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1.
  • Heimann, Mikael, 1951-, et al. (author)
  • Associative learning measured with ERP predicts deferred imitation using a strict observation only design in 14 to 15 month old children
  • 2013
  • In: Scandinavian Journal of Psychology. - : Wiley-Blackwell. - 0036-5564 .- 1467-9450. ; 54:1, s. 33-40
  • Journal article (peer-reviewed)abstract
    • Deferred imitation is an established procedure for behavioural measurement of early declarative-like memories in infancy and previous work has indicated a link between this type of memory and brain potentials in infants. The present study compared infants’ memory performance in this paradigm with electrophysiological indices of associative learning. Thirty children (mean age: 14.5 months) participated, of which 15 (9 boys) had acceptable ERP recordings that could be included in the final analysis. Deferred imitation was measured with an observation-only procedure using three actions and a 30 min delay. ERP was recorded with a High Density Net (128 electrodes) during associative learning. Change scores based on Nc, a middle latency component associated with attentional processes, predicted deferred imitation performance. Thus, associative learning measured with ERP predicts deferred imitation using a strict observation only design in 14 to15 month old children.
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2.
  • Heimann, Mikael, 1951-, et al. (author)
  • Behavioral and electrophysiological indices of learning in 14-month-old infants : Deferred imitation correlates with the Nc component
  • 2010
  • In: Developmental Psychobiology, Volume 52, Issue 7. - : Wiley. ; , s. 702-702
  • Conference paper (other academic/artistic)abstract
    •  Deferred imitation (DI) is an established memory paradigm that reflects early individual differences but the neural activity underlying DI is to a large extent uncharted. Thus, the present study investigated the relationship between event-related potentials (ERP) and behavioral (DI) indices of learning.Thirty 14-months-old children participated in the study, of which 15 (9 boys) had acceptable ERP data to be included in the analysis. DI was measured with the observation-only design using three actions and a 30 min delay. ERP was recorded with a High Density Net (128 electrodes) and the learning phase consisted of two pairs of pictures presented six times (PRES 1, 2, 3, 4, 5, and 6) while the test phase consisted of two violations: Associating two familiar pictures in a new combination (ASSO) or associating one familiar picture with a novel picture (NOV).The mean score of DI was 1.87 (SD = 1.06) and ERP data revealed an Nc within 300-600 ms post stimuli. The mean amplitude was higher for ASSO compared with PRES 5 and 6 (p < .05) but not between NOV and PRES 5 (p = .055) and PRES 6 (ns). Larger Nc change scores (ASSO - PRES5) correlated with better DI performance, rs (15) = .57; p < .05.These findings, if upheld in further analyses, suggest that behavioral memory performance is related to attention processes as reflected in the observed Nc. (FUNDING: Swedish Council for Working Life and Social Research # 2006-1040)
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4.
  • Nordqvist, Emelie, et al. (author)
  • An associative learning procedure measured by Event-Related Potentials correlates with event memory in 14 month old children
  • 2011
  • Conference paper (peer-reviewed)abstract
    • Deferred imitation (DI) reflects an early form of event memory but the underlying neural processes is to a large degree unknown. Thus, the present study examines how associative learning observed through event-related potentials (ERP) relates to DI as measured with an observation- only design.Thirty children participated in the study and acceptable ERP data was collected from 15 (9 boys). DI was measured with a thirty minutes delay and ERP was recorded with a Geodesic High Density Net with 128 electrodes. The ERP procedure consisted of two pairs of pictures presented six times (= the learning phase) and a test phase introducing two violations: Two familiar pictures in a new combination (ASSO) or a combination of one familiar and one novel picture (NOV). In addition, visual recognition memory was also measured.ERP revealed an Nc within 300-600 ms post stimuli. A higher mean amplitude was observed for ASSO (p < .05) and a marginal effect was noted for NOV (p = .055). Better DI performance correlated with larger Nc change scores between ASSO and the last presentation in the learning phase (rs (15) = .57; p < .05). Preliminary analyses of slow waves revealed no further relationship between ERP and DI and no significant correlation between DI and novelty preference. These findings indicate that electrophysiological indices of associative learning can be related to behavioral observations of early memory processes in young infants. 
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6.
  • Nordqvist, Emelie, et al. (author)
  • An electrophysiological index of associative learning correlates with event memories in 14 month old children
  • 2011
  • Conference paper (other academic/artistic)abstract
    • Deferred imitation (DI) is an early form of event memory that indexes early individual differences in infant cognition but the underlying neural processes is to a large degree uncharted. The present study examines how event-related potentials (ERPs) as a response to an associative learning procedure relates to DI measured with an observation-only design. Thirty children participated and acceptable ERP data was collected from 15 (9 boys).  DI was measured with a thirty minutes delay and ERP was recorded with a Geodesic High Density Net with 128 electrodes. The ERP procedure consisted of two pairs of pictures presented six times (= the learning phase) and a test phase introducing two violations: Two familiar pictures in a new combination (ASSO) or a combination of one familiar and one novel picture (NOV). In addition, visual recognition memory was also measured. ERP revealed an Nc within 300-600 ms post stimuli. A higher mean amplitude was observed for ASSO (p < .05) and a marginal effect was noted for NOV (p = .055). Better DI performance correlated with larger Nc change scores between ASSO and the last presentation in the learning phase (rs (15) = .57; p < .05). Preliminary analyses of early and late slow waves (800 to 1500ms post stimuli) revealed no further relationship between ERP and DI and no significant correlation between DI and visual recognition memory. This finding indicates a possible direct link between electrophysiological indices of learning and behavioral observations of declarative like memory processes in young infants.
