
    Univ Nantes, France; Univ Nantes, France.
    Carton, Thomas
    Biofortis, France.
    Bovin, Nicolai
    RAS, Russia.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Ruvoen-Clouet, Nathalie
    Univ Nantes, France; Oniris, France.
    Le Pendu, Jacques
    Univ Nantes, France.
    Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 12961Article in journal (Refereed)
    Abstract [en]

    Human strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAc beta 3Gal beta 4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of the FUT2 wild type allele in sera from young healthy adults. Nonetheless, in vitro infection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.

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  • 39.
    Barranco, Isabel
    et al.
    Univ Murcia, Spain.
    Padilla, Lorena
    Univ Murcia, Spain.
    Parrilla, Inmaculada
    Univ Murcia, Spain.
    Alvarez-Barrientos, Alberto
    Univ Extremadura, Spain.
    Perez-Patino, Cristina
    Univ Murcia, Spain.
    Pena, Fernando J.
    Univ Extremadura, Spain.
    Martinez, Emilio A.
    Univ Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Roca, Jordi
    Univ Murcia, Spain.
    Extracellular vesicles isolated from porcine seminal plasma exhibit different tetraspanin expression profiles2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 11584Article in journal (Refereed)
    Abstract [en]

    Seminal extracellular vesicles (EVs) include exosomes (phi 40-120 nm) and microvesicles (MVs, phi 120-1000 nm), which would be involved in multiple functional reproductive roles. The study aimed to establish which EV subtypes are present in pig semen, using a high-resolution flow cytometer to explore differences in their tetraspanin expression profile. The EVs were isolated from 12 pig ejaculates using serial ultracentrifugation and characterized by dynamic light scattering and electron microscopy for size and morphology as well as for tetraspanin expression using flow cytometry with Carboxyfluorescein succinimidyl ester (CFSE) and antibodies against CD9, CD63 and CD81. Pig semen contained a heterogeneous EV-population regarding size and morphology. Flow cytometric analysis demonstrated that the proportion of EVs expressing CD63 and CD9 was higher in MVs (P amp;lt; 0.001 and P amp;lt; 0.05, respectively) than in exosomes, while the opposite was true for CD81; higher (P amp;lt; 0.001) in exosomes than in MVs. In conclusion, (1) the new generation of flow cytometers are able to accurately identify EVs and to gate them in two size-different populations named exosomes and MVs. (2) Tetraspanins CD9, CD63 and CD81 are present in both seminal EVs, albeit with exosomes and MVs differing in expression profiles, suggesting dissimilar cargo and binding affinity.

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  • 40.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Spain.
    Perez-Patino, Cristina
    University of Murcia, Spain.
    Parrilla, Inmaculada
    University of Murcia, Spain.
    Ceron, Jose J.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Roca, Jordi
    University of Murcia, Spain.
    High total antioxidant capacity of the porcine seminal plasma (SP-TAC) relates to sperm survival and fertility2015In: Scientific Reports, E-ISSN 2045-2322, Vol. 5, no 18538Article in journal (Refereed)
    Abstract [en]

    The study attempted to clarify the role of total antioxidant capacity of seminal plasma (SP-TAC) on boar sperm survival and fertility after artificial insemination (AI). SP-TAC differed (P < 0.001) among boars (no = 15) and, to a lesser degree, among ejaculates within male (4 ejaculates/boar). SP-TAC also differed (P < 0.001) among ejaculate fractions (43 ejaculates and 3 fractions per ejaculate), of which the sperm-peak portion of the sperm rich ejaculate fraction (SRF) had the highest SP-TAC. SP-TAC was not correlated with sperm quality (motility and viability) or functionality (intracellular ROS generation and lipid peroxidation) of liquid AI-semen samples stored at 17 degrees C for 72 h (90 AI-samples), but the decline in sperm quality was larger (P < 0.05) in ejaculates with low, compared with high SP-TAC (hierarchically grouped). The SP-TAC differences among ejaculate portions agree with sperm cryosurvival rates (14 ejaculates from 7 boars), showing sperm from sperm-peak portion better (P < 0.01) post-thaw quality and functionality than those from the entire ejaculate (mainly post-SRF). Boars (no = 18) with high SP-TAC (hierarchically grouped) had higher (P < 0.05) fertility outcomes (5,546 AI-sows) than those with low SP-TAC. Measurement of SP-TAC ought to be a discriminative tool to prognosis fertility in breeding boars.

