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  • 201.
    Juras, Anna
    et al.
    Adam Mickiewicz Univ, Dept Human Evolutionary Biol, Inst Anthropol, Fac Biol, Umultowska 89, PL-61614 Poznan, Poland..
    Chylenski, Maciej
    Adam Mickiewicz Univ, Inst Archaeol, Fac Hist, Umultowska 89D, PL-61614 Poznan, Poland..
    Ehler, Edvard
    Adam Mickiewicz Univ, Dept Human Evolutionary Biol, Inst Anthropol, Fac Biol, Umultowska 89, PL-61614 Poznan, Poland.;ASCR, Lab Genom & Bioinformat, Inst Mol Genet, Vvi, Videnska 1083, Prague 14220 4, Czech Republic..
    Malmström, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Human Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zurkiewicz, Danuta
    Adam Mickiewicz Univ, Inst Archaeol, Fac Hist, Umultowska 89D, PL-61614 Poznan, Poland..
    Wlodarczak, Piotr
    Polish Acad Sci, Inst Archaeol & Ethnol, Slawkowska Str 17, PL-31016 Krakow, Poland..
    Wilk, Stanislaw
    Jagiellonian Univ, Inst Archaeol, Golebia 11, PL-31007 Krakow, Poland..
    Peska, Jaroslav
    Archaeol Ctr Olomouc, U Hradiska 42-6, Olomouc 77900, Czech Republic.;Palacky Univ Olomouc, Philosoph Fac, Sect Archaeol, Dept Hist, Hrade 5, Olomouc 77180, Czech Republic..
    Fojtik, Pavel
    Inst Archaeol Heritage Brno, Vvi, Kaloudova 30, Brno 61400, Czech Republic..
    Kralik, Miroslav
    Masaryk Univ, Fac Sci, Lab Morphol & Forens Anthropol LaMorFA, Dept Anthropol, Kotlarska 267-2, CS-61137 Brno, Czech Republic..
    Libera, Jerzy
    Marie Curie Sklodowska Univ, Inst Archaeol, Maria Curie Sklodowska Sq 4, PL-20031 Lublin, Poland..
    Baginska, Jolanta
    Muzeum Reg Janusza Petera, Ul Zamojska 2, PL-22600 Tomaszow Lubelski, Poland..
    Tunia, Krzysztof
    Polish Acad Sci, Inst Archaeol & Ethnol, Slawkowska Str 17, PL-31016 Krakow, Poland..
    Klochko, Viktor I.
    Natl Univ Kyiv Mohyla Acad, Inst Archaeol, Hryhoriya Skovorody St 2, UA-04655 Kiev, Ukraine..
    Dabert, Miroslawa
    Adam Mickiewicz Univ, Fac Biol, Mol Biol Tech Lab, Umultowska 89, PL-61614 Poznan, Poland..
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Human Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Johannesburg, Ctr Anthropol Res, Auckland Pk, ZA-2006 Johannesburg, South Africa..
    Kosko, Aleksander
    Adam Mickiewicz Univ, Inst Archaeol, Fac Hist, Umultowska 89D, PL-61614 Poznan, Poland..
    Mitochondrial genomes reveal an east to west cline of steppe ancestry in Corded Ware populations2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 11603Article in journal (Refereed)
    Abstract [en]

    From around 4,000 to 2,000 BC the forest-steppe north-western Pontic region was occupied by people who shared a nomadic lifestyle, pastoral economy and barrow burial rituals. It has been shown that these groups, especially those associated with the Yamnaya culture, played an important role in shaping the gene pool of Bronze Age Europeans, which extends into present-day patterns of genetic variation in Europe. Although the genetic impact of these migrations from the forest-steppe Pontic region into central Europe have previously been addressed in several studies, the contribution of mitochondrial lineages to the people associated with the Corded Ware culture in the eastern part of the North European Plain remains contentious. In this study, we present mitochondrial genomes from 23 Late Eneolithic and Bronze Age individuals, including representatives of the north-western Pontic region and the Corded Ware culture from the eastern part of the North European Plain. We identified, for the first time in ancient populations, the rare mitochondrial haplogroup X4 in two Bronze Age Catacomb culture-associated individuals. Genetic similarity analyses show close maternal genetic affinities between populations associated with both eastern and Baltic Corded Ware culture, and the Yamnaya horizon, in contrast to larger genetic differentiation between populations associated with western Corded Ware culture and the Yamnaya horizon. This indicates that females with steppe ancestry contributed to the formation of populations associated with the eastern Corded Ware culture while more local people, likely of Neolithic farmer ancestry, contributed to the formation of populations associated with western Corded Ware culture.

  • 202.
    Juvrud, Joshua
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bakker, Marta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Gredebäck, Gustaf
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Context dependent perception of apparent motion in 12-month-old infants and adultsIn: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322Article in journal (Other academic)
    Abstract [en]

    The current study examines if 12-month-old infants and adults perceptions of apparent motion stimuli are context dependent by measuring sensitivity to possible and impossible apparent motion performed by a human figure.  In Study 1, infants and adults viewed an apparent motion stimulus comprising of an arm moving from one side of a leg to the other. Results showed that both infants and adults reacted with larger pupil dilation when observing an impossible apparent motion, that is, larger pupil dilation when it appears that a hand passed through the leg as opposed to moving around the leg. Study 2 found no such effect when 12-month-old infants observed an object control stimulus with perceptually similar properties. These findings suggest that apparent motion perception is context dependent and that the constraints of the human body and human actions are taken into account when perceiving rapidly changing static images as fluid motion.

  • 203.
    Kamalakar, M. Venkata
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics. Chalmers, Dept Microtechnol & Nanosci, SE-41296 Gothenburg, Sweden..
    Dankert, Andre
    Chalmers, Dept Microtechnol & Nanosci, SE-41296 Gothenburg, Sweden..
    Kelly, Paul J.
    Univ Twente, Fac Sci & Technol, POB 217, NL-7500 AE Enschede, Netherlands.;Univ Twente, MESA Inst Nanotechnol, POB 217, NL-7500 AE Enschede, Netherlands..
    Dash, Saroj P.
    Chalmers, Dept Microtechnol & Nanosci, SE-41296 Gothenburg, Sweden..
    Inversion of Spin Signal and Spin Filtering in Ferromagnet vertical bar Hexagonal Boron Nitride-Graphene van der Waals Heterostructures2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 21168Article in journal (Refereed)
    Abstract [en]

    Two dimensional atomically thin crystals of graphene and its insulating isomorph hexagonal boron nitride (h-BN) are promising materials for spintronic applications. While graphene is an ideal medium for long distance spin transport, h-BN is an insulating tunnel barrier that has potential for efficient spin polarized tunneling from ferromagnets. Here, we demonstrate the spin filtering effect in cobalt vertical bar few layer h-BN vertical bar graphene junctions leading to a large negative spin polarization in graphene at room temperature. Through nonlocal pure spin transport and Hanle precession measurements performed on devices with different interface barrier conditions, we associate the negative spin polarization with high resistance few layer h-BN vertical bar ferromagnet contacts. Detailed bias and gate dependent measurements reinforce the robustness of the effect in our devices. These spintronic effects in two-dimensional van der Waals heterostructures hold promise for future spin based logic and memory applications.

  • 204.
    Karademir, Betul
    et al.
    Marmara Univ, Sch Med, Dept Biochem, Genet & Metab Dis Res & Invest Ctr, Istanbul, Turkey.
    Sari, Gulce
    Marmara Univ, Sch Med, Dept Biochem, Genet & Metab Dis Res & Invest Ctr, Istanbul, Turkey;Okan Univ, Fac Engn, Dept Genet & Bioengn, Istanbul, Turkey.
    Jannuzzi, Ayse Tarbin
    Istanbul Univ, Fac Pharm, Dept Pharmaceut Toxicol, Istanbul, Turkey.
    Musunuri, Sravani
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Wicher, Grzegorz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Grune, Tilman
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Toxicol, D-14558 Nuthetal, Germany;German Ctr Diabet Res DZD, D-85764 Munich, Germany;German Ctr Cardiovasc Res DZHK, D-10117 Berlin, Germany.
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Binzhou Med Univ, Med & Pharm Res Ctr, Yantai, Peoples R China.
    Hacioglu-Bay, Husniye
    Marmara Univ, Sch Med, Dept Anat, Istanbul, Turkey.
    Forsberg-Nilsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Jung, Tobias
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Toxicol, D-14558 Nuthetal, Germany;German Ctr Diabet Res DZD, D-85764 Munich, Germany;German Ctr Cardiovasc Res DZHK, D-10117 Berlin, Germany.
    Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 16318Article in journal (Refereed)
    Abstract [en]

    The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications. However neuropathic side effects are dose limiting for BTZ as many other chemotherapeutic agents. Therefore second-generation proteasome inhibitors have been developed including carfilzomib (CFZ). Aim of the present work was investigating the mechanisms of peripheral neuropathy triggered by the proteasome inhibitor BTZ and comparing the pathways affected by BTZ and CFZ, respectively. Neural stem cells, isolated from the cortex of E14 mouse embryos, were treated with BTZ and CFZ and mass spectrometry was used to compare the global protein pool of treated cells. BTZ was shown to cause more severe cytoskeletal damage, which is crucial in neural cell integrity. Excessive protein carbonylation and actin filament destabilization were also detected following BTZ treatment that was lower following CFZ treatment. Our data on cytoskeletal proteins, chaperone system, and protein oxidation may explain the milder neurotoxic effects of CFZ in clinical applications.

  • 205.
    Karlsson, Anna
    et al.
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.
    Cirenajwis, Helena
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.
    Ericson-Lindquist, Kajsa
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22185 Lund, Sweden;Reg Labs Reg Skane, Dept Pathol, SE-22185 Lund, Sweden.
    Brunnström, Hans
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22185 Lund, Sweden;Reg Labs Reg Skane, Dept Pathol, SE-22185 Lund, Sweden.
    Reuterswärd, Christel
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.
    Jonsson, Mats
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.
    Ortiz-Villalon, Cristian
    Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden.
    Hussein, Aziz
    Sahlgrens Univ Hosp, Dept Pathol & Cytol, Gothenburg, Sweden.
    Bergman, Bengt
    Sahlgrens Univ Hosp, Dept Resp Med, Gothenburg, Sweden.
    Vikström, Anders
    Univ Hosp Linkoping, Dept Pulm Med, Linkoping, Sweden.
    Monsef, Nastaran
    Linkoping Univ, Dept Pathol, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Karolinska Inst, Dept Med Solna & CMM, Resp Med Unit, Stockholm, Sweden;Karolinska Univ Hosp Solna, Stockholm, Sweden.
    Koyi, Hirsh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Karolinska Inst, Dept Med Solna & CMM, Resp Med Unit, Stockholm, Sweden;Karolinska Univ Hosp Solna, Stockholm, Sweden.
    de Petris, Luigi
    Karolinska Univ Hosp, Thorac Oncol Unit, Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Patthey, Annika
    Umea Univ Hosp, Dept Pathol, SE-90185 Umea, Sweden.
    Behndig, Annelie F.
    Umea Univ, Div Med, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden.
    Johansson, Mikael
    Umea Univ, Dept Radiat Sci, Oncol, SE-90185 Umea, Sweden.
    Planck, Maria
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden;Skane Univ Hosp, Dept Resp Med & Allergol, SE-22185 Lund, Sweden.
    Staaf, Johan
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 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.

