Replication limits

To evaluate the effect of indeterminate error on the data in Table 4.1, ten replicate determinations of the mass of a single penny were made, with results shown in Table 4.7. The standard deviation for the data in Table 4.1 is 0.051, and it is 0.0024 for the data in Table 4.7. The significantly better precision when determining the mass of a single penny suggests that the precision of this analysis is not limited by the balance used to measure mass, but is due to a significant variability in the masses of individual pennies. 

Figure 3 Periodic boundary conditions realized as the limit of finite clusters of replicated simulation cells. The limit depends in general on the asymptotic shape of the clusters here it is spherical. Cations are presented as shaded circles anions as open circles.

The specification development process is a data-driven activity that requires a validated analytical method. The levels of data needed include assay precision, replicate process results (process precision), and real-time stability profiles. A statistical analysis of these data is critical in setting a realistic specification. Most often, aggregation and fragmentation degradation mechanisms are common to protein and peptide therapeutics. Therefore, the SE-HPLC method provides a critical quality parameter that would need to be controlled by a specification limit. 

Practical considerations usually limit the number of replicate specimens of each kind that can be exposed for each period of test. At least two are recommended for obvious reasons, and if a larger number can be accommodated in the programme more valuable results can be secured—especially when it is desired to establish the reality of small differences in performance. For statistical analysis, five replicates are desirable. Accounts of statistical planning and analysis are given by F. H. Haynie in Reference 2 and in ASTM 016 1984. 

Hence, on increasing the number of replicate determinations both the values of and s/yfn decrease with the result that the confidence interval is smaller. There is, however, often a limit to the number of replicate analyses that can be sensibly performed. A method for estimating the optimum number of replicate determinations is given in Section 4.15. 

The two highest concentrations of tannic acid (0.051 and 0.034%) resulted in a linear increase of virus titer up to 21 days after inoculation, even though the reduction of starch lesion formation was 91 and 64%, respectively. Thus, the virus must have replicated beyond the limitation of starch lesions. Further experiments indicated that a systemic spread of the virus into the primary leaves in cucumber plants could be obtained by daily brushing the noninoculated primary leaves (only the cotyledons were inoculated) with tannic acid following a vacuum infiltration of whole plants with 0.051% tannic acid 24 hours after virus inoculation. Primary leaves were shielded by tinfoil during the inoculation of the cotyledons to prevent accidental infection. Aerosol O.T. (0.1%) was incorporated in tannic... 

When induced in macrophages, iNOS produces large amounts of NO which represents a major cytotoxic principle of those cells. Due to its affinity to protein-bound iron, NO can inhibit a number of key enzymes that contain iron in their catalytic centers. These include ribonucleotide reductase (rate-limiting in DNA replication), iron-sulfur cluster-dependent enzymes (complex I and II) involved in mitochondrial electron transport and cis-aconitase in the citric acid cycle. In addition, higher concentrations of NO,... 

A major limitation in the development of anti-HCV compounds was the lack of a virus replication system. This was finally overcome with the development of a novel replicon system that directed persistent replication in a cell culture format (Lohmann et al. 1999). Using such a system, it was possible to demonstrate antiviral activity of an NS3/4A inhibitor in a cell culture assay, and demonstrate potency on par with treatment with interferon-a (Pause et al. 2003). 

The antiviral efficacy of IFN-A, has been evaluated in vitro in hnman hepatocyte-derived cells. IFN-X rednced HBV replication but the results suggested that antiviral efficacy in vivo wonld be limited (Hong et al. 2007). 

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