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  • 41.
    Barrientos-Somarribas, Mauricio
    et al.
    Karolinska Inst, Sweden.
    Messina, David N.
    Stockholm Univ, Sweden.
    Pou, Christian
    Karolinska Inst, Sweden.
    Lysholm, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Bjerkner, Annelie
    Karolinska Univ Hosp, Sweden.
    Allander, Tobias
    Karolinska Univ Hosp, Sweden.
    Andersson, Björn
    Karolinska Inst, Sweden.
    Sonnhammer, Erik L. L.
    Stockholm Univ, Sweden.
    Discovering viral genomes in human metagenomic data by predicting unknown protein families2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 28Article in journal (Refereed)
    Abstract [en]

    Massive amounts of metagenomics data are currently being produced, and in all such projects a sizeable fraction of the resulting data shows no or little homology to known sequences. It is likely that this fraction contains novel viruses, but identification is challenging since they frequently lack homology to known viruses. To overcome this problem, we developed a strategy to detect ORFan protein families in shotgun metagenomics data, using similarity-based clustering and a set of filters to extract bona fide protein families. We applied this method to 17 virus-enriched libraries originating from human nasopharyngeal aspirates, serum, feces, and cerebrospinal fluid samples. This resulted in 32 predicted putative novel gene families. Some families showed detectable homology to sequences in metagenomics datasets and protein databases after reannotation. Notably, one predicted family matches an ORF from the highly variable Torque Teno virus (TTV). Furthermore, follow-up from a predicted ORFan resulted in the complete reconstruction of a novel circular genome. Its organisation suggests that it most likely corresponds to a novel bacteriophage in the microviridae family, hence it was named bacteriophage HFM.

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  • 42.
    Barrirero, Jenifer
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Nanostructured Materials. Linköping University, Faculty of Science & Engineering. Saarland Univ, Germany.
    Pauly, C.
    Saarland Univ, Germany.
    Engstler, M.
    Saarland Univ, Germany.
    Ghanbaja, J.
    Univ Lorraine, France.
    Ghafoor, Naureen
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Li, J.
    Univ Leoben, Austria.
    Schumacher, P.
    Univ Leoben, Austria.
    Odén, Magnus
    Linköping University, Department of Physics, Chemistry and Biology, Nanostructured Materials. Linköping University, Faculty of Science & Engineering.
    Muecklich, F.
    Saarland Univ, Germany.
    Eutectic modification by ternary compound cluster formation in Al-Si alloys2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 5506Article in journal (Refereed)
    Abstract [en]

    Al-alloys with Si as the main alloying element constitute the vast majority of Al castings used commercially today. The eutectic Si microstructure in these alloys can be modified from plate-like to coral-like by the addition of a small amount of a third element to improve ductility and toughness. In this investigation the effects of Eu and Yb are studied and their influence on the microstructure is compared to further understand this modification. The two elements impact the alloy differently, where Eu modifies Si into a coral-like structure while Yb does not. Atom probe tomography shows that Eu is present within the Si phase in the form of ternary compound Al2Si2Eu clusters, while Yb is absent in the Si phase. This indicates that the presence of ternary compound clusters within Si is a necessary condition for the formation of a coral-like structure. A crystallographic orientation relationship between Si and the Al2Si2Eu phase was found, where the following plane normals are parallel: 011(Si) //0001(Al2Si2Eu), 111(Si)//6 (7) over bar 10(Al2Si2Eu) and 011(Si)//6 (7) over bar 10(Al2Si2Eu). No crystallographic relationship was found between Si and Al2Si2Yb. The heterogeneous formation of coherent Al2Si2Eu clusters inside the Si-phase is suggested to trigger the modification of the microstructure.

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  • 43.
    Befekadu, Rahel
    et al.
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Grenegård, Magnus
    Orebro Univ, Sweden.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Christensen, Kjeld
    Karlstad Cent Hosp, Sweden; Orebro Univ Hosp, Sweden.
    Ramström, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Levels of soluble tumor necrosis factor receptor 1 and 2 are associated with survival after ST segment elevation myocardial infarction2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 14762Article in journal (Refereed)
    Abstract [en]

    The soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2) are suggested to play dual roles on physiological and pathophysiological actions of TNF-alpha. The aim of this study was to investigate the dynamic changes of these biomarkers in patients with ST-segment elevation myocardial infarction (STEMI). Blood was collected from 165 STEMI patients at admission, 1-3 days and 3 months after percutaneous coronary intervention (PCI) and from 40 healthy blood donors. sTNFR1 and sTNFR2 were measured with ELISA. The plasma levels of both sTNFR1 and sTNFR2 were significantly higher than in healthy donors at all three time points. We found no significant differences in sTNFR1 or sTNFR2 when comparing patients with patent versus occluded culprit vessels, or between patients having a thrombus aspiration or not. Survival analysis was performed comparing patients with levels of biomarkers above and below the median values at that time point. We found significant differences in survival for sTNFR2 in acute samples (p = 0.0151) and for both sTNFR1 and sTNFR2 in samples 1-3 days after PCI (p = 0.0054 and p = 0.0003, respectively). Survival analyses suggest that sTNFR1 or sTNFR2 could be promising markers to predict mortality in STEMI patients after PCI.