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7.
  • Andersson, C David, et al. (author)
  • Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
  • 2012
  • In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
  • Journal article (peer-reviewed)abstract
    • The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
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8.
  • Arja, Katriann, et al. (author)
  • Enhanced Fluorescent Assignment of Protein Aggregates by an Oligothiophene-Porphyrin-Based Amyloid Ligand
  • 2013
  • In: Macromolecular rapid communications. - : Wiley-VCH Verlag. - 1022-1336 .- 1521-3927. ; 34:9, s. 723-730
  • Journal article (peer-reviewed)abstract
    • Fluorescent probes identifying protein aggregates are of great interest, as deposition of aggregated proteins is associated with many devastating diseases. Here, we report that a fluorescent amyloid ligand composed of two distinct molecular moieties, an amyloidophilic pentameric oligothiophene and a porphyrin, can be utilized for spectral and lifetime imaging assessment of recombinant A 1-42 amyloid fibrils and A deposits in brain tissue sections from a transgenic mouse model with Alzheimers disease pathology. The enhanced spectral range and distinct lifetime diversity of this novel oligothiopheneporphyrin-based ligand allow a more precise assessment of heterogeneous amyloid morphology compared with the corresponding oligothiophene dye.
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9.
  • Berg, Kirsti, et al. (author)
  • A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies
  • 2014
  • In: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 9:3, s. e90964-
  • Journal article (peer-reviewed)abstract
    • Objective: An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies. Materials and Methods: Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CPN) with known spin concentration. Results: The absolute spin concentration could be quantified with a precision and accuracy better than +/- 10 mu M (k = 1). The spin concentration of samples stored at -80 degrees C could be reproduced after 6 months of storage well within the same error estimate. Conclusion: The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time.
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10.
  • Carlsson, Karin, et al. (author)
  • Effects on the conformation of FVIIa by sTF and Ca(2+) binding : Studies of fluorescence resonance energy transfer and quenching
  • 2011
  • In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 413:4, s. 545-549
  • Journal article (peer-reviewed)abstract
    • The apparent length of FVIIa in buffer solution was estimated by a FRET analysis. Two fluorescent probes, fluorescein linked to an inhibitor (FPR-chloromethyl ketone) and a rhodamine derivative (tetramethylrhodamine-5-maleimide), were covalently attached to FVIIa. The binding site of fluorescein was in the PD whereas rhodamine was positioned in the Gla domain, thus allowing a length measure over approximately the whole extension of the protein. From the FRET measurements the distances between the two probes were determined to 61.4 for free FVIIa and 65.5 Å for FVIIa bound to the soluble TF (sTF). Thus, the apparent distance from the FRET analysis was shown to increase with 4 Å upon formation of a complex with sTF in solution. However, by considering how protein dynamics, based on recently published molecular dynamics simulations of FVIIa and sTF:FVIIa (Ohkubo et al., 2010 J. Thromb. Haemost. 8, 1044-1053), can influence the apparent  fluorescence signal our calculations indicated that the global average conformation of active-site inhibited FVIIa is nearly unaltered upon ligation to sTF. Moreover, it is known that Ca2+ binding leads to activation of FVIIa, and we have for the first time demonstrated conformational changes in the environment of the active site upon Ca2+ binding by direct measurements, previously suggested based on indirect measurements (Persson & Petersen, 1995 Eur. J. Biochem. 234, 293-300). Interestingly, this Ca2+-induced conformational change can be noted even in the presence of an inhibitor. By forming the sTF:FVIIa complex the conformational change of the active site is further developed, leading to a more inaccessible active-site located probe.
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11.
  • Chateau, Denis, et al. (author)
  • Silica hybrid sol-gel materials with unusually high concentration of Pt-organic molecular guests : Studies of luminescence and nonlinear absorption of light
  • 2012
  • In: ACS Applied Materials and Interfaces. - Washington : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 4:5, s. 2369-2377
  • Journal article (peer-reviewed)abstract
    • The development of new photonic materials is a key step towards improvement of existing optical devices and for the preparation of a new generation of systems. Therefore synthesis of photonic hybrid materials with a thorough understanding and control of the microstructure-to-properties relationships is crucial. In this perspective, a new preparation method based on fast gelation reactions using simple dispersion of dyes without strong covalent bonding between dye and matrix has been developed. This new sol-gel method is demonstrated through synthesis of monolithic siloxane-based hybrid materials highly doped by various platinum(II) acetylide derivatives. Concentrations of the chromophores as high as 400 mM were obtained and resulted in unprecedented optical power limiting (OPL) performance at 532 nm of the surface-polished solids. Static and time-resolved photoluminescence of the prepared hybrid materials were consistent with both OPL data and previous studies of similar Pt(II) compounds in solution. The impacts of the microstructure and the chemical composition of the matrix on the spectroscopic properties, are discussed.
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12.
  • Domeij, Martin, et al. (author)
  • 2.2 kV SiC BJTs with low V(CESAT) fast switching and short-circuit capability
  • 2010
  • In: SILICON CARBIDE AND RELATED MATERIALS 2009, PTS 1 AND 2. ; , s. 1033-1036
  • Conference paper (peer-reviewed)abstract
    • This paper reports large active area (15 mm(2)) 4H-SiC BJTS with a low V(CESAT)=0.6 V at 1(C)=20 A (J(C)=133 A/cm(2)) and an open-base breakdown voltage BV(CEO)=2.3 kV at T=25 degrees C. The corresponding room temperature specific on-resistance R(SP.ON)=4.5 m Omega cm(2) is to the authors knowledge the lowest reported value for a large area SiC BJT blocking more than 2 kV. The onstate and blocking characteristics were analyzed by device simulation and found to be in good agreement with measurements. Fast switching with VcE rise- and fall-times in the range of 20-30 ns was demonstrated for a 6 A 1200 V rated SiC BJT. It was concluded that high dynamic base currents are essential for fast switching to charge the BJT parasitic base-collector capacitance. In addition, 10 mu s short-circuit capability with V(CE)=800 V was shown for the 1200 V BJT.
