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  • 51.
    Eriksson, Daniel
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bianchi, Matteo
    Uppsala Univ, Sweden.
    Landegren, Nils
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Dalin, Frida
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Skov, Jakob
    Karolinska Inst, Sweden.
    Hultin-Rosenberg, Lina
    Uppsala Univ, Sweden.
    Mathioudaki, Argyri
    Uppsala Univ, Sweden.
    Nordin, Jessika
    Uppsala Univ, Sweden.
    Hallgren, Asa
    Karolinska Inst, Sweden.
    Andersson, Goran
    Swedish Univ Agr Sci, Sweden.
    Tandre, Karolina
    Uppsala Univ, Sweden.
    Rantapaa Dahlqvist, Solbritt
    Umea Univ, Sweden.
    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.
    Ronnblom, Lars
    Uppsala Univ, Sweden.
    Hulting, Anna-Lena
    Not Found:[Eriksson, Daniel; Landegren, Nils; Dalin, Frida; Hallgren, Asa; Kampe, Olle] Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden; [Eriksson, Daniel; Bensing, Sophie; Kampe, Olle] Karolinska Univ Hosp, Dept Endocrinol Metab and Diabet, Stockholm, Sweden; [Bianchi, Matteo; Hultin-Rosenberg, Lina; Mathioudaki, Argyri; Nordin, Jessika; Meadows, Jennifer R. S.; Lindblad-Toh, Kerstin; Pielberg, Gerli Rosengren] Uppsala Univ, Dept Med Biochem and Microbiol, Sci Life Lab, Uppsala, Sweden; [Landegren, Nils; Dalin, Frida; Tandre, Karolina; Ronnblom, Lars] Uppsala Univ, Dept Med Sci, Sci Life Lab, Uppsala, Sweden; [Skov, Jakob; Bensing, Sophie] Karolinska Inst, Dept Mol Med and Surg, Stockholm, Sweden; [Andersson, Goran] Swedish Univ Agr Sci, Dept Anim Breeding and Genet, Uppsala, Sweden; [Dahlqvist, Solbritt Rantapaa; Dahlqvist, Per] Umea Univ, Dept Publ Hlth and Clin Med, Umea, Sweden; [Soderkvist, Peter; Wahlberg, Jeanette] Linkoping Univ, Dept Clin and Expt Med, Linkoping, Sweden; [Wahlberg, Jeanette] Linkoping Univ, Dept Endocrinol, Linkoping, Sweden; [Wahlberg, Jeanette] Linkoping Univ, Dept Med and Hlth Sci, Linkoping, Sweden; [Ekwall, Olov] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden; [Ekwall, Olov] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol and Inflammat Res, Gothenburg, Sweden; [Lindblad-Toh, Kerstin] Broad Inst MIT and Harvard, Cambridge, MA USA; [Kampe, Olle] KG Jebsen Ctr Autoimmune Dis, Bergen, Norway;.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Dahlqvist, Per
    Umea Univ, Sweden.
    Ekwall, Olov
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Meadows, Jennifer R. S.
    Uppsala Univ, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala Univ, Sweden; Broad Inst MIT and Harvard, MA USA.
    Bensing, Sophie
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Pielberg, Gerli Rosengren
    Uppsala Univ, Sweden.
    Kampe, Olle
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; KG Jebsen Ctr Autoimmune Dis, Norway.
    Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addisons disease in Sweden2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8395Article in journal (Refereed)
    Abstract [en]

    Autoimmune Addisons disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

  • 52.
    Eriksson, Jonatan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Zajac, Jakub
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. University of Calif San Francisco, CA USA.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2971Article in journal (Refereed)
    Abstract [en]

    Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT.

  • 53.
    Eriksson, Peter
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Tal, Alexey
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    Skallberg, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Hu, Zhang-Jun
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Boyd, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Plasma and Coating Physics. Linköping University, Faculty of Science & Engineering.
    Olovsson, Weine
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    Fairley, Neal
    Casa Software Ltd, Bay House, Teignmouth, United Kingdom.
    Abrikosov, Igor
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering. Materials Modeling and Development Laboratory, National University of Science and Technology “MISIS”, Moscow, Russia.
    Zhang, Xuanjun
    Faculty of Health Sciences, University of Macau, Macau, SAR, China.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6999Article in journal (Refereed)
    Abstract [en]

    The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue-and cellular level and during tumor treatment to reduce in vivo inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce3+ and Ce4+ of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on ab initio electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3-5 nm in size, have r(1)-relaxivities between 7-13 mM(-1) s(-1) and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.

  • 54.
    Ever Aguirre, Luis
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Ouyang, Liangqi
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Elfwing, Anders
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Hedblom, Mikael
    Univ Gothenburg, Sweden.
    Wulff, Angela
    Univ Gothenburg, Sweden.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Diatom frustules protect DNA from ultraviolet light2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5138Article in journal (Refereed)
    Abstract [en]

    The evolutionary causes for generation of nano and microstructured silica by photosynthetic algae are not yet deciphered. Diatoms are single photosynthetic algal cells populating the oceans and waters around the globe. They generate a considerable fraction (20-30%) of all oxygen from photosynthesis, and 45% of total primary production of organic material in the sea. There are more than 100,000 species of diatoms, classified by the shape of the glass cage in which they live, and which they build during algal growth. These glass structures have accumulated for the last 100 million of years, and left rich deposits of nano/microstructured silicon oxide in the form of diatomaceous earth around the globe. Here we show that reflection of ultraviolet light by nanostructured silica can protect the deoxyribonucleic acid (DNA) in the algal cells, and that this may be an evolutionary cause for the formation of glass cages.

  • 55.
    Fagerström, Johan
    et al.
    Linköping University, Department of Computer and Information Science. Linköping University, Faculty of Science & Engineering.
    Bång, Magnus
    Linköping University, Department of Computer and Information Science, Human-Centered systems. Linköping University, Faculty of Science & Engineering.
    Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Chew, Michelle
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping (ANOPIVA).
    LiSep LSTM: A Machine Learning Algorithm for Early Detection of Septic Shock2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 15132Article in journal (Refereed)
    Abstract [en]

    Sepsis is a major health concern with global estimates of 31.5 million cases per year. Case fatality rates are still unacceptably high, and early detection and treatment is vital since it significantly reduces mortality rates for this condition. Appropriately designed automated detection tools have the potential to reduce the morbidity and mortality of sepsis by providing early and accurate identification of patients who are at risk of developing sepsis. In this paper, we present "LiSep LSTM"; a Long Short-Term Memory neural network designed for early identification of septic shock. LSTM networks are typically well-suited for detecting long-term dependencies in time series data. LiSep LSTM was developed using the machine learning framework Keras with a Google TensorFlow back end. The model was trained with data from the Medical Information Mart for Intensive Care database which contains vital signs, laboratory data, and journal entries from approximately 59,000 ICU patients. We show that LiSep LSTM can outperform a less complex model, using the same features and targets, with an AUROC 0.8306 (95% confidence interval: 0.8236, 0.8376) and median offsets between prediction and septic shock onset up to 40 hours (interquartile range, 20 to 135 hours). Moreover, we discuss how our classifier performs at specific offsets before septic shock onset, and compare it with five state-of-the-art machine learning algorithms for early detection of sepsis.

  • 56.
    Fakhar-E-Alam, Muhammad
    et al.
    Linköping University, Department of Science and Technology. Linköping University, Faculty of Science & Engineering. University of Elect Science and Technology China, Peoples R China; GC University, Pakistan.
    Waseem Akram, M.
    University of Elect Science and Technology China, Peoples R China.
    Iqbal, Seemab
    GC University, Pakistan.
    Alimgeer, K. S.
    COMSATS Institute Informat Technology, Pakistan.
    Atif, M.
    King Saud University, Saudi Arabia; National Institute Laser and Optron, Pakistan.
    Sultana, Kishwar
    Linköping University, Department of Science and Technology. Linköping University, Faculty of Science & Engineering.
    Willander, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Wang, Zhiming M.
    University of Elect Science and Technology China, Peoples R China.
    Empirical Modeling of Physiochemical Immune Response of Multilayer Zinc Oxide Nanomaterials under UV Exposure to Melanoma and Foreskin Fibroblasts2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 46603Article in journal (Refereed)
    Abstract [en]

    Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX). Furthermore, PpIX-conjugated ZnO nanomaterials grown on the probe were inserted into human melanoma (FM55P) and foreskin fibroblasts cells (AG01518) under UV-A light exposure. Interestingly, significant cell necrosis was observed because of a loss in mitochondrial membrane potential just after insertion of the femtotip tool. Intense reactive oxygen species (ROS) fluorescence was observed after exposure to the ZnO NWs conjugated with PpIX femtotip model under UV exposure. Results were verified by applying several experimental techniques, e.g., ROS detection, MTT assay, and fluorescence spectroscopy. The present work reports experimental modelling of cell necrosis in normal human skin as well as a cancerous tissue. These obtained results pave the way for a more rational strategy for biomedical and clinical applications.

  • 57.
    Fallahshahroudi, Amir
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    de Kock, Nick
    Department of Chemistry - Biomedical Center, Analytical Chemistry and Science for Life Laboratory, Uppsala University, Sweden.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Ubhayasekera, S.J. Kumari A.
    Department of Chemistry - Biomedical Center, Analytical Chemistry and Science for Life Laboratory, Uppsala University, Sweden.
    Bergqvist, Jonas
    Department of Chemistry - Biomedical Center, Analytical Chemistry and Science for Life Laboratory, Uppsala University, Sweden.
    Wright, Dominic
    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.
    Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, p. 1-10, article id 15345Article in journal (Refereed)
    Abstract [en]

    Understanding the genetic basis of phenotypic diversity is a challenge in contemporary biology. Domestication provides a model for unravelling aspects of the genetic basis of stress sensitivity. The ancestral Red Junglefowl (RJF) exhibits greater fear-related behaviour and a more pronounced HPA-axis reactivity than its domesticated counterpart, the White Leghorn (WL). By comparing hormones (plasmatic) and adrenal global gene transcription profiles between WL and RJF in response to an acute stress event, we investigated the molecular basis for the altered physiological stress responsiveness in domesticated chickens. Basal levels of pregnenolone and dehydroepiandrosterone as well as corticosterone response were lower in WL. Microarray analysis of gene expression in adrenal glands showed a significant breed effect in a large number of transcripts with over-representation of genes in the channel activity pathway. The expression of the best-known steroidogenesis genes were similar across the breeds used. Transcription levels of acute stress response genes such as StAR, CH25 and POMC were upregulated in response to acute stress. Dampened HPA reactivity in domesticated chickens was associated with changes in the expression of several genes that presents potentially minor regulatory effects rather than by means of change in expression of critical steroidogenic genes in the adrenal.

  • 58.
    Figueiredo, Viviane
    et al.
    Univ Fed Rio de Janeiro, Brazil; Univ Fed Fluminense, Brazil; 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. Univ Fed Rio de Janeiro, Brazil; Univ Fed Fluminense, Brazil; Univ Fed Rio de Janeiro, Brazil.
    Rutting, Tobias
    Univ Gothenburg, Sweden.
    Evolution of nitrogen cycling in regrowing Amazonian rainforest2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 8538Article in journal (Refereed)
    Abstract [en]

    Extensive regions of tropical forests are subjected to high rates of deforestation and forest regrowth and both are strongly affect soil nutrient cycling. Nitrogen (N) dynamics changes during forest regrowth and the recovery of forests and functioning similar to pristine conditions depends on sufficient N availability. We show that, in a chronosequence of Amazonian forests, gross nitrification and, as a result, nitrate-to-ammonium (NO3- : NH4+) ratio were lower in all stages of regrowing forests (10 to 40 years) compared to pristine forest. This indicates the evolution of a more conservative and closed N cycle with reduced risk for N leaking out of the ecosystem in regrowing forests. Furthermore, our results indicate that mineralization and nitrification are decoupled in young regrowing forests (10 years), such as that high gross mineralization is accompanied by low gross nitrification, demonstrating a closed N cycle that at the same time maintains N supply for forest regrowth. We conclude that the status of gross nitrification in disturbed soil is a key process to understand the mechanisms of and time needed for tropical forest recovery.

  • 59.
    Forsberg, Mathias
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Hemmingsson, Carl
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Amano, Hiroshi
    Department of Electrical Engineering and Computer Science, Nagoya University, Japan.
    Pozina, Galia
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Dynamic properties of excitons in ZnO/AlGaN/GaN hybrid nanostructures2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 7889, p. 1-5Article in journal (Refereed)
    Abstract [en]

    Hybrid samples based on ZnO colloidal nanocrystals (NCs) deposited on AlGaN/GaN quantum well (QW) structures with different top barrier thickness d = 3, 6 and 9 nm are studied by time-resolved photoluminescence. Thermal behavior of the QW exciton lifetime in the hybrids and in the bare QW structures has been compared and it has been found that the QW exciton recombination rate increases in the hybrid having d = 3 nm and decreases in the hybrid with d = 6 nm, while no change has been observed for the structure with d = 9 nm. It is suggested that non-radiative resonance energy transfer from the QW excitons to the ZnO NCs and a variation of the surface potential can both influence the QW exciton lifetime in the hybrids.