  • 206.
    Karlsson, O. Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ramirez, Juan
    Öberg, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Malmqvist, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Engström, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Friberg, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Chi, Celestine N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Widersten, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Trave, Gilles
    Nilsson, Mikael T. I.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Jemth, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Design of a PDZbody, a bivalent binder of the E6 protein from human papillomavirus2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 9382Article in journal (Refereed)
    Abstract [en]

    Chronic infection by high risk human papillomavirus (HPV) strains may lead to cancer. Expression of the two viral oncoproteins E6 and E7 is largely responsible for immortalization of infected cells. The HPV E6 is a small (approximately 150 residues) two domain protein that interacts with a number of cellular proteins including the ubiquitin ligase E6-associated protein (E6AP) and several PDZ-domain containing proteins. Our aim was to design a high-affinity binder for HPV E6 by linking two of its cellular targets. First, we improved the affinity of the second PDZ domain from SAP97 for the C-terminus of HPV E6 from the high-risk strain HPV18 using phage display. Second, we added a helix from E6AP to the N-terminus of the optimized PDZ variant, creating a chimeric bivalent binder, denoted PDZbody. Full-length HPV E6 proteins are difficult to express and purify. Nevertheless, we could measure the affinity of the PDZbody for E6 from another high-risk strain, HPV16 (K-d = 65 nM). Finally, the PDZbody was used to co-immunoprecipitate E6 protein from HPV18-immortalized HeLa cells, confirming the interaction between PDZbody and HPV18 E6 in a cellular context.

  • 207.
    Karlsson, O Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sundell, Gustav N
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Andersson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ivarsson, Ylva
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Jemth, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Improved affinity at the cost of decreased specificity: a recurring theme in PDZ-peptide interactions.2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 34269Article in journal (Refereed)
    Abstract [en]

    The E6 protein from human papillomavirus (HPV) plays an important role during productive infection and is a potential drug target. We have previously designed a high affinity bivalent protein binder for the E6 protein, a fusion between a helix from the E6 associated protein and PDZØ9, an engineered variant (L391F/K392M) of the second PDZ domain from synapse associated protein 97 (SAP97 PDZ2). How the substitutions improve the affinity of SAP97 PDZ2 for HPV E6 is not clear and it is not known to what extent they affect the specificity for cellular targets. Here, we explore the specificity of wild type SAP97 PDZ2 and PDZØ9 through proteomic peptide phage display. In addition, we employ a double mutant cycle of SAP97 PDZ2 in which the binding kinetics for nine identified potential cellular peptide ligands are measured and compared with those for the C-terminal E6 peptide. The results demonstrate that PDZØ9 has an increased affinity for all peptides, but at the cost of specificity. Furthermore, there is a peptide dependent coupling free energy between the side chains at positions 391 and 392. This corroborates our previous allosteric model for PDZ domains, involving sampling of intramolecular energetic pathways.

  • 208.
    Karlsson, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Jiang, Liying
    Stockholm Univ, Dept Environm Sci & Analyt Chem, SE-10691 Stockholm, Sweden..
    Ersson, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Malmstrom, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Ilag, Leopold L.
    Stockholm Univ, Dept Environm Sci & Analyt Chem, SE-10691 Stockholm, Sweden..
    Brittebo, Eva B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Environmental neurotoxin interaction with proteins: Dose-dependent increase of free and protein-associated BMAA (beta-N-methylamino-L-alanine) in neonatal rat brain2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 15570Article in journal (Refereed)
    Abstract [en]

    beta-Methylamino-L-alanine (BMAA) is implicated in the aetiology of neurodegenerative disorders. Neonatal exposure to BMAA induces cognitive impairments and progressive neurodegenerative changes including intracellular fibril formation in the hippocampus of adult rats. It is unclear why the neonatal hippocampus is especially vulnerable and the critical cellular perturbations preceding BMAA-induced toxicity remains to be elucidated. The aim of this study was to compare the level of free and protein-associated BMAA in neonatal rat brain and peripheral tissues after different exposures to BMAA. Ultra-high performance liquid chromatography-tandem mass spectrometry analysis revealed that BMAA passed the neonatal blood-brain barrier and was distributed to all studied brain areas. BMAA was also associated to proteins in the brain, especially in the hippocampus. The level in the brain was, however, considerably lower compared to the liver that is not a target organ for BMAA. In contrast to the liver there was a significantly increased level of protein-association of BMAA in the hippocampus and other brain areas following repeated administration suggesting that the degradation of BMAA-associated proteins may be lower in neonatal brain than in the liver. Additional evidence is needed in support of a role for protein misincorporation in the neonatal hippocampus for long-term effects of BMAA.

  • 209.
    Kashif, Muhammad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Andersson, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Hassan, Sadia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Karlsson, Henning
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Senkowski, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Fryknäs, Mårten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Gustafsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    In vitro discovery of promising anti-cancer drug combinations using iterative maximisation of a therapeutic index2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 14118Article in journal (Refereed)
    Abstract [en]

    In vitro-based search for promising anti-cancer drug combinations may provide important leads to improved cancer therapies. Currently there are no integrated computational-experimental methods specifically designed to search for combinations, maximizing a predefined therapeutic index (TI) defined in terms of appropriate model systems. Here, such a pipeline is presented allowing the search for optimal combinations among an arbitrary number of drugs while also taking experimental variability into account. The TI optimized is the cytotoxicity difference (in vitro) between a target model and an adverse side effect model. Focusing on colorectal carcinoma (CRC), the pipeline provided several combinations that are effective in six different CRC models with limited cytotoxicity in normal cell models. Herein we describe the identification of the combination (Trichostatin A, Afungin, 17-AAG) and present results from subsequent characterisations, including efficacy in primary cultures of tumour cells from CRC patients. We hypothesize that its effect derives from potentiation of the proteotoxic action of 17-AAG by Trichostatin A and Afungin. The discovered drug combinations against CRC are significant findings themselves and also indicate that the proposed strategy has great potential for suggesting drug combination treatments suitable for other cancer types as well as for other complex diseases.

  • 210.
    Kawecki, Maciej
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Adlmann, Franz A.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Gutfreund, Philipp
    ILL Grenoble, 71 Ave Martyrs, F-38000 Grenoble, France.
    Falus, Peter
    ILL Grenoble, 71 Ave Martyrs, F-38000 Grenoble, France.
    Uhrig, David
    Oak Ridge Natl Lab, CNMS, 1 Bethel Valley Rd, Oak Ridge, TN 37831 USA.
    Gupta, Sudipta
    Farago, Bela
    ILL Grenoble, 71 Ave Martyrs, F-38000 Grenoble, France.
    Zolnierczuk, Piotr
    Forschungszentrum Juelich GmbH, Juelich Ctr Neutron Sci, Outstn SNS, 1 Bethel Valley Rd, Oak Ridge, TN 37831 USA.
    Cochran, Malcom
    Forschungszentrum Juelich GmbH, Juelich Ctr Neutron Sci, Outstn SNS, 1 Bethel Valley Rd, Oak Ridge, TN 37831 USA.
    Wolff, Max
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Direct measurement of topological interactions in polymers under shear using neutron spin echo spectroscopy2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 2823Article in journal (Refereed)
    Abstract [en]

    We present in-situ neutron spin echo measurements on an entangled polydimethylsiloxane melt under shear and demonstrate the ability to monitor nano-scale dynamics in flowing liquids. We report no changes in the topological interactions of the chains for shear rates approaching the inverse longest relaxation time. Further experiments following along this line will allow to systematically test the predictions of theories, like e.g. convective constraint release.

  • 211.
    Kear, Benjamin P.
    et al.
    Uppsala University, Music and Museums, Museum of Evolution. Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Aplin, Ken P.
    Smithsonian Inst, Div Mammals, Natl Museum Nat Hist, POB 37012, Washington, DC 20013 USA..
    Westerman, Michael
    La Trobe Univ, Dept Ecol Environm & Evolut, Melbourne, Vic 3086, Australia..
    Bandicoot fossils and DNA elucidate lineage antiquity amongst xeric-adapted Australasian marsupials2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 37537Article in journal (Refereed)
    Abstract [en]

    Bandicoots (Peramelemorphia) are a unique order of Australasian marsupials whose sparse fossil record has been used as prima facie evidence for climate change coincident faunal turnover. In particular, the hypothesized replacement of ancient rainforest-dwelling extinct lineages by antecedents of xeric-tolerant extant taxa during the late Miocene (-10 Ma) has been advocated as a broader pattern evident amongst other marsupial clades. Problematically, however, this is in persistent conflict with DNA phylogenies. We therefore determine the pattern and timing of bandicoot evolution using the first combined morphological + DNA sequence dataset of Peramelemorphia. In addition, we document a remarkably archaic new fossil peramelemorphian taxon that inhabited a latest Quaternary mosaic savannah-riparian forest ecosystem on the Aru Islands of Eastern Indonesia. Our phylogenetic analyses reveal that unsuspected dental homoplasy and the detrimental effects of missing data collectively obscure stem bandicoot relationships. Nevertheless, recalibrated molecular clocks and multiple ancestral area optimizations unanimously infer an early diversification of modern xeric-adapted forms. These probably originated during the late Palaeogene (30-40 Ma) alongside progenitors of other desert marsupials, and thus occupied seasonally dry heterogenous habitats long before the onset of late Neogene aridity.

  • 212.
    Kecheril Sadanandan, Sajith
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ranefall, Petter
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Le Guyader, Sylvie
    Center for Biosciences, Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge, Sweden.
    Wählby, Carolina
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Automated training of deep convolutional neural networks for cell segmentation2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 7860Article in journal (Refereed)
    Abstract [en]

    Deep Convolutional Neural Networks (DCNN) have recently emerged as superior for many image segmentation tasks. The DCNN performance is however heavily dependent on the availability of large amounts of problem-specific training samples. Here we show that DCNNs trained on ground truth created automatically using fluorescently labeled cells, perform similar to manual annotations.

  • 213.
    Kilinc, Gulsah Merve
    et al.
    Stockholm Univ, Dept Archaeol & Class Studies, S-10691 Stockholm, Sweden.
    Kashuba, Natalija
    Stockholm Univ, Dept Archaeol & Class Studies, S-10691 Stockholm, Sweden;Univ Oslo, Museum Cultural Hist, N-0164 Oslo, Norway.
    Yaka, Reyhan
    Middle East Tech Univ, Dept Biol Sci, TR-06800 Ankara, Turkey.
    Sumer, Arev Pelin
    Middle East Tech Univ, Dept Biol Sci, TR-06800 Ankara, Turkey.
    Yuncu, Eren
    Middle East Tech Univ, Dept Biol Sci, TR-06800 Ankara, Turkey.
    Shergin, Dmitrij
    Ivanov, Grigorij Leonidovich
    Irkutsk Museum Reg Studies, Irkutsk 664003, Irkutsk Oblast, Russia.
    Kichigin, Dmitrii
    Irkutsk State Univ, Lab Archaeol & Ethnog, Fac Hist & Methods, Dept Humanitarian & Aesthet Educ,Pedag Inst, Irkutsk 664011, Irkutsk Oblast, Russia;Irkutsk State Tech Univ, Irkutsk Natl Res Tech Univ, Lab Archaeol Paleoecol & Subsistence Strategies P, Irkutsk 664074, Irkutsk Oblast, Russia.
    Pestereva, Kjunnej
    MK Ammosov North Eastern Fed Univ NEFU, Fed State Autonomous Educ Inst Higher Educ, Yakutsk 677000, Sakha Republic, Russia.
    Volkov, Denis
    Ctr Preservat Hist & Cultural Heritage Amur Reg, Blagoveshchensk 675000, Amur Oblast, Russia.
    Mandryka, Pavel
    Siberian Fed Univ, Krasnoyarsk 660041, Krasnoyarskiy K, Russia.
    Kharinskii, Artur
    Irkutsk State Tech Univ, Irkutsk Natl Res Tech Univ, Lab Archaeol Paleoecol & Subsistence Strategies P, Irkutsk 664074, Irkutsk Oblast, Russia.
    Tishkin, Alexey
    Altai State Univ, Dept Archaeol Ethnog & Museol, Lab Interdisciplinary Studies Archaeol Western Si, Barnaul, Altaiskiy Kray, Russia.
    Ineshin, Evgenij
    Irkutsk State Univ, Lab Archaeol & Ethnog, Fac Hist & Methods, Dept Humanitarian & Aesthet Educ,Pedag Inst, Irkutsk 664011, Irkutsk Oblast, Russia.
    Kovychev, Evgeniy
    Transbaikal State Univ, Fac Hist, Chita 672039, Zabaykalsky Kra, Russia.
    Stepanov, Aleksandr
    MK Ammosov North Eastern Fed Univ NEFU, Fed State Autonomous Educ Inst Higher Educ, Yakutsk 677000, Sakha Republic, Russia.
    Alekseev, Aanatolij
    Acad Sci Sakha Republ, Inst Humanities Res & Indigenous Studies IHRISN, Yakutsk 677000, Sakha Republic, Russia.
    Fedoseeva, Svetlana Aleksandrovna
    Russian Acad Sci, Inst Arctic Archaeol & Paleoecol, Yakutsk 677000, Sakha Republic, Russia.
    Somel, Mehmet
    Middle East Tech Univ, Dept Biol Sci, TR-06800 Ankara, Turkey.
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Human Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Krzewinska, Maja
    Stockholm Univ, Dept Archaeol & Class Studies, S-10691 Stockholm, Sweden.
    Stora, Jan
    Stockholm Univ, Dept Archaeol & Class Studies, S-10691 Stockholm, Sweden.
    Gotherstrom, Anders
    Stockholm Univ, Dept Archaeol & Class Studies, S-10691 Stockholm, Sweden.
    Investigating Holocene human population history in North Asia using ancient mitogenomes2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8969Article in journal (Refereed)
    Abstract [en]

