Heme ferrous-hydroperoxo complexes: some theoretical considerations

We report density functional calculations on complexes of ferrous hemes with hydroperoxide, where the axial ligand trans to OOH(-) is imidazole, thiolate, or phenoxide. The geometrical parameters and charge distributions within the Fe-O-O-H moiety are identical between the ferrous complexes reported here and their ferric counterparts previously described, even though the latter contain one unpaired electron on iron as opposed to the former, which are diamagnetic. The extra negative charge upon going from a formally ferric state to formally ferrous appears to be distributed essentially on the porphyrin. These findings support recent experimental data showing that the ferrous state of certain hemoproteins can interact with peroxides in a catalytically competent fashion, cleaving the O-O bond heterolytically in a manner reminiscent of the "canonical" ferric-peroxo complexes, and contrary to any expectations based on the Fenton concept commonly invoked in non-heme chemistry.     

Alcohol and the heart: theoretical considerations

It is now well established that consumption of ethyl alcohol, both acute and chronic, exerts deleterious effects on the heart. Evidence is presented that the initial event that precipitates both acute and chronic changes reflects the physical effects of alcohol on membrane phospholipids and perhaps proteins. The presence of alcohol increases membrane fluidity, a condition that leads to an adaptive change in the phospholipid composition of the membranes, with resultant greater rigidity of the membranes. The effects of alcohol on the lipid bilayer of the plasma membrane, when combined with other nonspecific insults, may lead to a drastic increase in calcium permeability; the resulting calcium influx may cause cell necrosis and initiate irreversibly cardiomyopathy. It is likely that changes in membrane fluidity also exert profound effects on enzyme and transport activities of membrane-bound proteins. In addition, alcohol may interact directly with the hydrophobic regions of proteins. Such interactions may play an important role not only in membrane-bound proteins, but also in alcohol-induced changes in contractile proteins of the heart. It is suggested that, in general, the effects of alcohol are similar to those of other anesthetic agents, and that the elucidation of the pathogenesis of alcoholic cardiomyopathy may require a deeper understanding of the physical interaction among alcohol, phospholipids, and proteins.     

Some theoretical considerations on overflow production of metabolites

The overflow production of metabolites appears to be an energy spilling process in terms of life because part of the energy of the primary substrate remains in the metabolite produced. The other part of energy, which is liberated as reducing equivalents and/or ATP along the way to the product, must be wasted. This part is discussed to be responsible for the discrepancies between the theoretically possible and experimentally obtained product yields, because for the wasting process substrate or product are consumed. By reducing the amount of this superfluous energy the product yield should be increased. The auxiliary substrate concept occurs to be an appropriate method.     

Accuracy of RBE: experimental and theoretical considerations

The concept of the relative biological effectiveness (RBE) is essential for treatment planning in carbon ion therapy and for understanding the biological effects of high-LET radiation. As this quantity depends on many factors, both its experimental determination and the assessment of its uncertainty are not trivial. For the limiting case of zero dose, where the RBE takes its maximum value RBE_α, we present in this article a simple empirical-based approach to estimate its uncertainty. A Gaussian error calculus is applied to equally take into account both uncertainties from experiments with high- and low-LET radiation. From a theoretical point of view, we then infer, using a simple Monte Carlo model, the distribution of RBE_α values. This illustrates why the conventional error propagation approach is inappropriate in some cases. In these cases, likewise also the error estimates have to be obtained with a more sophisticated approach. Uncertainties of RBE, visualized by error bars, are of importance for treatment planning and also for setting up a precision goal for predicting biophysical models such as the local effect model.     