  • 60.
    Forsberg, Mathias
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Serban, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Hsiao, Ching-Lien
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Junaid, Muhammad
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Birch, Jens
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Pozina, Galia
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Near band gap luminescence in hybrid organic-inorganic structures based on sputtered GaN nanorods2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1170Article in journal (Refereed)
    Abstract [en]

    Novel hybrid organic-inorganic nanostructures fabricated to utilize non-radiative resonant energy transfer mechanism are considered to be extremely attractive for a variety of light emitters for down converting of ultaviolet light and for photovoltaic applications since they can be much more efficient compared to devices grown with common design. Organic-inorganic hybrid structures based on green polyfluorene (F8BT) and GaN (0001) nanorods grown by magnetron sputtering on Si (111) substrates are studied. In such nanorods, stacking faults can form periodic polymorphic quantum wells characterized by bright luminescence. In difference to GaN exciton emission, the recombination rate for the stacking fault related emission increases in the presence of polyfluorene film, which can be understood in terms of Forster interaction mechanism. From comparison of dynamic properties of the stacking fault related luminescence in the hybrid structures and in the bare GaN nanorods, the pumping efficiency of non-radiative resonant energy transfer in hybrids was estimated to be as high as 35% at low temperatures.

  • 61.
    Foyer, Pernilla
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology. Swedish National Defence College, Stockholm, Sweden.
    Wilsson, Erik
    Swedish Armed Forces Dog Instruction Centre, Märsta, Sweden.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Levels of maternal care in dogs affect adult off spring temperament2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed)
    Abstract [en]

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. Early experiences, such as maternal care, have been shown to have a profound and lasting effect on the future behaviour and physiology of offspring in rodents and primates. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother--‐offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs.

  • 62.
    Fryknäs, Mårten
    et al.
    Uppsala University, Sweden.
    Zhang, Xiaonan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Bremberg, Ulf
    Beactica, Sweden.
    Senkowski, Wojciech
    Uppsala University, Sweden.
    Hägg Olofsson, Maria
    Karolinska Institute, Sweden.
    Brandt, Peter
    Uppsala University, Sweden.
    Persson, Ingmar
    Swedish University of Agriculture Science, Sweden.
    D´arcy, Padraig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Gullbo, Joachim
    Uppsala University, Sweden.
    Nygren, Peter
    Uppsala University, Sweden.
    Kunz Schughart, Leoni
    Technical University of Dresden, Germany.
    Linder, Stig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
    Larsson, Rolf
    Uppsala University, Sweden.
    Iron chelators target both proliferating and quiescent cancer cells2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 38343Article in journal (Refereed)
    Abstract [en]

    Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation. Compounds that chelate iron possess anti-cancer activity, an effect largely attributed to inhibition of ribonucleotide reductase in proliferating cells. Here we show that iron chelators decrease mitochondrial energy production, an effect poorly tolerated by metabolically stressed tumor cells. These pleiotropic features make iron chelators an attractive option for the treatment of solid tumors containing heterogeneous populations of proliferating and quiescent cells.

  • 63.
    Garbrecht, Magnus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Saha, Bivas
    University of Calif Berkeley, CA 94720 USA.
    Schroeder, Jeremy
    Linköping University, Department of Physics, Chemistry and Biology. 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.
    Sands, Timothy D.
    Virginia Tech, VA 24061 USA; Virginia Tech, VA 24061 USA.
    Dislocation-pipe diffusion in nitride superlattices observed in direct atomic resolution2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 46092Article in journal (Refereed)
    Abstract [en]

    Device failure from diffusion short circuits in microelectronic components occurs via thermally induced migration of atoms along high-diffusivity paths: dislocations, grain boundaries, and free surfaces. Even well-annealed single-grain metallic films contain dislocation densities of about 1014 m-2; hence dislocation-pipe diffusion (DPD) becomes a major contribution at working temperatures. While its theoretical concept was established already in the 1950s and its contribution is commonly measured using indirect tracer, spectroscopy, or electrical methods, no direct observation of DPD at the atomic level has been reported. We present atomically-resolved electron microscopy images of the onset and progression of diffusion along threading dislocations in sequentially annealed nitride metal/semiconductor superlattices, and show that this type of diffusion can be independent of concentration gradients in the system but governed by the reduction of strain fields in the lattice.

  • 64.
    Gawel, Danuta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Li, Xinxiu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Matussek, Andreas
    Div Psychiat and Rehabil and Diagnost, Sweden; Karolinska Univ Hosp Huddinge, Sweden; Karolinska Univ Hosp, Sweden.
    Schäfer, Samuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Olsen, Renate Slind
    Div Psychiat and Rehabil and Diagnost, Sweden; Karolinska Inst, Sweden.
    Stenmarker, Margaretha
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Dept Paediat, Region Jönköping County, Sweden.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, 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 Linköping/Motala.
    An algorithm-based meta-analysis of genome- and proteome-wide data identifies a combination of potential plasma biomarkers for colorectal cancer2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 15575Article in journal (Refereed)
    Abstract [en]

    Screening programs for colorectal cancer (CRC) often rely on detection of blood in stools, which is unspecific and leads to a large number of colonoscopies of healthy subjects. Painstaking research has led to the identification of a large number of different types of biomarkers, few of which are in general clinical use. Here, we searched for highly accurate combinations of biomarkers by meta-analyses of genome- and proteome-wide data from CRC tumors. We focused on secreted proteins identified by the Human Protein Atlas and used our recently described algorithms to find optimal combinations of proteins. We identified nine proteins, three of which had been previously identified as potential biomarkers for CRC, namely CEACAM5, LCN2 and TRIM28. The remaining proteins were PLOD1, MAD1L1, P4HA1, GNS, C12orf10 and P3H1. We analyzed these proteins in plasma from 80 patients with newly diagnosed CRC and 80 healthy controls. A combination of four of these proteins, TRIM28, PLOD1, CEACAM5 and P4HA1, separated a training set consisting of 90% patients and 90% of the controls with high accuracy, which was verified in a test set consisting of the remaining 10%. Further studies are warranted to test our algorithms and proteins for early CRC diagnosis.

  • 65.
    Ghafoor, Naureen
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Petrov, Ivan
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering. Univ Illinois, IL 61801 USA; Univ Illinois, IL 61801 USA.
    Holec, D.
    Univ Leoben, Austria.
    Greczynski, Grzegorz
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Palisaitis, Justinas
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Persson, Per O A
    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.
    Birch, Jens
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Self-structuring in Zr1-xAlxN films as a function of composition and growth temperature2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 16327Article in journal (Refereed)
    Abstract [en]

    Nanostructure formation via surface-diffusion-mediated segregation of ZrN and AIN in Zr1-xAlxN films during high mobility growth conditions is investigated for 0 amp;lt;= x amp;lt;= 1. The large immiscibility combined with interfacial surface and strain energy balance resulted in a hard nanolabyrinthine lamellar structure with well-defined (semi) coherent c-ZrN and w-AlN domains of sub-nm to similar to 4 nm in 0.2 amp;lt;= x amp;lt;= 0.4 films, as controlled by atom mobility. For high AlN contents (x amp;gt; 0.49) Al-rich ZrN domains attain wurtzite structure within fine equiaxed nanocomposite wurtzite lattice. Slow diffusion in wurtzite films points towards crystal structure dependent driving force for decomposition. The findings of unlikelihood of isostructural decomposition in c-Zr1-xAlxN, and stability of w-Zr1-xAlxN (in large x films) is complemented with first principles calculations.

  • 66.
    Giordano, Giulia
    et al.
    Lund University, Sweden.
    Altafini, Claudio
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, Faculty of Science & Engineering.
    Qualitative and quantitative responses to press perturbations in ecological networks2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 11378Article in journal (Refereed)
    Abstract [en]

    Predicting the sign of press perturbation responses in ecological networks is challenging, due to the poor knowledge of the strength of the direct interactions among the species, and to the entangled coexistence of direct and indirect effects. We show in this paper that, for a class of networks that includes mutualistic and monotone networks, the sign of press perturbation responses can be qualitatively determined based only on the sign pattern of the community matrix, without any knowledge of parameter values. For other classes of networks, we show that a semi-qualitative approach yields sufficient conditions for community matrices with a given sign pattern to exhibit mutualistic responses to press perturbations; quantitative conditions can be provided as well for community matrices that are eventually nonnegative. We also present a computational test that can be applied to any class of networks so as to check whether the sign of the responses to press perturbations is constant in spite of parameter variations.

  • 67.
    Giuri, Antonella
    et al.
    CNR Nanotec, Italy; Univ Salento, Italy.
    Yuan, Zhongcheng
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Miao, Yanfeng
    Nanjing Tech Univ Nanjing Tech, Peoples R China.
    Wang, Jianpu
    Nanjing Tech Univ Nanjing Tech, Peoples R China.
    Gao, Feng
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Sestu, Nicola
    Univ Cagliari, Italy.
    Saba, Michele
    Univ Cagliari, Italy.
    Bongiovanni, Giovanni
    Univ Cagliari, Italy.
    Colella, Silvia
    CNR Nanotec, Italy; Univ Salento, Italy.
    Corcione, Carola Esposito
    Univ Salento, Italy.
    Gigli, Giuseppe
    CNR Nanotec, Italy.
    Listorti, Andrea
    CNR Nanotec, Italy; Univ Salento, Italy.
    Rizzo, Aurora
    CNR Nanotec, Italy.
    Ultra-Bright Near-Infrared Perovskite Light-Emitting Diodes with Reduced Efficiency Roll-off2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 15496Article in journal (Refereed)
    Abstract [en]

    Herein, an insulating biopolymer is exploited to guide the controlled formation of micro/nano-structure and physical confinement of alpha-delta mixed phase crystalline grains of formamidinium lead iodide (FAPbI(3)) perovskite, functioning as charge carrier concentrators and ensuring improved radiative recombination and photoluminescence quantum yield (PLQY). This composite material is used to build highly efficient near-infrared (NIR) FAPbI(3) Perovskite light-emitting diodes (PeLEDs) that exhibit a high radiance of 206.7 W/sr*m(2), among the highest reported for NIR-PeLEDs, obtained at a very high current density of 1000 mA/cm(2), while importantly avoiding the efficiency roll-off effect. In depth photophysical characterization allows to identify the possible role of the biopolymer in i) enhancing the radiative recombination coefficient, improving light extraction by reducing the refractive index, or ii) enhancing the effective optical absorption because of dielectric scattering at the polymer-perovskite interfaces. Our study reveals how the use of insulating matrixes for the growth of perovskites represents a step towards high power applications of PeLEDs.

  • 68.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ticha, Ivana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
    Haapaniemi, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Sun, Xiao-Feng
    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 Oncology.
    MTDH genetic variants in colorectal cancer patients2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is the second most common cancer worldwide and accounts for around 8.5% of all cancer related death. The colorectal carcinogenesis is a complex process of genetic alterations. For better prognosis it is very important to understand the composition of genetic alterations in a tumor. Astrocyte elevated gene-1 (AEG-1) has been shown to be overexpressed in CRC and had prognostic significance. The aim of this study was to determine the frequency and the spectrum of MTDH variants, and their relationship to clinicopathological variables in CRC patients. The study included tumors from 356 unselected CRC patients. Mutation analysis of the MTDH gene, including coding region and adjacent intronic sequences, was performed by direct DNA sequencing. We detected 42 intronic variants, whereby 25 were novel. Furthermore, we found eight exonic variants of which four, one missense (c.977C>G) and three frameshift mutations (c.533delA, c.1731delA, c.1340dupA), were novel. In silico prediction analyses revealed that four variants c.232G>T, c.533delA, c.1340dupA and c.1731delA were deleterious. There were no correlations between the MTDH variants and tumor stage, differentiation or patient survival. The detection of pathogenic mutations and alterations in functional protein domains suggest their involvement in tumorigenesis, although none of the variants had prognostic potential.