    Archaeogenomic studies have largely elucidated human population history in West Eurasia during the Stone Age. However, despite being a broad geographical region of significant cultural and linguistic diversity, little is known about the population history in North Asia. We present complete mitochondrial genome sequences together with stable isotope data for 41 serially sampled ancient individuals from North Asia, dated between c. 13,790 BP and c. 1,380 BP extending from the Palaeolithic to the Iron Age. Analyses of mitochondrial DNA sequences and haplogroup data of these individuals revealed the highest genetic affinity to present-day North Asian populations of the same geographical region suggesting a possible long-term maternal genetic continuity in the region. We observed a decrease in genetic diversity over time and a reduction of maternal effective population size (Ne) approximately seven thousand years before present. Coalescent simulations were consistent with genetic continuity between present day individuals and individuals dating to 7,000 BP, 4,800 BP or 3,000 BP. Meanwhile, genetic differences observed between 7,000 BP and 3,000 BP as well as between 4,800 BP and 3,000 BP were inconsistent with genetic drift alone, suggesting gene flow into the region from distant gene pools or structure within the population. These results indicate that despite some level of continuity between ancient groups and present-day populations, the region exhibits a complex demographic history during the Holocene.

  • 214.
    Kim, Dongyoo
    et al.
    Royal Inst Technol, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden..
    Vitos, Levente
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Royal Inst Technol, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden.;Wigner Res Ctr Phys, Res Inst Solid State Phys & Opt, H-1525 Budapest, Hungary..
    Tuned Magnetic Properties of L1(0)-MnGa/Co(001) Films by Epitaxial Strain2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 19508Article in journal (Refereed)
    Abstract [en]

    We demonstrate that the interface structure has a significant influence on the magnetic state of MnGa/Co films consisting of L1(0)-MnGa on face-centered-cubic Co(001) surface. We reveal an antiferromagnetic to ferromagnetic magnetization reversal as a function of the lateral lattice constant. The magnetization reversal mainly originates from localized states and weak hybridization at interface due to charge redistribution between muffin-tin spheres and interstitial region. The magnetic anisotropy energy of Mn/Co interface system is enhanced with increasing in-plane lattice constant, which is ascribed to the interface interactions and the above magnetization reversal.

  • 215.
    Klaesson, Axel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Grannas, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Ebai, Tonge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Heldin, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Koos, Björn
    Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
    Leino, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Raykova, Doroteya
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Oelrich, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Arngården, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Söderberg, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Landegren, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Improved efficiency of in situ protein analysis by proximity ligation using UnFold probes2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5400Article in journal (Refereed)
    Abstract [en]

    We have redesigned probes for in situ proximity ligation assay (PLA), resulting in more efficient localized detection of target proteins. In situ PLA depends on recognition of target proteins by pairs of antibody-oligonucleotide conjugates (PLA probes), which jointly give rise to DNA circles that template localized rolling circle amplification reactions. The requirement for dual recognition of the target proteins improves selectivity by ignoring any cross-reactivity not shared by the antibodies, and it allows detection of protein-protein interactions and post-translational modifications. We herein describe an improved design of the PLA probes -UnFold probes - where all elements required for formation of circular DNA strands are incorporated in the probes. Premature interactions between the UnFold probes are prevented by including an enzymatic "unfolding" step in the detection reactions. This allows DNA circles to form by pairs of reagents only after excess reagents have been removed. We demonstrate the performance of UnFold probes for detection of protein-protein interactions and post-translational modifications in fixed cells and tissues, revealing considerably more efficient signal generation. We also apply the UnFold probes to detect IL-6 in solution phase after capture on solid supports, demonstrating increased sensitivity over both normal sandwich enzyme-linked immunosorbent assays and conventional PLA assays.

  • 216.
    Klimesova, Eva
    et al.
    ELI Beamlines, Inst Phys AS CR, Vvi, Na Slovance 2, Prague 18221 8, Czech Republic.
    Kulyk, Olena
    ELI Beamlines, Inst Phys AS CR, Vvi, Na Slovance 2, Prague 18221 8, Czech Republic.
    Gu, Yanjun
    ELI Beamlines, Inst Phys AS CR, Vvi, Na Slovance 2, Prague 18221 8, Czech Republic.
    Dittrich, Laura
    ELI Beamlines, Inst Phys AS CR, Vvi, Na Slovance 2, Prague 18221 8, Czech Republic;Tech Univ Berlin, Inst Opt & Atomare Phys, ER 1-1,Str 17 Juni 135, D-10623 Berlin, Germany.
    Korn, Georg
    ELI Beamlines, Inst Phys AS CR, Vvi, Na Slovance 2, Prague 18221 8, Czech Republic.
    Hajdu, Janos
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics. ELI Beamlines, Inst Phys AS CR, Vvi, Na Slovance 2, Prague 18221 8, Czech Republic.
    Krikunova, Maria
    ELI Beamlines, Inst Phys AS CR, Vvi, Na Slovance 2, Prague 18221 8, Czech Republic;Tech Univ Berlin, Inst Opt & Atomare Phys, ER 1-1,Str 17 Juni 135, D-10623 Berlin, Germany.
    Andreasson, Jakob
    ELI Beamlines, Inst Phys AS CR, Vvi, Na Slovance 2, Prague 18221 8, Czech Republic;Chalmers Univ Technol, Dept Phys, Gothenburg, Sweden.
    Plasma channel formation in NIR laser-irradiated carrier gas from an aerosol nanoparticle injector2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 8851Article in journal (Refereed)
    Abstract [en]

    Aerosol nanoparticle injectors are fundamentally important for experiments where container-free sample handling is needed to study isolated nanoparticles. The injector consists of a nebuliser, a differential pumping unit, and an aerodynamic lens to create and deliver a focused particle beam to the interaction point inside a vacuum chamber. The tightest focus of the particle beam is close to the injector tip. The density of the focusing carrier gas is high at this point. We show here how this gas interacts with a near infrared laser pulse (800 nm wavelength, 120 fs pulse duration) at intensities approaching 10(16) Wcm(-2). We observe acceleration of gas ions to kinetic energies of 100s eV and study their energies as a function of the carrier gas density. Our results indicate that field ionisation by the intense near-infrared laser pulse opens up a plasma channel behind the laser pulse. The observations can be understood in terms of a Coulomb explosion of the created underdense plasma channel. The results can be used to estimate gas background in experiments with the injector and they open up opportunities for a new class of studies on electron and ion dynamics in nanoparticles surrounded by a low-density gas.

  • 217.
    Kocevski, Vancho
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Rusz, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Eriksson, Olle
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Sarma, Dipankar Das
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics. Indian Institute of Science, Bangalore-560 012, India.
    First-principles study of the influence of different interfaces and core types on the properties of CdSe/CdS core-shell nanocrystals2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 10865Article in journal (Refereed)
    Abstract [en]

    With the expanding field of nanoengineering and the production of nanocrystals (NCs) with higher quality and tunable size, having reliable theoretical calculations to complement the experimental results is very important. Here we present such a study of CdSe/CdS core-shell NCs using density functional theory, where we focus on dependence of the properties of these NCs on core types and interfaces between the core and the shell, as well as on the core/shell ratio. We show that the density of states and the absorption indices depend rather weakly on the type of interface and core type. We demonstrate that the HOMO wavefunction is mainly localised in the core of the nanocrystal, depending primarily on the core/shell ratio. On the other hand the LUMO wavefunction spreads more into the shell of the nanocrystal, where its confinement in the core is almost the same in each of the studied structural models. Furthermore, we show that the radiative lifetimes decrease with increasing core sizes due to changes in the dipolar overlap integral of the HOMO and LUMO wavefunctions. In addition, the electron-hole Coulomb interaction energies follow a similar pattern as the localisation of the wavefunctions, with the smaller NCs having higher Coulomb interaction energies.

  • 218.
    Kokosar, Milana
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden.
    Benrick, Anna
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden;Univ Skovde, Sch Hlth & Educ, Skovde, Sweden.
    Perfilyev, Alexander
    Lund Univ, Diabet Ctr, Scania Univ Hosp, Dept Clin Sci,Epigenet & Diabet,Clin Res Ctr, Malmo, Sweden.
    Nilsson, Emma
    Lund Univ, Diabet Ctr, Scania Univ Hosp, Dept Clin Sci,Epigenet & Diabet,Clin Res Ctr, Malmo, Sweden.
    Källman, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr,Ctr Bone & Arthrit R, Gothenburg, Sweden.
    Ling, Charlotte
    Lund Univ, Diabet Ctr, Scania Univ Hosp, Dept Clin Sci,Epigenet & Diabet,Clin Res Ctr, Malmo, Sweden.
    Stener-Victorin, Elisabet
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden.
    A Single Bout of Electroacupuncture Remodels Epigenetic and Transcriptional Changes in Adipose Tissue in Polycystic Ovary Syndrome2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1878Article in journal (Refereed)
    Abstract [en]

    A single bout of electroacupuncture results in muscle contractions and increased whole body glucose uptake in women with polycystic ovary syndrome (PCOS). Women with PCOS have transcriptional and epigenetic alterations in the adipose tissue and we hypothesized that electroacupuncture induces epigenetic and transcriptional changes to restore metabolic alterations. Twenty-one women with PCOS received a single bout of electroacupuncture, which increased the whole body glucose uptake. In subcutaneous adipose tissue biopsies, we identified treatment-induced expression changes of 2369 genes (Q < 0.05) and DNA methylation changes of 7055 individual genes (Q = 0.11). The largest increase in expression was observed for FOSB (2405%), and the largest decrease for LOC100128899 (54%). The most enriched pathways included Acute phase response signaling and LXR/RXR activation. The DNA methylation changes ranged from 1-16%, and 407 methylation sites correlated with gene expression. Among genes known to be differentially expressed in PCOS, electroacupuncture reversed the expression of 80 genes, including PPAR gamma and ADIPOR2. Changes in the expression of Nr4 alpha 2 and Junb are reversed by adrenergic blockers in rats demonstrating that changes in gene expression, in part, is due to activation of the sympathetic nervous system. In conclusion, low-frequency electroacupuncture with muscle contractions remodels epigenetic and transcriptional changes that elicit metabolic improvement.

