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PubMed2002

Identification and robust control of an experimental servo motor.

In this work, the design of a robust controller for an experimental laboratory-scale position control system based on a dc motor drive as well as the corresponding identification and robust stability analysis are presented. In order to carry out the robust design procedure, first, a classic closed-loop identification technique is applied and then, the parametrization by internal model control is used. The model uncertainty is evaluated under both parametric and global representation. For the latter case, an interesting discussion about the conservativeness of this description is presented by means of a comparison between the uncertainty disk and the critical perturbation radius approaches. Finally, conclusions about the performance of the experimental system with the robust controller are discussed using comparative graphics of the controlled variable and the Nyquist stability margin as a robustness measurement.

Computer Simulation↗
PubMed1999

Activation of CheY mutant D57N by phosphorylation at an alternative site, Ser-56.

The site of phosphorylation of the chemotaxis response regulator CheY is aspartate 57. When Asp-57 is replaced with an asparagine, the resultant protein can be phosphorylated at an alternative site. We report here that phosphorylation of this mutant protein, CheY D57N, at the alternative site affords the protein activity in vivo in the absence of CheZ. Using a direct phosphopeptide mapping approach, we identified the alternate phosphorylation site as serine 56. Introduction of a Ser-->Ala substitution at this position in wild-type CheY had no effect on function. However, replacement of Ser-56 with Ala in CheY D57N abrogated the activity seen in vivo for the CheY D57N single mutant protein, and no phosphorylation of the CheY S56A/D57N double mutant protein was observed in vitro. Construction and analysis of double mutants CheY D57N/T87A and CheY D57N/K109R, which were both inactive, suggested that phosphorylation at Ser-56 or Asp-57 may activate the protein by similar mechanisms. In contrast to CheY D57N, mutant CheY D57E displayed no activity in vivo, despite its ability to be phosphorylated in vitro. Acid-base stability analysis indicated that CheY D57E phosphorylates on an acidic residue, presumably Glu-57. These data suggest that a key determinant of the ability of a phosphoryl group to activate CheY is proximity to the hydrophobic core of the protein, with consequent opportunity to reposition key residues, irrespective of the chemical nature of the linkage attaching the phosphoryl group to CheY.

Amino Acid Substitution↗
PubMed2004

Analyzing intramolecular dynamics by fast Lyapunov indicators.

We report an analysis of intramolecular dynamics of the highly excited planar carbonyl sulfide below and at the dissociation threshold by the fast Lyapunov indicator method. By mapping out the variety of dynamical regimes in the phase space of this molecule, we obtain the degree of regularity of the system versus its energy. We combine this stability analysis with a periodic orbit search, which yields a family of elliptic periodic orbits in the regular part of phase space and a family of in-phase collinear hyperbolic orbits associated with the chaotic regime.

Journal Article↗
PubMed2002

Instability of thin liquid films by density variations: a new mechanism that mimics spinodal dewetting.

Based on the linear stability analysis and nonlinear simulations, conditions are established under which instability and dewetting of a thin liquid film can be engendered solely by the density variations (for example, due to confinement, layering, defects, and restructuring) related to changes in the local film thickness. An increase in the density with the increasing film thickness can stabilize a thermodynamically unstable film, and, equally interesting, a decrease in the density with increasing film thickness can render a thermodynamically stable film unstable. Morphological characteristics of this novel density variation induced instability closely resemble the well-known spinodal dewetting.

Journal Article↗
PubMed1975

[Study of the stability and the degradation of fluorescence in the immunofluorescence technic (FTA-ABS) using pulsed lasers].

The use of two pulsed lasers as excitation sources in the immunofluorescent technique FTA-ABS (fluorescent treponemal antibody absorption) shows that excitation of specimens by continuous or long-duration pulses of light (in the order of a millisecond) degrades the fluorescence in such a way that it is impossible to quantify exactly the fluorescent signal or repeat the analysis. Stability of fluorescence can be achieved by very short excitation pulses (in the order of a microsecond) and this fast fluorescent signal can be detected only by an electronic detection and recording system. With such a system, high precision is obtained by elimination of errors by the human eye.