  • 69.
    Gomez, Eliot
    et al.
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Simon, Daniel
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Surface Acoustic Waves to Drive Plant Transpiration.2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 45864Article in journal (Refereed)
    Abstract [en]

    Emerging fields of research in electronic plants (e-plants) and agro-nanotechnology seek to create more advanced control of plants and their products. Electronic/nanotechnology plant systems strive to seamlessly monitor, harvest, or deliver chemical signals to sense or regulate plant physiology in a controlled manner. Since the plant vascular system (xylem/phloem) is the primary pathway used to transport water, nutrients, and chemical signals-as well as the primary vehicle for current e-plant and phtyo-nanotechnology work-we seek to directly control fluid transport in plants using external energy. Surface acoustic waves generated from piezoelectric substrates were directly coupled into rose leaves, thereby causing water to rapidly evaporate in a highly localized manner only at the site in contact with the actuator. From fluorescent imaging, we find that the technique reliably delivers up to 6x more water/solute to the site actuated by acoustic energy as compared to normal plant transpiration rates and 2x more than heat-assisted evaporation. The technique of increasing natural plant transpiration through acoustic energy could be used to deliver biomolecules, agrochemicals, or future electronic materials at high spatiotemporal resolution to targeted areas in the plant; providing better interaction with plant physiology or to realize more sophisticated cyborg systems.

  • 70.
    Govorov, Igor
    et al.
    Karolinska Inst, Sweden.
    Bremme, Katarina
    Karolinska Inst, Sweden.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Holmstrom, Margareta
    Karolinska Univ, Sweden.
    Komlichenko, Eduard
    Almazov Natl Med Res Ctr, Russia.
    Chaireti, Roza
    Karolinska Inst, Sweden.
    Mints, Miriam
    Karolinska Inst, Sweden.
    Thrombin generation during a regular menstrual cycle in women with von Willebrand disease2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 17467Article in journal (Refereed)
    Abstract [en]

    Fluctuations of the sex steroids during the menstrual cycle might significantly influence hemostasis. This association, derived from a number of the observations on healthy women, is yet to be described in females affected by bleeding disorders. The aim of the current study was to assess the changes in hemostatic variables in women with vWD during two phases of the menstrual cycle (follicular and luteal) and to compare it with healthy controls. The study group included 12 vWD-affected females with regular menstrual cycle, with none of them being prescribed any hormonal treatment. The control group consisted of 102 healthy females, matched for age and BMI. Within the vWD group FVIII and FX were both significantly higher during follicular phase than in luteal phase (p=0.013 and p=0.033 respectively). AT, FII, FVII and FX were higher in women with vWD, compared with controls during both phases of the menstrual cycle (pamp;lt;0.0005, pamp;lt;0.0005, p=0.001 and pamp;lt;0.0005). In women with vWD, lag time and time to peak were prolonged during both phases of the menstrual cycle(pamp;lt;0.0005), while peak thrombin concentration was reduced (p=0.003 and p=0.002 during follicular and luteal phase respectively) compared to healthy peers. Lower levels of FVIII and FX during luteal phase may predispose women to the development of the menorrhagia - common complication of vWD. Women with vWD need more time to reach the peak thrombin concentration, while the latter still remains less than in healthy women. Higher levels of AT in vWD-affected females, compared to controls, may also contribute to the existing bleeding tendency in this cohort.

  • 71.
    Greczynski, Grzegorz
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering. Rhein Westfal TH Aachen, Germany.
    Mraz, S.
    Rhein Westfal TH Aachen, Germany.
    Hultman, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Schneider, J. M.
    Rhein Westfal TH Aachen, Germany.
    Selectable phase formation in VAlN thin films by controlling Al+ subplantation depth2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17544Article in journal (Refereed)
    Abstract [en]

    We report on a thin film synthesis technique which allows for unprecedented control over the crystalline phase formation in metastable transition metal nitride based layers. For the model material system of V0.26Al0.74N, a complete transition from hexagonal to supersaturated cubic structure is achieved by tuning the incident energy, hence subplantation depth, of Al+ metal ions during reactive hybrid high power impulse magnetron sputtering of Al target and direct current magnetron sputtering of V target in Ar/N-2 gas mixture. These findings enable the phase selective synthesis of novel metastable materials that combine excellent mechanical properties, thermal stability, and oxidation resistance.

  • 72.
    Groenning, Minna
    et al.
    University of Copenhagen, Denmark.
    Campos Melo, Raul Ivan
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hirschberg, Daniel
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Vestergaard, Bente
    University of Copenhagen, Denmark; University of Copenhagen, Denmark.
    Considerably Unfolded Transthyretin Monomers Preceed and Exchange with Dynamically Structured Amyloid Protofibrils2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 11443Article in journal (Refereed)
    Abstract [en]

    Despite numerous studies, a detailed description of the transthyretin (TTR) self-assembly mechanism and fibril structure in TTR amyloidoses remains unresolved. Here, using a combination of primarily small -angle X-ray scattering (SAXS) and hydrogen exchange mass spectrometry (HXMS) analysis, we describe an unexpectedly dynamic TTR protofibril structure which exchanges protomers with highly unfolded monomers in solution. The protofibrils only grow to an approximate final size of 2,900 kDa and a length of 70 nm and a comparative HXMS analysis of native and aggregated samples revealed a much higher average solvent exposure of TTR upon fibrillation. With SAXS, we reveal the continuous presence of a considerably unfolded TTR monomer throughout the fibrillation process, and show that a considerable fraction of the fibrillating protein remains in solution even at a late maturation state. Together, these data reveal that the fibrillar state interchanges with the solution state. Accordingly, we suggest that TTR fibrillation proceeds via addition of considerably unfolded monomers, and the continuous presence of amyloidogenic structures near the protofibril surface offers a plausible explanation for secondary nucleation. We argue that the presence of such dynamic structural equilibria must impact future therapeutic development strategies.

  • 73.
    Gubaydullin, A. R.
    et al.
    St Petersburg Academic University, Russia; University of Claude Bernard Lyon 1, France.
    Symonds, C.
    University of Claude Bernard Lyon 1, France.
    Bellessa, J.
    University of Claude Bernard Lyon 1, France.
    Ivanov, K. A.
    St Petersburg Academic University, Russia; ITMO University, Russia.
    Kolykhalova, E. D.
    St Petersburg Academic University, Russia; Ioffe Institute, Russia.
    Sasin, M. E.
    Ioffe Institute, Russia.
    Lemaitre, A.
    University of Paris Saclay, France.
    Senellart, P.
    University of Paris Saclay, France.
    Pozina, Galia
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Kaliteevski, M. A.
    St Petersburg Academic University, Russia; ITMO University, Russia; Ioffe Institute, Russia.
    Enhancement of spontaneous emission in Tamm plasmon structures2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 9014Article in journal (Refereed)
    Abstract [en]

    It was theoretically and experimentally demonstrated that in metal/semiconductor Tamm plasmon structures the probability of spontaneous emission can be increased despite losses in metal, and theoretical analysis of experimental results suggested that the enhancement could be as high as one order of magnitude. Tamm plasmon structure with quantum dots has been fabricated and the emission pattern has been measured. Electromagnetic modes of the structure have been analyzed and modification of spontaneous emission rates has been calculated showing a good agreement with experimentally observed emission pattern.

  • 74.
    Ha, Hojin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lantz, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ziegler, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Casas Garcia, Belén
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Estimating the irreversible pressure drop across a stenosis by quantifying turbulence production using 4D Flow MRI2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 46618Article in journal (Refereed)
    Abstract [en]

    The pressure drop across a stenotic vessel is an important parameter in medicine, providing a commonly used and intuitive metric for evaluating the severity of the stenosis. However, non-invasive estimation of the pressure drop under pathological conditions has remained difficult. This study demonstrates a novel method to quantify the irreversible pressure drop across a stenosis using 4D Flow MRI by calculating the total turbulence production of the flow. Simulation MRI acquisitions showed that the energy lost to turbulence production can be accurately quantified with 4D Flow MRI within a range of practical spatial resolutions (1-3 mm; regression slope = 0.91, R-2 = 0.96). The quantification of the turbulence production was not substantially influenced by the signal-to-noise ratio (SNR), resulting in less than 2% mean bias at SNR amp;gt; 10. Pressure drop estimation based on turbulence production robustly predicted the irreversible pressure drop, regardless of the stenosis severity and post-stenosis dilatation (regression slope = 0.956, R-2 = 0.96). In vitro validation of the technique in a 75% stenosis channel confirmed that pressure drop prediction based on the turbulence production agreed with the measured pressure drop (regression slope = 1.15, R-2 = 0.999, Bland-Altman agreement = 0.75 +/- 3.93 mmHg).

  • 75.
    Hagbom, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nybom, Rolf
    Karolinska Institute, Sweden.
    Hedlund, Kjell-Olof
    Swedish Institute Communicable Disease Control, Sweden.
    Wigzell, Hans
    Karolinska Institute, Sweden.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ionizing air affects influenza virus infectivity and prevents airborne-transmission2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 11431Article in journal (Refereed)
    Abstract [en]

    By the use of a modified ionizer device we describe effective prevention of airborne transmitted influenza A (strain Panama 99) virus infection between animals and inactivation of virus (greater than 97%). Active ionizer prevented 100% (4/4) of guinea pigs from infection. Moreover, the device effectively captured airborne transmitted calicivirus, rotavirus and influenza virus, with recovery rates up to 21% after 40 min in a 19 m(3) room. The ionizer generates negative ions, rendering airborne particles/aerosol droplets negatively charged and electrostatically attracts them to a positively charged collector plate. Trapped viruses are then identified by reverse transcription quantitative real-time PCR. The device enables unique possibilities for rapid and simple removal of virus from air and offers possibilities to simultaneously identify and prevent airborne transmission of viruses.

  • 76.
    Hagiwara, Akifumi
    et al.
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan. a-hagiwara@juntendo.ac.jp; Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
    Hori, Masaaki
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
    Kamagata, Koji
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
    Warntjes, Marcel
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. SyntheticMR AB, Linköping, Sweden.
    Matsuyoshi, Daisuke
    Araya Inc., Tokyo, Japan; Research Institute for Science and Engineering, Waseda University, Waseda, Japan; Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
    Nakazawa, Misaki
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
    Ueda, Ryo
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan; Department of Radiological Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan; Office of Radiation Technology, Keio University Hospital, Tokyo, Japan.
    Andica, Christina
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
    Koshino, Saori
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan; Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
    Maekawa, Tomoko
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan; Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
    Irie, Ryusuke
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan; Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
    Takamura, Tomohiro
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
    Kumamaru, Kanako Kunishima
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
    Abe, Osamu
    Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
    Aoki, Shigeki
    Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan.
    Myelin Measurement: Comparison Between Simultaneous Tissue Relaxometry, Magnetization Transfer Saturation Index, and T1w/T2w Ratio Methods2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 10554Article in journal (Refereed)
    Abstract [en]

    Magnetization transfer (MT) imaging has been widely used for estimating myelin content in the brain. Recently, two other approaches, namely simultaneous tissue relaxometry of R1 and R2 relaxation rates and proton density (SyMRI) and the ratio of T1-weighted to T2-weighted images (T1w/T2w ratio), were also proposed as methods for measuring myelin. SyMRI and MT imaging have been reported to correlate well with actual myelin by histology. However, for T1w/T2w ratio, such evidence is limited. In 20 healthy adults, we examined the correlation between these three methods, using MT saturation index (MTsat) for MT imaging. After calibration, white matter (WM) to gray matter (GM) contrast was the highest for SyMRI among these three metrics. Even though SyMRI and MTsat showed strong correlation in the WM (r?=?0.72), only weak correlation was found between T1w/T2w and SyMRI (r?=?0.45) or MTsat (r?=?0.38) (correlation coefficients significantly different from each other, with p values?amp;lt;?0.001). In subcortical and cortical GM, these measurements showed moderate to strong correlations to each other (r?=?0.54 to 0.78). In conclusion, the high correlation between SyMRI and MTsat indicates that both methods are similarly suited to measure myelin in the WM, whereas T1w/T2w ratio may be less optimal.

  • 77.
    Hedlund, Louise
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Whittle, Rosemary
    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.
    Effects of commercial hatchery processing on short- and long-term stress responses in laying hens2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 2367Article in journal (Refereed)
    Abstract [en]

    In commercial egg production, chicks are exposed to a potentially stressful procedure during their first day of life. Here, we investigated how this procedure affects the chickens in a short-as well as long-term perspective by conducting two behaviour tests and measuring corticosterone (CORT) and sex hormone levels at different time points. These results were compared with a group of control chickens from the same hatchery and incubator that did not go through the commercial hatchery routine. Chickens were continuously weighed, egg production data was collected and feather scoring was performed. We found that chicks have a significant increase in CORT during the hatchery process, which implies they are exposed to stress. During first weeks of life, these chicks were more fearful, had a higher CORT reactivity during restraint and weighed more than control chicks. Later in life, hatchery treated chickens had more feather damages and injuries on combs and wattles, a faster onset of egg laying and higher levels of estradiol. We conclude that processing at the commercial hatchery was a stressful event with short-and long-term effects on behaviour and stress reactivity, and potentially also positive effects on production. The results are relevant for a large number of individuals, since the chicken is by far the globally most common farm animal.