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  • 44.
    Bengtsson, Torbjorn
    et al.
    Orebro Univ, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. Orebro Univ, Sweden.
    Musa, Amani
    Orebro Univ, Sweden.
    Hultenby, Kjell
    Karolinska Inst, Sweden.
    Utterström, Johanna
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Sivler, Petter
    S2Medical AB, SE-58273 Linkoping, Sweden.
    Skog, Marten
    S2Medical AB, SE-58273 Linkoping, Sweden.
    Nayeri, Fariba
    PEAS Res Inst, Dept Infect Control, SE-58273 Linkoping, Sweden.
    Hellmark, Bengt
    Orebro Univ Hosp, Sweden.
    Soderquist, Bo
    Orebro Univ, Sweden; Orebro Univ Hosp, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    Orebro Univ, Sweden.
    Plantaricin NC8 alpha beta exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 3580Article in journal (Refereed)
    Abstract [en]

    The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 alpha beta were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 alpha and beta were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both L- and D-PLNC8 alpha beta caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. The D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, beta 1-22, beta 7-34 and beta 1-20 retained an inhibitory activity. The peptides diffused rapidly (2min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 alpha beta substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 alpha beta is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use.

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  • 45.
    Bengtsson, Torbjörn
    et al.
    Örebro University, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. Örebro University, Sweden.
    Musa, Amani
    Örebro University, Sweden.
    Hultenby, Kjell
    Karolinska Institutet, Sweden.
    Utterström, Johanna
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Sivlér, Petter
    S2Medical AB, 58273, Linköping, Sweden.
    Skog, Mårten
    S2Medical AB, 58273, Linköping, Sweden.
    Nayeri, Fariba
    Department of Infection Control, PEAS Research Institute, Linköping, Sweden.
    Hellmark, Bengt
    Department of Clinical Microbiology, Örebro University Hospital, Sweden.
    Söderquist, Bo
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, 70362, Örebro, Sweden; Department of Clinical Microbiology, Örebro University Hospital, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Sweden.
    Author Correction: Plantaricin NC8 aß exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1Article in journal (Other academic)
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  • 46.
    Bettiga, Arianna
    et al.
    IRCCS Osped San Raffaele, Italy.
    Aureli, Massimo
    University of Milan, Italy.
    Colciago, Giorgia
    IRCCS Osped San Raffaele, Italy.
    Murdica, Valentina
    University of Milan, Italy.
    Moschini, Marco
    IRCCS Osped San Raffaele, Italy.
    Luciano, Roberta
    IRCCS Osped San Raffaele, Italy.
    Canals, Daniel
    SUNY Stony Brook, NY 11794 USA.
    Hannun, Yusuf
    SUNY Stony Brook, NY 11794 USA.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. IRCCS Osped San Raffaele, Italy.
    Lavorgna, Giovanni
    IRCCS Osped San Raffaele, Italy.
    Colombo, Renzo
    IRCCS Osped San Raffaele, Italy.
    Bassi, Rosaria
    University of Milan, Italy.
    Samarani, Maura
    University of Milan, Italy.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy; University of Vita Salute San Raffaele, Italy.
    Salonia, Andrea
    University of Vita Salute San Raffaele, Italy.
    Benigni, Fabio
    IRCCS Osped San Raffaele, Italy.
    Bladder cancer cell growth and motility implicate cannabinoid 2 receptor-mediated modifications of sphingolipids metabolism2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 42157Article in journal (Refereed)
    Abstract [en]

    The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling. CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour. Both cell lines expressed similar CB2. Exposure to CB2 agonists inhibited BC growth, down-modulated Akt, induced caspase 3-activation and modified SL metabolism. Baseline SL analysis in cell lines showed differences linked to unique migratory behaviours and cytoskeletal re-arrangements. CB2 activation changed the SL composition of more aggressive RT112 cells by reducing (p amp;lt; 0.01) Gb3 ganglioside (-50 +/- 3%) and sphingosine 1-phosphate (S1P, -40 +/- 4%), which ended up to reduction in cell motility (-46 +/- 5%) with inhibition of p-SRC. CB2-selective antagonists, gene silencing and an inhibitor of SL biosynthesis partially prevented CB2 agonist-induced effects on cell viability and motility. CB2 activation led to ceramide-mediated BC cell apoptosis independently of SL constitutive composition, which instead was modulated by CB2 agonists to reduce cell motility.