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13.
  • Einarsson, Elisabeth, et al. (author)
  • Mosasaur bite marks on a plesiosaur propodial from the Campanian (Late Cretaceous) of southern Sweden
  • 2010
  • In: GFF. - : Informa UK Limited. - 1103-5897 .- 2000-0863. ; 132:2, s. 123-128
  • Journal article (peer-reviewed)abstract
    • Although plesiosaurs and mosasaurs co-existed for about 35 million years at the end of the Cretaceous, the fossil record documenting interactions between these two groups of marine reptiles is meagre. The discovery of deeply incised scars on a limb bone of an immature polycotylid plesiosaur from the latest early Campanian (in the European two-fold division of the Campanian Stage) of the Kristianstad Basin, southern Sweden, is thus significant because it represents a rare example of predation or scavenging on an immature polycotylid plesiosaur by a large mosasaur.
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14.
  • Ellingsen, Pal Gunnar, et al. (author)
  • Spectral correlation analysis of Amyloid beta plaque inhomogeneity from double staining experiments
  • 2013
  • In: Journal of Biomedical Optics. - : Society of Photo-optical Instrumentation Engineers (SPIE). - 1083-3668 .- 1560-2281. ; 18:10
  • Journal article (peer-reviewed)abstract
    • A spectral correlation algorithm for the analysis of hyperspectral fluorescence images is proposed by Ellingsen et al. [J. Biomed. Opt. 18, 020501 (2013)]. Here, it is applied to the analysis of double-stained A beta amyloid plaques being related to the Alzheimers disease (AD). Sections of APP/PS1 AD mice model brains are double stained with luminescent-conjugated oligothiophenes, known to bind to amyloid protein deposits. Hyperspectral fluorescence images of the brain sections are recorded and by applying the correlation algorithm the spectral inhomogeneity of the double-stained samples is mapped in terms of radial distribution and spectral content. To further investigate the progression of A beta amyloid plaque formation, 19 AD mice of different ages up to 23 months are characterized, enabling a statistical analysis of the plaque heterogeneity. In accordance with recent findings by Nystrom et al. [ACS Chem. Biol. 8, 1128-1133 (2013)], the spectral distribution within A beta plaques is found to vary with age throughout the lifespan of the mouse. With the new correlation algorithm, it is possible to quantify the spectral abundance of the two stains depending on the relative distance from the plaque center and mouse age. Thus, we demonstrate the use of the correlation analysis approach in double-staining experiments and how it is possible to relate these to structural/spectral changes in biological samples. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
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16.
  • Eriksson, Mikael, et al. (author)
  • The MAX IV Synchrotron Light Source
  • 2011
  • In: [Host publication title missing]. - 9789290833666 ; , s. 3026-3028
  • Conference paper (peer-reviewed)abstract
    • The MAX IV synchrotron radiation facility is currently being constructed in Lund, Sweden. It consists of a 3 GeV linac injector and 2 storage rings operated at 1.5 and 3 GeV respectively. The linac injector will also be used for the generation of short X-ray pulses. The three machines mentioned above are described with some emphasis on the effort to create a very small emittance in the 3 GeV ring. Some unconventional technical solutions will also be presented.
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17.
  • Glimsdal, Eirik, et al. (author)
  • Luminescence, singlet oxygen production, and optical power limiting of some diacetylide platinum(II) diphosphine complexes
  • 2010
  • In: Journal of Physical Chemistry A. - : ACS Publications. - 1089-5639 .- 1520-5215. ; 114:10, s. 3431-3442
  • Journal article (peer-reviewed)abstract
    • A series of four new trans-diphosphine Pt(II) diacetylide complexes, with a thiophene and two benzenoid rings in each acetylide ligand, have been synthesized and characterized with respect to optical absorption, spectrally and time-resolved luminescence, and optically nonlinear properties such as two-photon absorption cross section and optical power limiting. Density functional theory (DFT) calculations of a few ground state conformations of three Pt(II) diacetylide structures showed similar total energy for each geometry-optimized rotamer but some differences in the vertical excitation energies and in the ligand-to-metal charge-transfer character. The wavelengths of the calculated excitations were found to be red-shifted compared with peaks in the optical absorption spectra, but the general trends and shifts of wavelengths between the different structures are well reproduced. Static emission spectra for degassed samples in THF solution of the larger compounds showed small Stokes shifts and low fluorescence quantum yields, indicating fast intersystem crossing to the triplet manifold. More pronounced differences between the compounds were displayed in the phosphorescence data, in terms of spectral emission wavelengths and decay times. For instance, the phosphorescence decay of the compound with the thiophene ring close to the Pt center was found to be significantly faster than for the other compounds. A possible relationship between triplet lifetime and conformation of the compounds is discussed. It was also demonstrated that the quenching of the excited triplet states in air-saturated samples involves energy transfer to the oxygen triplet state, and subsequent generation of singlet oxygen showing the typical emission at approximately 1275 nm. The amount of produced singlet oxygen followed the phosphorescence yields of the solute molecules. Two-photon absorption cross sections (sigma(2)) were measured and showed values on the order of 10 GM at 780 nm for all compounds. Optical power limiting measurements of the new complexes in THF using 5 ns pulses, showed only slightly better performance at the wavelength of 532 nm compared to that of similar platinum compounds with only two aryl rings in each ligand. At 600 nm the complexes with three aryl rings were significantly better optical limiters than the smaller compounds with two aryl rings in the ligands.