  • 78.
    Henriksen, Rie
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Andersson, L
    Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    The domesticated brain: genetics of brain mass and brain structure in an avian species.2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed)
    Abstract [en]

    As brain size usually increases with body size it has been assumed that the two are tightly constrained and evolutionary studies have therefore often been based on relative brain size (i.e. brain size proportional to body size) rather than absolute brain size. The process of domestication offers an excellent opportunity to disentangle the linkage between body and brain mass due to the extreme selection for increased body mass that has occurred. By breeding an intercross between domestic chicken and their wild progenitor, we address this relationship by simultaneously mapping the genes that control inter-population variation in brain mass and body mass. Loci controlling variation in brain mass and body mass have separate genetic architectures and are therefore not directly constrained. Genetic mapping of brain regions indicates that domestication has led to a larger body mass and to a lesser extent a larger absolute brain mass in chickens, mainly due to enlargement of the cerebellum. Domestication has traditionally been linked to brain mass regression, based on measurements of relative brain mass, which confounds the large body mass augmentation due to domestication. Our results refute this concept in the chicken.

  • 79.
    Herberthson, Magnus
    et al.
    Linköping University, Department of Mathematics, Mathematics and Applied Mathematics. Linköping University, Faculty of Science & Engineering.
    Yolcu, Cem
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Westin, Carl-Fredrik
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Harvard Med Sch, MA 02115 USA.
    Özarslan, Evren
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Orientationally-averaged diffusion-attenuated magnetic resonance signal for locally-anisotropic diffusion2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4899Article in journal (Refereed)
    Abstract [en]

    Diffusion-attenuated MR signal for heterogeneous media has been represented as a sum of signals from anisotropic Gaussian sub-domains to the extent that this approximation is permissible. Any effect of macroscopic (global or ensemble) anisotropy in the signal can be removed by averaging the signal values obtained by differently oriented experimental schemes. The resulting average signal is identical to what one would get if the micro-domains are isotropically (e.g., randomly) distributed with respect to orientation, which is the case for "powdered" specimens. We provide exact expressions for the orientationally-averaged signal obtained via general gradient waveforms when the microdomains are characterized by a general diffusion tensor possibly featuring three distinct eigenvalues. This extends earlier results which covered only axisymmetric diffusion as well as measurement tensors. Our results are expected to be useful in not only multidimensional diffusion MR but also solid-state NMR spectroscopy due to the mathematical similarities in the two fields.

  • 80.
    Huguet, Carme
    et al.
    Univ Los Andes, Colombia.
    Routh, Joyanto
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Fietz, Susanne
    Stellenbosch Univ, South Africa.
    Lone, Mahjoor Ahmad
    Natl Taiwan Univ, Taiwan.
    Kalpana, M. S.
    CSIR, India.
    Ghosh, Prosenjit
    Indian Inst Sci, India.
    Mangini, Augusto
    Inst Umweltphys, Germany.
    Kumar, Vikash
    Natl Ctr Antarctic and Ocean Res, India.
    Rangarajan, Ravi
    Indian Inst Sci, India.
    Temperature and Monsoon Tango in a Tropical Stalagmite: Last Glacial-Interglacial Climate Dynamics2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5386Article in journal (Refereed)
    Abstract [en]

    High-resolution paleoclimate data on stable isotopes in a stalagmite were coupled to glycerol dialkyl glycerol tetraethers (GDGTs). The Indian Summer Monsoon (ISM) transitioned from limited rainfall during the Last Glacial Maximum (LGM) to intense precipitation during early Holocene (22 to 6 ka). This was associated with changes in stalagmite growth, abundance of branched (br) and isoprenoid (iso) GDGTs, as well as delta O-18, delta C-13, Sr/Ca and GDGT-derived signals providing both temperature and moisture information. The reconstructed mean annual air temperature (MAAT) of the most modern stalagmite sample at similar to 19 degrees C, matches the surface and cave MAAT, but was similar to 4 degrees C lower during LGM. Warming at the end of LGM occurred before ISM strengthened and indicate 6 ka lag consistent with sea surface temperature records. The isotope records during the Younger Dryas show rapid progressions to dry conditions and weak monsoons, but these shifts are not coupled to TEX86. Moreover, change to wetter and stronger ISM, along with warmer Holocene conditions are not continuous indicating a decoupling of local temperatures from ISM.

  • 81.
    Icenhour, Adriane
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bednarska, Olga
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Witt, Suzanne Tyson
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. 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).
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. 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).
    Elsenbruch, Sigrid
    Univ Duisburg Essen, Germany.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elucidating the putative link between prefrontal neurotransmission, functional connectivity, and affective symptoms in irritable bowel syndrome2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 13590Article in journal (Refereed)
    Abstract [en]

    Altered neural mechanisms are well-acknowledged in irritable bowel syndrome (IBS), a disorder of brain-gut-communication highly comorbid with anxiety and depression. As a key hub in corticolimbic inhibition, medial prefrontal cortex (mPFC) may be involved in disturbed emotion regulation in IBS. However, aberrant mPFC excitatory and inhibitory neurotransmission potentially contributing to psychological symptoms in IBS remains unknown. Using quantitative magnetic resonance spectroscopy (qMRS), we compared mPFC glutamate + glutamine (Glx) and gamma-aminobutyric acid (GABA+) concentrations in 64 women with IBS and 32 age-matched healthy women (HCs) and investigated their association with anxiety and depression in correlational and subgroup analyses. Applying functional magnetic resonance imaging (fMRI), we explored whether altered neurotransmission was paralleled by aberrant mPFC resting-state functional connectivity (FC). IBS patients did not differ from HCs with respect to mPFC GABA+ or Glx levels. Anxiety was positively associated with mPFC GABA+ concentrations in IBS, whereas Glx was unrelated to psychological or gastrointestinal symptoms. Subgroup comparisons of patients with high or low anxiety symptom severity and HCs revealed increased GABA+ in patients with high symptom severity, and lower mPFC FC with adjacent anterior cingulate cortex (ACC), a crucial region of emotion modulation. Our findings provide novel evidence that altered prefrontal inhibitory neurotransmission may be linked to anxiety in IBS.

  • 82.
    Ingberg, Edvin
    et al.
    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 Chemistry.
    Dock, Hua
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Ström, Jakob O
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Vårdvetenskapligt Forskningscentrum/Centre for Health Sciences, Örebro University Hospital, Region Örebro Län, Örebro, Sweden / School of Health and Medical Sciences, Örebro University, Örebro, Sweden..
    Method parameters’ impact on mortality and variability in mouse stroke experiments: a meta-analysis2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed)
    Abstract [en]

    Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specifi c pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters’ impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.

  • 83.
    Ingberg, Edvin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Ström, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. veÖrebro University Hospital, Sweden; Unirsity of Örebro, Sweden.
    Effects of high and low 17 beta-estradiol doses on focal cerebral ischemia in rats2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 20228Article in journal (Refereed)
    Abstract [en]

    The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17 beta-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17 beta-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17 beta-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17 beta-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17 beta-estradiol, the smaller the infarct.

  • 84.
    Islam, Rakibul
    et al.
    Harvard Medical Sch, MA USA; University of Oslo, Norway; Oslo University Hospital, Norway.
    Roger Eidet, Jon
    Oslo University Hospital, Norway.
    Badian, Reza A.
    Harvard Medical Sch, MA USA; University of Coll Southeast Norway, Norway; Innlandet Hospital Trust, Norway.
    Lippestad, Marit
    Harvard Medical Sch, MA USA; Oslo University Hospital, Norway; University of Oslo, Norway.
    Messelt, Edward
    University of Oslo, Norway.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Dartt, Darlene A.
    Harvard Medical Sch, MA USA; University of Oslo, Norway.
    Paaske Utheim, Tor
    Harvard Medical Sch, MA USA; University of Oslo, Norway; Oslo University Hospital, Norway; Innlandet Hospital Trust, Norway.
    Tissue Harvesting Site and Culture Medium Affect Attachment, Growth, and Phenotype of Ex Vivo Expanded Oral Mucosal Epithelial Cells2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 674Article in journal (Refereed)
    Abstract [en]

    Transplantation of cultured oral mucosal epithelial cells (OMECs) is a promising treatment strategy for limbal stem cell deficiency. In order to improve the culture method, we investigated the effects of four culture media and tissue harvesting sites on explant attachment, growth, and phenotype of OMECs cultured from Sprague-Dawley rats. Neither choice of media or harvesting site impacted the ability of the explants to attach to the culture well. Dulbeccos modified Eagles medium/Hams F12 (DMEM) and Roswell Park Memorial Institute 1640 medium (RPMI) supported the largest cellular outgrowth. Fold outgrowth was superior from LL explants compared to explants from the buccal mucosa (BM), HP, and transition zone of the lower lip (TZ) after six-day culture. Putative stem cell markers were detected in cultures grown in DMEM and RPMI. In DMEM, cells from TZ showed higher colony-forming efficiency than LL, BM, and HP. In contrast to RPMI, DMEM both expressed the putative stem cell marker Bmi-1 and yielded cell colonies. Our data suggest that OMECs from LL and TZ cultured in DMEM give rise to undifferentiated cells with high growth capacity, and hence are the most promising for treatment of limbal stem cell deficiency.

  • 85.
    Jamnig, Andreas
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Nanoscale engineering. Linköping University, Faculty of Science & Engineering. Univ Poitiers, France.
    Sangiovanni, Davide Giuseppe
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering. Ruhr Univ Bochum, Germany.
    Abadias, G.
    Univ Poitiers, France.
    Sarakinos, Kostas
    Linköping University, Department of Physics, Chemistry and Biology, Nanoscale engineering. Linköping University, Faculty of Science & Engineering.
    Atomic-scale diffusion rates during growth of thin metal films on weakly-interacting substrates2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 6640Article in journal (Refereed)
    Abstract [en]

    We use a combined experimental and theoretical approach to study the rates of surface diffusion processes that govern early stages of thin Ag and Cu film morphological evolution on weakly-interacting amorphous carbon substrates. Films are deposited by magnetron sputtering, at temperatures T-S between 298 and 413 K, and vapor arrival rates F in the range 0.08 to 5.38 monolayers/s. By employing in situ and real-time sheet-resistance and wafer-curvature measurements, we determine the nominal film thickness Theta at percolation (Theta(perc)) and continuous film formation (Theta(cont)) transition. Subsequently, we use the scaling behavior of Theta(perc) and Theta(cont) as a function of F and T-s, to estimate, experimentally, the temperature-dependent diffusivity on the substrate surface, from which we calculate Ag and Cu surface migration energy barriers E-D(exp) and attempt frequencies nu(exp)(0). By critically comparing E-D(exp) and nu(exp)(0) with literature data, as well as with results from our ab initio molecular dynamics simulations for single Ag and Cu adatom diffusion on graphite surfaces, we suggest that: (i) E-D(exp) and nu(exp)(0) correspond to diffusion of multiatomic clusters, rather than to diffusion of monomers; and (ii) the mean size of mobile clusters during Ag growth is larger compared to that of Cu. The overall results of this work pave the way for studying growth dynamics in a wide range of technologically-relevant weakly-interacting film/substrate systems-including metals on 2D materials and oxides-which are building blocks in next-generation nanoelectronic, optoelectronic, and catalytic devices.

  • 86.
    Jasim, Hajer
    et al.
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Folktandvarden Stockholm AB, Sweden.
    Carlsson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Hedenberg-Magnusson, Britt
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Folktandvarden Stockholm AB, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ernberg, Malin
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Saliva as a medium to detect and measure biomarkers related to pain2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 3220Article in journal (Refereed)
    Abstract [en]

    Saliva is often neglected as a body fluid of diagnostic or prognostic value, even though generally well accepted by the patients. This is due to lack of a standardized collection procedure. The aim of this study was to identify the ideal saliva collection technique and develop new sensitive methods to detect and analyse markers related to pain in healthy pain-free subjects. Plasma and five different saliva collection approached was evaluated during strictly controlled conditions. Levels of nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and brain derived neurotropic factor (BDNF) were determined using novel western blotting based technology. Glutamate and substance P (SP) was determined using commercial available methods. Several new isoforms were found for NGF, CGRP and BDNF in saliva. The isoform pattern showed significant variation in both expression and chemiluminescence levels between different collection methods. New sensitive methods to study pain related markers in saliva were developed in this study. Furthermore, we are first to demonstrate a correlation between the Glutamate concentration in stimulated whole saliva and blood. However, the fundamental conclusion drawn is the importance of consistency in the collection method.

