A joint model of the contractile system of striated muscle (dynamic version)

The Joint Model of the Contractile System of Muscle is a theoretical construction and the question is whether it may express adequately some aspects of the biological original. In addition to the previous results which presented preliminary calculations, simulation experiments have been performed with a dynamic version of the model. The relations found between the variables studied (length, shortening velocity, isotonic contraction load, shortening heat production rate and excess of effective activity), did not essentially differ from those established by preliminary calculations; the choice of appropriate parameter values and the introduction of some additional features in the system made it possible to obtain a better approximation of relations known from measurements on the biological object. The model discloses some relevant general aspects of the contractile system of "independent" generators of force and thus contributes to a specification of the relationships between molecular and macroscopic levels of contraction phenomena. Future development or correction of the concepts under consideration depend on more suitable empirical data and further simulation experiments.     

Impedance Analysis of Ion Transport Through Supported Lipid Membranes Doped with Ionophores: A New Kinetic Approach

Kinetics of facilitated ion transport through planar bilayer membranes are normally analyzed by electrical conductance methods. The additional use of electrical relaxation techniques, such as voltage jump, is necessary to evaluate individual rate constants. Although electrochemical impedance spectroscopy is recognized as the most powerful of the available electric relaxation techniques, it has rarely been used in connection with these kinetic studies. According to the new approach presented in this work, three steps were followed. First, a kinetic model was proposed that has the distinct quality of being general, i.e., it properly describes both carrier and channel mechanisms of ion transport. Second, the state equations for steady-state and for impedance experiments were derived, exhibiting the input–output representation pertaining to the model’s structure. With the application of a method based on the similarity transformation approach, it was possible to check that the proposed mechanism is distinguishable, i.e., no other model with a different structure exhibits the same input–output behavior for any input as the original. Additionally, the method allowed us to check whether the proposed model is globally identifiable (i.e., whether there is a single set of fit parameters for the model) when analyzed in terms of its impedance response. Thus, our model does not represent a theoretical interpretation of the experimental impedance but rather constitutes the prerequisite to select this type of experiment in order to obtain optimal kinetic identification of the system. Finally, impedance measurements were performed and the results were fitted to the proposed theoretical model in order to obtain the kinetic parameters of the system. The successful application of this approach is exemplified with results obtained for valinomycin–K⁺ in lipid bilayers supported onto gold substrates, i.e., an arrangement capable of emulating biological membranes.     

Modeling ultrasonic transient scattering from biological tissues including their dispersive properties directly in the time domain

Ultrasonic imaging in medical applications involves propagation and scattering of acoustic waves within and by biological tissues that are intrinsically dispersive. Analytical approaches for modeling propagation and scattering in inhomogeneous media are difficult and often require extremely simplifying approximations in order to achieve a solution. To avoid such approximations, the direct numerical solution of the wave equation via the method of finite differences offers the most direct tool, which takes into account diffraction and refraction. It also allows for detailed modeling of the real anatomic structure and combination/layering of tissues. In all cases the correct inclusion of the dispersive properties of the tissues can make the difference in the interpretation of the results. However, the inclusion of dispersion directly in the time domain proved until recently to be an elusive problem. In order to model the transient signal a convolution operator that takes into account the dispersive characteristics of the medium is introduced to the linear wave equation. To test the ability of this operator to handle scattering from localized scatterers, in this work, two-dimensional numerical modeling of scattering from an infinite cylinder with physical properties associated with biological tissue is calculated. The numerical solutions are compared with the exact solution synthesized from the frequency domain for a variety of tissues having distinct dispersive properties. It is shown that in all cases, the use of the convolutional propagation operator leads to the correct solution for the scattered field.     

The effect of biota on global climate

A model consisting of two blocks (equations) was proposed for the analytical study of the biosphere-climate system over great periods of time. The first equation describes the balance of carbon dioxide in the atmosphere and represents the biological block of the model. The second equation is the equation of the energy balance or the physical block of the system. The model is based on the most general conceptions of living matter and the evolution process. A possible interpretation of some events and phenomena in the earth history in terms of the model is given.     

