"... In PAGE 13: ... Of the 81 genes induced at 72 h in the time course study, 58 exhibited dose-dependent induction, although none achieved a plateau thus precluding ED50 determinations (Figure 3). GO analysis indicated that genes associated with oxidoreductase activity such as Cyp2b2 or Cyp3a2 were induced as early as 2 h ( Table4 ), while electron transport genes related to reductive reactions (e.g.... In PAGE 14: ... Genes involved in electron transport or reductive reactions such as Ephx1, Flt1 and Txn1 were also induced at 18 h. Several sterol metabolism- and cell proliferation-related genes were also differentially expressed ( Table4 ). The sterol metabolism-related gene, Srebf1, was repressed 4-18 h along with another sterol metabolism-related gene, Cyp17a1, at 12-18 h.... ..."

"... In PAGE 5: ... Table2 shows the metabolic rates for the different types of driving in our test, calculated by applying Equations 1 through 4 to the measured heart rate shown in Table 1A. These results are also shown in Figure 4 as the triangles, black for female and gray for male.... In PAGE 5: ... Because our test is for driving, with its relatively low exertion requirements, the met levels are all located at the lower end of the Figure 4 plots. It can be seen from Table2 that the ratio of driving-to- resting metabolic levels is higher than that of heart rates, ranging up to 156%. For drivers, the metabolic rates for the game, the real car on the freeway, and in the city ranged from about 1.... ..."

"... In PAGE 2: ...2 Graphical Representation of Pathways Figure 1: Graphical representation of pathways. For example, by applying the general rules as summarized in Table1 , we can visualize the pathways for glycolysis (metabolic) and apop- tosis (regulatory) pathway as in Figure 1. Al- though, visualizing regulatory pathways focus on binary interactions in many approaches of others, a flow representation should be considered.... ..."

"... In PAGE 7: ... In addition, cofactor compounds were not allowed to serve as substrates for reactions other than the ones where they serve as cofactors. RESULTS AND DISCUSSION Table1 will approximately go here. Analysis of the aromatic amino acid pathways Application of the three individual sets of generalized enzyme reactions to produce phenylalanine, tyrosine and tryptophan from chorismate and the corresponding cofactors and amino donors resulted in a rich array of novel compounds and pathways.... In PAGE 7: ... Analysis of the aromatic amino acid pathways Application of the three individual sets of generalized enzyme reactions to produce phenylalanine, tyrosine and tryptophan from chorismate and the corresponding cofactors and amino donors resulted in a rich array of novel compounds and pathways. A total of 246 compounds were produced from chorismate and the five generalized enzyme reactions in the phenylalanine pathway; 289 compounds were produced from the five generalized enzyme reactions in the tyrosine pathway; 58 compounds were produced from chorismate and the nine generalized enzyme reactions in the tryptophan pathway ( Table1 ). Through automated comparison of the compounds created and those catalogued in the KEGG and Chemical Abstracts Service (CAS) Registry, it was clear that the compounds fell into one of three categories: the compounds that are part of the original pathways, the compounds that exist in the KEGG database and are not part of the Hatzimanikatis et al.... In PAGE 8: ...The compounds that exist in the CAS but not the KEGG are intriguing compounds because there exists an organic synthesis route but not a reported biochemical synthesis route. A much larger number of compounds had no matches in either of the two databases, suggesting the existence of compounds that remain to be discovered or synthesized through protein and pathway engineering ( Table1 ). Furthermore, the diversity of biochemical compounds was increased by at least one order of magnitude when we combined generalized enzyme reactions from two of the three different pathways, and the largest number of compounds, almost 35,000, was generated when we combined the 15 generalized enzyme reactions in all three pathways (Table 1).... ..."

"... In PAGE 5: ... There were missing enzymes on the pathway that were assigned computationally. These enzymes are described in Table2 . Four of six missing clones were finally identified after intensive human curation.... ..."