Hormone receptor-coupling factor-adenylate cyclase interaction: theoretical considerations

The steady-state response properties of two current models for receptor/nucleotide coupling protein/adenylate cyclase systems are examined by computer modeling techniques. In the model of Levitzki (Trends Pharmac. Sci., May, 1982, pp. 203-208), a ligand may give rise to full or partial agonist behavior only. In the model of Stadel, DeLean, and Lefkowitz (1982) configurations of the rate constants can be found which lead not only to full or partial agonist behavior, but also to varying degrees of inhibition at sufficiently high concentrations of ligand, as observed experimentally in a variety of adenylate cyclase systems. In the latter model, it is also possible to find configurations of the rate constants for which addition of a ligand will lead to inhibition of adenylate cyclase activity. The nature of partial agonism and reasons as to why it may be expected to occur for a wide variety of ligands are discussed.     

Rattlesnake denning: theoretical considerations on winter temperatures

Aggregations of over-wintering rattlesnakes are considered as a hypothetical metabolic unit. Estimates of fat consumption are utilized to predict heat production during the denning season. Previously determined temperature heat production curves allow prediction of a mean body temperature for the winter season which is around 15°C above the ambient den site temperature. An estimate from the previously derived relationship between heat production per unit surface area and body temperature predicts a reduction in aggregate effective surface area of 40 % of the summed surface areas of the individual animals constituting the hypothetical aggregation.     

Yield components in Hevea brasiliensis– theoretical considerations

Abstract A theoretical analysis of yield components of Hevea brasiliensis is attempted in this paper. The effect of the major yield components, i.e. initial flow rate per unit length of tapping cut, length of the cut, percentage rubber content and plugging index on rubber yield is represented by the formula Variation in yield within and between clones can be ascribed to variation to any one of the above components. The importance of high growth rate for maintaining high yield throughout the life cycle of the tree is theoretically elucidated. While the present contention of a theoretical maximum yield of 9.5 t ha^?1 with a stand of 350 trees is questioned, the theoretical possibility of attaining that yield by increasing the stand per ha to 600 is analysed.     

Biomechanical experiments on excised myocardium: theoretical considerations

Both the specific functional form of a constitutive relation and the particular material parameters must be determined from experiments. Constitutive formulations based on experimental data are valid, however, only when the experimentally measured stresses closely represent the actual distribution of stress in a specimen. In this paper, we present theoretical considerations to help experimentalists identify conditions under which biaxial data obtained from thin slabs of non-contracting myocardium satisfy the above criterion. In particular, we present both a general framework to investigate, and specific numerical examples to illustrate, the influence of certain distributions of muscle fibers, in-plane shearing strains and particular stretching protocols on the distribution of stress within biaxially tested myocardial specimens.     

Some theoretical considerations regarding filter disk assays.

The concept of the efficiency of filter disk assays is examined from a theoretical viewpoint. It is shown that the approaches which have been recommended to measure efficiency in such assays are somewhat oversimplified and can lead to errors in data interpretation.     

Application of theoretical considerations to the analysis of ELISA data

Solid-phase immunoassays such as the ELISA are in routine use in many areas of biological research. Data from these assays are analyzed in a variety of ways, frequently without taking into account the immunochemical principles of the assay. The Reference Standard Method is often used and is suitable and convenient for obtaining concentration (or activity) values from the antigen-specific ELISA or spRIA, sandwich assays, and inhibition assays. The standard curve required for this method may be obtained by simple linear regression analysis of logarithmic or logitlogarithmic transformed data obtained from titration of the reference standard. The shape of the logarithmic plot of the reference standard provides information on the performance of the assay. Examining data from multiple dilutions of the samples is essential to assure that each titrates with the same slope as does the reference standard; the analysis routine must permit this comparison to be made. ELISANALYSIS is a program for the IBM PC which was developed to perform such analyses. It is presented here as a model, with sufficient information provided for the development of similar analytical routines by interested users. This approach to ELISA data analysis is presented as an alternative to complicated empirical curve-fitting systems and simple endpoint methods, which can be immunochemically misleading or, in some cases, even invalid. The consistent use of the described routines would encourage greater uniformity in the means of data interpretation and thereby enhance our understanding of immunobiology.     

