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- Abdurahman, Samir, 1965-, et al.
(författare)
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Activity of the small modified amino acid alpha-hydroxy glycineamide on in vitro and in vivo human immunodeficiency virus type 1 capsid assembly and infectivity
- 2008
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 52:10, s. 3737-3744
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Tidskriftsartikel (refereegranskat)abstract
- Upon maturation of the human immunodeficiency virus type 1 (HIV-1) virion, proteolytic cleavage of the Gag precursor protein by the viral protease is followed by morphological changes of the capsid protein p24, which will ultimately transform the virus core from an immature spherical to a mature conical structure. Virion infectivity is critically dependent on the optimal semistability of the capsid cone structure. We have reported earlier that glycineamide (G-NH(2)), when added to the culture medium of infected cells, inhibits HIV-1 replication and that HIV-1 particles with aberrant core structures were formed. Here we show that it is not G-NH(2) itself but a metabolite thereof, alpha-hydroxy-glycineamide (alpha-HGA), that is responsible for the antiviral activity. We show that alpha-HGA inhibits the replication of clinical HIV-1 isolates with acquired resistance to reverse transcriptase and protease inhibitors but has no effect on the replication of any of 10 different RNA and DNA viruses. alpha-HGA affected the ability of the HIV-1 capsid protein to assemble into tubular or core structures in vitro and in vivo, probably by binding to the hinge region between the N- and C-terminal domains of the HIV-1 capsid protein as indicated by matrix-assisted laser desorption ionization-mass spectrometry results. As an antiviral compound, alpha-HGA has an unusually simple structure, a pronounced antiviral specificity, and a novel mechanism of antiviral action. As such, it might prove to be a lead compound for a new class of anti-HIV substances.
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- Abdurahman, Samir, 1965-, et al.
(författare)
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Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology
- 2009
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Ingår i: Retrovirology. - : Springer Science and Business Media LLC. - 1742-4690. ; 6, s. 34-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Formation of an HIV-1 particle with a conical core structure is a prerequisite for the subsequent infectivity of the virus particle. We have previously described that glycineamide (G-NH2) when added to the culture medium of infected cells induces non-infectious HIV-1 particles with aberrant core structures. Results: Here we demonstrate that it is not G-NH2 itself but a metabolite thereof that displays antiviral activity. We show that conversion of G-NH2 to its antiviral metabolite is catalyzed by an enzyme present in bovine and porcine but surprisingly not in human serum. Structure determination by NMR suggested that the active G-NH2 metabolite was alpha-hydroxy-glycineamide (alpha-HGA). Chemically synthesized alpha-HGA inhibited HIV-1 replication to the same degree as G-NH2, unlike a number of other synthesized analogues of G-NH2 which had no effect on HIV-1 replication. Comparisons by capillary electrophoresis and HPLC of the metabolite with the chemically synthesized alpha-HGA further confirmed that the antiviral G-NH2-metabolite indeed was alpha-HGA. Conclusion: alpha-HGA has an unusually simple structure and a novel mechanism of antiviral action. Thus, alpha-HGA could be a lead for new antiviral substances belonging to a new class of anti-HIV drugs, i.e. capsid assembly inhibitors.
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- Abrahamsson, Gun, et al.
(författare)
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Exploiting institutional contradictions : the role of management accounting in continuous improvement implementation
- 2006
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Ingår i: Qualitative Research in Accounting & Management/Emerald. - Bradford : Emerald Group Publishing Limited. - 1176-6093 .- 1758-7654. ; 3:2, s. 126-144
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Based on an institutional perspective, this study explores the role of management accounting (MA) in promoting or impeding changes in the employees’ conceptions of shopfloor worker responsibility in a company trying to implement a Continuous Improvement (CI) working practice. Methodology/approach: We use an ethnographically inspired research method where weekly CI meetings in two workgroups were observed over a period of eight months and in-depth interviews with managers and operators were conducted regularly. Findings: The study reveals that active and skilful exploiters of inconsistencies within social arrangements may use MA as one important way of transforming a traditional vertical view of worker responsibility into a more horizontally-oriented view by: creating collective reflection and reasoned analysis of the limits of the present order; and, by visualizing and justifying an alternative model(s) of social behaviour. However, the study also shows that MA may contribute to the reinforcement of a vertical view by the use of group-level measures strictly as a one-way performance monitoring device. Research limitations/implications: Arguably, it is worthwhile to explore the existence of ‘institutional heterogeneity’ because our study highlights that ‘contradictions’ between social orders may not only nurture institutional stability, but may also be a necessary (although not sufficient) condition for institutional change.
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- Abrahamsson, Gun, 1961-, et al.
(författare)
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Problemlösningsarbete på låg organisatorisk nivå : Två studier om implementering respektive konkretisering av idéer om kundorderstyrd tillverkning
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The two studies reported in this thesis are about problem solving at a low organisational level in an organisational unit in a Swedish manufacturing company, which has adopted ideas of World Class Manufacturing. In the first study, we analyse, from an organisational learning perspective, the implementation of the well-known concept Continuous Improvement at shop-floor level and how management accounting may facilitate or impede improvement work. A case study was conducted in two workgroups in one production unit for about seven months. In one of the groups, management accounting facilitated improvement work with high organisational scope and, in the other group, impeded the organisational scope. Our conclusion is that management accounting may facilitate a high organisational scope by supporting the leadership style, stressing co-operation, dialog and participation, or, by the way the manager uses management accounting, make boundaries distinct between groups of employees and between departments, and therefore impede improvements with high organisational scope. In the second study, we analyse, from a rule-based behavioural perspective, how ideas of World Class Manufacturing are institutionalised in cross-functional problem solving at a low organisational level. A case study was carried out in two cross-functional weekly group meetings for about nine months. Problems raised and solutions decided followed a repeated pattern. The actors draw on instrumental rules, which can be described as technical as well as economic. We concluded that ideas of World Class Manufacturing were institutionalised as different variants of World Class Manufacturing in the different functions at a low organisational level. At the meetings, contradictory instrumental rules were activated by the functions and treated according to interaction rules. Two overall patterns of action, articulated the two main interaction rules guiding actors in how to treat contradictory ideas of World Class Manufacturing.
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