  • 219. Kong, P. P.
    et al.
    Sun, F.
    Xing, L. Y.
    Zhu, J.
    Zhang, S. J.
    Li, W. M.
    Liu, Q. Q.
    Wang, X. C.
    Feng, S. M.
    Yu, X. H.
    Zhu, J. L.
    Yu, R. C.
    Yang, W. G.
    Shen, G. Y.
    Zhao, Y. S.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Mao, H. K.
    Jin, C. Q.
    Superconductivity in Strong Spin Orbital Coupling Compound Sb2Se32014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 6679-Article in journal (Refereed)
    Abstract [en]

    Recently, A(2)B(3) type strong spin orbital coupling compounds such as Bi2Te3, Bi2Se3 and Sb2Te3 were theoretically predicated to be topological insulators and demonstrated through experimental efforts. The counterpart compound Sb2Se3 on the other hand was found to be topological trivial, but further theoretical studies indicated that the pressure might induce Sb2Se3 into a topological nontrivial state. Here, we report on the discovery of superconductivity in Sb2Se3 single crystal induced via pressure. Our experiments indicated that Sb2Se3 became superconductive at high pressures above 10 GPa proceeded by a pressure induced insulator to metal like transition at similar to 3 GPa which should be related to the topological quantum transition. The superconducting transition temperature (T-C) increased to around 8.0 K with pressure up to 40 GPa while it keeps ambient structure. High pressure Raman revealed that new modes appeared around 10 GPa and 20 GPa, respectively, which correspond to occurrence of superconductivity and to the change of T-C slop as the function of high pressure in conjunction with the evolutions of structural parameters at high pressures.

  • 220.
    Koripella, Ravi Kiran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Holm, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Dourado, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Mandava, Chandra Sekhar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Flores, Samuel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Sanyal, Suparna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    A conserved histidine in switch-II of EF-G moderates release of inorganic phosphate2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 12970Article in journal (Refereed)
    Abstract [en]

    Elongation factor G (EF-G), a translational GTPase responsible for tRNA-mRNA translocation possesses a conserved histidine (H91 in Escherichia coli) at the apex of switch-II, which has been implicated in GTPase activation and GTP hydrolysis. While H91A, H91R and H91E mutants showed different degrees of defect in ribosome associated GTP hydrolysis, H91Q behaved like the WT. However, all these mutants, including H91Q, are much more defective in inorganic phosphate (Pi) release, thereby suggesting that H91 facilitates Pi release. In crystal structures of the ribosome bound EF-G center dot GTP a tight coupling between H91 and the gamma-phosphate of GTP can be seen. Following GTP hydrolysis, H91 flips similar to 140 degrees in the opposite direction, probably with Pi still coupled to it. This, we suggest, promotes Pi to detach from GDP and reach the inter-domain space of EF-G, which constitutes an exit path for the Pi. Molecular dynamics simulations are consistent with this hypothesis and demonstrate a vital role of an Mg2+ ion in the process.

  • 221.
    Kotmool, Komsilp
    et al.
    Mahidol Wittayanusorn Sch, Dept Phys, Nakhon Pathom 73170, Thailand.;Thailand Ctr Excellence Phys, Commiss Higher Educ, Bangkok 10400, Thailand..
    Chakraborty, Sudip
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Bovornratanaraks, Thiti
    Thailand Ctr Excellence Phys, Commiss Higher Educ, Bangkok 10400, Thailand.;Chulalongkorn Univ, Fac Sci, Dept Phys, ECPRL, Bangkok 10330, Thailand..
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Royal Inst Technol KTH, Dept Mat & Engn, Appl Mat Phys, S-10044 Stockholm, Sweden..
    Role of relativity in high-pressure phase transitions of thallium2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42983Article in journal (Refereed)
    Abstract [en]

    We demonstrate the relativistic effects in high-pressure phase transitions of heavy element thallium. The known first phase transition from h. c. p. to f. c. c. is initially investigated by various relativistic levels and exchange-correlation functionals as implemented in FPLO method, as well as scalar relativistic scheme within PAW formalism. The electronic structure calculations are interpreted from the perspective of energetic stability and electronic density of states. The full relativistic scheme (FR) within L(S) DA performs to be the scheme that resembles mostly with experimental results with a transition pressure of 3 GPa. The s-p hybridization and the valence-core overlapping of 6s and 5d states are the primary reasons behind the f. c. c. phase occurrence. A recent proposed phase, i. e., a body-centered tetragonal (b. c. t.) phase, is confirmed with a small distortion from the f. c. c. phase. We have also predicted a reversible b. c. t. -> f. c. c. phase transition at 800 GPa. This finding has been suggested that almost all the III-A elements (Ga, In and Tl) exhibit the b. c. t. -> f. c. c. phase transition at extremely high pressure.

  • 222.
    Koumpouras, Konstantinos
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Bergman, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Eriksson, Olle
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Yudin, Dmitry
    ITMO Univ, St Petersburg 197101, Russia..
    A spin dynamics approach to solitonics2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 25685Article in journal (Refereed)
    Abstract [en]

    In magnetic materials a variety of non-collinear ground state configurations may emerge as a result of competition among exchange, anisotropy, and dipole-dipole interaction, yielding magnetic states far more complex than those of homogenous ferromagnets. Of particular interest in this study are particle-like configurations. These particle-like states, e.g., magnetic solitons, skyrmions, or domain walls, form a spatially localised clot of magnetic energy. In this paper we address topologically protected magnetic solitons and explore concepts that potentially might be relevant for logical operations and/or information storage in the rapidly advancing filed of solitonics (and skyrmionics). An ability to easily create, address, and manipulate such structures is among the prerequisite forming a basis of "-onics technology", and is investigated in detail here using numerical and analytical tools.

  • 223.
    Kozma, Radoslav
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Mörch, Patrik Rödin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Höglund, Jacob
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Genomic regions of speciation and adaptation among three species of grouse2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 812Article in journal (Refereed)
    Abstract [en]

    Understanding the molecular basis of adaption is one of the central goals in evolutionary biology and when investigated across sister species it can provide detailed insight into the mechanisms of speciation. Here, we sequence the genomes of 34 individuals from three closely related grouse species in order to uncover the genomic architecture of speciation and the genes involved in adaptation. We identify 6 regions, containing 7 genes that show lineage specific signs of differential selection across the species. These genes are involved in a variety of cell processes ranging from stress response to neural, gut, olfactory and limb development. Genome wide neutrality test statistics reveal a strong signal of population expansion acting across the genomes. Additionally, we uncover a 3.5 Mb region on chromosome 20 that shows considerably lower levels of differentiation across the three grouse lineages, indicating possible action of uniform selection in this region.

  • 224.
    Kristinsson, Hjalti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sargsyan, Ernest
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Smith, D. M.
    AstraZeneca, Discovery Sci Innovat Med & Early Dev Biotech Uni, Cambridge, England..
    Gopel, S. O.
    AstraZeneca R&D Gothenburg, CVMD Biosci, Gothenburg, Sweden..
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 4657Article in journal (Refereed)
    Abstract [en]

    In obesity fasting levels of both glucagon and insulin are elevated. In these subjects fasting levels of the free fatty acid palmitate are raised. We have demonstrated that palmitate enhances glucose-stimulated insulin secretion from isolated human islets via free fatty acid receptor 1 (FFAR1/GPR40). Since FFAR1 is also present on glucagon- secreting alpha-cells, we hypothesized that palmitate simultaneously stimulates secretion of glucagon and insulin at fasting glucose concentrations. In addition, we hypothesized that concomitant hypersecretion of glucagon and insulin was also contributed by reduced somatostatin secretion. We found basal glucagon, insulin and somatostatin secretion and respiration from human islets, to be enhanced during palmitate treatment at normoglycemia. Secretion of all hormones and mitochondrial respiration were lowered when FFAR1 or fatty acid beta-oxidation was inhibited. The findings were confirmed in the human beta-cell line EndoC-beta H1. We conclude that fatty acids enhance both glucagon and insulin secretion at fasting glucose concentrations and that FFAR1 and enhanced mitochondrial metabolism but not lowered somatostatin secretion are crucial in this effect. The ability of chronically elevated palmitate levels to simultaneously increase basal secretion of glucagon and insulin positions elevated levels of fatty acids as potential triggering factors for the development of obesity and impaired glucose control.

  • 225.
    Kudryashova, Elena
    et al.
    Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA..
    Koneru, Pratibha C.
    Ohio State Univ, Ctr Retroviral Res, Columbus, OH 43210 USA.;Ohio State Univ, Coll Pharm, 500 W 12Th Ave, Columbus, OH 43210 USA..
    Kvaratskhelia, Mamuka
    Ohio State Univ, Ctr Retroviral Res, Columbus, OH 43210 USA.;Ohio State Univ, Coll Pharm, 500 W 12Th Ave, Columbus, OH 43210 USA..
    Strömstedt, Adam A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
    Lu, Wuyuan
    Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA..
    Kudryashov, Dmitri S.
    Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA.;Ohio State Univ, Publ Hlth Preparedness Infect Dis Program, Columbus, OH 43210 USA..
    Thermodynamic instability of viral proteins is a pathogen-associated molecular pattern targeted by human defensins2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 32499Article in journal (Refereed)
    Abstract [en]

    Human defensins are innate immune defense peptides with a remarkably broad repertoire of anti-pathogen activities. In addition to modulating immune response, inflammation, and angiogenesis, disintegrating bacterial membranes, and inactivating bacterial toxins, defensins are known to intercept various viruses at different stages of their life cycles, while remaining relatively benign towards human cells and proteins. Recently we have found that human defensins inactivate proteinaceous bacterial toxins by taking advantage of their low thermodynamic stability and acting as natural "anti-chaperones", i.e. destabilizing the native conformation of the toxins. In the present study we tested various proteins produced by several viruses (HIV-1, PFV, and TEV) and found them to be susceptible to destabilizing effects of human alpha-defensins HNP-1 and HD-5 and the synthetic theta-defensin RC-101, but not beta-defensins hBD-1 and hBD-2 or structurally related plant-derived peptides. Defensin-induced unfolding promoted exposure of hydrophobic groups otherwise confined to the core of the viral proteins. This resulted in precipitation, an enhanced susceptibility to proteolytic cleavage, and a loss of viral protein activities. We propose, that defensins recognize and target a common and essential physico-chemical property shared by many bacterial toxins and viral proteins - the intrinsically low thermodynamic protein stability.