Evaluation Studies as Topic↗
PubMed1985

Physico-chemical model of a protocell.

A physico-chemical model of a self-maintaining unity or protocell is constructed on the basis of reaction and diffusion processes. The surface motion of the protocell is taken into account explicitly by a so-called Stefan condition, which leads to a nonlinear feedback to the reaction and diffusion processes. The spatio-temporal dynamics in the neighbourhood of the steady states is investigated in the framework of linear stability analysis with the use of an expansion in terms of spherical harmonics Ylm. It is shown that modes with l greater than or equal to 2 become successively unstable with increasing nutrient supply. The leading instability with l = 2 initiates a process of the nonlinear dynamics which is interpreted as the onset of division. A stabilizing effect of surface tension is also discussed.

Cell Division↗
PubMed2004

Genetic networks with canalyzing Boolean rules are always stable.

We determine stability and attractor properties of random Boolean genetic network models with canalyzing rules for a variety of architectures. For all power law, exponential, and flat in-degree distributions, we find that the networks are dynamically stable. Furthermore, for architectures with few inputs per node, the dynamics of the networks is close to critical. In addition, the fraction of genes that are active decreases with the number of inputs per node. These results are based upon investigating ensembles of networks using analytical methods. Also, for different in-degree distributions, the numbers of fixed points and cycles are calculated, with results intuitively consistent with stability analysis; fewer inputs per node implies more cycles, and vice versa. There are hints that genetic networks acquire broader degree distributions with evolution, and hence our results indicate that for single cells, the dynamics should become more stable with evolution. However, such an effect is very likely compensated for by multicellular dynamics, because one expects less stability when interactions among cells are included. We verify this by simulations of a simple model for interactions among cells.

Animals↗
PubMedDate not supplied

Cost-effectiveness analysis and the formulary decision-making process.

BACKGROUND: Faced with high drug expenditures in an environment of cost containment, drug formulary systems, particularly in managed care, have become more dependent on pharmacoeconomic evaluations to assess the value of new products. Within pharmacoeconomics (PE), cost-effectiveness analysis (CEA) is the most commonly used method. However, current methodological concerns about CEA have limited its practical contribution to the formulary process. Advances in analysis are likely to improve the relevance of CEA over time. OBJECTIVE: The purpose of this paper is to review CEA, its limitations, and its applications in formulary decision making in order to promote greater utility of CEA for managed care pharmacists. SUMMARY: Enhancements to CEA, such as the development of modeling software, rank-order stability analysis, cost-consequence analysis (CCA), and budget impact analysis are discussed. A combined method of CCA-CEA and standardized guidelines are suggested to improve the impact of CEA in the drug formulary process. CONCLUSION: Along with advances in its methodology and relevant standardized guidelines, CEA will gain increased importance in formulary decision making, helping to assure the goal of cost containment while ensuring quality of care.

Cost-Benefit Analysis↗
PubMed1999

Dynamical analysis of gene networks requires both mRNA and protein expression information.

One of the important goals of biology is to understand the relationship between DNA sequence information and nonlinear cellular responses. This relationship is central to the ability to effectively engineer cellular phenotypes, pathways, and characteristics. Expression arrays for monitoring total gene expression based on mRNA can provide quantitative insight into which gene or genes are on or off; but this information is insufficient to fully predict dynamic biological phenomena. Using nonlinear stability analysis we show that a combination of gene expression information at the message level and at the protein level is required to describe even simple models of gene networks. To help illustrate the need for such information we consider a mechanistic model for circadian rhythmicity which shows agreement with experimental observations when protein and mRNA information are included and we propose a framework for acquiring and analyzing experimental and mathematically derived information about gene networks.

Animals↗
PubMed1999

Hydrodynamic Instability of Liquid Films on Moving Fibers.