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  • Gustafsson, Håkan, et al. (author)
  • Fe(III) distribution varies substantially within and between atherosclerotic plaques
  • 2014
  • In: Magnetic Resonance in Medicine. - United States : John Wiley & Sons. - 0740-3194 .- 1522-2594. ; 2:71, s. 885-892
  • Journal article (peer-reviewed)abstract
    • PURPOSE:Vulnerable atherosclerotic plaques are structurally weak and prone to rupture, presumably due to local oxidative stress. Redox active iron is linked to oxidative stress and the aim of this study was to investigate the distribution of Fe(III) in carotid plaques and its relation to vulnerability for rupture.METHODS:Atherosclerotic plaques from 10 patients (three asymptomatic and seven symptomatic) were investigated. Plaque vulnerability was classified using ultrasound and immunohistochemistry and correlated to Fe(III) measured by electron paramagnetic resonance spectroscopy.RESULTS:Large intra-plaque Fe(III) variations were found. Plaques from symptomatic patients had a higher Fe(III) concentration as compared with asymptomatic plaques (0.36 ± 0.21 vs. 0.06 ± 0.04 nmol Fe(III)/mg tissue, P < 0.05, in sections adjoining narrowest part of the plaques). All but one plaque from symptomatic patients showed signs of cap rupture. No plaque from asymptomatic patients showed signs of cap rupture. There was a significant increase in cap macrophages in plaques from symptomatic patients compared with asymptomatic patients (31 ± 11% vs. 2.3 ± 2.3%, P < 0.01).CONCLUSION:Fe(III) distribution varies substantially within atherosclerotic plaques. Plaques from symptomatic patients had significantly higher concentrations of Fe(III), signs of cap rupture and increased cap macrophage activity.
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20.
  • Gustavsson, Mikael, 1983, et al. (author)
  • Estimation of Maximum Loss - A comparison study
  • 2010
  • In: SHO2010: INTERNATIONAL SYMPOSIUM ON OCCUPATIONAL SAFETY AND HYGIENE. - 9789729950469 ; , s. 280-284
  • Conference paper (other academic/artistic)abstract
    • Petroleum refineries are at risk due to the flammability of both the raw material and the products. In addition to the threat to the working force there is also an apparent economical risk associated with the processing of flammable compounds. This economical risk is not only due to the direct impact of a fire or explosion but also includes the cost of business interruption in case of a shutdown due to an accident. As with any situation that involves economical risks refineries may share their risk with insurers. The premium is then based on the size of the financial risk. Thus a decision has to be made by the operator how to share the risk of economical losses with insurance companies at a fair price. However, the decision process is not easy and it generally includes modelling of various scenarios to determine to which extent the process area can be damaged if, for example, a pipe rupture occurs. On the extreme end of modelling the so called Estimated Maximum Loss (EML) scenarios are found. These scenarios try to predict the maximum loss a particular installation can sustain due to an accident. Unfortunately a standard model for estimation of maximum loss does not exist. It means that brokers reach different results on the same scenario due to applying different models and different assumptions. Thus an operator may face uncertainty during the decision process. Hence improvements should be made not only to the models used but also to the concept of EML itself. Therefore, a study has been conducted on a case "Preem Refinery" where several scenarios previously had been modelled by two different brokers using two different softwares, ExTool and SLAM. The aim of this paper is to review the concept of EML and to analyse the used models to see which parameters that influenced the results. The results of the study show that: Overpressure damage threshold values, cloud weights, and releasable inventory are the main sources of deviation in the modelled scenarios; Clear cut-off values for the probabilities of an accident should be used to avoid the "not plausible" argument sometimes heard. As for improving the models themselves, no clear reason for working with threshold values when it comes to overpressure damage can be found. A continuous curve seems more fitting in the age of computers. The possibility to shift such a curve to account for the difference in overpressure sustainability between different types of process equipment could also be explored; and, there are many aspects to investigate further in order to make potential loss predictions more reliable, and this should be well worthwhile since a lot of money is at stake when plant owners and insurers decide on insurance limits and premiums.
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21.
  • Gustavsson, Mikael, 1983, et al. (author)
  • Evaluating EML Modeling Tools for Insurance Purposes: A Case Study
  • 2010
  • In: International Journal of Chemical Engineering. - : Hindawi Limited. - 1687-806X .- 1687-8078. ; 2010:Article ID 104370
  • Journal article (peer-reviewed)abstract
    • As with any situation that involves economical risk refineries may share their risk with insurers. The decision process generally includes modelling to determine to which extent the process area can be damaged. On the extreme end of modelling the so-called Estimated Maximum Loss (EML) scenarios are found. These scenarios predict the maximum loss a particular installation can sustain. Unfortunately no standard model for this exists. Thus the insurers reach different results due to applying different models and different assumptions. Therefore, a study has been conducted on a case in a Swedish refinery where several scenarios previously had been modelled by two different insurance brokers using two different softwares, ExTool and SLAM. This study reviews the concept of EML and analyses the used models to see which parameters are most uncertain. Also a third model, EFFECTS, was employed in an attempt to reach a conclusion with higher reliability.
