Designing experiments that aid in the identification of regulatory networks.

Predictive mathematical models of the interactions of a genetic network can provide insight into the mechanisms of gene regulation, the role of various genes within a network and how multiple genes interact leading to complex traits. However, identification of the parameters and interactions is currently a limiting step in the development of such models. This work reviews the state of the art for design of experiments in biological systems and demonstrates the need for improved design of experiments through the use of a model system. Appropriate design of experiments has a profound impact on the ability to identify a model and on the quality of resulting identified model. Key issues include the selection of appropriate input sequences (e.g. random, independent multivariate inputs) and the selection of the sampling frequencies. This work demonstrates that these issues are especially important in the identification of biochemical networks and that the traditional biochemical approach is incapable of truly identifying the behavior present in such networks.     

The Bionic Anticipation of Natural Disasters

After major natural disasters, such as the recent earthquake-tsunami event in South Asia, reports appear about the mysterious ability of animals to anticipate and to escape the impending danger. This is an opportunity to recall the long history of this phenomenon in the traditions of different civilizations, to evaluate Chinese efforts, 30-40 years ago, to use this phenomenon for earthquake prediction, and to judge its state of acceptance in modem science. An effort is made to introduce this phenomenon as a research field of modem bionics. The timing is favorable since, increasingly, infrared thermal anomalies, monitored from satellite, suggesting litho-atmospheric processes, are found to precede earthquakes. They were unexpected by seismologists and are here suggested to essentially reflect the energy conversion patterns responsible for the signals monitored by animals. The aim is to learn from animals in the long term how natural disasters can better be anticipated, and how simple technical warning systems can be developed. Some challenges are analyzed. One is interpretation of the nature of energy release prior to the main earthquake disaster resulting in ＂macro-anomaly＂ precursors, another is better to understand the effect on animal senses. The role of non-linear cooperative phenomena including tsunamitype waves is emphasized.     

Clockwise and counterclockwise hysteresis characterize state changes in the same aquatic ecosystem

Incremental increases in a driver variable, such as nutrients or detritus, can trigger abrupt shifts in aquatic ecosystems that may exhibit hysteretic dynamics and a slow return to the initial state. A model system for understanding these dynamics is the microbial assemblage that inhabits the cup‐shaped leaves of the pitcher plant Sarracenia purpurea. With enrichment of organic matter, this system flips within three days from an oxygen‐rich state to an oxygen‐poor state. In a replicated greenhouse experiment, we enriched pitcher‐plant leaves at different rates with bovine serum albumin (BSA), a molecular substitute for detritus. Changes in dissolved oxygen (DO) and undigested BSA concentration were monitored during enrichment and recovery phases. With increasing enrichment rates, the dynamics ranged from clockwise hysteresis (low), to environmental tracking (medium), to novel counter‐clockwise hysteresis (high). These experiments demonstrate that detrital enrichment rate can modulate a diversity of hysteretic responses within a single aquatic ecosystem, and suggest different management strategies may be needed to mitigate the effects of high vs. low rates of detrital enrichment.     

Experimental studies of competition between enantiomers in chiral liquid chromatography through their system peaks

Competition between the (+)- and (?) enantiomers of 2,2,2-trifluoro-1-(9-anthryl) ethanol as mobile phase additives was indicated by the chromatographic behavior of their system peaks. Two types of chiral stationary phases were used, one based on dinitrobenzoylphenylglycine and the other on dinitrobenzylphenylethylamine plus tartaric acid. The racemic mixture was used as the mobile phase additive and k′ of their system peaks was studied as a function of the mixture concentration in the mobile phase in both cases. A shift in k′ of the two system peaks was observed and considered as an indication that competition occurred. The areas of the two system peaks were also studied as a function of the concentration of the enantiomers in the samples, using two different compositions of the mobile phase. The dependency of system peaks' area on the sample composition indicated whether competition between the enantiomers occurred. One mobile phase contained 0.1 mM of the racemic mixture, where the area of the two retained system peaks behaved independently, i.e., only the peak corresponding to the enantiomer was affected by its presence in the sample. The other mobile phase contained 0.75 mM of the racemic mixture, and both peaks were affected by the injection of any one of the enantiomers. The interdependency of the system peaks' area on both the enantiomers indicated that their distribution in the chiral system was interrelated due to mutual interactions. A quantitative treatment of the interdependency and competition was excluded, due to the irreversible adsorption of the two enantiomers on the chiral stationary phase after using overloading concentrations. This irreversible adsorption was visualized by the appearance of two retained system peaks of the two residual enantiomers. These system peaks were detected only when the sample contained pure enantiomers due to competition between the enantiomer in the sample with the residual enantiomers in the stationary phase. © 1994 Wiley-Liss, Inc.     