  • 226.
    Kuehn, Danilo
    et al.
    Univ Potsdam, Inst Phys & Astron, Karl Liebknecht Str 24-25, D-14476 Potsdam, Germany;Helmholtz Zentrum Berlin Mat & Energie GmbH, Albert Einstein Str 15, D-12489 Berlin, Germany.
    Mueller, Moritz
    Univ Basque Country, CSIC, Ctr Fis Mat, Paseo Manuel de Lardizabal 5, E-20018 Donostia San Sebastian, Spain;DIPC, Paseo Manuel de Lardizabal 5, E-20018 Donostia San Sebastian, Spain;CIC nanoGUNE, Ave Tolosa 76, E-20018 Donostia San Sebastian, Spain.
    Sorgenfrei, Florian
    Univ Potsdam, Inst Phys & Astron, Karl Liebknecht Str 24-25, D-14476 Potsdam, Germany;Helmholtz Zentrum Berlin Mat & Energie GmbH, Albert Einstein Str 15, D-12489 Berlin, Germany.
    Giangrisostomi, Erika
    Helmholtz Zentrum Berlin Mat & Energie GmbH, Albert Einstein Str 15, D-12489 Berlin, Germany.
    Jay, Raphael M.
    Univ Potsdam, Inst Phys & Astron, Karl Liebknecht Str 24-25, D-14476 Potsdam, Germany.
    Ovsyannikov, Ruslan
    Helmholtz Zentrum Berlin Mat & Energie GmbH, Albert Einstein Str 15, D-12489 Berlin, Germany.
    Mårtensson, Nils
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Sanchez-Portal, Daniel
    Univ Basque Country, CSIC, Ctr Fis Mat, Paseo Manuel de Lardizabal 5, E-20018 Donostia San Sebastian, Spain;DIPC, Paseo Manuel de Lardizabal 5, E-20018 Donostia San Sebastian, Spain.
    Foehlisch, Alexander
    Univ Potsdam, Inst Phys & Astron, Karl Liebknecht Str 24-25, D-14476 Potsdam, Germany;Helmholtz Zentrum Berlin Mat & Energie GmbH, Albert Einstein Str 15, D-12489 Berlin, Germany.
    Directional sub-femtosecond charge transfer dynamics and the dimensionality of 1T-TaS22019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 488Article in journal (Refereed)
    Abstract [en]

    For the layered transition metal dichalcogenide 1T-TaS2, we establish through a unique experimental approach and density functional theory, how ultrafast charge transfer in 1T-TaS2 takes on isotropic three-dimensional character or anisotropic two-dimensional character, depending on the commensurability of the charge density wave phases of 1T-TaS2. The X-ray spectroscopic core-hole-clock method prepares selectively in-and out-of-plane polarized sulfur 3p orbital occupation with respect to the 1T-TaS2 planes and monitors sub-femtosecond wave packet delocalization. Despite being a prototypical two-dimensional material, isotropic three-dimensional charge transfer is found in the commensurate charge density wave phase (CCDW), indicating strong coupling between layers. In contrast, anisotropic two-dimensional charge transfer occurs for the nearly commensurate phase (NCDW). In direct comparison, theory shows that interlayer interaction in the CCDW phase - not layer stacking variations - causes isotropic three-dimensional charge transfer. This is presumably a general mechanism for phase transitions and tailored properties of dichalcogenides with charge density waves.

  • 227.
    Kullberg, Joel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, BioVenture Hub, Molndal, Sweden.
    Hedström, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, BioVenture Hub, Molndal, Sweden.
    Brandberg, John
    Sahlgrens Univ Hosp, Dept Radiol, Gothenburg, Sweden.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Lars E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, BioVenture Hub, Molndal, Sweden.
    Bergström, Göran
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, BioVenture Hub, Molndal, Sweden.
    Automated analysis of liver fat, muscle and adipose tissue distribution from CT suitable for large-scale studies.2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10425Article in journal (Refereed)
    Abstract [en]

    Computed Tomography (CT) allows detailed studies of body composition and its association with metabolic and cardiovascular disease. The purpose of this work was to develop and validate automated and manual image processing techniques for detailed and efficient analysis of body composition from CT data. The study comprised 107 subjects examined in the Swedish CArdioPulmonary BioImage Study (SCAPIS) using a 3-slice CT protocol covering liver, abdomen, and thighs. Algorithms were developed for automated assessment of liver attenuation, visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, thigh muscles, subcutaneous, subfascial (SFAT) and intermuscular adipose tissue. These were validated using manual reference measurements. SFAT was studied in selected subjects were the fascia lata could be visually identified (approx. 5%). In addition, precision of manual measurements of intra- (IPAT) and retroperitoneal adipose tissue (RPAT) and deep- and superficial SAT was evaluated using repeated measurements. Automated measurements correlated strongly to manual reference measurements. The SFAT depot showed the weakest correlation (r = 0.744). Automated VAT and SAT measurements were slightly, but significantly overestimated (≤4.6%, p ≤ 0.001). Manual segmentation of abdominal sub-depots showed high repeatability (CV ≤ 8.1%, r ≥ 0.930). We conclude that the low dose CT-scanning and automated analysis makes the setup suitable for large-scale studies.

  • 228.
    Kullinger, Merit
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health). Region Västmanland – Uppsala University, Center for Clinical Research, Hospital of Västmanland Västerås, Sweden.
    Granfors, Michaela
    Department of Clinical Science, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Kieler, Helle
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Discrepancy between pregnancy dating methods affects obstetric and neonatal outcomes: a population-based register cohort study2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6936Article in journal (Refereed)
    Abstract [en]

    To assess associations between discrepancy of pregnancy dating methods and adverse pregnancy, delivery, and neonatal outcomes, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for discrepancy categories among all singleton births from the Medical Birth Register (1995–2010) with estimated date of delivery (EDD) by last menstrual period (LMP) minus EDD by ultrasound (US) -20 to +20 days. Negative/positive discrepancy was a fetus smaller/larger than expected when dated by US (EDD postponed/changed to an earlier date). Large discrepancy was <10th or >90th percentile. Reference was median discrepancy ± 2 days. Odds for diabetes and preeclampsia were higher in pregnancies with negative discrepancy, and for most delivery outcomes in case of large positive discrepancy (+9 to +20 days): shoulder dystocia [OR 1.16 (95% CI 1.01–1.33)] and sphincter injuries [OR 1.13 (95% CI 1.09–1.17)]. Odds for adverse neonatal outcomes were higher in large negative discrepancy (–4 to –20 days): low Apgar score [OR 1.18 (95% CI 1.09–1.27)], asphyxia [OR 1.18 (95% CI 1.11–1.25)], fetal death [OR 1.47 (95% CI 1.32–1.64)], and neonatal death [OR 2.19 (95% CI 1.91–2.50)]. In conclusion, especially, large negative discrepancy was associated with increased risks of adverse perinatal outcomes. 

  • 229.
    Kumar, Rajnish
    et al.
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,NOVUM, 4th Floor, S-14186 Stockholm, Sweden.
    Kumar, Amit
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,NOVUM, 4th Floor, S-14186 Stockholm, Sweden.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Darreh-Shori, Taher
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,NOVUM, 4th Floor, S-14186 Stockholm, Sweden.
    Discovery of novel choline acetyltransferase inhibitors using structure-based virtual screening2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 16287Article in journal (Refereed)
    Abstract [en]

    Alzheimer disease and related dementias are major challenges, demanding urgent needs for earliest possible diagnosis to optimize the success rate in finding effective therapeutic interventions. Mounting solid scientific premises point at the core acetylcholine-biosynthesizing cholinergic enzyme, ChAT as a legitimate in vivo target for developing positron emission tomography biomarker for early diagnosis and/or monitoring therapeutic responses in the neurodegenerative dementias. Up-to-date, no PET tracer ligands for ChAT are available. Here we report for the first time a novel hierarchical virtual screening approach on a commercial library of similar to 300,000 compounds, followed by in vitro screening of the hits by a new High-Throughput ChAT assay. We report detailed pharmacodynamic data for three identified selective novel ChAT ligands with IC50 and K-i values ranging from similar to 7 to 26 mu M. In addition, several novel selective inhibitors of the acetylcholine-degrading enzymes, AChE and BuChE were identified, with one of the compounds showing an IC50-value of similar to 6 mu M for AChE. In conclusion, this report provides an excellent starting platform for designing and optimizing potent and selective ChAT ligands, with high potential as PET-imaging probe for early diagnosis of AD, and related dementias, such as Down's syndrome and Lewy body disorders.

  • 230.
    Kumar, Rajnish
    et al.
    Karolinska Inst, Ctr Alzheimer Res, 4th Floor, S-14186 Huddinge, Sweden.;Novum, Dept Neurobiol Care Sci & Soc, 4th Floor, S-14186 Huddinge, Sweden.;Novum, Div Translat Alzheimer Neurobiol, 4th Floor, S-14186 Huddinge, Sweden..
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Darreh-Shori, Taher
    Karolinska Inst, Ctr Alzheimer Res, 4th Floor, S-14186 Huddinge, Sweden.;Novum, Dept Neurobiol Care Sci & Soc, 4th Floor, S-14186 Huddinge, Sweden.;Novum, Div Translat Alzheimer Neurobiol, 4th Floor, S-14186 Huddinge, Sweden..
    Novel ligands of Choline Acetyltransferase designed by in silico molecular docking, hologram QSAR and lead optimization2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 31247Article in journal (Refereed)
    Abstract [en]

    Recent reports have brought back the acetylcholine synthesizing enzyme, choline acetyltransferase in the mainstream research in dementia and the cholinergic anti-inflammatory pathway. Here we report, a specific strategy for the design of novel ChAT ligands based on molecular docking, Hologram Quantitative Structure Activity Relationship (HQSAR) and lead optimization. Molecular docking was performed on a series of ChAT inhibitors to decipher the molecular fingerprint of their interaction with the active site of ChAT. Then robust statistical fragment HQSAR models were developed. A library of novel ligands was generated based on the pharmacophoric and shape similarity scoring function, and evaluated in silico for their molecular interactions with ChAT. Ten of the top scoring invented compounds are reported here. We confirmed the activity of alpha-NETA, the only commercially available ChAT inhibitor, and one of the seed compounds in our model, using a new simple colorimetric ChAT assay (IC50 similar to 88 nM). In contrast, alpha-NETA exhibited an IC50 of -30 mu M for the ACh-degrading cholinesterases. In conclusion, the overall results may provide useful insight for discovering novel ChAT ligands and potential positron emission tomography tracers as in vivo functional biomarkers of the health of central cholinergic system in neurodegenerative disorders, such as Alzheimer's disease.

  • 231.
    Kundu, Ashis
    et al.
    Indian Inst Technol Guwahati, Dept Phys, Gauhati 781039, Assam, India..
    Ghosh, Srikrishna
    Indian Inst Technol Guwahati, Dept Phys, Gauhati 781039, Assam, India..
    Banerjee, Rudra
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Ghosh, Subhradip
    Indian Inst Technol Guwahati, Dept Phys, Gauhati 781039, Assam, India..
    Sanyal, Biplab
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    New quaternary half-metallic ferromagnets with large Curie temperatures2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1803Article in journal (Refereed)
    Abstract [en]

    New magnetic materials with high Curie temperatures for spintronic applications are perpetually sought for. In this paper, we present an ab initio study of the structural, electronic and magnetic properties of Quaternary Heusler compounds CoX'Y'Si where X' is a transition metal with 4d electrons and Y' is either Fe or Mn. We find five new half-metallic ferromagnets with spin polarisation nearly 100% with very high Curie temperatures. The variation of Curie temperatures as a function of valence electrons can be understood from the calculated inter-atomic exchange interaction parameters. We also identify a few other compounds, which could be potential half-metals with suitable application of pressure or with controlled doping. Our results reveal that the half-metallicity in these compounds is intricately related to the arrangements of the magnetic atoms in the Heusler lattice and hence, the interatomic exchange interactions between the moments. The trends in the atomic arrangements, total and local magnetic moments, interatomic magnetic exchange interactions and Curie temperatures are discussed with fundamental insights.