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25.
  • Karlsson, Magnus, 1972-, et al. (author)
  • Indications of Recovery from Hypoxia in the Inner Stockholm Archipelago
  • 2010
  • In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 39:7, s. 486-495
  • Journal article (peer-reviewed)abstract
    • Improved benthic conditions compared to the 1990s were found during benthic investigations, including sediment and benthic macrofauna in the inner Stockholm archipelago during 2008. In the 1990s, these areas were dominated by black and laminated surface sediments and very sparse fauna. A clear relationship was found when comparing sediment status with the benthic macrofauna. Reduced surface sediment and impoverished macroinvertebrate community was only found at one sampling station representing an enclosed part of the inner archipelago, whereas the other seven stations, with depths ranging from 20 to 50 m, had oxidized surface sediments and considerable biomasses of benthic macrofauna (6-65 g m(-2)) dominated by the invading polychaete Marenzelleria neglecta. An extrapolation of the results shows that, within the investigated area, the coverage of reduced surface sediments had decreased from approximately 17% in the late 1990s to 4% in 2008.
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26.
  • Karlsson, Magnus, et al. (author)
  • Modellering av fosforomsättningen i Östhammarsfjärden. Simulering av åtgärder mot internbelastning
  • 2011
  • Reports (other academic/artistic)abstract
    • Effekten av att kemiskt behandla sedimenten i Östhammarsfjärden för att minska läckaget av fosfor från sedimenten har undersökts med hjälp av en massbalansmodell. Resultaten från simuleringarna visar att en fullskalig behandling av sedimenten sannolikt skulle ge en betydande minskning av fosforkoncentrationen i vattnet och därtill kopplad primärproduktion. Samtidigt kan det konstateras att det finns osäkerheter i bedömningen relaterat till mätosäkerheter i det empiriska underlaget och antaganden i modellen. Östhammarsfjärden och intilliggande Granfjärden har extremt höga halter av fosfor och klorofyll i vattenmassan trots att den landbaserade tillförseln inte är anmärkningsvärt hög.  En orsak till detta är den långsamma vattenomsättningen till följd av fjärdarnas avsnördhet. En annan trolig orsak är ett betydande utbyte av fosfor mellan vatten och sediment under vissa delar av året.
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27.
  • Kindahl, Tomas, et al. (author)
  • Photophysical and DFT Characterization of Novel Pt(II)-Coupled 2,5-Diaryloxazoles for Nonlinear Optical Absorption
  • 2012
  • In: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 116:47, s. 11519-11530
  • Journal article (peer-reviewed)abstract
    • Several new bis-phosphine platinum(II) complexes with 2,5-diaryl-substituted oxazole-containing alkyne ligands have been synthesized and optically characterized in solution. Measurements of nonlinear absorption showed strong attenuation of laser light at 532 and 600 nm. The light absorption of the Pt complexes was shifted from the near-UV region for the ground state to the red region for the excited triplet state, and was associated with large extinction coefficients. The optical limiting effect can be explained by triplet-triplet excited state absorption in conjunction with fast excited singlet to-triplet intersystem crossing and slow triplet to-ground-state decay, in comparison with the pulse length of the laser. DFT calculations show good predictability of the S-0-S-1 and S-0-T-1 energy gaps and offer insight into the interaction strength between Pt and the alkyne ligands. The use of this type of ligand, with weak absorption for the Pt(II) complexes in the visual wavelength range as a key feature, enables the possibility to further improve these molecular systems for nonlinear absorption applications.
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29.
  • Leemann, Simon, et al. (author)
  • Status of the MAX IV Storage Rings
  • 2010
  • In: Proceedings of IPAC’10. - 9789290833529 ; , s. 2618-2620
  • Conference paper (peer-reviewed)abstract
    • In 2009 the MAX IV facility was granted funding by Swedish authorities. Construction of the facility will begin this summer and user operation is expected by 2015. MAX IV will consist of a 3.4 GeV linac as a driver for a short-pulse radiation facility (with planned upgrade to a seeded/cascaded FEL) as well as an injector for two storage rings at different energies serving user communities in separate spectral ranges. Thanks to a novel compact multibend-achromat design, the 3 GeV ring will deliver a 500 mA electron beam with a horizontal emittance below 0.3 nmrad to x-ray insertion devices located in 19 dispersion-free 5 m straight sections. When the 3 GeV ring goes into operation in 2015 it is expected to become the highest electron-brightness storage ring light source world-wide. The 1.5 GeV ring will serve as a replacement for both present-day MAX II and MAX III storage rings. Its below 6 nm rad horizontal emittance electron beam will be delivered to IR and UV insertion devices in twelve 3.5 m straight sections. We report on design progress for the two new storage rings of the MAX IV facility.
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30.
  • Lim, Elaine T, et al. (author)
  • Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population.
  • 2014
  • In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:7
  • Journal article (peer-reviewed)abstract
    • Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10-8) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10-117). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10-4), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.
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31.
  • Lindgren, Anders E. G., et al. (author)
  • Chemical Probes to Study ADP-Ribosylation : Synthesis and Biochemical Evaluation of Inhibitors of the Human ADP-Ribosyltransferase ARTD3/PARP3
  • 2013
  • In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:23, s. 9556-9568
  • Journal article (peer-reviewed)abstract
    • The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of SS compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that substituents on the phenyl ring resulted in poor solubility. Certain variations at the meso position were tolerated and caused a large shift in the binding pose. Changes to the ethylene linker that connects the quinazolinone to the amide were also investigated but proved detrimental to binding. By combination of synthetic organic chemistry and structure-based design, two selective inhibitors of ARTD3 were discovered.
