Successful Extrapolation

Conway has suggested a method that seems to give results in agreement with those of a second entirely different method, the ionic vibration method (see later discussion). Conway found that plotting the partial molar volume of a series of electrolytes involving large cations (e.g., a tetraalkylammonium series) and a constant smaller 

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Because of the multiple degradation pathways that may take place at elevated temperature, protein stability monitoring data may not conform to the Arrhenius relationship, and the maximum temperature selected for accelerated stability studies must be carefully selected. Gu et al. [32] described the different mechanisms of inactivation of interleukin-1 (3 (IL-1 (3) in solution above and below 39°C. In this example, the multiple mechanisms precluded the prediction of formulation shelf life from accelerated temperature data. In contrast, by working at 40° C and lower, Perlman and Nguyen [33] were able to successfully extrapolate data from stability studies of tissue plasminogen activator down to 5°C. 

Typically, microsomal fractions are used for TDI analysis, but in many cases TDI is performed in rCYPs. The ability to use rCYPs for TDI relies on the accurate ability to extrapolate the rCYP data [186]. The second requirement for successful extrapolation of rCYP data is that the clearance pathways of the inhibitor in question are understood. For example, raloxifene has been shown to be a strong MBI of CYP3A4 in microsomes and rCYPs, but in hepatocytes the most predominant pathway is glucuronadation, which would effectively mask any CYP3A4 inactivation observed in... 

Wienkers, L.C. (2002) Factors confounding the successful extrapolation of in vitro CYP3A inhibition information to the in vivo condition. European Journal of Pharmaceutical Sciences, 15 (3),... 

The same research group has further performed radical carbonylation reactions on the same microreactor system [36]. First, alkyl halides were initiated and effectively reacted with pressurized carbon monoxide to form carbonyl compounds. The principle was subsequently successfully extrapolated to the multicomponent coupling reactions. 1-Iodooctane, carbon monoxide and methyl vinyl ketone were reacted in the presence of 2,2 -azobis(2,4-dimethylvaleronitrile) (V-65) as an initiator and tributyltin hydride or tris(trimethylsilyl)silane (TTMSS) as catalyst (Scheme 15). 

Extrapolation. The correlation can be successfully extrapolated from the smaller sample S, to the larger population P, where n. Accurate estimation of the property in the larger population P without the cost of time and resources would greatly help the innovation of new products. 

Analytical SFC units are perfectly suited for optimizing the chromatographic conditions to maximize the process throughput. The separation of TSO racemate developed on an analytical system was therefore successfully extrapolated to a pilot unit equipped with a 50-mm id DAC column (System Supersep 50, Novasep) and integrating a CO2 recycling loop. 

Quantitative Structure-Activity Relationships (QSAR) express the biological potencies of a series of related compounds as a linear function of their physicochemical properties. A major reason for deriving a QSAR hypothesis is the hope that some aspect of the QSAR can be successfully extrapolated, to produce compounds of potency higher than any of those from which the QSAR was derived. Unfortunately, the QSAR literature does not contain many examples of successful extrapolation, or "predictive successes."(i) Even these few examples would be vulnerable to the following criticisms ... 

The successful extrapolations are relatively small in magnitude, the potency enhancement in only one Instance being appreciably more than twofold. 

The actual number of superior compounds associated with each individual successful extrapolation is rather small. 

Sooner or later" the compounds embodying the successful extrapolations would have been stumbled upon in any case. (Of course, actual medicinal chemistry programs have finite lifetimes, dependent in part on their own success, such that a "later" which is insufficiently "sooner" may become a "never" )... 

A different approach to the problem of fluid interfacial structure advocates capillary waves, which have no analogue in the bulk, as the proper modes of the interfacial fluctuations. While originally designed for low temperatures, capillary wave theory has been successfully extrapolated into the critical region of three-dimensional fluids. ... 

A. Aromatic ring systems represent the final class of hydrocarbons to be considered. The discussion will center on the benzene ring, but many more complicated systems have been examined in detail, and it has been found that most of the arguments used in the case of the simple slx-membered ring can be successfully extrapolated to those systems including the aromatic heterocyclic ring compounds. 

ZEPHYR was a considerable success in that it managed to demonstrate a breeding factor of two — that is, two plutonium nuclei were created for every one destroyed. Despite its success, extrapolating from ZEPHYR to a full-sized 100 MW reactor would have been a step too far, and so a second reactor, ZEUS, was designed to simulate as closely as practicable the size and composition of the proposed fast reactor to be built at Dounreay (the DFR). It was an important source of reactor physics information for the DER design and, later, for use in the early operation ofDER. 

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