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  • 47.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, no 29824Article in journal (Refereed)
    Abstract [en]

    Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and T-reg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and T-reg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the T-reg cell fraction was lower (p amp;lt; 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more T-reg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger.

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  • 48.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Systemic corticosteroids improve tendon healing when given after the early inflammatory phase2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 12468Article in journal (Refereed)
    Abstract [en]

    Inflammation initiates tendon healing and then normally resolves more or less completely. Unresolved inflammation might disturb the remodeling process. We hypothesized that suppression of inflammation during the early remodeling phase by systemic dexamethasone treatment can improve healing. 36 rats underwent Achilles tendon transection and were randomized to dexamethasone or saline on days 0-4 after surgery (early inflammatory phase), and euthanasia day 7. Another 54 rats received injections days 5-9 (early remodeling phase) and were euthanized day 12 for mechanical, histological and flow cytometric evaluation. Dexamethasone treatment days 0-4 reduced the cross-sectional area, peak force and stiffness by day 7 to less than half (p amp;lt; 0.001 for all), while material properties (peak stress and elastic modulus) were not significantly affected. In contrast, dexamethasone treatment days 5-9 increased peak force by 39% (p = 0.002) and stiffness by 58% (p amp;lt; 0.001). The cross-sectional area was reduced by 42% (p amp;lt; 0.001). Peak stress and elastic modulus were more than doubled (p amp;lt; 0.001 for both). Semi-quantitative histology at day 12 showed that late dexamethasone treatment improved collagen alignment, and flow cytometry revealed reduced numbers of CD8a(+) cytotoxic T cells in the tendon callus. These results suggest that downregulation of lingering inflammation during the early remodeling phase can improve healing.

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  • 49.
    Blystad, Ida
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine.
    Warntjes, Marcel, Jan Bertus
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). School of Technology and Health, KTH Royal Institute of Technology, Stockholm, Sweden.
    Lundberg, Peter
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
    Tisell, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Quantitative MRI using relaxometry in malignant gliomas detects contrast enhancement in peritumoral oedema2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 17986Article in journal (Refereed)
    Abstract [en]

    Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R1), transverse relaxation (R2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R1-difference-map. The quantitative R1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.

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    Quantitative MRI using relaxometry in malignant gliomas detects contrast enhancement in peritumoral oedema.
  • 50.
    Bokhorst, John-Melle
    et al.
    Radboud Univ Nijmegen, Netherlands.
    Nagtegaal, Iris D.
    Radboud Univ Nijmegen, Netherlands.
    Fraggetta, Filippo
    Gravina Hosp, Italy.
    Vatrano, Simona
    Gravina Hosp, Italy.
    Mesker, Wilma
    Leids Univ, Netherlands.
    Vieth, Michael
    Friedrich Alexander Univ Erlangen Nuremberg, Germany.
    van der Laak, Jeroen
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Radboud Univ Nijmegen, Netherlands.
    Ciompi, Francesco
    Radboud Univ Nijmegen, Netherlands.
    Deep learning for multi-class semantic segmentation enables colorectal cancer detection and classification in digital pathology images2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 8398Article in journal (Refereed)
    Abstract [en]

    In colorectal cancer (CRC), artificial intelligence (AI) can alleviate the laborious task of characterization and reporting on resected biopsies, including polyps, the numbers of which are increasing as a result of CRC population screening programs ongoing in many countries all around the globe. Here, we present an approach to address two major challenges in the automated assessment of CRC histopathology whole-slide images. We present an AI-based method to segment multiple (n=14 ) tissue compartments in the H &E-stained whole-slide image, which provides a different, more perceptible picture of tissue morphology and composition. We test and compare a panel of state-of-the-art loss functions available for segmentation models, and provide indications about their use in histopathology image segmentation, based on the analysis of (a) a multi-centric cohort of CRC cases from five medical centers in the Netherlands and Germany, and (b) two publicly available datasets on segmentation in CRC. We used the best performing AI model as the basis for a computer-aided diagnosis system that classifies colon biopsies into four main categories that are relevant pathologically. We report the performance of this system on an independent cohort of more than 1000 patients. The results show that with a good segmentation network as a base, a tool can be developed which can support pathologists in the risk stratification of colorectal cancer patients, among other possible uses. We have made the segmentation model available for research use on .

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