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Land management in the American southwest: a state-and-transition approach to ecosystem complexity.

State-and-transition models are increasingly being used to guide rangeland management. These models provide a relatively simple, management-oriented way to classify land condition (state) and to describe the factors that might cause a shift to another state (a transition). There are many formulations of state-and-transition models in the literature. The version we endorse does not adhere to any particular generalities about ecosystem dynamics, but it includes consideration of several kinds of dynamics and management response to them. In contrast to previous uses of state-and-transition models, we propose that models can, at present, be most effectively used to specify and qualitatively compare the relative benefits and potential risks of different management actions (e.g., fire and grazing) and other factors (e.g., invasive species and climate change) on specified areas of land. High spatial and temporal variability and complex interactions preclude the meaningful use of general quantitative models. Forecasts can be made on a case-by-case basis by interpreting qualitative and quantitative indicators, historical data, and spatially structured monitoring data based on conceptual models. We illustrate how science- based conceptual models are created using several rangeland examples that vary in complexity. In doing so, we illustrate the implications of designating plant communities and states in models, accounting for varying scales of pattern in vegetation and soils, interpreting the presence of plant communities on different soils and dealing with our uncertainty about how those communities were assembled and how they will change in the future. We conclude with observations about how models have helped to improve management decision-making.

Conservation of Natural Resources↗

The human obesity gene map: the 1997 update.

An update of the human obesity gene map incorporating published results up to October 1997 is presented. Evidence from Mendelian disorders exhibiting obesity as a clinical feature; single-gene mutation rodent models; quantitative trait loci uncovered in human genome-wide scans and in crossbreeding experiments with mouse, rat, and pig models; association and case-control studies with candidate genes; and linkage studies with genes and other markers is reviewed. All chromosomal locations of the animal loci are converted into human genome locations based on syntenic relationships between the genomes. A complete listing of all of these loci reveals that all but chromosome Y of the 24 human chromosomes are represented. Some chromosomes show at least three putative loci related to obesity on both arms (1, 2, 6, 8, 11, and 20) and several on one chromosome arm only (3p, 4q, 5q, 7q, 12q, 13q, 15q, 15p, 22q, and Xq). Studies reporting negative association and linkage results are also listed, with the exception of the unlinked markers from genome-wide scans.

Animals↗

Reducing the influence of the partial volume effect on SPECT activity quantitation with 3D modelling of spatial resolution in iterative reconstruction.

Quantitative parameters such as the maximum and total counts in a volume are influenced by the partial volume effect. The magnitude of this effect varies with the non-stationary and anisotropic spatial resolution in SPECT slices. The objective of this investigation was to determine whether iterative reconstruction which includes modelling of the three-dimensional (3D) spatial resolution of SPECT imaging can reduce the impact of the partial volume effect on the quantitation of activity compared with filtered backprojection (FBP) techniques which include low-pass, and linear restoration filtering using the frequency distance relationship (FDR). The iterative reconstruction algorithms investigated were maximum-likelihood expectation-maximization (MLEM), MLEM with ordered subset acceleration (ML-OS), and MLEM with acceleration by the rescaled-block-iterative technique (ML-RBI). The SIMIND Monte Carlo code was used to simulate small hot spherical objects in an elliptical cylinder with and without uniform background activity as imaged by a low-energy ultra-high-resolution (LEUHR) collimator. Centre count ratios (CCRs) and total count ratios (TCRs) were determined as the observed counts over true counts. CCRs were unstable while TCRs had a bias of approximately 10% for all iterative techniques. The variance in the TCRs for ML-OS and ML-RBI was clearly elevated over that of MLEM, with ML-RBI having the smaller elevation. TCRs obtained with FDR-Wiener filtering had a larger bias (approximately 30%) than any of the iterative reconstruction methods but near stationarity is also reached. Butterworth filtered results varied by 9.7% from the centre to the edge. The addition of background has an influence on the convergence rate and noise properties of iterative techniques.

Humans↗

A mathematical model for tear drainage through the canaliculi.

PURPOSE: Tear drainage through the canaliculi has been extensively studied experimentally but there has been no attempt to develop a quantitative model for this process. In this paper, we develop a mathematical model for the tear drainage through the canaliculi. METHODS: The mathematical model is based on the experimental findings of Doane, according to which the muscle action during a blink drives the tear drainage. In this paper, mathematical models are developed for the tear flow and the canalicular deformation, and the model equations are solved to predict the tear drainage rates. RESULTS: The drainage rates depend on various physiological parameters. The time to attain a steady state during the drainage process can vary from about 0.0010 s to 0.0546 s, and the tear drainage rate can vary from 0.10 microl/min to 4.00 microl/min for a normal tear film, for physiologically reasonable values of various system parameters. CONCLUSIONS: The model predictions agree with various physiological experiments, at least qualitatively. The model also helps resolve the differences between various tear drainage experiments.