Buoyancy of some Palaeozoic ammonoids and their hydrostatic properties based on empirical 3D‐models

The interpretation of the function of the ammonoid phragmocone as a buoyancy device is now widely accepted among ammonoid researchers. During the 20^th century, several theoretical models were proposed for the role of the chambered shell (phragmocone); accordingly, the phragmocone had hydrostatic properties, which enabled it to attain neutral buoyancy, presuming it was partially filled with gas. With new three‐dimensional reconstructions of ammonoid shells, we are now able to test these hypothetical models using empirical volume data of actual ammonoid shells. We investigated three Palaeozoic ammonoids (Devonian and Carboniferous), namely Fidelites clariondi, Diallagites lenticulifer and Goniatites multiliratus, to reconstruct their hydrostatic properties, their syn vivo shell orientation and their buoyancy. According to our models, measurements and calculations, these specimens had aperture orientations of 19°, 64° and 125° during their lives. Although none of our results coincide with the aperture orientation of the living Nautilus, they do verify the predictions for shell orientations based on published theoretical models. Our calculations also show that the shorter the body chamber, the poorer was the hydrodynamic stability of the animal. This finding corroborates the results of theoretical models from the 1990s. With these results, which are based on actual specimens, we favour the rejection of hypotheses suggesting a purely benthonic mode of life of ammonoids. Additionally, it is now possible to assess hydrodynamic properties of the shells through ontogeny and phylogeny, leading to insights to validate theoretical modes of life and habitat through the animal's life.     

Are We all Natural Dualists? A Cognitive Developmental Approach*

The article takes to task the well-established anthropological claim that non-Western peoples are free from the traps of dualistic thinking. Although Vezo informants in Madagascar produce statements that could be used to support such a claim, experimental procedures that target their inferential reasoning reveal that they systematically differentiate between mind and body, between the biological processes that determine the organism and the social processes that shape personhood. This suggests that there is a significant discrepancy between people's explicit linguistic statements and their implicit theoretical knowledge. Moreover, developmental data show that such implicit theoretical presuppositions are essential to the production and transmission of cultural knowledge. Thus, Vezo children, who do not as yet differentiate between the biological mechanism of birth and the social mechanism of nurture, are still unable to grasp a salient aspect of Vezo culture, namely the causally integrated set of ideas that guide the way adults classify the social world. These findings have significant theoretical and methodological implications for the constitution of anthropological knowledge.     

Determination of three-dimensional imaging properties of a light microscope system. Partial confocal behavior in epifluorescence microscopy.

We have determined the three-dimensional image-forming properties of an epifluorescence microscope for use in obtaining very high resolution three-dimensional images of biological structures by image processing methods. Three-dimensional microscopic data is collected as a series of two-dimensional images recorded at different focal planes. Each of these images contains not only in-focus information from the region around the focal plane, but also out-of-focus contributions from the remainder of the specimen. Once the imaging properties of the microscope system are characterized, powerful image processing methods can be utilized to remove the out-of-focus information and to correct for image distortions. Although theoretical calculations for the behavior of an aberration-free microscope system are available, the properties of real lenses under the conditions used for biological observation are often far from an ideal. For this reason, we have directly determined the image-forming properties of an epifluorescence microscope under conditions relevant to biological observations. Through-focus series of a point object (fluorescently-coated microspheres) were recorded on a charge-coupled device image detector. From these images, the three-dimensional point spread function and its Fourier transform, the optical transfer function, were derived. There were significant differences between the experimental results and the theoretical models which have important implications for image processing. The discrepancies can be explained by imperfections of the microscope system, nonideal observation conditions, and partial confocal effects found to occur with epifluorescence illumination. Understanding the optical behavior of the microscope system has indicated how to optimize specimen preparation, data collection, and processing protocols to obtain significantly improved images.     

Testing the metabolic theory of ecology

The metabolic theory of ecology (MTE) predicts the effects of body size and temperature on metabolism through considerations of vascular distribution networks and biochemical kinetics. MTE has also been extended to characterise processes from cellular to global levels. MTE has generated both enthusiasm and controversy across a broad range of research areas. However, most efforts that claim to validate or invalidate MTE have focused on testing predictions. We argue that critical evaluation of MTE also requires strong tests of both its theoretical foundations and simplifying assumptions. To this end, we synthesise available information and find that MTE's original derivations require additional assumptions to obtain the full scope of attendant predictions. Moreover, although some of MTE's simplifying assumptions are well supported by data, others are inconsistent with empirical tests and even more remain untested. Further, although many predictions are empirically supported on average, work remains to explain the often large variability in data. We suggest that greater effort be focused on evaluating MTE's underlying theory and simplifying assumptions to help delineate the scope of MTE, generate new theory and shed light on fundamental aspects of biological form and function.     

