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False-positive determinations of activity against nonreplicating M. tuberculosis may arise from carryover of compounds from the nonreplicating stage of the assay that act in the replicating stage.
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Metabolism was similar between the two replicating stages.
Subsequent malaria smears and qPCR remained negative and no evidence of asexual or replicating stages were found.
8323 genes were annotated with sequence reads across the two asexually replicating stages of the parasite life cycle.
Ideally, a prime-boost approach comprising of a prophylactic vaccine with subunit, viral vectored or DNA-based vaccines, based on late-stage antigens induced in the dormant stage (transition from replicating to non-replicating stage, latency antigens) or resuscitation/reactivation stage, should have maximum impact on all stages of Mtb infection [ 2, 6, 10- 15].
PCNA has previously been shown to form distinct DNA replication foci in the parasites during replicating trophozoite stage.
Because the nonreplicating assay is bacteriostatic and coupled to a replicating outgrowth stage to permit surviving cells to increase in biomass, a replicating-inactive drug must be nonreplicating-bactericidal to give an NR-MIC90 (Fig. 1).
Approximately one-third (29/85) of the most significant non-MHC SNPs in Stage 1 (Table 1) had original GWAS P-values <0.10 in both the TDT and CMH tests, with only two of these SNPs further replicating in Stage 2 (rs11583328 and rs10469900) (Table 2).
Chemotherapy of symptomatic toxoplasmosis is mandatory; however, available drug regimens including pyrimethamine plus sulfadiazine, clindamycin, and atovaquone are limited and are only effective against the replicating tachyzoite stage [ 9].
Let the significance level of the discovery stage be α D, which means that markers with P(1) < α D are selected and replicated in the replication stage.
Each replicate stage of the study included procedurally different parts A and B according to the subdivision of the raters into subgroups of 10 and 2. Thus, the study included replicate parts I-A and II-A with 10 different raters in each and replicate parts I-B and II-B with 2 different raters in each.
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