Blinking↗

A model of auditory perception as front end for automatic speech recognition.

A front end for automatic speech recognizers is proposed and evaluated which is based on a quantitative model of the "effective" peripheral auditory processing. The model simulates both spectral and temporal properties of sound processing in the auditory system which were found in psychoacoustical and physiological experiments. The robustness of the auditory-based representation of speech was evaluated in speaker-independent, isolated word recognition experiments in different types of additive noise. The results show a higher robustness of the auditory front end in noise, compared to common mel-scale cepstral feature extraction. In a second set of experiments, different processing stages of the auditory front end were modified to study their contribution to robust speech signal representation in detail. The adaptive compression stage which enhances temporal changes of the input signal appeared to be the most important processing stage towards robust speech representation in noise. Low-pass filtering of the fast fluctuating envelope in each frequency band further reduces the influence of noise in the auditory-based representation of speech.

Auditory Perception↗

Control of rabbit nictitating membrane movements. I. A computer model of the retractor bulbi muscle and the associated orbital mechanics.

Our objective in this study is to synthesize existing experimental data by constructing a realistic neuromechanical control model of rabbit nictitating membrane (NM) movements. We model the retractor bulbi muscle at the motor unit level because this is the level of nervous system control and also facilitates comparison with experimental data. Our motor unit model is derived from an earlier model of muscle activation based on calcium kinetics and includes a post-activation potentiation mechanism. Motor units are combined into a model of whole muscle that includes length-tension and force-velocity effects. Finally, we incorporate the muscle model into a biomechanical model in which the globe and NM are represented as a system of inertial, viscous, and elastic elements. The model takes patterns of neural signals (in the form of impulses) as input and produces movement of the NM as output. Our muscle model quantitatively accounts for data on isometric force development and decay for twitch, double shock, and tetanic stimulation. The complete model may be used for analysis of the relationship of motoneuron activity to behavior or as a realistic response generator in models of NM conditioning. This study also highlights gaps in the experimental data on the rabbit NM effector system.

Animals↗

Dynamical coupling of PBPK/PD and AUC-based toxicity models for arsenic in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan.

A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models were developed for arsenic (As) in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan. The PBPK/PD model structure consisted of muscle, gill, gut wall, alimentary canal, and liver, which were interconnected by blood circulation. We integrate the target organ concentrations and dynamic response describing uptake, metabolism, and disposition of As and the associated area-under-curve (AUC)-based toxicological dynamics following an acute exposure. The model validations were compared against the field observations from real tilapia farms and previously published uptake/depuration experimental data, indicating that predicted and measured As concentrations in major organs of tilapia were in good agreement. The model was utilized to reasonably simulate and construct a dose-dependent dynamic response between mortality effect and equilibrium target organ concentrations. Model simulations suggest that tilapia gills may serve as a surrogate sensitive biomarker of short-term exposure to As. This integrated As PBPK/PD/AUC model quantitatively estimates target organ concentration and dynamic response in tilapia and is a strong framework for future waterborne metal model development and for refining a biologically-based risk assessment for exposure of aquatic species to waterborne metals under a variety of scenarios.

Animals↗

Cell proliferation and carcinogenesis models: general principles with illustrations from the rodent liver system.

Rates of cell proliferation, cell death, and cell differentiation affect the risk of cancer profoundly. An increase in cell proliferation rates leads to an increase in mutation rates per unit of time, which, in turn, leads to an increase in the risk of cancer. An increase in cell division rates relative to death or differentiation rates may lead to an increase in the population of critical target cells, which, again, leads to an increase in cancer risk. These fundamental principles are well illustrated by the rodent liver model for carcinogenesis. In this paper I briefly discuss some of the consequences of incorporating cell proliferation kinetics into quantitative models of cancer risk assessment. Consideration of cell kinetics can shed light on apparently paradoxical observations, such as the observation that the administration of two different promoters may lead to the same volume fraction in the rodent liver, with one promoter giving rise to a large number of small foci and the other to a small number of large foci. Another observation that can be illuminated by a consideration of cellular proliferation kinetics is the phenomenon of the inverse dose-rate effect. It has been observed with exposure to high LET radiation and to certain chemicals that fractionation of a given total dose of the agent leads to an increased life-time probability of tumor. A biological explanation of this finding can be given in terms of the effect of the agent on cell proliferation kinetics.

Animals↗

Potentiation and inhibition of tumor cell invasion by host cells and mediators.