  • 232.
    Kurtenbach, Stefan
    et al.
    Ruhr Univ Bochum, Dept Cell Physiol, D-44780 Bochum, Germany..
    Giessl, Andreas
    Univ Erlangen Nurnberg, Dept Biol, Anim Physiol, D-91058 Erlangen, Germany..
    Strömberg, Siv
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Molecular Cell Biology.
    Kremers, Jan
    Univ Hosp Erlangen, Dept Ophthalmol, D-91054 Erlangen, Germany.;Friedrich Alexander Univ Erlangen Nurnberg, Dept Anat 2, D-91054 Erlangen, Germany..
    Atorf, Jenny
    Univ Hosp Erlangen, Dept Ophthalmol, D-91054 Erlangen, Germany..
    Rasche, Sebastian
    Ruhr Univ Bochum, Dept Cell Physiol, D-44780 Bochum, Germany..
    Neuhaus, Eva M.
    Univ Hosp Jena, Dept Pharmacol & Toxikol, D-07747 Jena, Germany..
    Herve, Denis
    Univ Paris 06, Inst Fer Moulin, INSERM, UMR S839, F-75005 Paris, France..
    Brandstaetter, Johann Helmut
    Univ Erlangen Nurnberg, Dept Biol, Anim Physiol, D-91058 Erlangen, Germany..
    Asan, Esther
    Univ Wurzburg, Inst Anat & Cell Biol, D-97070 Wurzburg, Germany..
    Hatt, Hanns
    Ruhr Univ Bochum, Dept Cell Physiol, D-44780 Bochum, Germany..
    Kilimann, Manfred W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Molecular Cell Biology. Max Planck Inst Expt Med, Dept Mol Neurobiol, Gottingen, Germany.
    The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 8409Article in journal (Refereed)
    Abstract [en]

    BEACH domain proteins are involved in membrane protein traffic and human diseases, but their molecular mechanisms are not understood. The BEACH protein LRBA has been implicated in immune response and cell proliferation, and human LRBA mutations cause severe immune deficiency. Here, we report a first functional and molecular phenotype outside the immune system of LRBA-knockout mice: compromised olfaction, manifesting in reduced electro-olfactogram response amplitude, impaired food-finding efficiency, and smaller olfactory bulbs. LRBA is prominently expressed in olfactory and vomeronasal chemosensory neurons of wild-type mice. Olfactory impairment in the LRBA-KO is explained by markedly reduced concentrations (20-40% of wild-type levels) of all three subunits alpha(olf), beta(1) and gamma(13) of the olfactory heterotrimeric G-protein, G(olf), in the sensory cilia of olfactory neurons. In contrast, cilia morphology and the concentrations of many other proteins of olfactory cilia are not or only slightly affected. LRBA is also highly expressed in photoreceptor cells, another cell type with a specialized sensory cilium and heterotrimeric G-protein-based signalling; however, visual function appeared unimpaired by the LRBA-KO. To our knowledge, this is the first observation that a BEACH protein is required for the efficient subcellular localization of a lipid-anchored protein, and of a ciliary protein.

  • 233.
    Lagali, Neil S.
    et al.
    Linkoping Univ, Inst Clin & Expt Med, Dept Ophthalmol, S-58183 Linkoping, Sweden;Sorlandet Hosp Arendal, Dept Ophthalmol, Arendal, Norway.
    Badian, Reza A.
    Oslo Univ Hosp, Dept Med Biochem, Unit Regenerat Med, N-0407 Oslo, Norway;Univ Oslo, N-0407 Oslo, Norway;Univ South Eastern Norway, Fac Visual & Hlth Sci, Natl Ctr Opt Vis & Eye Care, Kongsberg, Norway.
    Liu, Xu
    Oyelegesenteret Tromso, Fjaerevegen 6, N-9024 Tomasjord, Norway.
    Feldreich, Tobias R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Sci, Falun, Sweden.
    Arnlov, Johan
    Dalarna Univ, Sch Hlth & Social Sci, Falun, Sweden;Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Utheim, Tor Paaske
    Oslo Univ Hosp, Dept Med Biochem, Unit Regenerat Med, N-0407 Oslo, Norway;Univ Oslo, N-0407 Oslo, Norway;Sorlandet Hosp Arendal, Dept Ophthalmol, Arendal, Norway.
    Dahlin, Lars B.
    Lund Univ, Skane Univ Hosp, Dept Translat Med Hand Surg, S-20502 Malmo, Sweden.
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Family Med, S-90187 Umea, Sweden.
    Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 92018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 14248Article in journal (Refereed)
    Abstract [en]

    Type 2 diabetes mellitus is characterized by a low-grade inflammation; however, mechanisms leading to this inflammation in specific tissues are not well understood. The eye can be affected by diabetes; thus, we hypothesized that inflammatory changes in the eye may parallel the inflammation that develops with diabetes. Here, we developed a non-invasive means to monitor the status of inflammatory dendritic cell (DC) subsets in the corneal epithelium as a potential biomarker for the onset of inflammation in type 2 diabetes. In an age-matched cohort of 81 individuals with normal and impaired glucose tolerance and type 2 diabetes, DCs were quantified from wide-area maps of the corneal epithelial sub-basal plexus, obtained using clinical in vivo confocal microscopy (IVCM). With the onset of diabetes, the proportion of mature, antigen-presenting DCs increased and became organized in clusters. Out of 92 plasma proteins analysed in the cohort, tumor necrosis factor receptor super family member 9 (TNFRSF9) was associated with the observed maturation of DCs from an immature to mature antigen-presenting phenotype. A low-grade ocular surface inflammation observed in this study, where resident immature dendritic cells are transformed into mature antigen-presenting cells in the corneal epithelium, is a process putatively associated with TNFRSF9 signalling and may occur early in the development of type 2 diabetes. IVCM enables this process to be monitored non-invasively in the eye.

  • 234.
    Lai, Kuei-Hung
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy. Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan.;Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung 807, Taiwan..
    Liu, Yi-Chang
    Kaohsiung Med Univ Hosp, Dept Internal Med, Div Hematol Oncol, Kaohsiung 807, Taiwan.;Kaohsiung Med Univ, Coll Med, Fac Med, Dept Internal Med, Kaohsiung 807, Taiwan..
    Su, Jui-Hsin
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan..
    El-Shazly, Mohamed
    Ain Shams Univ, Dept Pharmacognosy & Nat Prod Chem, Fac Pharm, Org African Unity St, Cairo 11566, Egypt..
    Wu, Chih-Fung
    Kaohsiung Med Univ Hosp, Dept Surg, Div Surg Oncol, Kaohsiung 807, Taiwan..
    Du, Ying-Chi
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan.;Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung 807, Taiwan..
    Hsu, Yu-Ming
    Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung 807, Taiwan..
    Yang, Juan-Cheng
    China Med Univ, Sch Pharm, Coll Pharm, Taichung, Taiwan.;China Med Univ Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan..
    Weng, Ming-Kai
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan..
    Chou, Chia-Hua
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan..
    Chen, Guan-Yu
    China Med Univ, Sch Pharm, Coll Pharm, Taichung, Taiwan.;China Med Univ Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan..
    Chen, Yu-Cheng
    China Med Univ, PhD Program Canc Biol & Drug Discovery, Taichung, Taiwan.;Acad Sinica, Taichung, Taiwan..
    Lu, Mei-Chin
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan..
    Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp902016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 36170Article in journal (Refereed)
    Abstract [en]

    Two new scalarane sesterterpenoids, 12 beta-(3'beta-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12 beta-(3'beta-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 mu g/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase II alpha expression. The apoptotic-inducing effect of 3 was supported by the in vivo experiment through suppressing the volume of xenograft tumor growth (47.58%) compared with the control. Compound 1 apoptotic mechanism of action in Molt 4 cells was further elucidated through inducing ROS generation, calcium release and ER stress. Using the molecular docking analysis, 1 exhibited more binding affinity to N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. The expression of Hsp90 client proteins, Akt, p70(S6k), NF kappa B, Raf-1, p-GSK3 beta, and XIAP, MDM 2 and Rb2, and CDK4 and Cyclin D3, HIF1 and HSF1 were suppressed by the use of 1. However, the expression of Hsp70, acetylated tubulin, and activated caspase 3 were induced after 1 treatment. Our results suggested that the proapoptotic effect of the isolates is mediated through the inhibition of Hsp90 and topoisomerase activities.

  • 235.
    Lampropoulou, Evgenia
    et al.
    Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece..
    Logoviti, Ioanna
    Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece..
    Koutsioumpa, Marina
    Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece.;Univ Calif Los Angeles, David Geffen Sch Med, Vatche & Tamar Manoukian Div Digest Dis, Ctr Syst Biomed, Los Angeles, CA 90095 USA..
    Hatziapostolou, Maria
    Nottingham Trent Univ, Sch Sci & Technol, Dept Biosci, Nottingham NG11 8NS, England..
    Polytarchou, Christos
    Nottingham Trent Univ, Sch Sci & Technol, Dept Biosci, Nottingham NG11 8NS, England..
    Skandalis, Spyros S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Univ Patras, Dept Chem, Lab Biochem, GR-26504 Patras, Greece.
    Hellman, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fousteris, Manolis
    Univ Patras, Dept Pharm, Lab Med Chem, GR-26504 Patras, Greece..
    Nikolaropoulos, Sotirios
    Univ Patras, Dept Pharm, Lab Med Chem, GR-26504 Patras, Greece..
    Choleva, Efrosini
    Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece..
    Lamprou, Margarita
    Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece..
    Skoura, Angeliki
    Univ Patras, Comp Engn & Informat Dept, Patras, Greece..
    Megalooikonomou, Vasileios
    Univ Patras, Comp Engn & Informat Dept, Patras, Greece..
    Papadimitriou, Evangelia
    Univ Patras, Dept Pharm, Lab Mol Pharmacol, GR-26504 Patras, Greece..
    Cyclin-dependent kinase 5 mediates pleiotrophin-induced endothelial cell migration2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5893Article in journal (Refereed)
    Abstract [en]

    Pleiotrophin (PTN) stimulates endothelial cell migration through binding to receptor protein tyrosine phosphatase beta/zeta (RPTP beta/zeta) and alpha(nu)beta(3) integrin. Screening for proteins that interact with RPTP beta/zeta and potentially regulate PTN signaling, through mass spectrometry analysis, identified cyclindependent kinase 5 (CDK5) activator p35 among the proteins displaying high sequence coverage. Interaction of p35 with the serine/threonine kinase CDK5 leads to CDK5 activation, known to be implicated in cell migration. Protein immunoprecipitation and proximity ligation assays verified p35-RPTP beta/zeta interaction and revealed the molecular association of CDK5 and RPTP beta/zeta. In endothelial cells, PTN activates CDK5 in an RPTP beta/zeta- and phosphoinositide 3-kinase (PI3K)-dependent manner. On the other hand, c-Src, alpha(nu)beta(3) and ERK1/2 do not mediate the PTN-induced CDK5 activation. Pharmacological and genetic inhibition of CDK5 abolished PTN-induced endothelial cell migration, suggesting that CDK5 mediates PTN stimulatory effect. A new pyrrolo[2,3-alpha] carbazole derivative previously identified as a CDK1 inhibitor, was found to suppress CDK5 activity and eliminate PTN stimulatory effect on cell migration, warranting its further evaluation as a new CDK5 inhibitor. Collectively, our data reveal that CDK5 is activated by PTN, in an RPTP beta/zeta-dependent manner, regulates PTN-induced cell migration and is an attractive target for the inhibition of PTN pro-angiogenic properties.

  • 236.
    Landegren, Nils
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sharon, Donald
    Freyhult, Eva
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Hallgren, Åsa
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eriksson, Daniel
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bensing, Sophie
    Wahlberg, Jeanette
    Nelson, Lawrence M
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Husebye, Eystein S
    Anderson, Mark S
    Snyder, Michael
    Kämpe, Olle
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 12016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20104Article in journal (Refereed)
    Abstract [en]

    Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.