A theoretical model of DNA curvature

Distortions from the uniform idealized B-DNA structure are investigated in terms of differential interactions between adjacent nucleotide pairs on the basis of conformational energy calculations. A theoretical model of DNA curvature is proposed based on the evaluation of the curvature vector defined in the complex plane and the corresponding variance. The model appears to contain the basic physical features for translating the deterministic fluctuations of DNA sequences in superstructure elements. It allows the quantitative reproduction of all the available gel electrophoresis experiments on both periodical polynucleotides and tracts of DNAs as well as the theoretical prediction of the sequence dependent DNA writhing in good agreement with the experimental data. The general pattern of agreement between the theoretical and experimental data and the biological significance of the results obtained allow an extensive application of the model for the screening of DNA regions which are possible candidates for protein recognition.     

Modeling the dynamics of the solvated SL1 domain of HIV-1 genomic RNA

A mode-coupling solution of the Smoluchowski diffusion equation (MCD theory), designed to describe the dynamics of wobbling macromolecules in water, is applied to a macromolecular bead model including water beads in the nearest layers. The necessary statistical averages are evaluated by time averaging along a molecular dynamics (MD) trajectory where both solute and water are introduced as atomistic models. The cross peaks in (1)H nuclear Overhauser effect spectroscopy (NOESY) NMR spectra that are routinely measured to determine biological structures are here calculated for the mutated 23 nucleotides stem-loop fragment of the SL1 domain in the HIV-1(Lai) genomic RNA. The calculations are in acceptable agreement with experiments without requiring any screening of the hydrodynamic interactions. The screening of hydrodynamics was necessary in previous MCD calculations obtained by using the same full atomistic MD trajectory, but a nonsolvated frictional model.     

Effect of immigration on a chaotic insect population

Recently, the most convincing evidence of complex dynamics and chaos in biological populations has been presented for Tribolium castaneaum, a classic laboratory model insect. In this note, the robustness of this system is investigated and a constant immigration term is added to the adult population equation. It has been found that such perturbation to the model can either have a complicating effect (when the isolated system is periodic) or a simplifying one (when the system is chaotic in isolation).     

Extracting Labeled Topological Patterns from Samples of Networks

An advanced graph theoretical approach is introduced that enables a higher level of functional interpretation of samples of directed networks with identical fixed pairwise different vertex labels that are drawn from a particular population. Compared to the analysis of single networks, their investigation promises to yield more detailed information about the represented system. Often patterns of directed edges in sample element networks are too intractable for a direct evaluation and interpretation. The new approach addresses the problem of simplifying topological information and characterizes such a sample of networks by finding its locatable characteristic topological patterns. These patterns, essentially sample-specific network motifs with vertex labeling, might represent the essence of the intricate topological information contained in all sample element networks and provides as well a means of differentiating network samples. Central to the accurateness of this approach is the null model and its properties, which is needed to assign significance to topological patterns. As a proof of principle the proposed approach has been applied to the analysis of networks that represent brain connectivity before and during painful stimulation in patients with major depression and in healthy subjects. The accomplished reduction of topological information enables a cautious functional interpretation of the altered neuronal processing of pain in both groups.     

Synthesis of New Styrylquinoline Cellular Dyes,Fluorescent Properties,Cellular Localization and Cytotoxic Behavior

New styrylquinoline derivatives with their photophysical constants are described. The synthesis was achieved via Sonogashira coupling using the newly developed heterogeneous nano-Pd/Cu catalyst system, which provides an efficient synthesis of high purity products. The compounds were tested in preliminary fluorescent microscopy studies to in order to identify their preferable cellular localization, which appeared to be in the lipid cellular organelles. The spectroscopic properties of the compounds were measured and theoretical TD-DFT calculations were performed. A biological analysis of the quinolines that were tested consisted of cytotoxicity assays against normal human fibroblasts and colon adenocarcinoma cells. All of the compounds that were studied appeared to be safe and indifferent to cells in a high concentration range. The presented results suggest that the quinoline compounds that were investigated in this study may be valuable structures for development as fluorescent dyes that could have biological applications.     