  • 87.
    Jasim, Hajer
    et al.
    Karolinska Institute, Sweden; Scandinavian Centre Orofacial Neurosci SCON, Sweden; Folktandvarden Stockholm AB, Sweden.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Hedenberg-Magnusson, Britt
    Karolinska Institute, Sweden; Scandinavian Centre Orofacial Neurosci SCON, Sweden; Folktandvarden Stockholm AB, Sweden.
    Ernberg, Malin
    Karolinska Institute, Sweden; Scandinavian Centre Orofacial Neurosci SCON, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    The proteomic profile of whole and glandular saliva in healthy pain-free subjects2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 39073Article in journal (Refereed)
    Abstract [en]

    Determination of the variability in the salivary proteome is a prerequisite for the development of saliva as a diagnostic and prognostic tool in particular physiological states. In this context, it is important that technical variability induced by sample collection and processing is kept at minimum to be able to reproducibly assess variability in states of health and disease. In the current study, the proteome profile in unstimulated and stimulated whole, parotid and sublingual saliva was investigated using two-dimensional gel electrophoresis. Saliva samples were structurally collected from ten examined and characterized healthy individuals during the exactly same conditions. The results demonstrated that different collection methods provide clear differences in the snapshot of the salivary proteome and also in the relative amount of specific proteins. The variable nature of the salivary proteome suggests that different approaches may have to be adopted when studying its composition or its possible role as an indicator for particular physiological states. The results emphasize the importance of consistency when collecting saliva samples for proteomic analysis.

  • 88.
    Jastrzebska, Kamila
    et al.
    Polish Academic Science, Poland.
    Walczak, Magdalena
    Jagiellonian University, Poland.
    Eligiusz Cieslak, Przemyslaw
    Polish Academic Science, Poland.
    Szumiec, Lukasz
    Polish Academic Science, Poland.
    Turbasa, Mateusz
    Polish Academic Science, Poland.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Blasiak, Tomasz
    Jagiellonian University, Poland.
    Rodriguez Parkitna, Jan
    Polish Academic Science, Poland.
    Loss of NMDA receptors in dopamine neurons leads to the development of affective disorder-like symptoms in mice2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 37171Article in journal (Refereed)
    Abstract [en]

    The role of changes in dopamine neuronal activity during the development of symptoms in affective disorders remains controversial. Here, we show that inactivation of NMDA receptors on dopaminergic neurons in adult mice led to the development of affective disorder-like symptoms. The loss of NMDA receptors altered activity and caused complete NMDA-insensitivity in dopamine-like neurons. Mutant mice exhibited increased immobility in the forced swim test and a decrease in social interactions. Mutation also led to reduced saccharin intake, however the preference of sweet taste was not significantly decreased. Additionally, we found that while mutant mice were slower to learn instrumental tasks, they were able to reach the same performance levels, had normal sensitivity to feedback and showed similar motivation to exert effort as control animals. Taken together these results show that inducing the loss of NMDA receptor-dependent activity in dopamine neurons is associated with development of affective disorder-like symptoms.

  • 89.
    Johansson, Leif I.
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Armiento, Rickard
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, The Institute of Technology.
    Avila, Jose
    Synchrotron SOLEIL, France .
    Xia, Chao
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Lorcy, Stephan
    Synchrotron SOLEIL, France .
    Igor A., Abrikosov
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, The Institute of Technology.
    Asensio, Maria C.
    Synchrotron SOLEIL, France .
    Virojanadara, Chariya
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Multiple π-bands and Bernal stacking of multilayer graphene on C-face SiC, revealed by nano-Angle Resolved Photoemission2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, no 4157Article in journal (Refereed)
    Abstract [en]

    Only a single linearly dispersing π-band cone, characteristic of monolayer graphene, has so far been observed in Angle Resolved Photoemission (ARPES) experiments on multilayer graphene grown on C-face SiC. A rotational disorder that effectively decouples adjacent layers has been suggested to explain this. However, the coexistence of μm-sized grains of single and multilayer graphene with different azimuthal orientations and no rotational disorder within the grains was recently revealed for C-face graphene, but conventional ARPES still resolved only a single π-band. Here we report detailed nano-ARPES band mappings of individual graphene grains that unambiguously show that multilayer C-face graphene exhibits multiple π-bands. The band dispersions obtained close to the K-point moreover clearly indicate, when compared to theoretical band dispersion calculated in the framework of the density functional method, Bernal (AB) stacking within the grains. Thus, contrary to earlier claims, our findings imply a similar interaction between graphene layers on C-face and Si-face SiC.

  • 90.
    Johansson, Patrik
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Jullesson, David
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Elfwing, Anders
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Liin, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Musumeci, Chiara
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Zeglio, Erica
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Solin, Niclas
    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.
    Electronic polymers in lipid membranes2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 11242Article in journal (Refereed)
    Abstract [en]

    Electrical interfaces between biological cells and man-made electrical devices exist in many forms, but it remains a challenge to bridge the different mechanical and chemical environments of electronic conductors (metals, semiconductors) and biosystems. Here we demonstrate soft electrical interfaces, by integrating the metallic polymer PEDOT-S into lipid membranes. By preparing complexes between alkyl-ammonium salts and PEDOT-S we were able to integrate PEDOT-S into both liposomes and in lipid bilayers on solid surfaces. This is a step towards efficient electronic conduction within lipid membranes. We also demonstrate that the PEDOT-S@alkyl-ammonium: lipid hybrid structures created in this work affect ion channels in the membrane of Xenopus oocytes, which shows the possibility to access and control cell membrane structures with conductive polyelectrolytes.

  • 91.
    Johansson-Åkhe, Isak
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Mirabello, Claudio
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wallner, Björn
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Predicting protein-peptide interaction sites using distant protein complexes as structural templates2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4267Article in journal (Refereed)
    Abstract [en]

    Protein-peptide interactions play an important role in major cellular processes, and are associated with several human diseases. To understand and potentially regulate these cellular function and diseases it is important to know the molecular details of the interactions. However, because of peptide flexibility and the transient nature of protein-peptide interactions, peptides are difficult to study experimentally. Thus, computational methods for predicting structural information about protein-peptide interactions are needed. Here we present InterPep, a pipeline for predicting protein-peptide interaction sites. It is a novel pipeline that, given a protein structure and a peptide sequence, utilizes structural template matches, sequence information, random forest machine learning, and hierarchical clustering to predict what region of the protein structure the peptide is most likely to bind. When tested on its ability to predict binding sites, InterPep successfully pinpointed 255 of 502 (50.7%) binding sites in experimentally determined structures at rank 1 and 348 of 502 (69.3%) among the top five predictions using only structures with no significant sequence similarity as templates. InterPep is a powerful tool for identifying peptide-binding sites; with a precision of 80% at a recall of 20% it should be an excellent starting point for docking protocols or experiments investigating peptide interactions. The source code for InterPred is available at http://wallnerlab.org/InterPep/.

  • 92.
    Jonasson, Lena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Grauen Larsen, H.
    Lund University, Sweden; Skåne University Hospital Malmö, Sweden.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gullstrand, B.
    Lund University, Sweden; Skåne University Hospital Lund, Sweden.
    Bengtsson, A. A.
    Lund University, Sweden; Skåne University Hospital Lund, Sweden.
    Schiopu, A.
    Lund University, Sweden; Skåne University Hospital Malmö, Sweden.
    Stress-induced release of the S100A8/A9 alarmin is elevated in coronary artery disease patients with impaired cortisol response2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17545Article in journal (Refereed)
    Abstract [en]

    Psychological stress is thought to be an important trigger of cardiovascular events, yet the involved pathways and mediators are largely unknown. Elevated systemic levels of the pro-inflammatory alarmin S100A8/A9 correlate with poor prognosis in coronary artery disease (CAD) patients. Here, we investigated the links between S100A8/A9 release and parameters of anti-inflammatory glucocorticoid secretion in two different cohorts subjected to a psychological stress test. In the first cohort of 60 CAD patients, psychological stress induced a rapid increase of circulating S100A8/A9. This rapid S100A8/A9 response strongly correlated with elevated evening saliva cortisol levels, suggesting an association with a dysregulatedhy pothalamic-pituitary-adrenal (HPA) axis. In the second cohort of 27 CAD patients and 28 controls, elevated S100A8/A9 levels were still detectable 24 h after stress in 40% of patients and 36% of controls, with a tendency for higher levels in patients. The sustained S100A8/A9 response was associated with a poor rapid cortisol release after stress in patients, but not in the control group. Our findings reveal for the first time that acute psychological stress induces elevated levels of S100A8/A9. We also provide hypothesis-generating evidence that dysregulated cortisol secretion in CAD patients might be associated with an exaggerated pro-inflammatory S100A8/A9 response.

  • 93.
    Jonsson, Emma H.
    et al.
    University of Gothenburg, Sweden.
    Bendas, Johanna
    Technical University of Dresden, Germany.
    Weidner, Kerstin
    Technical University of Dresden, Germany.
    Wessberg, Johan
    University of Gothenburg, Sweden.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. University of Gothenburg, Sweden.
    Backlund Wasling, Helena
    University of Gothenburg, Sweden.
    Croy, Ilona
    Technical University of Dresden, Germany.
    The relation between human hair follicle density and touch perception2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2499Article in journal (Refereed)
    Abstract [en]

    Unmyelinated low threshold C-tactile fibers moderate pleasant aspects of touch. These fibers respond optimally to stroking stimulation of the skin with slow velocities (1-10 cm/s). Low threshold mechanoreceptors are arranged around hair follicles in rodent skin. If valid also in humans, hair follicle density (HFD) may relate to the perceived pleasantness of stroking tactile stimulation. We conducted two studies that examined the relation between HFD and affective touch perception in humans. In total, 138 healthy volunteers were stroked on the forearm and rated the pleasantness and intensity. Stimulation was performed by a robotic tactile stimulator delivering C-tactile optimal (1, 3, 10 cm/s) and non-optimal (0.1, 0.3, 30 cm/s) stroking velocities. Additionally, a measure of discriminative touch was applied in study 2. HFD of the same forearm was determined using the Cyanoacrylate Skin Stripping Method (CSSM), which we validated in a pretest. Women had higher HFD than men, which was explained by body size and weight. Furthermore, women rated affective touch stimuli as more pleasant and had higher tactile acuity. Depilation did not affect touch perception. A weak relationship was found between the C-tactile specific aspects of affective touch perception and HFD, and the hypothesis of HFD relating to pleasant aspects of stroking only received weak support.

  • 94.
    Kabakci, Zeynep
    et al.
    Univ Zurich, Switzerland.
    Kappeli, Simon
    Univ Zurich, Switzerland.
    Cantù, Claudio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Univ Zurich, Switzerland.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Konig, Christiane
    Univ Zurich, Switzerland.
    Toggweiler, Janine
    Univ Zurich, Switzerland.
    Gentili, Christian
    Univ Zurich, Switzerland.
    Ribaudo, Giovanni
    Univ Padua, Italy.
    Zagotto, Giuseppe
    Univ Padua, Italy.
    Basler, Konrad
    Univ Zurich, Switzerland.
    Pinna, Lorenzo A.
    Univ Padua, Italy.
    Cozza, Giorgio
    Univ Padua, Italy.
    Ferrari, Stefano
    Univ Zurich, Switzerland.
    Pharmacophore-guided discovery of CDC25 inhibitors causing cell cycle arrest and tumor regression2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1335Article in journal (Refereed)
    Abstract [en]

    CDC25 phosphatases play a key role in cell cycle transitions and are important targets for cancer therapy. Here, we set out to discover novel CDC25 inhibitors. Using a combination of computational methods, we defined a minimal common pharmacophore in established CDC25 inhibitors and performed virtual screening of a proprietary library. Based on the availability of crystal structures for CDC25A and CDC25B, we implemented a molecular docking strategy and carried out hit expansion/optimization. Enzymatic assays revealed that naphthoquinone scaffolds were the most promising CDC25 inhibitors among selected hits. At the molecular level, the compounds acted through a mixed-type mechanism of inhibition of phosphatase activity, involving reversible oxidation of cysteine residues. In 2D cell cultures, the compounds caused arrest of the cell cycle at the G1/S or at the G2/M transition. Mitotic markers analysis and time-lapse microscopy confirmed that CDK1 activity was impaired and that mitotic arrest was followed by death. Finally, the compounds induced differentiation, accompanied by decreased stemness properties, in intestinal crypt stem cell-derived Apc/K-Ras-mutant mouse organoids, and led to tumor regression and reduction of metastatic potential in zebrafish embryo xenografts used as in vivo model.

