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Träfflista för sökning "WFRF:(Johansson Mikael) srt2:(1995-1999)"

Sökning: WFRF:(Johansson Mikael) > (1995-1999)

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  • Sundberg, Kathrin, et al. (författare)
  • Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons
  • 1998
  • Ingår i: Carcinogenesis. - 0143-3334 .- 1460-2180. ; 19:3, s. 433-436
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have identified allelic variants of the human glutathione transferase (GST) Pi gene and showed that the two different encoded proteins with isoleucine (GSTP1-1/I-105) or valine (GSTP1-1/V-105) at position 105, respectively, differ significantly in their catalytic activities with model substrates. Moreover, recent epidemiological studies have demonstrated that individuals differing in the expression of these allelic variants also differ in susceptibility to tumour formation in certain organs, including such in which polycyclic aromatic hydrocarbons (PAH) may be etiological factors. In the present study the catalytic efficiencies (kcat/Km) of these GSTP1-1 variants were determined with a number of stereoisomeric bay-region diol epoxides, known as the ultimate mutagenic and carcinogenic metabolites of PAH, including those from chrysene, benzo[a]pyrene and dibenz[a,h]anthracene. In addition, GSTP1-1 mutants in which amino residue 105 is alanine (GSTP1-1/A-105) or tryptophan (GSTP1-1/W-105) have been constructed and characterized. GSTP1-1/V-105 was found to be more active than GSTP1-1/I-105 in conjugation reactions with the bulky diol epoxides of PAH, being up to 3-fold as active towards the anti- and syn-diol epoxide enantiomers with R-absolute configuration at the benzylic oxiranyl carbon. Comparing the four enzyme variants, GSTP1-1/A-105 generally demonstrated the highest kcat/Km value and GSTP1-1/W-105 the lowest with the anti-diol epoxides. A close correlation was observed between the volume occupied by the amino acid residue at position 105 and the value of kcat/Km. With the syn-diol epoxides, such a correlation was observed with alanine, valine and isoleucine, whereas tryptophan was associated with increased kcat/Km values. The mutational replacement of isoleucine with alanine or tryptophan at position 105 did not alter the enantio selectivity of the GSTP1-1 variants compared with the naturally occurring allelic variants GSTP1-1/I-105 and GSTP1-1/V-105. Since the amino acid at position 105 forms part of the substrate binding site (H-site) the effect of increasing bulkiness is expected to cause restricted access of the diol epoxide and proper alignment of the two reactants for efficient glutathionylation. In conclusion, the present study indicates that individuals who are homozygous for the allele GSTP1* B (coding for GSTP1-1/V-105) display a higher susceptibility to malignancy because of other factors than a decreased catalytic efficiency of GSTP1-1/V-105 in the detoxication of carcinogenic diol epoxides of benzo[a]pyrene or structurally related PAH.
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4.
  • Andersson, Mikael, et al. (författare)
  • The Influence of the Degree of Cross-linking, Type of Ligand and Support on the Chemical Stability of Chromatography Media Intended for protein Purification
  • 1998
  • Ingår i: Process Biochemistry. - 1359-5113 .- 1873-3298. ; 33:1, s. 47-55
  • Tidskriftsartikel (refereegranskat)abstract
    • The release of organic compounds from different liquid chromatography media in static conditions has been analysed with a total organic carbon (TOC) analyser. TOC results show that chemical stability increases with the degree of cross-linking in agarose beaded chromatography media and thus extend the working pH-range of the media. Of the unsubstituted chromatography media investigated, Sepharose® 6B, Sepharose CL-6B, Sepharose 4 Fast Flow, Sepharose 6 Fast Flow and Sepharose High Performance, the latter was the most stable medium. Sepharose High Performance releases only about 0·06% of its total carbon content after 1 week in 0·01 m HCl. Agarose beads are more stable to basic conditions (pH 14) compared with acidic conditions (pH 2). From UV spectroscopic and gel filtration results it was found that all Sepharose media release low amounts of 5-(hydroxymethyl)-2-furaldehyde and agarose fragments in acidic conditions. To investigate the effect of different ligands on chemical stability Q Sepharose 6 Fast Flow, DEAE Sepharose 6 Fast Flow, SP Sepharose 6 Fast Flow, CM Sepharose 6 Fast Flow, Phenyl Sepharose 6 Fast Flow, Octyl Sepharose 4 Fast Flow media were also studied under static conditions. In basic conditions it was found that all these chromatography media release carbon compounds to a higher extent than the unsubstituted Sepharose support. In addition, Hofmann elimination of Q and DEAE groups contributes to the decrease in the carbon content of the corresponding anion exchangers. During exposure to acidic conditions (pH 2) the release of carbon compounds was lower than the release from the support to which the ligands were coupled. The exceptions are Octyl Sepharose 4 Fast Flow and SP Sepharose 6 Fast Flow. In the case of Octyl Sepharose 4 Fast Flow, the ligand did not seem to influence chemical stability, whereas the SP group increases the degradation of the Sepharose support. In the case of SP Sepharose 6 Fast Flow the stability in acidic conditions can be improved by increasing the ionic strength. Anion exchangers based on different support polymers (agarose-, polystyrene-, methacrylate- and polyvinyl-based matrixes) were studied under static conditions. Agarose-based anion exchanger was the most stable in basic conditions (pH 14). In acidic conditions (pH 2) the chemical stability was about the same for many different anion exchangers.