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32.
  • Lindgren, Anders E. G., et al. (author)
  • PARP Inhibitor with Selectivity Toward ADP-Ribosyltransferase ARTD3/PARP3
  • 2013
  • In: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 8:8, s. 1698-1703
  • Journal article (peer-reviewed)abstract
    • Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12, members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.
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33.
  • Lindgren, Lars-Erik, et al. (author)
  • Simulation of hydroforming of steel tube made of metastable stainless steel
  • 2010
  • In: International journal of plasticity. - : Elsevier BV. - 0749-6419 .- 1879-2154. ; 26:11, s. 1576-1590
  • Journal article (peer-reviewed)abstract
    • The Olson-Cohen model for strain induced deformation, further developed by Stringfellow and others, has been calibrated together with a flow stress model for the plastic deformation of metastable stainless steel. Special validation tests for checking one of the limitations of the model have also been carried out. The model has been implemented into a commercial finite element code using a staggered approach for integrating the stress-strain relations with the microstructure model. Results from a thermo-mechanical coupled simulation of hydroforming of a tube have been compared with corresponding experiments. The agreement between experimental results of radial expansion and martensite fraction and the corresponding computed results is good.
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34.
  • Lindgren, Mikael, et al. (author)
  • Amyloid oligomers: spectroscopic characterization of amyloidogenic protein states
  • 2010
  • In: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 277:6, s. 1380-1388
  • Research review (peer-reviewed)abstract
    • It is assumed that protein fibrils manifested in amyloidosis result from an aggregation reaction involving small misfolded protein sequences being in an oligomeric or prefibrillar state. This review covers recent optical spectroscopic studies of amyloid protein misfolding, oligomerization and amyloid fibril growth. Although amyloid fibrils have been studied using established protein-characterization techniques throughout the years, their oligomeric precursor states require sensitive detection in real-time. Here, fluorescent staining is commonly performed using thioflavin T and other small fluorescent molecules such as 4-(dicyanovinyl)- julolidine and 1-amino-8-naphtalene sulphonate that have high affinity to hydrophobic patches. Thus, populated oligomeric intermediates and related prefibrillar structures have been reported for several human amyloidogenic systems, including amyloid-beta protein, prion protein, transthyretin, alpha-synuclein, apolipoprotein C-II and insulin. To obtain information on the progression of the intermediate states, these were monitored in terms of fluorescence parameters, such as anisotropy, and quantum efficiency changes upon protein binding. Recently, new antibody stains have allowed precise monitoring of the oligomer size and distributions using multicolor labelling and single molecule detection. Moreover, a pentameric thiophene derivative (p-FTAA) was reported to indicate early precursors during A-beta(1-40) fibrillation, and was also demonstrated in real-time visualization of cerebral protein aggregates in transgenic AD mouse models by multiphoton microscopy. Conclusively, molecular probes and optical spectroscopy are now entering a phase enabling the in vivo interrogation of the role of oligomers in amyloidosis. Such techniques used in parallel with in vitro experiments, of increasing detail, will probably couple structure to pathogenesis in the near future.
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35.
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36.
  • Malmaeus, Mikael, et al. (author)
  • Estimating the amount of mobile phosphorus in Baltic coastal soft sediments of central Sweden
  • 2012
  • In: Boreal environment research. - 1239-6095 .- 1797-2469. ; 17:6, s. 425-436
  • Journal article (peer-reviewed)abstract
    • A new dataset based on 102 sediment cores was examined to estimate the amount of phosphorus (P) that will eventually be released to the water column from the Baltic coastal sediments along the Swedish coast between Öregrund and Oxelösund. Total P (P tot) concentration in the surface sediments varied between 840 and 7100 μg g -1 dry weight (dw) with an average of 1650 μg g -1 dw. In deep sediments, the P tot concentration was around 1000 μg g -1 with small variation. The difference between surface concentration and the stable, deeper, concentration represents P to be released, i.e. the mobile P. Pools of mobile P varied between 1.5 and 18.2 g m -2. Correlations between surface P tot concentrations and amounts of mobile P were strong (r 2 = 0.88). We estimate the amount of mobile P in the coastal sediments of the investigated region to be between 1000 and 4000 tonnes. Assuming a turnover time of the mobile P between three and ten years gives an average annual P release of 100-1300 tonnes yr -1.
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37.
  • Maria Psonka-Antonczyk, Katarzyna, et al. (author)
  • Nanoscopic and Photonic Ultrastructural Characterization of Two Distinct Insulin Amyloid States
  • 2012
  • In: International Journal of Molecular Sciences. - : MDPI AG, POSTFACH, CH-4005 BASEL, SWITZERLAND. - 1661-6596 .- 1422-0067. ; 13:2, s. 1461-1480
  • Journal article (peer-reviewed)abstract
    • Two different conformational isoforms or amyloid strains of insulin with different cytotoxic capacity have been described previously. Herein these filamentous and fibrillar amyloid states of insulin were investigated using biophysical and spectroscopic techniques in combination with luminescent conjugated oligothiophenes (LCO). This new class of fluorescent probes has a well defined molecular structure with a distinct number of thiophene units that can adopt different dihedral angles depending on its binding site to an amyloid structure. Based on data from surface charge, hydrophobicity, fluorescence spectroscopy and imaging, along with atomic force microscopy (AFM), we deduce the ultrastructure and fluorescent properties of LCO stained insulin fibrils and filaments. Combined total internal reflection fluorescence microscopy (TIRFM) and AFM revealed rigid linear fibrous assemblies of fibrils whereas filaments showed a short curvilinear morphology which assemble into cloudy deposits. All studied LCOs bound to the filaments afforded more blue-shifted excitation and emission spectra in contrast to those corresponding to the fibril indicating a different LCO binding site, which was also supported by less efficient hydrophobic probe binding. Taken together, the multi-tool approach used here indicates the power of ultrastructure identification applying AFM together with LCO fluorescence interrogation, including TIRFM, to resolve structural differences between amyloid states.