Estimation of a Nonlinear Density-Dependence Parameter for Wild Turkey

Abstract: Although previous research and theory has suggested that wild turkey (Meleagris gallopavo) populations may be subject to some form of density dependence, there has been no effort to estimate and incorporate a density-dependence parameter into wild turkey population models. To estimate a functional relationship for density dependence in wild turkey, we analyzed a set of harvest-index time series from 11 state wildlife agencies. We tested for lagged correlations between annual harvest indices using partial autocorrelation analysis. We assessed the ability of the density-dependent theta-Ricker model to explain harvest indices over time relative to exponential or random walk growth models. We tested the homogeneity of the density-dependence parameter estimates (θ) from 3 different harvest indices (spring harvest no. reported harvest/effort, survey harvest/effort) and calculated a weighted average based on each estimate's variance and its estimated covariance with the other indices. To estimate the potential bias in parameter estimates from measurement error, we conducted a simulation study using the theta-Ricker with known values and lognormally distributed measurement error. Partial autocorrelation function analysis indicated that harvest indices were significantly correlated only with their value at the previous time step. The theta-Ricker model performed better than the exponential growth or random walk models for all 3 indices. Simulation of known parameters and measurement error indicated a strong positive upward bias in the density-dependent parameter estimate, with increasing measurement error. The average density-dependence estimate, corrected for measurement error ranged 0.25 ≤ θC ≤ 0.49, depending on the amount of measurement error and assumed spring harvest rate. We infer that density dependence is nonlinear in wild turkey, where growth rates are maximized at 39-42% of carrying capacity. The annual yield produced by density-dependent population growth will tend to be less than that caused by extrinsic environmental factors. This study indicates that both density-dependent and density-independent processes are important to wild turkey population growth, and we make initial suggestions on incorporating both into harvest management strategies.     

Sensitive analysis of α-synuclein by nonlinear laser wave mixing coupled with capillary electrophoresis

Multi-photon nonlinear laser wave-mixing spectroscopy is a novel absorption-based technique that offers excellent detection sensitivity for biomedical applications, including early diagnosis and investigation of neurodegenerative diseases. α-Synuclein is linked to Parkinson's disease (PD), and characterization of its oligomers and quantification of the protein may contribute to understanding PD. The laser wave-mixing signal has a quadratic dependence on analyte concentration, and hence the technique is effective in monitoring small changes in concentration within biofluids. A wide variety of labels can be employed for laser wave-mixing detection due to its ability to detect both chromophores and fluorophores. In this investigation, two fluorophores and a chromophore are studied and used as labels for the detection of α-synuclein. Wave-mixing detection limits of PD-related protein conjugated with fluorescein isothiocyanate, QSY 35 acetic acid, succinimidyl ester, and Chromeo P503 were determined to be 1.4 × 10⁻¹³ M, 1.4 × 10⁻¹⁰ M, and 1.9 × 10⁻¹³ M, respectively. Based on the laser probe volume used, the corresponding mass detection limits were determined to be 1.1 × 10⁻²³ mol, 1.1 × 10⁻²⁰ mol, and 1.5 × 10⁻²³ mol. This study also presents molecular-based separation and quantification of α-synuclein by laser wave mixing coupled with capillary electrophoresis.     

Electronic structure and polarizabilities of some heterocycles: I. Hydroxypyrazoles and related systems

The (hyper)polarizabilities of different tautomer forms of hydroxypyrazoles and pyrazolones have been calculated by the finite-field procedure in the MNDO approximation and the sum of states formalism in the PPP approximation, with all singly- and doubly-excited electronic configurations in the CI method. It was shown that while in the ground electronic state the values of the (hyper) polarizabilities are not essentially different, in the first excited singlet Franck-Condon state an increase of the molecular polarizabilities of some tautomers is observed. This increase is attributed to a specific change in the electronic structure of the excited state, demonstrated by the localization of the electronic transition in the different pyrazolone tautomers. The electron-donor capabilities of phenyl-substituted hydroxypyrazoles and pyrazolones are discussed.     

Application of nonlinear estimation in the exploration of dose-response relationship

In this paper a nonlinear model depending of one modifying factor to study the dependence of the PAPOVA virus reduction factor to the irradiant dose. In this model, least squares estimates of the parameters are obtained using the linearization method with the initial guesses values. An extension of the initial exponential model is proposed when the viral material is influenced by some modifying factors.