  • 237.
    Lanekoff, Ingela
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Pacific Northwest Natl Lab, Div Phys Sci, Richland, WA 99352 USA..
    Cha, Jeeyeon
    Cincinnati Childrens Hosp Med Ctr, Div Reprod Sci, Cincinnati, OH 45229 USA.;Vanderbilt Univ, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Kyle, Jennifer E.
    Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99352 USA..
    Dey, Sudhansu K.
    Cincinnati Childrens Hosp Med Ctr, Div Reprod Sci, Cincinnati, OH 45229 USA..
    Laskin, Julia
    Pacific Northwest Natl Lab, Div Phys Sci, Richland, WA 99352 USA..
    Burnum-Johnson, Kristin E.
    Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99352 USA..
    Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 33023Article in journal (Refereed)
    Abstract [en]

    Here we demonstrate that conditional deletion of mouse uterine Trp53 (p53(d/d)), molecularly linked to mTORC1 activation and causally linked to premature uterine senescence and preterm birth, results in aberrant lipid signatures within the heterogeneous cell types of embryo implantation sites on day 8 of pregnancy. In situ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) was used to characterize the molecular speciation of free fatty acids, monoacylglycerol species, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53(d/d) mice and floxed littermates. Implantation sites from p53(d/d) mice exhibited distinct spatially resolved changes demonstrating accumulation of DG species, depletion of Ox-PC species, and increase in species with more unsaturated acyl chains, including arachidonic and docosahexaenoic acid. Understanding abnormal changes in the abundance and localization of individual lipid species early in the progression to premature birth is an important step toward discovering novel targets for treatments and diagnosis.

  • 238.
    Lebret, Karen
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Centre for Ecology and Evolution in Microbial model Systems - EEMiS, Department of Biology and Environmental Science, Linnæus University, SE-391 82, Kalmar, Sweden.
    Östman, Örjan
    Department of Aquatic Resources, Swedish University of Agricultural Sciences, Skolgatan 6, SE-742 42, Öregrund, Sweden.
    Langenheder, Silke
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Drakare, Stina
    Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences - SLU, PO Box 7050, SE-750 07, Uppsala, Sweden.
    Guillemette, François
    Research Center on Watershed – Aquatic Ecosystem Interactions (RIVE), Department of Environmental Sciences, Université du Québec à Trois-Rivières, Québec, Canada.
    Lindström, Eva S.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    High abundances of the nuisance raphidophyte Gonyostomum semen in brown water lakes are associated with high concentrations of iron2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 13463Article in journal (Refereed)
    Abstract [en]

    Algal blooms occur frequently in lakes and oceans and the causes and consequences of those are often studied. In this study, we focus on a less well known type of algal bloom by the freshwater raphidophyte Gonyostomum semen. This species’ abundance and occurrence is increasing, especially in brown water lakes, the most abundant lake type in the boreal zone. The aim of the study was to investigate which environmental factors are associated with G. semen by statistical evaluation of field data of 95 Swedish lakes over five years. Although we found G. semen to be associated with dark waters it was, contrary to our expectations, mainly high concentrations of iron, and only to a lesser extent high TOC (total organic carbon) concentrations, that were associated with blooms of G. semen. In addition, high phosphorus concentrations and low pH also appear to facilitate G. semen blooms. We suggest that browning of lakes caused by increased iron concentrations may decrease net heterotrophy by fostering heavy algal blooms, i.e. the opposite to commonly assumed effects of increased DOM (dissolved organic matter).

  • 239.
    Lee, Jee-Yong
    et al.
    Pohang Univ Sci & Technol, Grad Inst Ferrous Technol, Pohang 37673, South Korea..
    Koo, Yang Mo
    Pohang Univ Sci & Technol, Grad Inst Ferrous Technol, Pohang 37673, South Korea.;Pohang Univ Sci & Technol, Dept Mat Sci & Engn, Pohang 37673, South Korea..
    Lu, Song
    Royal Inst Technol, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden..
    Vitos, Levente
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Royal Inst Technol, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden.;Wigner Res Ctr Phys, Inst Solid State Phys & Opt, POB 49, H-1525 Budapest, Hungary..
    Kwon, Se Kyun
    Pohang Univ Sci & Technol, Grad Inst Ferrous Technol, Pohang 37673, South Korea..
    The behaviour of stacking fault energy upon interstitial alloying2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 11074Article in journal (Refereed)
    Abstract [en]

    Stacking fault energy is one of key parameters for understanding the mechanical properties of face-centered cubic materials. It is well known that the plastic deformation mechanism is closely related to the size of stacking fault energy. Although alloying is a conventional method to modify the physical parameter, the underlying microscopic mechanisms are not yet clearly established. Here, we propose a simple model for determining the effect of interstitial alloying on the stacking fault energy. We derive a volumetric behaviour of stacking fault energy from the harmonic approximation to the energy-lattice curve and relate it to the contents of interstitials. The stacking fault energy is found to change linearly with the interstitial content in the usual low concentration domain. This is in good agreement with previously reported experimental and theoretical data.

  • 240.
    Lee, Juwon
    et al.
    Dongguk Univ, QSRC, Seoul 100715, South Korea..
    Subramaniam, Nagarajan Ganapathi
    Dongguk Univ, QSRC, Seoul 100715, South Korea.;Dongguk Univ, Nano Informat Technol Acad, Seoul 100715, South Korea..
    Kowalik, Iwona Agnieszka
    Polish Acad Sci, Inst Phys, PL-02668 Warsaw, Poland..
    Nisar, Jawad
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Lee, Jaechul
    Dongguk Univ, QSRC, Seoul 100715, South Korea..
    Kwon, Younghae
    Dongguk Univ, QSRC, Seoul 100715, South Korea..
    Lee, Jaechoon
    Dongguk Univ, QSRC, Seoul 100715, South Korea..
    Kang, Taewon
    Dongguk Univ, QSRC, Seoul 100715, South Korea.;Dongguk Univ, Nano Informat Technol Acad, Seoul 100715, South Korea.;Hindustan Univ, Clean Energy & Nano Convergence Ctr CENCON, Madras 603103, Tamil Nadu, India..
    Peng, Xiangyang
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Arvanitis, Dimitri
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Royal Inst Technol KTH, Dept Mat & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden..
    Towards a new class of heavy ion doped magnetic semiconductors for room temperature applications2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 17053Article in journal (Refereed)
    Abstract [en]

    The article presents, using Bi doped ZnO, an example of a heavy ion doped oxide semiconductor, highlighting a novel p-symmetry interaction of the electronic states to stabilize ferromagnetism. The study includes both ab initio theory and experiments, which yield clear evidence for above room temperature ferromagnetism. ZnBixO1-x thin films are grown using the pulsed laser deposition technique. The room temperature ferromagnetism finds its origin in the holes introduced by the Bi doping and the p-p coupling between Bi and the host atoms. A sizeable magnetic moment is measured by means of x-ray magnetic circular dichroism at the O K-edge, probing directly the spin polarization of the O(2p) states. This result is in agreement with the theoretical predictions and inductive magnetometry measurements. Ab initio calculations of the electronic and magnetic structure of ZnBixO1-x at various doping levels allow to trace the origin of the ferromagnetic character of this material. It appears, that the spin-orbit energy of the heavy ion Bi stabilizes the ferromagnetic phase. Thus, ZnBixO1-x doped with a heavy non-ferromagnetic element, such as Bi, is a credible example of a candidate material for a new class of compounds for spintronics applications, based on the spin polarization of the p states.

  • 241.
    Li, Chun-Mei
    et al.
    Shenyang Normal Univ, Coll Phys Sci & Technol, Shenyang 110034, Peoples R China.;Chinese Acad Sci, Inst Met Res, Shenyang Natl Lab Mat Sci, 72 Wenhua Rd, Shenyang 110016, Peoples R China..
    Johansson, Börje
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Dept Mat Sci & Engn, S-10044 Stockholm, Sweden.; Dalian Univ Technol, Sch Phys & Optoelect Technol, Dalian 116024, Peoples R China.;Dalian Univ Technol, Coll Adv Sci & Technol, Dalian 116024, Peoples R China..
    Vitos, Levente
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Dept Mat Sci & Engn, S-10044 Stockholm, Sweden.;Wigner Res Ctr Phys, Res Inst Solid State Phys & Opt, POB 49, HU-1525 Budapest, Hungary..
    Physical mechanism of delta-delta '-epsilon phase stability in plutonium2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 5632Article in journal (Refereed)
    Abstract [en]

    Based on first-principle calculations, we have systematically explored the nature of the elastic stability and the delta-delta'-epsilon phase transitions in pure Pu at high temperature. It is found that, both the electronphonon coupling and the spin fluctuation effects tend to decrease the tetragonal elastic constant (C') of delta-Pu, accounting for its anomalous softening at high temperature. The lattice thermal expansion together with the electron-phonon coupling can stiffen C' of epsilon-Pu, promoting its mechanical stability at high temperature. The delta-epsilon transition is calculated to take place around 750-800 K, and is dominated by the phonon vibration. The delta' intermediate phase is realized around 750 K mainly because of the thermal spin fluctuation.

  • 242.
    Li, Hu
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Daukiya, Lakshya
    Institut de Sciences des Matériaux de Mulhouse.
    Haldar, Soumyajyoti
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Lindblad, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics.
    Sanyal, Biplab
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Eriksson, Olle
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Aubel, Dominique
    Institut de Sciences des Matériaux de Mulhouse.
    Hajjar-Garreau, Samar
    Institut de Sciences des Matériaux de Mulhouse.
    Simon, Laurent
    Institut de Sciences des Matériaux de Mulhouse.
    Leifer, Klaus
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Site-selective local fluorination of graphene induced by focused ion beam irradiation2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 19719Article in journal (Refereed)
    Abstract [en]

    The functionalization of graphene remains an important challenge for numerous applications expected by this fascinating material. To keep advantageous properties of graphene after modification or functionalization of its structure, local approaches are a promising road. A novel technique is reported here that allows precise site-selective fluorination of graphene. The basic idea of this approach consists in the local radicalization of graphene by focused ion beam (FIB) irradiation and simultaneous introduction of XeF2 gas. A systematic series of experiments were carried out to outline the relation between inserted defect creation and the fluorination process. Based on a subsequent X-ray photoelectron spectroscopy (XPS) analysis, a 6-fold increase of the fluorine concentration on graphene under simultaneous irradiation was observed when compared to fluorination under normal conditions. The fluorine atoms are predominately localized at the defects as indicated from scanning tunneling microscopy (STM). The experimental findings are confirmed by density functional theory which predicts a strong increase of the binding energy of fluorine atoms when bound to the defect sites. The developed technique allows for local fluorination of graphene without using resists and has potential to be a general enabler of site-selective functionalization of graphene using a wide range of gases.

