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Table 1.

AIC comparison of linear and non-linear dose-response models.

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Table 1 Expand

Table 2.

AIC comparison for simplification of indicated models.

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Table 2 Expand

Fig 1.

Comparison of mono and co-cultured dose-response trajectories in AIC-selected models for 4 compounds.

A) 4−aminophenol exhibited separate intercepts but equivalent slopes for mono-cultured fibroblasts (blue trace) and fibroblasts co-cultured with hepatocytes (red trace). B) Cyclophosphamide exhibited separate trajectories for mono-cultured fibroblasts (blue trace) and fibroblasts co-cultured with hepatocytes (red trace). C) Paroxon exhibited indistinguishable trajectories for mono-cultured fibroblasts and fibroblasts co-cultured with hepatocytes (purple trace). D) Ticlopedine exhibited separate intercepts but equivalent slopes for mono-cultured fibroblasts (blue trace) and fibroblasts co-cultured with hepatocytes (red trace).

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Fig 1 Expand

Fig 2.

Comparison of A) GAMM, B) ANCOVA and C) ANOVA for cyclophosphamide.

ANOCOVA and ANOVA demonstrate insensitivity to the local maximum dose-response indicated by GAMM.

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Fig 2 Expand

Fig 3.

Pearson residuals of A) GAMM, B) ANCOVA and C) ANOVA for cyclophosphamide dose-response.

GAMM exhibits a more even distribution of residuals than does ANCOVA or ANOVA (red trace).

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Fig 3 Expand

Fig 4.

Graphic comparison of alternative models for paroxon dose-response.

The AIC preferred model (A, Wi = 0.64) fails to distinguish mono from co-cultured response (purple trace), while the less-preferred, yet still competitive model (B, Wi = 0.36) exhibits a modest difference in intercepts (red vs. blue trace).

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Fig 4 Expand

Fig 5.

Graphic comparison of alternative models for ticlopedine dose-response.

The AIC preferred model (A, Wi = 0.71) exhibits a non-linear response for both mono and co-cultured fibroblasts, while the less-preferred, yet still competitive model (B, Wi = 0.21) exhibits a linear response.

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Fig 5 Expand