The stability of liquid films on moving fibers is studied with a focus on effects caused by film-solid adhesion interactions and hydrodynamic interactions between the film and the surrounding gas. We show that at high fiber velocities (large Reynolds numbers) the film-gas hydrodynamic interactions induce instability in films, which would, otherwise, be stabilized by the adhesion interactions at static conditions. Two types of unstable modes caused by hydrodynamic factors are found: the first corresponds to the Kelvin-Helmholtz waves induced by inertia effects; the second, induced by viscosity effects, is observed at smaller (yet still large) Reynolds numbers when the Kelvin-Helmholtz instability is suppressed. Linear stability analysis of the system of coupled hydrodynamic equations of film and gas flow is performed by the method of normal modes. We derive the general dispersion relation as an implicit equation with respect to the mode frequency. In the limit of vanishing fiber velocities, the obtained equation provides the dispersion equation for motionless fibers. The conditions of film stability and unstable modes are analyzed in terms of two dimensionless parameters, the adhesion factor, which quantifies the intensity of film-fiber interactions, and the Weber number, which quantifies the intensity of film-gas interactions. The Reynolds number determines the regions of validity of the inviscid and viscous regimes of film instability. The results are illustrated by estimates of the stability conditions for moving fibers in terms of the stability diagram, the critical film thickness, the fastest unstable mode, and the corresponding characteristic break-up time. Although the methods developed are applicable for any type of liquid-solid interaction, the estimates were made for the long-range van der Waals interactions. Practical applications include various technologies related to fabrication and chemical modifications of fibers and fiber products, e.g., spin finishing and lubrication. Copyright 1999 Academic Press.

Journal Article↗
PubMed2005

Improved global robust asymptotic stability criteria for delayed cellular neural networks.

This paper considers the problem of global robust stability analysis of delayed cellular neural networks (DCNNs) with norm-bounded parameter uncertainties. In terms of a linear matrix inequality, a new sufficient condition ensuring a nominal DCNN to have a unique equilibrium point which is globally asymptotically stable is proposed. This condition is shown to be a generalization and improvement over some previous criteria. Based on the stability result, a robust stability condition is developed, which contains an existing robust stability result as a special case. An example is provided to demonstrate the reduced conservativeness of the proposed results.

Algorithms↗
PubMed2005

The development of bioactive triple helix-forming oligonucleotides.

We are developing triple helix-forming oligonucleotides (TFOs) as gene targeting reagents in mammalian cells. We have described psoralen-conjugated TFOs containing 2'-O-methyl (2'OMe) and 2'-O-aminoethoxy (AE) ribose substitutions. TFOs with a cluster of 3-4 AE residues, with all other sugars as 2'OMe, were bioactive in a gene knockout assay in mammalian cells. In contrast, TFOs with one or two clustered, or three dispersed, AE residues were inactive. Thermal stability analysis of the triplexes indicated that there were only incremental differences between the active and inactive TFOs. However the active and inactive TFOs could be distinguished by their association kinetics. The bioactive TFOs showed markedly greater on-rates than the inactive TFOs. It appears that the on-rate is a better predictor of TFO bioactivity than thermal stability. Our data are consistent with a model in which a cluster of 3-4 AE residues stabilizes the nucleation event that precedes formation of a complete triplex. It is likely that triplexes in cells are much less stable than triplexes in vitro probably as a result of elution by chromatin-associated translocases and helicases. Consequently the biologic assay will favor TFOs that can bind and rebind genomic targets quickly.

Animals↗
PubMed2004

Density-driven instabilities of variable-viscosity miscible fluids in a capillary tube.