  • 243.
    Li, Hui
    et al.
    Fudan Univ, Sch Informat Sci & Technol, State Key Lab ASIC & Syst, Shanghai 200433, Peoples R China..
    Wen, Chenyu
    Fudan Univ, Sch Informat Sci & Technol, State Key Lab ASIC & Syst, Shanghai 200433, Peoples R China..
    Zhang, Youwei
    Fudan Univ, Sch Informat Sci & Technol, State Key Lab ASIC & Syst, Shanghai 200433, Peoples R China..
    Wu, Dongping
    Fudan Univ, Sch Informat Sci & Technol, State Key Lab ASIC & Syst, Shanghai 200433, Peoples R China..
    Zhang, Shi-Li
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Qiu, Zhi-Jun
    Fudan Univ, Sch Informat Sci & Technol, State Key Lab ASIC & Syst, Shanghai 200433, Peoples R China..
    Accelerating Gas Adsorption on 3D Percolating Carbon Nanotubes2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 21313Article in journal (Refereed)
    Abstract [en]

    In the field of electronic gas sensing, low-dimensional semiconductors such as single-walled carbon nanotubes (SWCNTs) can offer high detection sensitivity owing to their unprecedentedly large surface-to-volume ratio. The sensitivity and responsivity can further improve by increasing their areal density. Here, an accelerated gas adsorption is demonstrated by exploiting volumetric effects via dispersion of SWCNTs into a percolating three-dimensional (3D) network in a semiconducting polymer. The resultant semiconducting composite film is evaluated as a sensing membrane in field effect transistor (FET) sensors. In order to attain reproducible characteristics of the FET sensors, a pulsed-gate-bias measurement technique is adopted to eliminate current hysteresis and drift of sensing baseline. The rate of gas adsorption follows the Langmuir-type isotherm as a function of gas concentration and scales with film thickness. This rate is up to 5 times higher in the composite than only with an SWCNT network in the transistor channel, which in turn results in a 7-fold shorter time constant of adsorption with the composite. The description of gas adsorption developed in the present work is generic for all semiconductors and the demonstrated composite with 3D percolating SWCNTs dispersed in functional polymer represents a promising new type of material for advanced gas sensors.

  • 244.
    Li, Xiaoqing
    et al.
    North Carolina State Univ, Dept Mat Sci & Engn, Raleigh, NC 27695 USA;Wigner Res Ctr Phys, Res Inst Solid State Phys & Opt, POB 49, H-1525 Budapest, Hungary;KTH Royal Inst Technol, Dept Mat Sci & Engn, S-10044 Stockholm, Sweden.
    Irving, Douglas L.
    North Carolina State Univ, Dept Mat Sci & Engn, Raleigh, NC 27695 USA.
    Vitos, Levente
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Wigner Res Ctr Phys, Res Inst Solid State Phys & Opt, POB 49, H-1525 Budapest, Hungary;KTH Royal Inst Technol, Dept Mat Sci & Engn, S-10044 Stockholm, Sweden.
    First-principles investigation of the micromechanical properties of fcc-hcp polymorphic high-entropy alloys2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 11196Article in journal (Refereed)
    Abstract [en]

    High-entropy alloys offer a promising alternative in several high-technology applications concerning functional, safety and health aspects. Many of these new alloys compete with traditional structural materials in terms of mechanical characteristics. Understanding and controlling their properties are of the outmost importance in order to find the best single-or multiphase solutions for specific uses. Here, we employ first-principles alloy theory to address the micro-mechanical properties of five polymorphic high-entropy alloys in their face-centered cubic (fcc) and hexagonal close-packed (hcp) phases. Using the calculated elastic parameters, we analyze the mechanical stability, elastic anisotropy, and reveal a strong correlation between the polycrystalline moduli and the average valence electron concentration. We investigate the ideal shear strength of two selected alloys under shear loading and show that the hcp phase possesses more than two times larger intrinsic strength than that of the fcc phase. The derived half-width of the dislocation core predicts a smaller Peierls barrier in the fcc phase confirming its increased ductility compared to the hcp one. The present theoretical findings explain a series of important observations made on dual-phase alloys and provide an atomic-level knowledge for an intelligent design of further high-entropy materials.

  • 245.
    Li, Xiaoqing
    et al.
    KTH Royal Inst Technol, Dept Mat Sci & Engn, S-10044 Stockholm, Sweden..
    Schonecker, Stephan
    KTH Royal Inst Technol, Dept Mat Sci & Engn, S-10044 Stockholm, Sweden..
    Simon, Eszter
    Budapest Univ Technol & Econ, Dept Theoret Phys, HU-1111 Budapest, Hungary..
    Bergqvist, Lars
    KTH Royal Inst Technol, Dept Mat & Nano Phys, SE-16440 Kista, Sweden..
    Zhang, Hualei
    KTH Royal Inst Technol, Dept Mat Sci & Engn, S-10044 Stockholm, Sweden.;Xi An Jiao Tong Univ, Frontier Inst Sci & Technol, Ctr Microstruct Sci, Xian 710054, Peoples R China..
    Szunyogh, Laszlo
    Budapest Univ Technol & Econ, Dept Theoret Phys, HU-1111 Budapest, Hungary.;MTA BME Condensed Matter Res Grp, HU-1111 Budapest, Hungary..
    Zhao, Jijun
    Dalian Univ Technol, Key Lab Mat Modificat Laser Ion & Electron Beams, Minist Educ, Dalian 116024, Peoples R China..
    Johansson, Börje
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Dept Mat Sci & Engn, S-10044 Stockholm, Sweden..
    Vitos, Levente
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Dept Mat Sci & Engn, S-10044 Stockholm, Sweden.;Wigner Res Ctr Phys, Res Inst Solid State Phys & Opt, HU-1525 Budapest, Hungary..
    Tensile strain-induced softening of iron at high temperature2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 16654Article in journal (Refereed)
    Abstract [en]

    In weakly ferromagnetic materials, already small changes in the atomic configuration triggered by temperature or chemistry can alter the magnetic interactions responsible for the non-random atomicspin orientation. Different magnetic states, in turn, can give rise to substantially different macroscopic properties. A classical example is iron, which exhibits a great variety of properties as one gradually removes the magnetic long-range order by raising the temperature towards its Curie point of T-C(degrees) = 1043 K. Using first-principles theory, here we demonstrate that uniaxial tensile strain can also destabilise the magnetic order in iron and eventually lead to a ferromagnetic to paramagnetic transition at temperatures far below T-C(degrees). In consequence, the intrinsic strength of the ideal single-crystal body-centred cubic iron dramatically weakens above a critical temperature of similar to 500 K. The discovered strain-induced magneto-mechanical softening provides a plausible atomic-level mechanism behind the observed drop of the measured strength of Fe whiskers around 300-500 K. Alloying additions which have the capability to partially restore the magnetic order in the strained Fe lattice, push the critical temperature for the strength-softening scenario towards the magnetic transition temperature of the undeformed lattice. This can result in a surprisingly large alloying-driven strengthening effect at high temperature as illustrated here in the case of Fe-Co alloy.

  • 246. Li, Xiaoqing
    et al.
    Tian, Fuyang
    Schonecker, Stephan
    Zhao, Jijun
    Vitos, Levente
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Ab initio-predicted micro-mechanical performance of refractory high-entropy alloys2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 12334Article in journal (Refereed)
    Abstract [en]

    Recently developed high-entropy alloys (HEAs) consisting of multiple principal elements represent a new field of metallurgy and have demonstrated appealing properties for a wide range of applications. Using ab initio alloy theory, we reveal the alloying effect on the elastic properties and the ideal tensile strength (ITS) in the [001] direction of four body-centered cubic (bcc) refractory HEAs based on Zr, V, Ti, Nb, and Hf. We find that these HEAs show high elastic anisotropy and large positive Cauchy pressure, suggesting good extrinsic ductility. Starting from ZrNbHf, it is found that the ITS decreases with equimolar Ti addition. On the other hand, if both Ti and V are added to ZrNbHf, the ITS is enhanced by about 42%. An even more captivating effect is the ITS increase by about 170%, if Ti and V are substituted for Hf. The alloying effect on the ITS is explained by the d-band filling. An intrinsic brittle-to-ductile transition is found in terms of the failure mode under uniaxial tension. These investigations suggest that intrinsically ductile HEAs with high ideal strength can be achieved by controlling the proportion of group four elements to group five elements.

  • 247.
    Li, Yan-Ling
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Luo, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Chen, Xiao-Jia
    Zeng, Zhi
    Lin, Hai-Qing
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Formation of Nanofoam carbon and re-emergence of Superconductivity in compressed CaC62013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 3331-Article in journal (Refereed)
    Abstract [en]

    Pressure can tune material's electronic properties and control its quantum state, making some systems present disconnected superconducting region as observed in iron chalcogenides and heavy fermion CeCu2Si2. For CaC6 superconductor (T-c of 11.5 K), applying pressure firstTc increases and then suppresses and the superconductivity of this compound is eventually disappeared at about 18 GPa. Here, we report a theoretical finding of the re-emergence of superconductivity in heavily compressed CaC6. The predicted phase III (space group Pmmn) with formation of carbon nanofoam is found to be stable at wide pressure range with a Tc up to 14.7 K at 78 GPa. Diamond-like carbon structure is adhered to the phase IV (Cmcm) for compressed CaC6 after 126 GPa, which has bad metallic behavior, indicating again departure from superconductivity. Re-emerged superconductivity in compressed CaC6 paves a new way to design new-type superconductor by inserting metal into nanoporous host lattice.

  • 248.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, BioVenture Hub, Mölndal, Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, BioVenture Hub, Mölndal, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Proof of principle study of a detailed whole-body image analysis technique, "Imiomics", regarding adipose and lean tissue distribution2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7388Article in journal (Refereed)
    Abstract [en]

    This "proof-of-principle" study evaluates if the recently presented "Imiomics" technique could visualize how fat and lean tissue mass are associated with local tissue volume and fat content at high/unprecedented resolution. A whole-body quantitative water-fat MRI scan was performed in 159 men and 167 women aged 50 in the population-based POEM study. Total fat and lean mass were measured by DXA. Fat content was measured by the water-fat MRI. Fat mass and distribution measures were associated to the detailed differences in tissue volume and fat concentration throughout the body using Imiomics. Fat mass was positively correlated (r > 0.50, p < 0.05) with tissue volume in all subcutaneous areas of the body, as well as volumes of the liver, intraperitoneal fat, retroperitoneal fat and perirenal fat, but negatively to lung volume. Fat mass correlated positively with volumes of paravertebral muscles, and muscles in the ventral part of the thigh and lower limb. Fat mass was distinctly correlated with the fat content in subcutaneous adipose tissue at the trunk. Lean mass was positively related to the large skeletal muscles and the skeleton. The present study indicates the Imiomics technique to be suitable for studies of fat and lean tissue distribution, and feasible for large scale studies.

  • 249. Lindgren, Johan
    et al.
    Sjovall, Peter
    Carney, Ryan M.
    Cincotta, Aude
    Uvdal, Per
    Hutcheson, Steven W.
    Gustafsson, Ola
    Lefevre, Ulysse
    Escuillie, Francois
    Heimdal, Jimmy
    Engdahl, Anders
    Gren, Johan A.
    Kear, Benjamin P.
    Uppsala University, Music and Museums, Museum of Evolution. Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Wakamatsu, Kazumasa
    Yans, Johan
    Godefroit, Pascal
    Molecular composition and ultrastructure of Jurassic paravian feathers2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 13520Article in journal (Refereed)
    Abstract [en]

    Feathers are amongst the most complex epidermal structures known, and they have a well-documented evolutionary trajectory across non-avian dinosaurs and basal birds. Moreover, melanosome-like microbodies preserved in association with fossil plumage have been used to reconstruct original colour, behaviour and physiology. However, these putative ancient melanosomes might alternatively represent microorganismal residues, a conflicting interpretation compounded by a lack of unambiguous chemical data. We therefore used sensitive molecular imaging, supported by multiple independent analytical tests, to demonstrate that the filamentous epidermal appendages in a new specimen of the Jurassic paravian Anchiornis comprise remnant eumelanosomes and fibril-like microstructures, preserved as endogenous eumelanin and authigenic calcium phosphate. These results provide novel insights into the early evolution of feathers at the sub-cellular level, and unequivocally determine that melanosomes can be preserved in fossil feathers.

  • 250.
    Lindh, E. Mattias
    et al.
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Lundberg, Petter
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Lanz, Thomas
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Mindemark, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry. Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Edman, Ludvig
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Publisher Correction: The Weak Microcavity as an Enabler for Bright and Fault-tolerant Light-emitting Electrochemical Cells2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8697Article in journal (Other academic)
2345678 201 - 250 of 471
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