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1.
  • Eriksson, Therese, et al. (författare)
  • Cycloidal magnetic order in the compound IrMnSi
  • 2005
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 71:17
  • Tidskriftsartikel (refereegranskat)abstract
    • A new compound, IrMnSi, has been synthesized, and its crystal structure and magnetic properties have been investigated by means of neutron powder diffraction, magnetization measurements, and first-principles theory. The crystal structure is found to be of the TiNiSi type (ordered Co2P, space groupPnma). The Mn-projected electronic states are situated at the Fermi level, giving rise to metallic binding, whereas a certain degree of covalent character is observed for the chemical bond between the Ir and Si atoms. A cycloidal, i.e., noncollinear, magnetic structure was observed below 460 K, with the propagation vector q=[0,0,0.4530(5)] at 10 K. The magnetism is dominated by large moments on the Mn sites, 3.8μB∕atom from neutron diffraction. First-principles theory reproduces the propagation vector of the experimental magnetic structure as well as the angles between the Mn moments. The calculations further result in a magnetic moment of 3.2μB for the Mn atoms, whereas the Ir and Si moments are negligible, in agreement with observations. A calculation that more directly incorporates electron-electron interactions improves the agreement between the theoretical and experimental magnetic moments. A band mechanism is suggested to explain the observed magnetic order.
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2.
  • Andersen, Malin, 1977-, et al. (författare)
  • Alternative promoter usage of the membrane glycoprotein CD36
  • 2006
  • Ingår i: BMC Molecular Biology. - : Springer Science and Business Media LLC. - 1471-2199. ; 7, s. 8-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation.Results: We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters.Conclusion: Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.
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3.
  • Andersen, Malin, 1977-, et al. (författare)
  • In silico detection of sequence variations modifying transcriptional regulation
  • 2008
  • Ingår i: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 4:1, s. e5-
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN ( regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation.
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4.
  • Blomberg, Lars, et al. (författare)
  • Electric Field Diagnostics in the Jovian System : Brief Scientific Case and Instrumentation Overview
  • 2006
  • Ingår i: Proceedings of the 6th IAA International Conference on Low-Cost Planetary Missions. ; , s. 335-340
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The Jovian plasma environment exhibits a variety of plasma flow interactions with magnetised as well as unmagnetised bodies, making it a good venue for furthering our understanding of solar wind - magnetosphere / ionosphere interactions. On an overall scale the solar wind interacts with the Jovian magnetosphere, much like at Earth but with vastly different temporal and spatial scales. Inside the Jovian magnetosphere the co-rotating plasma interacts with the inner moons. The latter interaction is slower and more stable than the corresponding interaction between the solar wind and the planets, and can thus provide additional information on the principles of the interaction mechanisms. Because of the wealth of expected low-frequency waves, as well as the predicted quasi-static electric fields and plasma drifts in the interaction regions between different parts of the Jovian system, a most valuable component in future payloads would be a double-probe electric field instrument. Recent developments in low-mass instrumentation facilitate electric field measurements on spinning planetary spacecraft, which we here exemplify.
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5.
  • Ekblad, Torun, 1977- (författare)
  • Chemical Synthesis of Affibody Molecules for Protein Detection and Molecular Imaging
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Proteins are essential components in most processes in living organisms. The detection and quantification of specific proteins can be used e.g. as measures of certain physiological conditions, and are therefore of great importance. This thesis focuses on development of affinity-based bioassays for specific protein detection. The use of Affibody molecules for specific molecular recognition has been central in all studies in this thesis. Affibody molecules are affinity proteins developed by combinatorial protein engineering of the 58-residue protein A-derived Z domain scaffold. In the first paper, solid phase peptide synthesis is investigated as a method to generate functional Affibody molecules. Based on the results from this paper, chemical synthesis has been used throughout the following papers to produce Affibody molecules tailored with functional groups for protein detection applications in vitro and in vivo.   In paper I, an orthogonal protection scheme was developed to enable site-specific chemical introduction of three different functional probes into synthetic Affibody molecules. Two of the probes were fluorophores that were used in a FRET-based binding assay to detect unlabeled target proteins. The third probe was biotin, which was used as an affinity handle for immobilization onto a solid support. In paper II, a panel of Affibody molecules carrying different affinity handles were synthesized and evaluated as capture ligands on microarrays. Paper III describes the synthesis of an Affibody molecule that binds to the human epidermal growth factor receptor type 2, (HER2), and the site-specific incorporation of a mercaptoacetyl-glycylglycylglycine (MAG3) chelating site in the peptide sequence to allow for radiolabeling with 99mTc. The derivatized Affibody molecule was found to retain its binding capacity, and the 99mTc-labeling was efficient and resulted in a stable chelate formation. 99mTc-labeled Affibody molecules were evaluated as in vivo HER2-targeting imaging agents in mice. In the following studies, reported in papers IV-VI, the 99mTc-chelating sequence was engineered in order to optimize the pharmacokinetic properties of the radiolabeled Affibody molecules and allow for high-contrast imaging of HER2-expressing tumors and metastatic lesions. The main conclusion from these investigations is that the biodistribution of Affibody molecules can be dramatically modified by amino acid substitutions directed to residues in the MAG3-chelator. Finally, paper VII is a report on the chemical synthesis and chemoselective ligation to generate a cross-linked HER2-binding Affibody molecule with improved thermal stability and tumor targeting capacity.   Taken together, the studies presented in this thesis illustrate how peptide synthesis can be used for production and modification of small affinity proteins, such as Affibody molecules for protein detection applications.
