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- Dahlgren, Markus, et al.
(författare)
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Design, Synthesis, and Multivariate Quantitative Structure-Activity Relationship of Salicylanilides-Potent Inhibitors of Type III Secretion in Yersinia
- 2007
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 50:24, s. 6177-6188
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Tidskriftsartikel (refereegranskat)abstract
- Analogues to the salicylanilide N-(4-Chlorophenyl)-2-acetoxy-3,5-diiodobenzamide, 1a, an inhibitor of type III secretion (T3S) in Yersinia, were selected, synthesized, and biologically evaluated in three cycles. First, a set of analogues with variations in the salicylic acid ring moiety was synthesized to probe possible structural variation. A basic structure-activity relationship was established and then used to cherry-pick compounds from a principal component analysis score plot of salicylanilides to generate a second set. A third set with increased likelihood of biological activity was designed using D-optimal onion design. A quantitative structure-activity relationship model using hierarchical partial least-square regression to latent structures (Hi-PLS) was computed using PLS score vectors of building blocks correlated to the % inhibition of T3S as a response. A PLS discriminant analysis (PLS-DA) model was derived using the same descriptor set as that for the Hi-PLS model. Both models were validated with an external test set.
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| 5. |
- Kauppi, Anna M., 1971-, et al.
(författare)
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Inhibitors of type III secretion in Yersinia : design, synthesis and multivariate QSAR of 2-sulfonamino-benzanilides
- 2007
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier Ltd. - 0968-0896 .- 1464-3391. ; 15:22, s. 6994-7011
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Compound 1, 2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-5-chloro-N-(3,4-dichloro-phenyl)-benzamide, was identified as a putative type III secretion inhibitor in Yersinia, and the compound thus has a potential to be used to prevent or treat bacterial infections. A set of seven analogues was synthesized and evaluated in a type III secretion dependent reporter-gene assay with viable bacterial to give basic SAR. A second set of 19 compounds was obtained by statistical molecular design in the building block and product space and subsequent synthesis. Evaluation in the reporter-gene assay showed that the compounds ranged from non-active to compounds more potent than 1. Based on the data multivariate QSAR models were established and the final Hi-PLS model showed good correlation between experimentally determined % inhibition and the calculated % inhibition of the reporter-gene signal.
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| 7. |
- Thorgeirsson, Thorgeir E, et al.
(författare)
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A variant associated with nicotine dependence, lung cancer and peripheral arterial disease
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 452:7187, s. 9-638
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.
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| 8. |
- Ahlstrand, Christina, 1957, et al.
(författare)
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Reliabilitetstestning av Purdue Pegboard® (finmotoriktest).
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I MQ-FAS studien, vars syfte var att ändra muskelspänningsmönstret hos kvinnor med kroniska nackbesvär, ingick ett besticktorkningsmoment som en standardiserad arbetsuppgift i hemmet. För validering av denna besticktorkning har en pilotstudie genomförts, 12 personer torkade bestick vid två tillfällen. I studien, som utfördes av 2 testledare, ingick även ett finmotorikstest (Purdue Pegboard), ansträngningsskattning (Borg RPE-skalan) samt ett frågeformulär. Detta test kan med vissa justeringar troligen vara användbart som ett mått på arbetsförmåga av övre extremiteter vid utförande av arbetssyssla i hemmet, och jämföra individ med sig själv, för att mäta om funktionsnedsättning eller ökning har skett. Dock skall poängteras att detta var en pilotstudie och ytterligare studie av reliabilitet och validitet rekommenderas innan testet används i stor utsträckning för att mäta om funktionsnedsättning eller ökning har skett.
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| 9. |
- Alkan Olsson, Johanna, et al.
(författare)
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How participatory can participatory modeling be? Degrees of influence of stakeholder and expert perspectives in six dimensions of participatory modeling
- 2007
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Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 56:1, s. 207-214
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Tidskriftsartikel (refereegranskat)abstract
- The authors are involved in a project aiming at the development of a methodology for participatory modeling as a tool for public participation in water resource management. In this paper, some examples of different degrees of stakeholder influence in six key dimensions of participatory modeling are identified and discussed. Arnstein's (A ladder of citizen participation. Journal of the American Institute of Planners, 1969, 4, 216–224) critical discussion of different degrees of “real” decision-making power is taken as a point of departure to assess possible degrees of stakeholder influence. Can we as participatory modelers be sure that we are really inviting our research objects to an equal communicative relationship where local perspectives, knowledge and priorities are respected to the same extent as central and/or expert perspectives? This paper presents an approach that could be used as a tool for structured reflection to avoid unreflective tendencies towards expert knowledge dominance and low degree of stakeholders' real influence over the process.
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