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  • Berling, Clas, et al. (författare)
  • Methods for introducing improvements at work
  • 1998
  • Ingår i: Proceedings of the Sixth International Symposium on Human Factors in Organisational Design and Management,Netherlands,0001-01-02. ; , s. 555-565
  • Konferensbidrag (refereegranskat)
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  • Christiansson, Marie-Therese, et al. (författare)
  • En inter-organisatorisk förändringsanalys : utveckling av kund-/leverantörsprocessen
  • 1997
  • Konferensbidrag (refereegranskat)abstract
    • Dagens sätt att göra affärer innebär ett ökat partnerskap och ett ökat datautbyte mellan organisationer i sökandet efter effektivitet och konkurrensfördelar. Affärsrelationer mellan leverantörer och kunder är beroende av att informationen flödar på ett strukturerat sätt mellan deras organisationer för att tillgodose respektive parts informationsbehov, dvs inter-organisatoriska informationssystem (IOIS). En metodutveckling pågår inom VINST-projektet där målet är att utveckla kunskap om och utforma en användbar metod som stöd vid verksamhetsutveckling av inter-organisatorisk karaktär. Denna rapport bygger på en metodprövande aktionsforskning vid en gemensam förändringsanalys som PartnerTech AB och en av deras kunder bedrivit med stöd av FA/SIMMetoden. Den metodtillämpning och metodutveckling som skett analyseras och diskuteras utifrån frågorna; hur en leverantör tillsammans med kunden kan utveckla den gemensamma kund-leverantörsprocessen och hur verksamhetsutvecklare kan använda FA/SIMM för att kartlägga och driva förbättring av inter-organisatoriska processer. Rapporten pekar bl a på behov av anpassade projektstrategier, arbetsformer och notation samt metodkomponenter för interaktionsanalys och uppföljning av åtgärder.
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  • Collin, Peter, et al. (författare)
  • Lateral-torsional buckling of continuous bridge girders
  • 1998
  • Ingår i: Journal of constructional steel research. - 0143-974X .- 1873-5983. ; 45:2, s. 217-235
  • Tidskriftsartikel (refereegranskat)abstract
    • The resistance of bridge girders with respect to lateral-torsional buckling at support is strongly influenced by the moment gradient. In most design methods this influence is taken into account by the use of a correct critical bending moment in the slenderness parameter λ. This critical moment is influenced by the shape of the moment diagram as well as the distortion of the cross-section and the restraint from the web and stiffeners, if any. In this paper, a method for the calculation of the critical moment is presented. A further effect of the moment gradient is that the stresses due to lateral bending of the flange in connection with lateral-torsional buckling does not coincide with the maximum of stresses caused by bending in the vertical plane. This is taken into account by performing the check for lateral-torsional buckling in a design section at some distance from the support. A design procedure based on this concept has been introduced in Eurocode 3 Part 2: Steel Bridges
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  • Resultat 1-10 av 68
  • [1]234567Nästa
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