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6.
  • Engfeldt, Torun, et al. (författare)
  • Chemical Synthesis of Triple-Labelled Three-Helix Bundle Binding Proteins for Specific Fluorescent Detection of Unlabelled Protein
  • 2005
  • Ingår i: ChemBioChem (Print). - : Wiley. - 1439-4227 .- 1439-7633. ; 6:6, s. 1043-1050
  • Tidskriftsartikel (refereegranskat)abstract
    • Site-specifically triple-labelled three-helix bundle affinity proteins (affibody molecules) have been produced by total chemical Synthesis. The 58 aa affinity proteins were assembled on an automated peptide synthesizer, followed by manual on-resin incorporation of three different reporter groups. An orthogonal protection strategy was developed for the site-specific introduction of 5-(2-aminethylamino)-1-nophthalenesulfonic acid (EDANS) and 6(7-nitrobenzofurazon-4-yiamino)-hexanoic acid (NBDX), constituting a donor/acceptor pair for fluorescence resonance energy transfer (FRET), and a biotin moiety, used for surface immobilization. Circular dichroism and biosensor studies of the synthetic proteins and their recombinant counterparts revealed that the synthetic proteins were folded and retained their binding specificities. The biotin-conjugated protein could be immobilized onto a streptavidin surface without loss of activity. The synthetic, doubly fluorescent-labelled affinity proteins were shown to function as fluorescent biosensors in an assay for the specific detection of unlabelled human IgG and IgA.
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7.
  • Eriksson, Anders, et al. (författare)
  • RPC-LAP : The Rosetta Langmuir probe instrument
  • 2007
  • Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 128:04-jan, s. 729-744
  • Forskningsöversikt (refereegranskat)abstract
    • The Rosetta dual Langmuir probe instrument, LAP, utilizes the multiple powers of a pair of spherical Langmuir probes for measurements of basic plasma parameters with the aim of providing detailed knowledge of the outgassing, ionization, and subsequent plasma processes around the Rosetta target comet. The fundamental plasma properties to be studied are the plasma density, the electron temperature, and the plasma flow velocity. However, study of electric fields up to 8 kHz, plasma density fluctuations, spacecraft potential, integrated UV flux, and dust impacts is also possible. LAP is fully integrated in the Rosetta Plasma Consortium (RPC), the instruments of which together provide a comprehensive characterization of the cometary plasma.
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8.
  • Eriksson, Carina, et al. (författare)
  • Antifeedants and feeding stimulants in bark extracts of ten woody non-host species of the pine weevil, Hylobius abietis
  • 2008
  • Ingår i: Journal of Chemical Ecology. - : Springer Science and Business Media LLC. - 0098-0331 .- 1573-1561. ; 34:10, s. 1290-1297
  • Tidskriftsartikel (refereegranskat)abstract
    • Bark of ten woody species, known to be rejected as a food source by the pine weevil, Hylobius abietis, were sequentially extracted by a Soxhlet apparatus with pentane followed by methanol. Species were alder (Alnus glutinosa), aspen (Populus tremula), beech (Fagus sylvatica), guelder rose (Viburnum opulus), holly (Ilex aquifolium), horse chestnut (Aesculus hippocastanum), lilac (Syringa vulgaris), spindle tree (Evonymus europaeus), walnut (Juglans regia), and yew (Taxus baccata). Bark of each species was collected in southern Scandinavia during the summer. Resulting extracts were tested for antifeedant activity against the pine weevil by a micro-feeding choice assay. At a dose corresponding to that in the bark, methanol extracts from Aesculus, Taxus, Ilex, and Populus were antifeedant active, while pentane extracts of Aesculus, Fagus, Syringa, and Viburnum were stimulatory. Four known antifeedants against H. abietis, the straight-chained carboxylic acids, hexanoic and nonanoic acid (C6 and C9), carvone, and carvacrol were identified by gas chromatography (GC)-mass spectrometry (MS) in several extracts. The major constituents were identified and tested for feeding deterrence. The aromatic compounds benzyl alcohol and 2-phenylethanol are new non-host plant-derived feeding deterrents for the pine weevil. Additionally, two feeding stimulants, beta-sitosterol and 5-(hydroxymethyl)-2-furaldehyde, were identified. One active methanol extract of Aesculus bark was sequentially fractionated by liquid chromatography, and major compounds were tentatively identified as branched alcohols and esters of hexanoic acid. Five commercially available hexanoate esters and two commercially available branched alcohols were identified as new active antifeedants. Both stimulatory and inhibiting compounds were found in the same extracts and co-eluted in the same or adjacent fractions. The mix of semiochemicals of opposite activity in each extract or fraction could explain the stimulatory-, inhibitory-, or sometimes neutral activity. Generally, such co-occurrence confounds the isolation of antifeedants.
