However, in genotype 2b infection in our study, there was no significant difference in the HCV RNA level between SVR and non-SVR patients, as shown in Table 1. Previously, the role of the ISDR in the contribution to SVR in genotype 1 and 2a has been discussed in detail in the context of serum HCV RNA level, and multiple substitutions in the ISDR are related to a low HCV RNA level and high SVR rate. However, it is not known which of these two factors is directly associated with viral clearance. Consideration of this three-sided relationship of ISDR, HCV RNA level and SVR rate in genotype2b infection leads to the suggestion that amino acid variation in ISDR to be more direct contributor for SVR. In spite of these findings, there were still limitations in our study. First, because genotype 2b infection only accounts for 10% of all HCV infection in Japan, the number of studied patients was rather small, especially non-SVR patients. In addition, because genotype 2b HCV contains as many as 3033 amino acids, it is possible that BKM120 cost incorrect amino acids or regions were judged as significant in the complete HCV ORF comparison study as a result of type I errors. Therefore, if more patients were available for the analysis, the statistical power detecting the meaningful differences would be greater. Secondly, we could not include the IL28B SNP analysis in this study. If we could have combined the information of IL28B SNPs with the full HCV ORF information, a more comprehensive analysis would have been achieved. In conclusion, we have shown that viral sequences were more diverse in SVR patients infected with genotype 2b HCV. Through systematic comparison between SVR and non-SVR patients, we have also shown that several localized regions were extracted as hot spots whose amino acid substitutions were closely related to the final outcome by affecting the relapse rate in the PEG-IFN/RBV therapy. Our results reveal a potentially important influence of the circadian system on platelet function in humans. Many previous studies have investigated the day/night patterns in platelet function, but ours is the first to determined the influence on platelet function of the circadian system separate from the influences of the changes in behavior and environment that normally occur across the day and night, including changes in sleep/wake state, supine/upright posture, rest/activity, fasting/ feeding, and the light/dark cycle. A better understanding of the relative importance of circadian rhythms and behaviors on platelet function is important especially for the increasing number of shift workers, travelers across time zones, and people with sleep disorders in whom influences of the circadian system are uncoupled from those of their behaviors. Shift workers, including even permanent night workers, typically experience chronic and/or recurrent misalignment between the circadian system and the sleep/wake cycle. Also sleep disorders, especially circadian rhythm sleep disorders, are associated with chronic and/or recurrent circadian misalignment. In jet lag, the misalignment is transient, although the number of days required for reentrainment may depend on the organ systems involved.