A linear stability analysis is presented for variable-viscosity miscible fluids in an unstable configuration; that is, a heavier fluid placed above a lighter one in a vertically oriented capillary tube. The initial interface thickness is treated as a parameter to the problem. The analysis is based on the three-dimensional Stokes equations, coupled to a convection-diffusion equation for the concentration field, in cylindrical coordinates. When both fluids have identical viscosities, the dispersion relations show that for all values of the governing parameters the three-dimensional mode with an azimuthal wave number of one represents the most unstable disturbance. The stability results also indicate the existence of a critical Rayleigh number of about 920, below which all perturbations are stable. For the variable viscosity case, the growth rate does not depend on which of the two fluids is more viscous. For every parameter combination the maximum of the eigenfunctions tends to shift toward the less viscous fluid. With increasing mobility ratio, the instability is damped uniformly. We observe a crossover of the most unstable mode from azimuthal to axisymmetric perturbations for Rayleigh numbers greater than 10(5) and high mobility ratios. Hence, the damping influence is much stronger on the three-dimensional mode than the corresponding axisymmetric mode for large Rayleigh numbers. For a fixed mobility ratio, similar to the constant viscosity case, the growth rates are seen to reach a plateau for Rayleigh numbers in excess of 10(6). At higher mobility ratios, interestingly, the largest growth rates and unstable wave numbers are obtained for intermediate interface thicknesses. This demonstrates that, for variable viscosities, thicker interfaces can be more unstable than their thinner counterparts, which is in contrast to the constant viscosity result where growth rate was seen to decline monotonically with increasing interface thickness.

Models, Theoretical↗
PubMed2001

Electronic detection of single-base mismatches in DNA with ferrocene-modified probes.

Genotyping and gene-expression monitoring is critical to the study of the association between genetics and drug response (pharmacogenomics) and the association of sequence variation with heritable phenotypes. Recently, we developed an entirely electronic method for the detection of DNA hybridization events by the site-specific incorporation of ferrocenyl derivatives into DNA oligonucleotides. To perform rapid and accurate point mutation detection employing this methodology, two types of metal-containing signaling probes with varying redox potentials are required. In this report we describe a new ferrocene-containing phosphoramidite 9 that provides a range of detectable redox potentials. Using automated DNA/RNA synthesis techniques the two ferrocenyl complexes were inserted at various positions along oligonucleotide probes. Thermal stability analysis of these metal-containing DNA oligonucleotides indicates that incorporation of 9 resulted in no destabilization of the duplex. A mixture of oligonucleotides containing compounds 9 and I was analyzed by alternating current voltammetry (ACV) monitored at the 1st harmonic. The data demonstrate that the two ferrocenyl oligonucleotide derivatives can be distinguished electrochemically. A CMS-DNA array was prepared on an array of gold electrodes on a printed circuit board substrate with a self-assembled mixed monolayer, coupled to an electronic detection system. Experiments for the detection of a single-base match utilizing two signaling probes were carried out. The results demonstrate that rapid and accurate detection of a single-base mismatch can be achieved by using these dual-signaling probes on CMS-DNA chips.

Base Pair Mismatch↗
PubMed1997

Dynamics of two-component biochemical systems in interacting cells; synchronization and desynchronization of oscillations and multiple steady states.

Systems of interacting cells containing a metabolic pathway with an autocatalytic reaction are investigated. The individual cells are considered to be identical and are described by differential equations proposed for the description of glycolytic oscillations. The coupling is realized by exchange of metabolites across the cell membranes. No constraints are introduced concerning the number of interacting systems, that is, the analysis applies also to populations with a high number of cells. Two versions of the model are considered where either the product or the substrate of the autocatalytic reaction represents the coupling metabolite (Model I and II, respectively). Model I exhibits a unique steady state while model II shows multistationary behaviour where the number of steady states increases strongly with the number of cells. The characteristic polynomials used for a local stability analysis are factorized into polynomials of lower degrees. From the various factors different Hopf bifurcations may result in leading for model I, either to asynchronous oscillations with regular phase shifts or to synchronous oscillations of the cells depending on the strength of the coupling and on the cell density. The multitude of steady states obtained for model II may be grouped into one class of states which are always unstable and another class of states which may undergo bifurcations leading to synchronous oscillations within subgroups of cells. From these bifurcations numerous different oscillatory regimes may emerge. Leaving the near neighbourhood of the boundary of stability, secondary bifurcations of the limit cycles occur in both models. By symmetry breaking the resulting oscillations for the individual cells lose their regular phase shifts. These complex dynamic phenomena are studied in more detail for a low number of interacting cells. The theoretical results are discussed in the light of recent experimental data on the synchronization of oscillations in populations of yeast cells.