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9.
  • Eriksson, Johan, et al. (författare)
  • Using Timber in a multi-body design environment to develop reliable embedded software
  • 2008
  • Ingår i: Intelligent vehicle iniative (IVI) technology controls and navigation systems, 2008. - Warrendale, Pa. : Society of Automotive Engineers, Incorporated. - 9780768020359 - 768020352 - 0768020352
  • Konferensbidrag (refereegranskat)abstract
    • A major challenge for the automotive industry is to reduce the development time while meeting quality assessments for their products. This calls for new design methodologies and tools that scale with the increasing amount and complexity of embedded systems in today's vehicles.In this paper we undertake an approach to embedded software design based on executable models expressed in the high-level modelling paradigm of Timber. In this paper we extend previous work on Timber with a multi-paradigm design environment, aiming to bridge the gap between engineering disciplines by multi-body co-simulation of vehicle dynamics, embedded electronics, and embedded executable models. Its feasibility is demonstrated on a case study of a typical automotive application (traction control), and its potential advantages are discussed, as highlighted below:shorter time to market through concurrent, co-operative distributed engineering, andreduced cost through adequate system design and dimensioning, andimproved efficiency of the design process through migration and reuse of executable software components, andreduced need for hardware testing, by specification verification on the executable model early in the design process, andimproved quality, by opening up for formal methods for verification.
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10.
  • Eriksson, Ulrika, 1974- (författare)
  • Impact of autocrine factors on physiology and productivity in Trichoplusia ni serum-free cultures
  • 2005
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this study was to increase the understanding of the mechanisms regulating cell proliferation and recombinant protein production in serum-free cultures of Trichoplusia ni (T. ni) insect cells.Conditioned medium (CM) was shown to contain both stimulatory and inhibitory factors (CM factors) influencing cell growth. Metalloproteinase (MP) activity was the major factor responsible for the growth stimulating effect of CM as shown by using the specific MP inhibitor DL-thiorphan. MPs may exist in several different molecular mass forms due to autoproteolysis. Although the main band of the MP was determined to be around 48 kDa, precursor forms above 48 kDa as well as autocatalytic degradation products below the main band could be observed. It is not clear whether all forms of the MP or just the main band is involved in the growth regulation. Further, a proteinase inhibitor could be identified in the inhibitory fraction. Thus, we speculate that the proteinase inhibitor may be part of an autocrine system regulating cell proliferation.Analysis of the cell cycle phase distribution revealed a high proportion of cells in the G1 (80-90 %) and a low proportion of cells in the S and G2/M phases (10-20 %) during the whole culture, indicating that S and G2/M are short relative to G1. After inoculation, a drastic decrease in the S phase population together with a simultaneous increase of cells in G1 and G2/M could be observed as a lagphase on the growth curve and this may be interpreted as a temporary replication stop. When the cells were released from the initial arrest, the S phase population gradually increased again. This was initiated earlier in CM-supplemented cultures, and agrees with the earlier increase in cell concentration. Thus, these data suggests a correlation between CM factors and the cell cycle dynamics.In cultures supplied with CM, a clear positive effect on specific productivity was observed, with a 30 % increase in per cell productivity. The specific productivity was also maintained at a high level much longer time than in fresh-medium cultures. The positive effect observed after 20 h coincided with the time a stimulatory effect on cell growth first was seen. Thus, the productivity may be determined by the proliferation potential of the culture. A consequence of this would be that the secreted MP indirectly affects productivity.Finally, the yeast extract from Express Five SFM contains factors up to 35 kDa which are essential for T. ni cell growth. The optimal concentration was determined to be 2.5-fold that in normal medium, while higher concentrations were inhibitory. However although vital, they were not solely responsible for the growth-enhancing effect, as some other, more general, component present in yeast extract was needed for proliferation as well.
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