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38.
  • Marwaha, Sania, et al. (author)
  • N-acylated derivatives of sulfamethoxazole and sulfafurazole inhibit intracellular growth of Chlamydia trachomatis
  • 2014
  • In: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 58:5, s. 2968-2971
  • Journal article (peer-reviewed)abstract
    • Antibacterial compounds with novel modes of action are needed for management of bacterial infections. Here we describe a high-content screen of 9,800 compounds identifying acylated sulfonamides as novel growth inhibitors of the sexually transmitted pathogen Chlamydia trachomatis. The effect was bactericidal and distinct from that of sulfonamide antibiotics, as para-aminobenzoic acid did not reduce efficacy. Chemical inhibitors play an important role in Chlamydia research as probes of potential targets and as drug development starting points.
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39.
  • Mubeen, Saad (author)
  • Modeling and Timing Analysis of Industrial Component-Based Distributed Real-time Embedded Systems
  • 2012
  • Licentiate thesis (other academic/artistic)abstract
    • The model- and component-based development approach has emerged as an attractive option for the development of Distributed Real-time Embedded (DRE) systems. In this thesis we target several issues such as modeling of legacy communication, extraction of end-to-end timing models and support for holistic response-time analysis of industrial component-based DRE systems.We introduce a new approach for modeling legacy network communication in component-based DRE systems. By introducing special-purpose components to encapsulate and abstract the communication protocols in DRE systems, we allow the use of legacy nodes and legacy protocols in a component- and model-based software engineering environment. The proposed approach also supports the state-of-the-practice development of component-based DRE systems.The Controller Area Network (CAN) is one of the widely used real-time networks in DRE systems especially in automotive domain. We identify that the existing analysis of CAN does not support common message transmission patterns which are implemented by some high-level protocols used in the industry. Consequently, we extend the existing analysis to facilitate the worst-case response-time computation of these transmission patterns. The extended analysis is generally applicable to any high-level protocol for CAN that uses periodic, sporadic, or both periodic and sporadic transmission of messages.Because an end-to-end timing model should be available to perform the holistic response-time analysis, we present a method to extract the end-to-end timing models from component-based DRE systems. In order to show the applicability of our modeling techniques and extended analysis, we provide a proof of concept by extending the existing industrial component model (Rubus Component Model), implementing the holistic response-time analysis along with the extended analysis of CAN in the industrial tool suite (Rubus-ICE), and conducting an automotive case study.
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40.
  • Mårtensson, Frida, et al. (author)
  • Abstract, concrete and emotional words in the mental lexicon : A coding scheme for analyzing verbal descriptions of word meanings
  • 2011
  • In: The Third Conference of the Scandinavian Association for Language and Cognition, SALC III. - Copenhagen : University of Copenhagen. ; , s. 86-87
  • Conference paper (peer-reviewed)abstract
    • Previous research has suggested that abstract and concrete semantics are processed and conceptualized differently (Pulvermüller 1999, Crutch & Warrington 2005; Fuster 2009). Specifically, concrete semantics is assumed to be processed by posterior, sensory brain areas, as opposed to an anterior processing of abstract semantic information. In addition, other researchers raise the question whether emotional words should be included in the abstract category (Altarriba & Bauer 2004, Kousta et al. 2009).Following this, the present study proposes a method for analyzing spontaneous discourse produced by aphasic and healthy subjects describing the meanings of abstract, concrete, and emotional words. Linguistic data related to word meanings were obtained by asking subjects to describe the meanings of nouns varying in concreteness and emotional arousal freely and as detailed as possible, a method based on Barsalou & Wiemer-Hastings (2005). Subjects with anterior/posterior lesions and healthy controls were hypothesized to differ in their retrieval and verbalization of semantic information related to the cue words, with posterior lesions affecting concrete semantic features and anterior lesions affecting higher levels of abstraction and structuring of information. Emotional information, partly processed by subcortical structures, was expected to be well-preserved despite cortical lesions.A coding scheme was developed in order to capture semantic and structural information in the transcribed material, taking the following factors into account:Type of information in an utterance: general/personal:episodic/personal:evaluative/procedural cuesClauses: main/subordinateRelation between produced content word and cue word: contextual/ property-basedSemantic information of produced content words: abstract/ concrete/emotionalWhether the topic is maintainedWhether the information is semantically acceptableThe proposed coding scheme makes it possible to investigate how different brain lesions affect retrieval and expression of semantic information with differing degrees of abstractness.Altarriba, J. & Bauer, L.M. (2004). The distinctiveness of emotion concepts: A comparison between emotion, abstract, and concrete words. The American Journal of Psychology 117(3), 389-410.Barsalou, L.W. & Wiemer-Hastings, K. (2005). Situating Abstract Concepts. In Grounding Cognition: The Role of Perception and Action in Memory, Language, and Thinking. Pecher, D. & Zwaan, R.A.(Eds). Cambridge: Cambridge University Press.Crutch, S.J. & Warrington, E.K. (2005). Abstract and concrete concepts have structurally different representational frameworks. Brain 128, 615-627.Fuster, J. (2009) Cortex and memory: Emergence of a new paradigm. Journal of Cognitive Neuroscience 21,11, 2047-2072.Kousta, S-T., Vigliocco, G., Vinson, D.P Andrews, M. (2009). Happiness is... an abstract word. The role of affect in abstract knowledge representation. In N.A. Taatgen & H. van Rijn (Eds.), Proceedings of the 31st Annual Conference of the Cognitive Science Society, 1115-1120. Austin, TX: Cognitive Science Society.Pulvermüller, F. (1999). Words in the brain's language. Behavioral and Brain Sciences 22, 253-336.