  • 95.
    Kaliteevski, M. A.
    et al.
    St Petersburg Academic University, Russia; Russian Academy of Science, St-Petersburg, Russia.
    Ivanov, K. A.
    St Petersburg Academic University, Russia .
    Pozina, Galia
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Gallant, A. J.
    University of Durham, England .
    Single and double bosonic stimulation of THz emission in polaritonic systems2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, no 5444Article in journal (Refereed)
    Abstract [en]

    The influence of the surrounding cavity on the efficiency of different types of polaritonic emitters of THz radiation has been analysed. It is demonstrated that THz lasing threshold in realistic structures cannot be achieved without a THz cavity, due to destruction of polaritons via excitonic Mott transition. Even modest values of cavity quality factor (not exceeding 50) provide significant quantum efficiency.

  • 96.
    Kaneko, Tomoyuki
    et al.
    Tokyo Medical and Dent University, Japan .
    Nomura, Fumimasa
    Tokyo Medical and Dent University, Japan .
    Hamada, Tomoyo
    Tokyo Medical and Dent University, Japan .
    Abe, Yasuyuki
    Daiichi Sankyo Co Ltd, Japan .
    Takamori, Hideo
    Daiichi Sankyo Co Ltd, Japan .
    Sakakura, Tomoko
    Daiichi Sankyo Co Ltd, Japan .
    Takasuna, Kiyoshi
    Daiichi Sankyo Co Ltd, Japan .
    Sanbuissho, Atsushi
    Daiichi Sankyo Co Ltd, Japan .
    Hyllner, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Sartipy, Peter
    Cellartis AB, Sweden .
    Yasuda, Kenji
    Tokyo Medical and Dent University, Japan .
    On-chip in vitro cell-network pre-clinical cardiac toxicity using spatiotemporal human cardiomyocyte measurement on a chip2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, no 04670Article in journal (Refereed)
    Abstract [en]

    To overcome the limitations and misjudgments of conventional prediction of arrhythmic cardiotoxicity, we have developed an on-chip in vitro predictive cardiotoxicity assay using cardiomyocytes derived from human stem cells employing a constructive spatiotemporal two step measurement of fluctuation (short-term variability; STV) of cells repolarization and cell-to-cell conduction time, representing two origins of lethal arrhythmia. Temporal STV of field potential duration (FPD) showed a potential to predict the risks of lethal arrhythmia originated from repolarization dispersion for false negative compounds, which was not correctly predicted by conventional measurements using animal cells, even for non-QT prolonging clinical positive compounds. Spatial STV of conduction time delay also unveiled the proarrhythmic risk of asynchronous propagation in cell networks, whose risk cannot be correctly predicted by single-cell-based measurements, indicating the importance of the spatiotemporal fluctuation viewpoint of in vitro cell networks for precise prediction of lethal arrhythmia reaching clinical assessment such as thorough QT assay.

  • 97.
    Karlsson, Anna
    et al.
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Cirenajwis, Helena
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Ericson-Lindquist, Kajsa
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Pathology, Regional Laboratories Region Skåne, Lund, Sweden.
    Brunnstrom, Hans
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Pathology, Regional Laboratories Region Skåne, Lund, Sweden.
    Reutersward, Christel
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Jönsson, Mats
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    Ortiz-Villalon, Cristian
    Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Hussein, Aziz
    Department of Pathology and cytology, Sahlgrenska university hospital, Gothenburg, Sweden.
    Bergman, Bengt
    Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Monsef, Nastaran
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Branden, Eva
    Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden; Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
    Koyi, Hirsh
    Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden; Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
    de Petris, Luigi
    Thoracic Oncology Unit, Karolinska University Hospital and Department Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Micke, Patrick
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Patthey, Annika
    Department of Pathology, Umeå University Hospital, Umeå, Sweden.
    Behndig, Annelie F.
    Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden.
    Johansson, Mikael
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Planck, Maria
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden; Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund, Sweden.
    Staaf, Johan
    Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund, Sweden.
    A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 5207Article in journal (Refereed)
    Abstract [en]

    Accurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11-199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.