Animals↗
PubMed1999

Mode locking and Arnold tongues in integrate-and-fire neural oscillators.

An analysis of mode-locked solutions that may arise in periodically forced integrate-and-fire (IF) neural oscillators is introduced based upon a firing map formulation of the dynamics. A q:p mode-locked solution is identified with a spike train in which p firing events occur in a period qDelta, where Delta is the forcing period. A linear stability analysis of the map of firing times around such solutions allows the determination of the Arnold tongue structure for regions in parameter space where stable solutions exist. The analysis is verified against direct numerical simulations for both a sinusoidally forced IF system and one in which a periodic sequence of spikes is used to induce a biologically realistic synaptic input current. This approach is extended to the case of two synaptically coupled IF oscillators, showing that mode-locked states can exist for some self-consistently determined common period of repetitive firing. Numerical simulations show that such solutions have a bursting structure where regions of spiking activity are interspersed with quiescent periods before repeating. The influence of the synaptic current upon the Arnold tongue structure is explored in the regime of weak coupling.

Action Potentials↗
PubMed2000

Nonlinear analysis of the shearing instability in granular gases

It is known that a finite-size homogeneous granular fluid develops a hydrodynamiclike instability when dissipation crosses a threshold value. This instability is analyzed in terms of modified hydrodynamic equations: first, a source term is added to the energy equation which accounts for the energy dissipation at collisions and the phenomenological Fourier law is generalized according to previous results. Second, a rescaled time formalism is introduced that maps the homogeneous cooling state into a nonequilibrium steady state. A nonlinear stability analysis of the resulting equations is done which predicts the appearance of flow patterns. A stable modulation of density and temperature is produced that does not lead to clustering. Also a global decrease of the temperature is obtained, giving rise to a decrease of the collision frequency and dissipation rate. Good agreement with molecular dynamics simulations of inelastic hard disks is found for low dissipation.

Journal Article↗
PubMed2001

Combined treatment with specific ligands for PPARgamma:RXR nuclear receptor system markedly inhibits the expression of cytochrome P450arom in human granulosa cancer cells.

Our previous study demonstrated that PPARgamma specific ligand troglitazone (TGZ) or RXR specific ligand LG100268 (LG) alone decreased the aromatase activity in cultured human ovarian granulosa cells from pre-ovulatory follicles, and combined treatment caused an even greater reduction in this activity. Since similar manners of effects of TGZ or/and LG on the aromatase activity in human ovarian granulosa cancer cell line were observed, we performed the detailed analysis of the mechanisms of these effects using this cell line. The changes in the aromatase activity were associated with comparable changes in the P450arom mRNA levels based on a RNase protection assay. A nuclear run-on assay indicated the P450arom transcript to decrease by 40 and 66% at 24 and 48 h, respectively, after TGZ plus LG treatment. An RNA stability analysis showed the half-life of P450arom mRNA to decrease from 13 to 9 h after the TGZ plus LG treatment. The inhibitory effect of TGZ plus LG on the aromatase activity and P450arom mRNA may not be mediated by the cAMP-PKA pathway that is usually implicated in the regulation of aromatase activity in granulosa cells: because (1) the aromatase activity stimulated by forskolin was not inhibited by TGZ plus LG; (2) the specific PKA inhibitor H89 could not block the inhibitory effect of TGZ plus LG on the aromatase activity; and (3) the luciferase activity of P450arom promoter II did not decrease by the addition of TGZ and LG in transfected cells either at a basic state or in the states stimulated by forskolin or PGE2, respectively. Taken together, these results indicate that TGZ plus LG inhibited the aromatase activity and also decreased the P450arom mRNA level in granulosa cancer cells, and the loss of P450arom mRNA expression was considered to be due to both the decreased transcription and rapid degradation of its RNA.

Aromatase↗