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44.
  • Mårtensson, Frida, et al. (author)
  • Sensory-specific anomic aphasia following left occipital lesions : data from free oral descriptions of concrete word meanings
  • 2013
  • In: The Scandinavian Association for Language and Cognition. SALC IV, June 12-14, 2013. University of Eastern Finland, Joensuu. - Joensuu : University of Eastern Finland.
  • Conference paper (peer-reviewed)abstract
    • Nouns with a high degree of semantic specificity (e.g., ‘robin’) can be assumed to be more closelyrelated to sensory information as opposed to more non-specific nouns belonging to the same lexicalsemantic hierarchy (e.g., ‘animal’) (Rosch, 1978). As the majority of concrete nouns denote thingsthat can be experienced visually, activation of visual information might be necessary for concrete noun processing, in which case damage to visual (occipital) cortex might selectively affect morespecific nouns. Supporting this idea, nouns (e.g., ’table’) and verbs (e.g., ’kick’) have been found toactivate brain regions involved in experiencing their referred objects and actions (Pulvermüller & Fadiga 2010).Individuals with lesions in visual brain areas have previously been shown to have difficulties accessing words related to the visual modality (Manning 2000; Gainotti 2004). In these studies, the focus has been on comparing different modes of presentation (e.g., visual/tactile/verbal). However, it could further be hypothesised that when visual areas are damaged, the degree of visual semantic content would also affect performance.The present study investigated hierarchical lexical semantic structure in free oral descriptions of concrete word meanings produced by a subject (ZZ) diagnosed with anomic aphasia due to left occipital lesions. The focus of the analysis was production of a) nouns at different levels of semanticspecificity (e.g. ‘robin’–‘bird’–‘animal’) and b) words describing sensory or motor experiences (e.g. ‘blue’, ‘soft’, ‘fly’).Results showed that in contrast to healthy and aphasic controls, who produced words at all levels of specificity and mainly vision-related sensory information, ZZ produced almost exclusively nouns at the most non-specific levels and words associated with sound and movement, suggesting that his anomia is sensory-specific and dependent on the modality of the semantic content of words.ReferencesCrutch, S.J. & Warrington, E.K. (2008). Contrasting patterns of comprehension for superordinate, basic level, and subordinate names in semantic dementia and aphasic stroke patients. Cognitive Neuropsychology 25(4), 582-600.Gainotti, G. (2004). A metanalysis of impaired and spared naming for different categories of knowledge in patients with a visuo-verbal disconnection. Neuropsychologia 42, 299-319.Manning, L. (2000). Loss of visual imagery and defective recognition of parts of wholes in optic aphasia.NeuroCase 6 (2), 111-128.Rosch, E. (1978). Principles of categorization. In: Rosch, Eleanor and Barbara B. Lloyd, eds., Cognition and Categorization. Hillsdale, NJ: Lawrence Erlbaum, pp. 27-48.Pulvermüller, F. & Fadiga, L. (2010). Active perception: sensorimotor circuits as a cortical basis for language. Nature Reviews Neuroscience 11, 351-360.
  •  
45.
  • Mårtensson, Frida, et al. (author)
  • Sensory-specific anomic aphasia following left occipital lesions : Data from free oral descriptions of concrete word meanings
  • 2014
  • In: Neurocase. - : Informa UK Limited. - 1355-4794 .- 1465-3656. ; 20:2, s. 192-207
  • Journal article (peer-reviewed)abstract
    • The present study investigated hierarchical lexical semantic structure in oral descriptions of concrete word meanings produced by a subject (ZZ) diagnosed with anomic aphasia due to left occipital lesions. The focus of the analysis was production of a) nouns at different levels of semantic specificity (e.g., "robin"-"bird"-"animal") and b) words describing sensory or motor experiences (e.g., "blue," "soft," "fly"). Results show that in contrast to healthy and aphasic controls, who produced words at all levels of specificity and mainly vision-related sensory information, ZZ produced almost exclusively nouns at the most non-specific levels and words associated with sound and movement.
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46.
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47.
  • Mårtensson, Johan, et al. (author)
  • Growth of language-related brain areas after foreign language learning
  • 2012
  • In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 63:1, s. 240-244
  • Journal article (peer-reviewed)abstract
    • The influence of adult foreign-language acquisition on human brain organization is poorly understood. We studied cortical thickness and hippocampal volumes of conscript interpreters before and after three months of intense language studies. Results revealed increases in hippocampus volume and in cortical thickness of the left middle frontal gyrus, inferior frontal gyrus, and superior temporal gyrus for interpreters relative to controls. The right hippocampus and the left superior temporal gyrus were structurally more malleable in interpreters acquiring higher proficiency in the foreign language. Interpreters struggling relatively more to master the language displayed larger gray matter increases in the middle frontal gyrus. These findings confirm structural changes in brain regions known to serve language functions during foreign-language acquisition.
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