A culture model for invasion of rat mesothelial cell layer by rat ascites hepatoma cells has been developed. By using this quantitative model, the preculture with macrophages (0.1 less than macrophage/tumor cell less than 1.0) was found to enhance both the in vitro and in vivo invasive potentials of the tumor cells. This potentiation appears to be mediated partly by oxygen radicals generated by the cocultured macrophages. The in vitro invasive capacity was also augmented by pretreating the tumor cells with TGF-beta or with activated platelets. A factor with anti-invasive potential (IIF) was extracted from rat liver. It inhibited the directed migration but not the growth of the tumor cells and was effective on their in vivo invasion and metastasis, as well.

Animals↗

[Mechanism of tumor cell invasion studied by a culture model--modification of invasiveness by host mediators].

A culture model for invasion of rat mesothelial cell layer by rat ascites hepatoma cells has been developed. By using this quantitative model, we have recently found that the invasiveness of tumor cells is not only genetically determined but is greatly influenced by their interactions with host cells and host mediators. The preculture with macrophages was found to enhance both the in vitro and in vivo invasive potentials of the tumor cells. This potentiation appears to be mediated partly by oxygen radicals generated by the cocultured macrophages. The in vitro invasive capacity was also augmented by pretreating the tumor cells with TGF-beta, or with activated platelets. In the in vitro invasion assay system, tumor cells did not invade against cultured mesothelial cell monolayers without fetal calf serum. Serum could be completely substituted by oleoyl-lysophosphatidic acid (LPA) or bacterial phospholipase D (PLD), suggesting a possible participation of particular signaling cascade, PLD-LPA(PA) system, in the invasion of certain tumor cells.

Animals↗

Quantitative structure-based modeling applied to characterization and prediction of chemical toxicity.

Quantitative modeling methods, relating aspects of chemical structure to biological activity, have long been applied to the prediction and characterization of chemical toxicity. The early linear free-energy approaches of Hansch and Free Wilson provided a fundamental scientific framework for the quantitative correlation of chemical structure with biological activity and spurred many developments in the field of quantitative structure-activity relationships (QSARs). In addition to modeling of chemical toxicity, these methods have been extensively applied to modeling of medicinal properties of chemicals. However, there are important differences in the nature and objectives of these two applications, which have led to the evolution of different modeling approaches (namely, the need for treating sets of noncongeneric toxic compounds). In this paper are discussed those approaches to chemical toxicity that have taken a more "personalized" configuration and have undergone implementation into software programs able to perform the various steps of the assessment of the hazard posed by the chemicals. These models focus both on a variety of toxicological endpoints and on key elements of toxicity mechanisms, such as metabolism.

Automation↗

A critical review of experimental observations on ear-drum structure and function.

This paper presents a review of the experimental data available concerning ear-drum structure, properties and behaviour, in order to provide a basis for quantitative modelling and to identify areas where further information is required. The review of anatomy and structure indicates a lack of quantitative data about thickness, fibre distribution, three-dimensional curvature, and post-natal development. The mechanical properties of the ear-drum and attached structures are very poorly known, particularly with respect to isotropy, uniformity and damping. A historical review of observations of ear-drum vibration patterns shows general agreement that at low frequencies the displacements of the manubrium are smaller than those of the surrounding drum. Possible reasons are suggested for the apparent incompatibility of Békésy's capacitive-probe measurements with this picture.

Animals↗

Dynamic modeling of renal blood flow in Dahl hypertensive and normotensive rats.

A method is proposed in this paper which allows characterization of renal autoregulatory dynamics and efficiency using quantitative mathematical methods. Based on data from rat experiments, where arterial blood pressure and renal blood flow are measured, a quantitative model for renal blood flow dynamics is constructed. The mathematical structure for the dynamics is chosen as a "grey-box model," i.e. the model structure is inspired from physiology, but the actual parameters is found by numerical methods. Based on a number of experiments, features are extracted from the estimated parameters, which describe myogenic responses and tubuloglomerular feedback responses separately. The method is applied to data from normo- and hypertensive Dahl rats, and a discriminator that separates data from normotensive Dahl R rats and hypertensive Dahl S rats is constructed.

Adaptation, Physiological↗

Does reflection polarization by plants influence colour perception in insects? Polarimetric measurements applied to a polarization-sensitive model retina of Papilio butterflies.