Computer simulation of DNA supercoiling in a simple elastomechanical approximation

DNA supercoiling is both an interesting problem from the theoretical point of view and an important phenomenon affecting DNA functions in vivo. Experimentally, however, hardly more than the overall hydrodynamic shape, superhelical density, and enzymic or chemical reactivity of the parameters that are in some way related to DNA secondary and tertiary structure in the superhelical state can be determined. Consequently, it is highly desirable to build up models of DNA supercoiling that, on the one hand, match the above type of global data and, on the other, take advantage of the knowledge about DNA structure at lower levels of complexity, i.e., with linear DNA molecules and its synthetic models. One possible approach, presented here, deals with an extension of Fuller's and Benham's general ideas concerning an elastomechanical model of DNA supercoiling. We extend their model with an algorithm suitable for numerical calculations and construct a fast computer program, ROPASE , that displays the rod shapes as dependent on its elastic properties and applied stress. Development of this program made inevitable a detailed analysis of the input parameters found to be degenerate in the sense that not all of them should be considered variable to generate the whole set of possible solutions of the model. Many calculations were performed using ROPASE to test its properties and the properties of the elastomechanical model. Representative DNA shapes are presented.     

The catalytic mechanism of protein tyrosine phosphatases revisited.

Experimental and theoretical studies of the catalytic mechanism in protein tyrosine phosphatases and dual specific phosphatases are reviewed. The structural properties of these enzymes contributing to the efficient rate enhancement of phosphate monoester hydrolysis have been established during the last decade. There are, however, uncertainties in the interpretation of available experimental data that make the commonly assumed reaction mechanism somewhat doubtful. Theoretical calculations as well as analysis of crystal structures point towards an alternative interpretation of the ionisation state in the reactive complex.     

Diffusion models for chemotaxis: a statistical analysis of noninteractive unicellular movement.

A program is developed for applying stochastic differential equations to models for chemotaxis. First a few of the experimental and theoretical models for chemotaxis both for swimming bacteria and for cells migrating along a substrate are reviewed. In physical and biological models of deterministic systems, finite difference equations are often replaced by a limiting differential equation in order to take advantage of the ease in the use of calculus. A similar but more intricate methodology is developed here for stochastic models for chemotaxis. This exposition is possible because recent work in probability theory gives ease in the use of the stochastic calculus for diffusions and broad applicability in the convergence of stochastic difference equations to a stochastic differential equation. Stochastic differential equations suggest useful data for the model and provide statistical tests. We begin with phenomenological considerations as we analyze a one-dimensional model proposed by Boyarsky, Noble, and Peterson in their study of human granulocytes. In this context, a theoretical model consists in identifying which diffusion best approximates a model for cell movement based upon theoretical considerations of cell physiology. Such a diffusion approximation theorem is presented along with discussion of the relationship between autocovariance and persistence. Both the stochastic calculus and the diffusion approximation theorem are described in one dimension. Finally, these tools are extended to multidimensional models and applied to a three-dimensional experimental setup of spherical symmetry.     

A systems approach to morphogenesis in Arabidopsis thaliana: II. Modeling the regulation of shoot apical meristem structure

Two models of the mechanism maintaining a zonal structure in the shoot apical meristem (SAM) were built based on the analysis of experimental data on the interactions between CLV1, CLV2, CLV3, and WUS genes and the concepts of their role in this mechanism. The first model, a simple one-dimensional model with two morphogens, which is a variant of Wolpert’s French flag model [1], describes the regulation of zone distribution along the SAM vertical axis. Despite a number of simplifications, this model has stationary solutions with biologically meaningful interpretation. The simplifying assumptions were successively abandoned in constructing a two-dimensional model of the mechanism underlying the regulation of SAM structure. This model provides a better understanding of the distributed system that regulates the SAM structure, and allows more detailed formalization of the modern concepts and experimental data concerning this mechanism.