Validation and adjustment of the mathematical prediction model for human sweat rate responses to outdoor environmental conditions

Under outdoor conditions this model was over estimating sweat loss response in shaded (low solar radiation) environments, and underestimating the response when solar radiation was high (open field areas). The present study was conducted in order to adjust the model to be applicable under outdoor environmental conditions. Four groups of fit acclimated subjects participated in the study. They were exposed to three climatic conditions (30 degrees, 65% rh; 31 degrees C, 40% rh; and 40 degrees C, 20% rh) and three levels of metabolic rate (100, 300 and 450 W) in shaded and sunny areas while wearing shorts, cotton fatigues (BDUs) or protective garments. The original predictive equation for sweat loss was adjusted for the outdoor conditions by evaluating separately the radiative heat exchange, short-wave absorption in the body and long-wave emission from the body to the atmosphere and integrating them in the required evaporation component (Ereq) of the model, as follows: Hr = 1.5SL0.6/I(T) (watt) H1 = 0.047Me.th/I(T) (watt), where SL is solar radiation (W.m-2), Me.th is the Stephan Boltzman constant, and I(T) is the effective clothing insulation coefficient. This adjustment revealed a high correlation between the measured and expected values of sweat loss (r = 0.99, p < 0.0001).     

A generalized F mixture model for cure rate estimation

Cure rate estimation is an important issue in clinical trials for diseases such as lymphoma and breast cancer and mixture models are the main statistical methods. In the last decade, mixture models under different distributions, such as exponential, Weibull, log-normal and Gompertz, have been discussed and used. However, these models involve stronger distributional assumptions than is desirable and inferences may not be robust to departures from these assumptions. In this paper, a mixture model is proposed using the generalized F distribution family. Although this family is seldom used because of computational difficulties, it has the advantage of being very flexible and including many commonly used distributions as special cases. The generalised F mixture model can relax the usual stronger distributional assumptions and allow the analyst to uncover structure in the data that might otherwise have been missed. This is illustrated by fitting the model to data from large-scale clinical trials with long follow-up of lymphoma patients. Computational problems with the model and model selection methods are discussed. Comparison of maximum likelihood estimates with those obtained from mixture models under other distributions are included.     

Investigation of membrane disruption in the reaction catalyzed by cholesterol oxidase

Dye leakage experiments were undertaken to investigate the membrane disruption properties of cholesterol oxidase. Inspection of the X-ray crystal structures of cholesterol oxidase suggested that an active-site "lid" opens in order to bind substrate [Li, J., Vrielink, A., Brick, P., & Blow, D. M. (1993) Biochemistry 32, 11507-11515]. We tested whether the interaction of the putative active-site lid with the membrane was sufficiently disruptive of the membrane structure to cause leakage or lysis of the cell membrane. Vesicles (100 nm) composed of egg phosphatidylcholine, 2-palmitoyl-3-oleoyl-1-sn-phosphatidylethanolamine, and 2-palmitoyl-3-oleoyl-1-sn-phosphatidylcholine were used in this study to mimic biomembranes. To separate the effects of membrane binding from conversion of cholesterol to cholest-4-en-3-one, the active-site mutant E361Q was utilized. In the reaction catalyzed by E361Q, isomerization of the cholest-5-en-3-one intermediate is suppressed and cholest-5-en-3-one is the major product isolated. Furthermore, E361Q produces cholest-5-en-3-one 20-fold more slowly than wild type produces cholest-4-en-3-one from cholesterol. Wild-type and E361Q cholesterol oxidases bind to vesicles with an apparent K(D) of approximately 25 microM, as measured by quenching of intrinsic tryptophan fluorescence, irrespective of headgroup size and cholesterol content. Membrane disruption was measured by leakage of the encapsulated marker carboxyfluorescein. Leakage was observed with cholesterol-containing vesicles and wild-type enzyme only; the rate of leakage was dependent on the rate of cholest-4-en-3-one production. E361Q did not induce membrane disruption, regardless of vesicle type tested. Thus, binding of cholesterol oxidase to the membrane and partitioning of cholesterol into the active site does not sufficiently perturb the bilayer to cause leakage of vesicle contents. Formation of the product cholest-4-en-3-one, however, does increase membrane permeability. Expansion of the lipid bilayer upon conversion of cholesterol to cholest-4-en-3-one is the likely cause of this increased permeability.