First principles investigation of singly reduced cytochrome P450.

1. The application of novel ab initio quantum mechanical methods to the states in the catalytic cycle of cytochrome P450 following the first reduction step is described. 2. A good correlation was found between the calculated energy of reduction and the experimentally determined redox potential for a range of substrate- and substrate analogue-bound systems. 3. On reduction of the haem system, the ground state of Fe remains Fe3+. On binding of a CO molecule, Fe adopts a low-spin Fe2+ state, in agreement with experiment. However, on binding of an O2 molecule, calculations indicate that the system adopts a ferric superoxide ground state, in which the Fe is in a low-spin Fe3+ state.     

The influence of organic chelators on the toxicity of copper to embryos of the pacific oyster,Crassostrea gigas

The effects of copper on the development ofCrassostrea gigas embryos were determined with a 48-hr static bioassay. In filtered, sterilized seawater from Bodega Bay, California, the LC₁₀₀ was 20g Cu/L, and the LC₅₀ was 12g Cu/L. Destruction of the naturally occurring dissolved organic material in the culture water by UV oxidation decreased embryo survival at 10g Cu/L.The addition to seawater of five organic chelators (ethylenediaminetetraacetic acid (EDTA), sodium citrate, glycine, and oxalate at 1×10^–6 M, and humic matter at 2 mg/L) increased embryo survival. EDTA and humic matter were the most effective chelators; EDTA significantly increased survival at 100g Cu/L and humic matter did so at 40g Cu/L. The ability of a chelator to increase survival was related to the stability constant of the copper-chelator complex.This work was supported by the U.S. Nuclear Regulatory Commission (Memorandum of Understanding with the U.S. Department of Energy) and by the U.S. Department of Energy (contract number W-7405-ENG-48).     

Flexure dose: the low-dose limit of effective fractionation

Total radiation dose often can be increased without subsequent increases in the severity of tissue injury by using reduced doses per fraction. The flexure dose, df, is defined as the largest fractional dose for which further fractionation produces no significant change in the total dose required to reach a specified effect level. Thus, df is clinically relevant in that it represents the limit of effective dose fractionation. For those tissues in which injury reflects depletion of a critical proportion of target cells, the flexure dose is a measure of the extent of the initial, nearly linear portion of the dose-survival curve. More generally, the flexure dose is a measure of the extent of the initial, nearly linear portion of a dose-response curve in organized tissue, whatever its relationship to clonogenic target cells might be. Several quantitative expressions for df are derived. The characteristic common to these is that each defines the flexure dose as a multiple of the ratio alpha/beta of the parameters of the linear-quadratic model of cell survival or dose response, where the multiple is a measure of experimental or statistical resolution. These multiples tend to fall within a limited range, thereby defining the "region of flexure" via the inequality 0.05 (alpha/beta) less than or equal to df less than or equal to 0.15 (alpha/beta). Estimates of the region of flexure are presented for a variety of normal and neoplastic tissues.     

The relation between aerobic fitness and serum cholesterol levels in a large employed population

BACKGROUND. The purpose of this epidemiologic study was to determine the extent to which aerobic fitness was associated with total cholesterol/HDL-C ratios greater than 5.0 in 10,455 adults. The confounding effects of age, gender, income, body fat, smoking, and alcohol use were also examined. METHODS. A step test was used to estimate aerobic fitness, and serum cholesterol was measured in a certified lab. Lifestyle information was gathered using written questionnaires, and body fat was assessed using skinfold measurements. RESULTS. High fitness levels were associated with low prevalence of elevated total/HDL-C ratios. After controlling for the potential confounders, adults classified as having excellent, very good, good, or fair aerobic fitness levels were .46, .64, .61, and .85 times as likely to have elevated ratios compared to poorly fit adults, respectively. High-level fitness was also related to high HDL-C levels and low total cholesterol levels. DISCUSSION. Cause-and-effect conclusions are not warranted; however, poorly fit adults appear to be at increased risk of elevated levels of serum cholesterol.     

Looking at innovative multihospital systems: how marketing differs

Multihospital systems are an important and growing component in the health care delivery system in the United States. Because formalized marketing is relatively new in multihospital systems, the potential to increase the marketing productivity of member hospitals is great. The more is known about how these systems function, the more effective will be the public and private decision making involving these systems. To that end, the authors position marketing in multihospital systems as an innovative technology and examine comparative profiles of innovative and noninnovative multihospital systems. More innovative systems, scoring higher on the marketing innovation attribute index, are characterized by greater information systems and communication support, as well as a stronger commitment to the marketing function. Strategic implications and future research directions are explored.