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Bias of maximum likelihood estimator of intraclass correlation (1991)

Wang, C. S. ; Yandell, B. S. ; Rutledge, J. J.

Springer

Theoretical and applied genetics 82 (1991), S. 421-424

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ISSN: 1432-2242

Keywords: Intraclass correlation ; Maximum likelihood estimator ; Bias

Source: Springer Online Journal Archives 1860-2000

Topics: Biology

Notes: Summary A bias correction was derived for the maximum likelihood estimator (MLE) of the intraclass correlation. The bias consisted of two parts: a correction from MLE to the analysis of variance estimator (ANOVA) and the bias of ANOVA. The total possible bias was always negative and depended upon both the degree of correlation and the design size and balance. The first part of the bias was an exact algebraic expression from MLE to ANOVA, and the corrected estimator by this part was ANOVA. It was also shown that the first correction term was equivalent to Fisher's reciprocal bias correction on hisZ scores. The total possible bias of MLE was large for small and moderate samples. Relative biases were larger for small parametric values and vice versa. To ensure a relative bias less than 10% assuming an intraclass correlation of 0.025, which is not unusual in most of the animal genetic studies, the total number of observations (N) should be not less than 500. From a design point of view, minimum bias occurred atn = 2, the minimum family size possible, underN fixed.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00588594

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A novel suicide inhibitor strategy for antiparasitic drug development (1991)

Wang, C. C.

New York, N.Y. : Wiley-Blackwell

Journal of Cellular Biochemistry 45 (1991), S. 49-53

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ISSN: 0730-2312

Keywords: Trypanosoma brucei ; ornithine decarboxylase ; in vivo half-life ; PEST hypothesis ; DL-α-Difluoromethylornithine ; Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: DL-α-Difluoromethylornithine (DFMO), a suicide inhibitor of eukaryotic ornithine decarboxylase (ODC), has therapeutic activities against African trypanosomiasis. The Ki, value of DFMO for ODC of Trypanosoma brucei is somewhat higher than that for mouse ODC. The therapeutic efficacy of DFMO cannot therefore be attributed to a preferential inhibition of the parasite enzyme. The T. brucei gene encoding ODC was cloned and sequenced, and the derived amino acid sequence has 61.5% homology with that of mouse ODC, except that the C-terminal 36 amino acids of the mouse enzyme are missing from the parasite enzyme. The cloned T. brucei and mouse ODC genes were expressed in ODC-deficient Chinese hamster ovary cells (CHO) where the T. brucei enzyme was stable, but mouse ODC was unstable. Thus, the observed difference in intracellular stability is a property of the ODC protein itself, rather than of the cellular environment in which it is expressed. A chimeric ODC composed of the amino terminus of trypanosome ODC and the C-terminus of mouse ODC also was rapidly degraded in CHO cells, suggesting that peptide sequences in the mouse ODC carboxy-terminus determine its stability.The relatively slow turnover of the parasite enzyme constitutes the basis of selective antitrypanosomal action of DFMO. By this same token, many other proteins known to perform crucial functions in bacteria, fungi, protozoa, helminths, etc., also may have shorter half-lives in the mammalian hosts than in parasites. Suicide inhibitors of these proteins may have desirable characteristics as good chemotherapeutic agents. This new approach could provide an additional strategy for controlling infectious diseases.

Additional Material: 2 Ill.