  • 98.
    Keasar, Chen
    et al.
    Ben Gurion Univ Negev, Israel.
    McGuffin, Liam J.
    Univ Reading, England.
    Wallner, Björn
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Chopra, Gaurav
    Purdue Univ, IN USA.
    Adhikari, Badri
    Univ Missouri, MO USA.
    Bhattacharya, Debswapna
    Auburn Univ, AL 36849 USA.
    Blake, Lauren
    Lawrence Berkeley Natl Lab, CA 94720 USA.
    Bortot, Leandro Oliveira
    Univ Sao Paulo, Brazil.
    Cao, Renzhi
    Univ Missouri, MO USA.
    Dhanasekaran, B. K.
    Indian Inst Sci, India.
    Dimas, Itzhel
    Lawrence Berkeley Natl Lab, CA 94720 USA.
    Faccioli, Rodrigo Antonio
    Univ Sao Paulo, Brazil.
    Faraggi, Eshel
    Res and Informat Syst LLC, CA USA; IU Sch Med, IN USA; Nationwide Childrens Hosp, OH USA.
    Ganzynkowicz, Robert
    Univ Gdansk, Poland.
    Ghosh, Sambit
    Indian Inst Sci, India.
    Ghosh, Soma
    Indian Inst Sci, India.
    Gieldon, Artur
    Univ Gdansk, Poland.
    Golon, Lukasz
    Univ Gdansk, Poland.
    He, Yi
    Univ Calif, CA USA.
    Heo, Lim
    Seoul Natl Univ, South Korea.
    Hou, Jie
    Univ Missouri, MO USA.
    Khan, Main
    Univ Massachusetts, MA USA.
    Khatib, Firas
    Univ Massachusetts, MA USA.
    Khoury, George A.
    Princeton Univ, NJ 08544 USA.
    Kieslich, Chris
    Texas AandM Univ, TX USA.
    Kim, David E.
    Univ Washington, WA 98195 USA; Univ Washington, WA 98195 USA.
    Krupa, Pawel
    Univ Gdansk, Poland.
    Lee, Gyu Rie
    Seoul Natl Univ, South Korea.
    Li, Hongbo
    Univ Missouri, MO USA; NorthEast Normal Univ, Peoples R China; Univ Missouri, MO USA.
    Li, Jilong
    Univ Missouri, MO USA.
    Lipska, Agnieszka
    Univ Gdansk, Poland.
    Liwo, Adam
    Univ Gdansk, Poland.
    Maghrabi, Ali Hassan A.
    Not Found:[Keasar, Chen; Sidi, Tomer] Ben Gurion Univ Negev, Dept Comp Sci, Beer Sheva, Israel; [McGuffin, Liam J.] Univ Reading, Sch Biol Sci, Biomed Sci Div, Reading RG6 6AS, Berks, England; [Wallner, Bjorn] Linkoping Univ, Dept Phys Chem and Biol, Div Bioinformat, Linkoping, Sweden; [Chopra, Gaurav] Purdue Univ, Dept Chem, Coll Sci, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Drug Discovery, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Inflammat Immunol and Infect Dis, W Lafayette, IN USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Integrat Neurosci, W Lafayette, IN USA; [Adhikari, Badri; Cao, Renzhi; Hou, Jie; Li, Hongbo; Li, Jilong; Cheng, Jianlin] Univ Missouri, Dept Elect Engn and Comp Sci, Columbia, MO USA; [Bhattacharya, Debswapna] Auburn Univ, Dept Comp Sci and Software Engn, Auburn, AL 36849 USA; [Blake, Lauren; Dimas, Itzhel; Crivelli, Silvia N.] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA; [Bortot, Leandro Oliveira] Univ Sao Paulo, Lab Biol Phys, Fac Pharmaceut Sci Ribeirao Preto, Sao Paulo, Brazil; [Dhanasekaran, B. K.; Ghosh, Sambit; Ghosh, Soma] Indian Inst Sci, Mol Biophys Unit and IISC Math Initiat, Bangalore, Karnataka, India; [Faccioli, Rodrigo Antonio; Defelicibus, Alexandre; Botazzo Delbem, Alexandre Claudio] Univ Sao Paulo, Inst Math and Comp Sci, Sao Paulo, Brazil; [Faraggi, Eshel] Res and Informat Syst LLC, Carmel, CA USA; [Faraggi, Eshel] IU Sch Med, Dept Biochem and Mol Biol, Indianapolis, IN USA; [Faraggi, Eshel] Nationwide Childrens Hosp, Res Inst, Batelle Ctr Math Med, Columbus, OH USA; [Ganzynkowicz, Robert; Gieldon, Artur; Golon, Lukasz; Krupa, Pawel; Lipska, Agnieszka; Liwo, Adam; Mozolewska, Magdalena A.; Sieradzan, Adam K.; Slusarz, Magdalena; Slusarz, Rafal; Wirecki, Tomasz; Zaborowski, Bartlomiej; Czaplewski, Cezary; Kloczkowski, Andrzej] Univ Gdansk, Fac Chem, Gdansk, Poland; [He, Yi] Univ Calif, Sch Engn, Merced, CA USA; [Heo, Lim; Lee, Gyu Rie] Seoul Natl Univ, Dept Chem, Seoul, South Korea; [Khan, Main; Khatib, Firas; Shah, Anand; Trieber, Nicholas] Univ Massachusetts, Dept Comp and Informat Sci, Dartmouth, MA USA; [Khoury, George A.; Smadbeck, James] Princeton Univ, Dept Chem and Biol Engn, Princeton, NJ 08544 USA; [Kieslich, Chris; Floudas, Christodoulos] Texas AandM Univ, Texas AandM Energy Inst, College Stn, TX USA; [Kim, David E.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA; [Kim, David E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA; [Li, Hongbo] NorthEast Normal Univ, Sch Comp Sci and Informat Technol, Changchun, Jilin, Peoples R China; [Li, Hongbo] Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO USA; [Mirdita, Milot; Soeding, Johannes] Max Planck Inst Biophys Chem, Gottingen, Germany; [Mirzaei, Shokoufeh] Calif State Polytech Univ Pomona, Pomona, CA 91768 USA; [Onel, Melis; Shah, Utkarsh; Tamamis, Phanourios] Texas AandM Univ, Artie McFerrin Dept Chem Engn, College Stn, TX USA; [Ovchinnikov, Sergey] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA; [Yin, Yanping; Scheraga, Harold] Cornell Univ, Baker Lab Chem and Chem Biol, Ithaca, NY USA; [Zhang, Yang] Univ Michigan, Dept Computat Med and Bioinformat, Ann Arbor, MI 48109 USA; [Bacardit, Jaume] Newcastle Univ, Sch Comp, Interdisciplinary Comp and Complex BioSyst ICOS Res, Newcastle Upon Tyne, Tyne and Wear, England; [Baranowski, Maciej; Oldziej, Stanislaw] Univ Gdansk, Intercollegiate Fac Biotechnol, Gdansk, Poland; [Baranowski, Maciej; Oldziej, Stanislaw] Med Univ Gdansk, Gdansk, Poland; [Chapman, Nicholas; Flatten, Jeff; Popovic, Zoran; Baker, David] Univ Washington, Dept Comp Sci and Engn, Ctr Game Sci, Seattle, WA 98195 USA; [Cooper, Seth] Northeastern Univ, Coll Comp and Informat Sci, Boston, MA 02115 USA; [Levitt, Michael] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA; [Crivelli, Silvia N.] Univ Calif Davis, Dept Comp Sci, Davis, CA 95616 USA;.
    Mirdita, Milot
    Max Planck Inst Biophys Chem, Germany.
    Mirzaei, Shokoufeh
    Calif State Polytech Univ Pomona, CA 91768 USA.
    Mozolewska, Magdalena A.
    Univ Gdansk, Poland.
    Onel, Melis
    Texas AandM Univ, TX USA.
    Ovchinnikov, Sergey
    Univ Washington, WA 98195 USA.
    Shah, Anand
    Univ Massachusetts, MA USA.
    Shah, Utkarsh
    Texas AandM Univ, TX USA.
    Sidi, Tomer
    Ben Gurion Univ Negev, Israel.
    Sieradzan, Adam K.
    Univ Gdansk, Poland.
    Slusarz, Magdalena
    Univ Gdansk, Poland.
    Slusarz, Rafal
    Univ Gdansk, Poland.
    Smadbeck, James
    Princeton Univ, NJ 08544 USA.
    Tamamis, Phanourios
    Texas AandM Univ, TX USA.
    Trieber, Nicholas
    Univ Massachusetts, MA USA.
    Wirecki, Tomasz
    Univ Gdansk, Poland.
    Yin, Yanping
    Cornell Univ, NY USA.
    Zhang, Yang
    Univ Michigan, MI 48109 USA.
    Bacardit, Jaume
    Newcastle Univ, England.
    Baranowski, Maciej
    Univ Gdansk, Poland; Med Univ Gdansk, Poland.
    Chapman, Nicholas
    Univ Washington, WA 98195 USA.
    Cooper, Seth
    Northeastern Univ, MA 02115 USA.
    Defelicibus, Alexandre
    Univ Sao Paulo, Brazil.
    Flatten, Jeff
    Univ Washington, WA 98195 USA.
    Koepnick, Brian
    Not Found:[Keasar, Chen; Sidi, Tomer] Ben Gurion Univ Negev, Dept Comp Sci, Beer Sheva, Israel; [McGuffin, Liam J.] Univ Reading, Sch Biol Sci, Biomed Sci Div, Reading RG6 6AS, Berks, England; [Wallner, Bjorn] Linkoping Univ, Dept Phys Chem and Biol, Div Bioinformat, Linkoping, Sweden; [Chopra, Gaurav] Purdue Univ, Dept Chem, Coll Sci, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Drug Discovery, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Inflammat Immunol and Infect Dis, W Lafayette, IN USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Integrat Neurosci, W Lafayette, IN USA; [Adhikari, Badri; Cao, Renzhi; Hou, Jie; Li, Hongbo; Li, Jilong; Cheng, Jianlin] Univ Missouri, Dept Elect Engn and Comp Sci, Columbia, MO USA; [Bhattacharya, Debswapna] Auburn Univ, Dept Comp Sci and Software Engn, Auburn, AL 36849 USA; [Blake, Lauren; Dimas, Itzhel; Crivelli, Silvia N.] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA; [Bortot, Leandro Oliveira] Univ Sao Paulo, Lab Biol Phys, Fac Pharmaceut Sci Ribeirao Preto, Sao Paulo, Brazil; [Dhanasekaran, B. K.; Ghosh, Sambit; Ghosh, Soma] Indian Inst Sci, Mol Biophys Unit and IISC Math Initiat, Bangalore, Karnataka, India; [Faccioli, Rodrigo Antonio; Defelicibus, Alexandre; Botazzo Delbem, Alexandre Claudio] Univ Sao Paulo, Inst Math and Comp Sci, Sao Paulo, Brazil; [Faraggi, Eshel] Res and Informat Syst LLC, Carmel, CA USA; [Faraggi, Eshel] IU Sch Med, Dept Biochem and Mol Biol, Indianapolis, IN USA; [Faraggi, Eshel] Nationwide Childrens Hosp, Res Inst, Batelle Ctr Math Med, Columbus, OH USA; [Ganzynkowicz, Robert; Gieldon, Artur; Golon, Lukasz; Krupa, Pawel; Lipska, Agnieszka; Liwo, Adam; Mozolewska, Magdalena A.; Sieradzan, Adam K.; Slusarz, Magdalena; Slusarz, Rafal; Wirecki, Tomasz; Zaborowski, Bartlomiej; Czaplewski, Cezary; Kloczkowski, Andrzej] Univ Gdansk, Fac Chem, Gdansk, Poland; [He, Yi] Univ Calif, Sch Engn, Merced, CA USA; [Heo, Lim; Lee, Gyu Rie] Seoul Natl Univ, Dept Chem, Seoul, South Korea; [Khan, Main; Khatib, Firas; Shah, Anand; Trieber, Nicholas] Univ Massachusetts, Dept Comp and Informat Sci, Dartmouth, MA USA; [Khoury, George A.; Smadbeck, James] Princeton Univ, Dept Chem and Biol Engn, Princeton, NJ 08544 USA; [Kieslich, Chris; Floudas, Christodoulos] Texas AandM Univ, Texas AandM Energy Inst, College Stn, TX USA; [Kim, David E.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA; [Kim, David E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA; [Li, Hongbo] NorthEast Normal Univ, Sch Comp Sci and Informat Technol, Changchun, Jilin, Peoples R China; [Li, Hongbo] Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO USA; [Mirdita, Milot; Soeding, Johannes] Max Planck Inst Biophys Chem, Gottingen, Germany; [Mirzaei, Shokoufeh] Calif State Polytech Univ Pomona, Pomona, CA 91768 USA; [Onel, Melis; Shah, Utkarsh; Tamamis, Phanourios] Texas AandM Univ, Artie McFerrin Dept Chem Engn, College Stn, TX USA; [Ovchinnikov, Sergey] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA; [Yin, Yanping; Scheraga, Harold] Cornell Univ, Baker Lab Chem and Chem Biol, Ithaca, NY USA; [Zhang, Yang] Univ Michigan, Dept Computat Med and Bioinformat, Ann Arbor, MI 48109 USA; [Bacardit, Jaume] Newcastle Univ, Sch Comp, Interdisciplinary Comp and Complex BioSyst ICOS Res, Newcastle Upon Tyne, Tyne and Wear, England; [Baranowski, Maciej; Oldziej, Stanislaw] Univ Gdansk, Intercollegiate Fac Biotechnol, Gdansk, Poland; [Baranowski, Maciej; Oldziej, Stanislaw] Med Univ Gdansk, Gdansk, Poland; [Chapman, Nicholas; Flatten, Jeff; Popovic, Zoran; Baker, David] Univ Washington, Dept Comp Sci and Engn, Ctr Game Sci, Seattle, WA 98195 USA; [Cooper, Seth] Northeastern Univ, Coll Comp and Informat Sci, Boston, MA 02115 USA; [Levitt, Michael] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA; [Crivelli, Silvia N.] Univ Calif Davis, Dept Comp Sci, Davis, CA 95616 USA;.
    Popovic, Zoran
    Univ Washington, WA 98195 USA.
    Zaborowski, Bartlomiej
    Univ Gdansk, Poland.
    Baker, David
    Univ Washington, WA 98195 USA.
    Cheng, Jianlin
    Univ Missouri, MO USA.
    Czaplewski, Cezary
    Univ Gdansk, Poland.
    Botazzo Delbem, Alexandre Claudio
    Univ Sao Paulo, Brazil.
    Floudas, Christodoulos
    Texas AandM Univ, TX USA.
    Kloczkowski, Andrzej
    Univ Gdansk, Poland.
    Oldziej, Stanislaw
    Univ Gdansk, Poland; Med Univ Gdansk, Poland.
    Levitt, Michael
    Stanford Univ, CA 94305 USA.
    Scheraga, Harold
    Cornell Univ, NY USA.
    Seok, Chaok
    Not Found:[Keasar, Chen; Sidi, Tomer] Ben Gurion Univ Negev, Dept Comp Sci, Beer Sheva, Israel; [McGuffin, Liam J.] Univ Reading, Sch Biol Sci, Biomed Sci Div, Reading RG6 6AS, Berks, England; [Wallner, Bjorn] Linkoping Univ, Dept Phys Chem and Biol, Div Bioinformat, Linkoping, Sweden; [Chopra, Gaurav] Purdue Univ, Dept Chem, Coll Sci, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Drug Discovery, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Inflammat Immunol and Infect Dis, W Lafayette, IN USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Integrat Neurosci, W Lafayette, IN USA; [Adhikari, Badri; Cao, Renzhi; Hou, Jie; Li, Hongbo; Li, Jilong; Cheng, Jianlin] Univ Missouri, Dept Elect Engn and Comp Sci, Columbia, MO USA; [Bhattacharya, Debswapna] Auburn Univ, Dept Comp Sci and Software Engn, Auburn, AL 36849 USA; [Blake, Lauren; Dimas, Itzhel; Crivelli, Silvia N.] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA; [Bortot, Leandro Oliveira] Univ Sao Paulo, Lab Biol Phys, Fac Pharmaceut Sci Ribeirao Preto, Sao Paulo, Brazil; [Dhanasekaran, B. K.; Ghosh, Sambit; Ghosh, Soma] Indian Inst Sci, Mol Biophys Unit and IISC Math Initiat, Bangalore, Karnataka, India; [Faccioli, Rodrigo Antonio; Defelicibus, Alexandre; Botazzo Delbem, Alexandre Claudio] Univ Sao Paulo, Inst Math and Comp Sci, Sao Paulo, Brazil; [Faraggi, Eshel] Res and Informat Syst LLC, Carmel, CA USA; [Faraggi, Eshel] IU Sch Med, Dept Biochem and Mol Biol, Indianapolis, IN USA; [Faraggi, Eshel] Nationwide Childrens Hosp, Res Inst, Batelle Ctr Math Med, Columbus, OH USA; [Ganzynkowicz, Robert; Gieldon, Artur; Golon, Lukasz; Krupa, Pawel; Lipska, Agnieszka; Liwo, Adam; Mozolewska, Magdalena A.; Sieradzan, Adam K.; Slusarz, Magdalena; Slusarz, Rafal; Wirecki, Tomasz; Zaborowski, Bartlomiej; Czaplewski, Cezary; Kloczkowski, Andrzej] Univ Gdansk, Fac Chem, Gdansk, Poland; [He, Yi] Univ Calif, Sch Engn, Merced, CA USA; [Heo, Lim; Lee, Gyu Rie] Seoul Natl Univ, Dept Chem, Seoul, South Korea; [Khan, Main; Khatib, Firas; Shah, Anand; Trieber, Nicholas] Univ Massachusetts, Dept Comp and Informat Sci, Dartmouth, MA USA; [Khoury, George A.; Smadbeck, James] Princeton Univ, Dept Chem and Biol Engn, Princeton, NJ 08544 USA; [Kieslich, Chris; Floudas, Christodoulos] Texas AandM Univ, Texas AandM Energy Inst, College Stn, TX USA; [Kim, David E.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA; [Kim, David E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA; [Li, Hongbo] NorthEast Normal Univ, Sch Comp Sci and Informat Technol, Changchun, Jilin, Peoples R China; [Li, Hongbo] Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO USA; [Mirdita, Milot; Soeding, Johannes] Max Planck Inst Biophys Chem, Gottingen, Germany; [Mirzaei, Shokoufeh] Calif State Polytech Univ Pomona, Pomona, CA 91768 USA; [Onel, Melis; Shah, Utkarsh; Tamamis, Phanourios] Texas AandM Univ, Artie McFerrin Dept Chem Engn, College Stn, TX USA; [Ovchinnikov, Sergey] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA; [Yin, Yanping; Scheraga, Harold] Cornell Univ, Baker Lab Chem and Chem Biol, Ithaca, NY USA; [Zhang, Yang] Univ Michigan, Dept Computat Med and Bioinformat, Ann Arbor, MI 48109 USA; [Bacardit, Jaume] Newcastle Univ, Sch Comp, Interdisciplinary Comp and Complex BioSyst ICOS Res, Newcastle Upon Tyne, Tyne and Wear, England; [Baranowski, Maciej; Oldziej, Stanislaw] Univ Gdansk, Intercollegiate Fac Biotechnol, Gdansk, Poland; [Baranowski, Maciej; Oldziej, Stanislaw] Med Univ Gdansk, Gdansk, Poland; [Chapman, Nicholas; Flatten, Jeff; Popovic, Zoran; Baker, David] Univ Washington, Dept Comp Sci and Engn, Ctr Game Sci, Seattle, WA 98195 USA; [Cooper, Seth] Northeastern Univ, Coll Comp and Informat Sci, Boston, MA 02115 USA; [Levitt, Michael] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA; [Crivelli, Silvia N.] Univ Calif Davis, Dept Comp Sci, Davis, CA 95616 USA;.
    Soeding, Johannes
    Max Planck Inst Biophys Chem, Germany.
    Vishveshwara, Saraswathi
    Not Found:[Keasar, Chen; Sidi, Tomer] Ben Gurion Univ Negev, Dept Comp Sci, Beer Sheva, Israel; [McGuffin, Liam J.] Univ Reading, Sch Biol Sci, Biomed Sci Div, Reading RG6 6AS, Berks, England; [Wallner, Bjorn] Linkoping Univ, Dept Phys Chem and Biol, Div Bioinformat, Linkoping, Sweden; [Chopra, Gaurav] Purdue Univ, Dept Chem, Coll Sci, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Drug Discovery, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Inflammat Immunol and Infect Dis, W Lafayette, IN USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Integrat Neurosci, W Lafayette, IN USA; [Adhikari, Badri; Cao, Renzhi; Hou, Jie; Li, Hongbo; Li, Jilong; Cheng, Jianlin] Univ Missouri, Dept Elect Engn and Comp Sci, Columbia, MO USA; [Bhattacharya, Debswapna] Auburn Univ, Dept Comp Sci and Software Engn, Auburn, AL 36849 USA; [Blake, Lauren; Dimas, Itzhel; Crivelli, Silvia N.] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA; [Bortot, Leandro Oliveira] Univ Sao Paulo, Lab Biol Phys, Fac Pharmaceut Sci Ribeirao Preto, Sao Paulo, Brazil; [Dhanasekaran, B. K.; Ghosh, Sambit; Ghosh, Soma] Indian Inst Sci, Mol Biophys Unit and IISC Math Initiat, Bangalore, Karnataka, India; [Faccioli, Rodrigo Antonio; Defelicibus, Alexandre; Botazzo Delbem, Alexandre Claudio] Univ Sao Paulo, Inst Math and Comp Sci, Sao Paulo, Brazil; [Faraggi, Eshel] Res and Informat Syst LLC, Carmel, CA USA; [Faraggi, Eshel] IU Sch Med, Dept Biochem and Mol Biol, Indianapolis, IN USA; [Faraggi, Eshel] Nationwide Childrens Hosp, Res Inst, Batelle Ctr Math Med, Columbus, OH USA; [Ganzynkowicz, Robert; Gieldon, Artur; Golon, Lukasz; Krupa, Pawel; Lipska, Agnieszka; Liwo, Adam; Mozolewska, Magdalena A.; Sieradzan, Adam K.; Slusarz, Magdalena; Slusarz, Rafal; Wirecki, Tomasz; Zaborowski, Bartlomiej; Czaplewski, Cezary; Kloczkowski, Andrzej] Univ Gdansk, Fac Chem, Gdansk, Poland; [He, Yi] Univ Calif, Sch Engn, Merced, CA USA; [Heo, Lim; Lee, Gyu Rie] Seoul Natl Univ, Dept Chem, Seoul, South Korea; [Khan, Main; Khatib, Firas; Shah, Anand; Trieber, Nicholas] Univ Massachusetts, Dept Comp and Informat Sci, Dartmouth, MA USA; [Khoury, George A.; Smadbeck, James] Princeton Univ, Dept Chem and Biol Engn, Princeton, NJ 08544 USA; [Kieslich, Chris; Floudas, Christodoulos] Texas AandM Univ, Texas AandM Energy Inst, College Stn, TX USA; [Kim, David E.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA; [Kim, David E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA; [Li, Hongbo] NorthEast Normal Univ, Sch Comp Sci and Informat Technol, Changchun, Jilin, Peoples R China; [Li, Hongbo] Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO USA; [Mirdita, Milot; Soeding, Johannes] Max Planck Inst Biophys Chem, Gottingen, Germany; [Mirzaei, Shokoufeh] Calif State Polytech Univ Pomona, Pomona, CA 91768 USA; [Onel, Melis; Shah, Utkarsh; Tamamis, Phanourios] Texas AandM Univ, Artie McFerrin Dept Chem Engn, College Stn, TX USA; [Ovchinnikov, Sergey] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA; [Yin, Yanping; Scheraga, Harold] Cornell Univ, Baker Lab Chem and Chem Biol, Ithaca, NY USA; [Zhang, Yang] Univ Michigan, Dept Computat Med and Bioinformat, Ann Arbor, MI 48109 USA; [Bacardit, Jaume] Newcastle Univ, Sch Comp, Interdisciplinary Comp and Complex BioSyst ICOS Res, Newcastle Upon Tyne, Tyne and Wear, England; [Baranowski, Maciej; Oldziej, Stanislaw] Univ Gdansk, Intercollegiate Fac Biotechnol, Gdansk, Poland; [Baranowski, Maciej; Oldziej, Stanislaw] Med Univ Gdansk, Gdansk, Poland; [Chapman, Nicholas; Flatten, Jeff; Popovic, Zoran; Baker, David] Univ Washington, Dept Comp Sci and Engn, Ctr Game Sci, Seattle, WA 98195 USA; [Cooper, Seth] Northeastern Univ, Coll Comp and Informat Sci, Boston, MA 02115 USA; [Levitt, Michael] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA; [Crivelli, Silvia N.] Univ Calif Davis, Dept Comp Sci, Davis, CA 95616 USA;.
    Xu, Dong
    Not Found:[Keasar, Chen; Sidi, Tomer] Ben Gurion Univ Negev, Dept Comp Sci, Beer Sheva, Israel; [McGuffin, Liam J.] Univ Reading, Sch Biol Sci, Biomed Sci Div, Reading RG6 6AS, Berks, England; [Wallner, Bjorn] Linkoping Univ, Dept Phys Chem and Biol, Div Bioinformat, Linkoping, Sweden; [Chopra, Gaurav] Purdue Univ, Dept Chem, Coll Sci, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Drug Discovery, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Inflammat Immunol and Infect Dis, W Lafayette, IN USA; [Chopra, Gaurav] Purdue Univ, Purdue Inst Integrat Neurosci, W Lafayette, IN USA; [Adhikari, Badri; Cao, Renzhi; Hou, Jie; Li, Hongbo; Li, Jilong; Cheng, Jianlin] Univ Missouri, Dept Elect Engn and Comp Sci, Columbia, MO USA; [Bhattacharya, Debswapna] Auburn Univ, Dept Comp Sci and Software Engn, Auburn, AL 36849 USA; [Blake, Lauren; Dimas, Itzhel; Crivelli, Silvia N.] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA; [Bortot, Leandro Oliveira] Univ Sao Paulo, Lab Biol Phys, Fac Pharmaceut Sci Ribeirao Preto, Sao Paulo, Brazil; [Dhanasekaran, B. K.; Ghosh, Sambit; Ghosh, Soma] Indian Inst Sci, Mol Biophys Unit and IISC Math Initiat, Bangalore, Karnataka, India; [Faccioli, Rodrigo Antonio; Defelicibus, Alexandre; Botazzo Delbem, Alexandre Claudio] Univ Sao Paulo, Inst Math and Comp Sci, Sao Paulo, Brazil; [Faraggi, Eshel] Res and Informat Syst LLC, Carmel, CA USA; [Faraggi, Eshel] IU Sch Med, Dept Biochem and Mol Biol, Indianapolis, IN USA; [Faraggi, Eshel] Nationwide Childrens Hosp, Res Inst, Batelle Ctr Math Med, Columbus, OH USA; [Ganzynkowicz, Robert; Gieldon, Artur; Golon, Lukasz; Krupa, Pawel; Lipska, Agnieszka; Liwo, Adam; Mozolewska, Magdalena A.; Sieradzan, Adam K.; Slusarz, Magdalena; Slusarz, Rafal; Wirecki, Tomasz; Zaborowski, Bartlomiej; Czaplewski, Cezary; Kloczkowski, Andrzej] Univ Gdansk, Fac Chem, Gdansk, Poland; [He, Yi] Univ Calif, Sch Engn, Merced, CA USA; [Heo, Lim; Lee, Gyu Rie] Seoul Natl Univ, Dept Chem, Seoul, South Korea; [Khan, Main; Khatib, Firas; Shah, Anand; Trieber, Nicholas] Univ Massachusetts, Dept Comp and Informat Sci, Dartmouth, MA USA; [Khoury, George A.; Smadbeck, James] Princeton Univ, Dept Chem and Biol Engn, Princeton, NJ 08544 USA; [Kieslich, Chris; Floudas, Christodoulos] Texas AandM Univ, Texas AandM Energy Inst, College Stn, TX USA; [Kim, David E.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA; [Kim, David E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA; [Li, Hongbo] NorthEast Normal Univ, Sch Comp Sci and Informat Technol, Changchun, Jilin, Peoples R China; [Li, Hongbo] Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO USA; [Mirdita, Milot; Soeding, Johannes] Max Planck Inst Biophys Chem, Gottingen, Germany; [Mirzaei, Shokoufeh] Calif State Polytech Univ Pomona, Pomona, CA 91768 USA; [Onel, Melis; Shah, Utkarsh; Tamamis, Phanourios] Texas AandM Univ, Artie McFerrin Dept Chem Engn, College Stn, TX USA; [Ovchinnikov, Sergey] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA; [Yin, Yanping; Scheraga, Harold] Cornell Univ, Baker Lab Chem and Chem Biol, Ithaca, NY USA; [Zhang, Yang] Univ Michigan, Dept Computat Med and Bioinformat, Ann Arbor, MI 48109 USA; [Bacardit, Jaume] Newcastle Univ, Sch Comp, Interdisciplinary Comp and Complex BioSyst ICOS Res, Newcastle Upon Tyne, Tyne and Wear, England; [Baranowski, Maciej; Oldziej, Stanislaw] Univ Gdansk, Intercollegiate Fac Biotechnol, Gdansk, Poland; [Baranowski, Maciej; Oldziej, Stanislaw] Med Univ Gdansk, Gdansk, Poland; [Chapman, Nicholas; Flatten, Jeff; Popovic, Zoran; Baker, David] Univ Washington, Dept Comp Sci and Engn, Ctr Game Sci, Seattle, WA 98195 USA; [Cooper, Seth] Northeastern Univ, Coll Comp and Informat Sci, Boston, MA 02115 USA; [Levitt, Michael] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA; [Crivelli, Silvia N.] Univ Calif Davis, Dept Comp Sci, Davis, CA 95616 USA;.
    Crivelli, Silvia N.
    Lawrence Berkeley Natl Lab, CA 94720 USA; Univ Calif Davis, CA 95616 USA.
    An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP122018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 9939Article in journal (Refereed)
    Abstract [en]

    Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly available at the WeFold website providing a wealth of data that remains to be tapped. Here, we analyze the results of the 2014 and 2016 pipelines showing improvements according to the CASP assessment as well as areas that require further adjustments and research.

  • 99.
    Keller, Lukas
    et al.
    Goethe Univ, Germany.
    Al Mamoori, Mohanad K. I.
    Goethe Univ, Germany.
    Pieper, Jonathan
    Goethe Univ, Germany.
    Gspan, Christian
    Graz Ctr Electron Microscopy, Austria.
    Stockem, Irina
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    Schroeder, Christian
    Bielefeld Univ Appl Sci, Germany.
    Barth, Sven
    Vienna Univ Technol, Austria.
    Winkler, Robert
    Graz Centre for Electron Microscopy, Graz, Austria.
    Plank, Harald
    Graz Univ Technol, Austria.
    Pohlit, Merlin
    Goethe Univ, Germany.
    Mueller, Jens
    Goethe Univ, Germany.
    Huth, Michael
    Goethe Univ, Germany.
    Direct-write of free-form building blocks for artificial magnetic 3D lattices2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6160Article in journal (Refereed)
    Abstract [en]

    By the fabrication of periodically arranged nanomagnetic systems it is possible to engineer novel physical properties by realizing artificial lattice geometries that are not accessible via natural crystallization or chemical synthesis. This has been accomplished with great success in two dimensions in the fields of artificial spin ice and magnetic logic devices, to name just two. Although first proposals have been made to advance into three dimensions (3D), established nanofabrication pathways based on electron beam lithography have not been adapted to obtain free-form 3D nanostructures. Here we demonstrate the direct-write fabrication of freestanding ferromagnetic 3D nano-architectures. By employing micro-Hall sensing, we have determined the magnetic stray field generated by our free-form structures in an externally applied magnetic field and we have performed micromagnetic and macro-spin simulations to deduce the spatial magnetization profiles in the structures and analyze their switching behavior. Furthermore we show that the magnetic 3D elements can be combined with other 3D elements of different chemical composition and intrinsic material properties.

  • 100.
    Khayyeri, Hanifeh
    et al.
    Lund University, Sweden.
    Blomgran, Parmis
    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.
    Turunen, Mikael J.
    University of Eastern Finland, Finland.
    Lowgren, Annika
    Lund University, Sweden.
    Guizar-Sicairos, Manuel
    Paul Scherrer Institute, Switzerland.
    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.
    Isaksson, Hanna
    Lund University, Sweden.
    Achilles tendon compositional and structural properties are altered after unloading by botox2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 13067Article in journal (Refereed)
    Abstract [en]

    Tendon function and homeostasis rely on external loading. This study investigates the biological mechanisms behind tendon biomechanical function and how the mechanical performance is affected by reduced daily loading. The Achilles tendons of 16 weeks old female Sprague Dawley rats (n = 40) were unloaded for 5 weeks by inducing muscle paralysis with botulinum toxin injections in the right gastrocnemius and soleus muscles. The contralateral side was used as control. After harvest, the tendons underwent biomechanical testing to assess viscoelasticity (n = 30 rats) and small angle X-ray scattering to determine the structural properties of the collagen fibrils (n = 10 rats). Fourier transform infrared spectroscopy and histological staining (n = 10 rats) were performed to investigate the collagen and proteoglycan content. The results show that the stiffness increased in unloaded tendons, together with an increased collagen content. Creep and axial alignment of the collagen fibers were reduced. Stress-relaxation increased whereas hysteresis was reduced in response to unloading with botox treatment. Our findings indicate that altered matrix deposition relies on mechanical loading to reorganize the newly formed tissue, without which the viscoelastic behavior is impaired. The results demonstrate that reduced daily loading deprives tendons of their viscoelastic properties, which could increase the risk of injury.

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