Communicating about ocean health: theoretical and practical considerations

As anthropogenic stressors threaten the health of marine ecosystems, there is a need to better understand how the public processes and responds to information about ocean health. Recent studies of public perceptions about ocean issues report high concern but limited knowledge, prompting calls for information campaigns to mobilize public support for ocean restoration policy. Drawing on the literature from communication, psychology and related social science disciplines, we consider a set of social-cognitive challenges that researchers and advocates are likely to encounter when communicating with the public about ocean health and emerging marine diseases—namely, the psychological distance at which ocean issues are construed, the unfamiliarity of aquatic systems to many members of the public and the potential for marine health issues to be interpreted through politicized schemas that encourage motivated reasoning over the dispassionate consideration of scientific evidence. We offer theory-based strategies to help public outreach efforts address these challenges and present data from a recent experiment exploring the role of message framing (emphasizing the public health or environmental consequences of marine disease) in shaping public support for environmental policy.     

Cell-cell, cell-substrate adhesion: theoretical and experimental considerations

Cell-cell adhesion plays a fundamental role in tissue and organ development, cell mediated immunity and blood flow. In the present study a micro-mechanical model of specific adhesion is presented. Analytical expressions are derived for the adhesive energy density (gamma) at zero speed of peeling for the cases of immobile (trapped) as well as laterally mobile bonds. It is shown that gamma increases in both cases with the increasing density of bonds and with the binding of affinity of unstressed bonds. In the case of laterally mobile bonds gamma also increases with the extent of peeling. The analytical results are shown to be valid whether or not one takes into account of the bending stiffness of adhering membranes. It is also shown that gamma does not depend on the functional form of bond elasticity. The effect of the speed of peeling on the number density distribution of attached bonds is considered next. Numerical solutions for the energy required to separate conjugated cell pairs are presented. The theoretical predictions are then used to analyze experimental data on red cell aggregation and adhesion between a cytotoxic-T cell and its target cell. The results show that the binding affinity of unstressed bonds and their number density before conjugation can be obtained from data on slow peeling of cell-pairs. The information on the diffusivity of bonds, their stiffness and their rates of attachment and detachment are more difficult to obtain, requiring a set of experiments with increasing rates of separation (conjugation) of cell-pairs.     

Mass isotopomer analysis: theoretical and practical considerations.

A theory of mass isotopomer analysis based on the well-known principle of isotope dilution mass spectrometry is reviewed. An algorithm for the determination of isotope incorporation into a metabolic substrate from a labeled precursor using mass isotopomer analysis is presented. The steps include the determination of the contribution of the derivatization reagent to the observed spectrum of the derivatized substrate and the correction of contribution from 13C natural abundance using multiple linear regression analysis. Examples of the application of this theory to determine the spectrum of the trimethylsilyl derivative of the 'pure unlabeled' or mononuclidic cholesterol, and the calculation of mass isotopomer distribution in cholesterol due to tracer incorporation using this 'pure unlabeled' spectrum, are also provided.     

The economics of acetone-butanol fermentation: theoretical and market considerations

Acetone-butanol (AB) fermentation was once run commercially in many countries until these chemicals could be made more cheaply from fossil oil sources. Research into the revitalisation of the process has shown that the process could once again be run economically in niche markets if run in a relatively small industrial scale processing low-grade agricultural products. The following analysis is intended to help identify suitable niche markets.     

Apomorphine in Huntington's chorea: clinical observations and theoretical considerations

Five patients, four definitively diagnosed as suffering from Huntington's disease and the fifth with abnormal involuntary movements (AIM) and dementia but no apparent family history of the disease, were administered apomorphine. Although the short duration of action and stressful side-effects produced by apomorphine limited its use regarding a complete dose- and time-response evaluation, slight to marked diminution of AIM was seen in all patients. Optimal doses ranged from 1–2 mg across patients, producing a significant reduction in AIM for the entire hour of observations. Theoretical interpretations of these effects regarding dopaminergic receptor stimulation and/or blockade by apomorphine are discussed.