Using imaging polarimetry, we have measured some typical reflection-polarization patterns of plant surfaces (leaves and flowers) under different illuminations. Using a quantitative model to determine photon absorptions in the weakly polarization-sensitive (PS approximately 2) photoreceptors of Papilio butterflies, we have calculated the influence of reflection polarization on the colours of leaves and flowers perceived by PAPILIO: Compared with a retina containing polarization-blind colour receptors, the colour loci of specularly reflecting and, thus, strongly polarizing areas on a plant are slightly shifted, which could cause the perception of false colours. However, the colour of specularly reflecting surfaces is strongly masked by white glare, which may prevent the perception of polarization-induced hue shifts. Although the perception of polarizational false colours by Papilio butterflies was previously demonstrated with artificial, strongly colour-saturated and totally linearly polarized stimuli, we expect that the weak polarization sensitivity of Papilio photoreceptors hardly influences colour perception under natural conditions.

Animals↗

Pattern generation in the lobster (Panulirus) stomatogastric ganglion. II. Pyloric network simulation.

1. Results from the companion paper were incorporated into a physiologically realistic computer model of the three principal cell types (PD/AB, LP, PY) of the pyloric network in the stomatogastric ganglion. Parameters for the model were mostly calculated (sometimes estimated) from experimental data rather than fitting the model to observed output patterns. 2. The initial run was successful in predicting several features of the pyloric pattern: the observed gap between PD and LP bursts, the appropriate sequence of the activity periods (PD, LP, PY), and a substantial PY burst not properly simulated by an earlier model. 3. The major discrepancy between model and observed patterns was the too-early occurrence of the PY burst, which resulted in a much shortened LP burst. Motivated by this discrepancy, additional investigations were made of PY properties. A hyperpolarization-enabled depolarization-activated hyperpolarizing conductance change was discovered which may make an important contribution to the late phase of PY activity in the normal burst cycle. Addition of this effect to the model brought its predictions more in line with observed patterns. 4. Other discrepancies between model and observation were instructive and are discussed. The findings force a substantial revision in previously held ideas on pattern production in the pyloric system. More weight must be given to functional properties of individual neurons and less to properties arising purely from network interactions. This shift in emphasis may be necessary in more complicated systems as well. 5. An example has been provided of the value quantitative modeling can be to network physiology. Only through rigorous quantitative testing can qualitative theories of how the nervous system operates be substantiated.

Animals↗

QSAR study of 1,8-naphthyridin-4-ones as inhibitors of photosystem II.

The effect of substituents on in vitro activity of 20 1,8-naphthyridin-4-ones, a novel class of photosystem II inhibitors, was studied. A four-parameter QSAR model based on the molecular connectivity indices was developed which accounts for about 87% of the variations in inhibitory potencies of these compounds. The model suggests that the position, size, and polarity of substituents are factors that predominantly control their activity. By using physicochemical constants, a quantitative model for both 1,8-naphthyridin-4-ones and structurally related 2-trifluoromethyl-4-hydroxyquinoline derivatives was proposed.

Computer Simulation↗

Cell growth dynamics in long-term bladder carcinogenesis.

A biologically based probabilistic model of the carcinogenic process has been developed based on a two-stage theory of carcinogenesis. The model has been validated utilizing experimental urinary bladder carcinogenesis studies in the rat, with an emphasis on quantification of cell dynamics. Critical parameters tracked through this process include mitotic rates, cell loss and birth rates, and irreversible cellular transitions from normal to initiated to transformed states. Analyses demonstrate the sensitivity of tumor incidence to the timing and magnitude of changes to these cellular variables. Modeling has been applied to genotoxic compounds, such as N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, and non-genotoxic compounds, such as sodium saccharin. For the latter compounds, complex administration regimens have been studied, including two-generation experiments, initiation-promotion experiments, and sodium saccharin administration following ulceration and regenerative hyperplasia. Modeling indicates that the effects of such compounds can be explained entirely on the basis of cytotoxicity and consequent hyperplasia. Quantitative modeling based on biological processes has the potential for direct application to carcinogenic risk assessment.

Cell Division↗

Risk assessment of non-genotoxic carcinogens.

Rates of cell proliferation, cell death, and cell differentiation affect the risk of cancer profoundly. An increase in cell proliferation rates leads to an increase in mutation rates per unit of time, which, in turn, leads to an increase in the risk of cancer. An increase in cell division rates relative to death or differentiation rates may lead to an increase in the population of critical target cells, which, again, leads to an increase in cancer risk. These fundamental principles are well illustrated by the rodent liver model for carcinogenesis. In this paper, we shall briefly discuss some of the consequences of incorporating cell proliferation kinetics into quantitative models of cancer risk assessment. Consideration of cell kinetics can shed light on apparently paradoxical observations such as, e.g. the observation that the administration of two different promoters may lead to the same volume fraction in the rodent liver, with one promoter giving rise to a large number of small foci, and the other to a small number of large foci. Some consequences of explicitly considering cell proliferation kinetics in malignant foci are briefly discussed.

Animals↗