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Mechanisms for discordant alternans.

INTRODUCTION: Discordant alternans has the potential to produce larger alternans of the ECG T wave than concordant alternans, but its mechanism is unknown. METHODS AND RESULTS: We demonstrate by one- and two-dimensional simulation of action potential propagation models that discordant alternans can form spontaneously in spatially homogeneous tissue through one of two mechanisms, due to the interaction of conduction velocity and action potential duration restitution at high pacing frequencies or through the dispersion of diastolic interval produced by ectopic foci. In discordant alternans due to the first mechanism, the boundaries marking regions of alternans with opposite phase arise far from the stimulus site, move toward the stimulus site, and stabilize. Dynamic splitting of action potential duration restitution curves due to electrotonic coupling plays a crucial role in this stability. Larger tissues and faster pacing rates are conducive to multiple boundaries, and inhomogeneities of tissue properties facilitate or inhibit formation of boundaries. CONCLUSION: Spatial inhomogeneities of electrical restitution properties are not required to produce discordant alternans.

Action Potentials↗

Controlling chaos in a fast diode resonator using extended time-delay autosynchronization: Experimental observations and theoretical analysis.

We stabilize unstable periodic orbits of a fast diode resonator driven at 10.1 MHz (corresponding to a drive period under 100 ns) using extended time-delay autosynchronization. Stabilization is achieved by feedback of an error signal that is proportional to the difference between the value of a state variable and an infinite series of values of the state variable delayed in time by integral multiples of the period of the orbit. The technique is easy to implement electronically and it has an all-optical counterpart that may be useful for stabilizing the dynamics of fast chaotic lasers. We show that increasing the weights given to temporally distant states enlarges the domain of control and reduces the sensitivity of the domain of control on the propagation delays in the feedback loop. We determine the average time to obtain control as a function of the feedback gain and identify the mechanisms that destabilize the system at the boundaries of the domain of control. A theoretical stability analysis of a model of the diode resonator in the presence of time-delay feedback is in good agreement with the experimental results for the size and shape of the domain of control. (c) 1997 American Institute of Physics.

Journal Article↗

In vitro reconstitution of a light-harvesting gene product: deletion mutagenesis and analyses of pigment binding.

AB96, a gene encoding a Pisum sativum chlorophyll a/b binding protein [Coruzzi et al. (1983) J. Biol. Chem. 258, 1399-1402], can be expressed in Escherichia coli and reconstituted with pigments by the procedure described by Plumley and Schmidt [(1987) Proc. Natl. Acad. Sci. U.S.A. 84, 146-150]. Following purification by polyacrylamide gel electrophoresis, the reconstituted pigment-protein complex (CP2) is shown to have similar pigment-binding characteristics to native CP2 complexes isolated from thylakoid membranes. Therefore, the AB96 gene product contains binding sites for chlorophylls a and b and xanthophylls, all of which are necessary for optimal reconstitution in vitro. Absorption, fluorescence, and circular dichroism spectroscopy indicate that the pigments are oriented accurately and that chlorophylls a and b are adjoined for energy transfer. Studies with proteins produced after deletion mutagenesis of AB96 indicate that NH2-terminal amino acids 1-21 and COOH-terminal amino acids 219-228 do not play a role in pigment binding. In contrast, amino acids 50-57 and 204-212 (encompassing one of three conserved histidine residues) are essential for reconstitution. Residues near the presumed NH2- and COOH-terminal alpha-helix boundaries (22-49 and 213-218, respectively) affect the stability of reconstituted CP2 during electrophoresis at 4 degrees C. Correlation of diminished chlorophyll a binding with disappearance of a negative circular dichroism near 684 nm suggests that amino acids 213-218 near the COOH-terminal boundary of the third membrane-spanning helix affect the binding of some chlorophyll a molecules.

Amino Acid Sequence↗

Assessing the implant/bone interface by using natural frequency analysis.

OBJECTIVE: A number of techniques have been proposed for detecting the stability of dental implants. However, the clinical applicability of those methods is still limited. The purpose of this study was to evaluate a new innovative, noninvasive, minimum-contact method for the stability assessment of dental implants. STUDY DESIGN: Natural frequency is a physical property of a structure, which is strongly related to its boundary conditions. In this study, a modal testing technique was carried out to measure the natural frequency of dental implants. The implants were fixed by a metal clamp stand and were excited to vibrate by an impulse hammer. A noncontact piezoelectric microphone then acoustically acquired the vibration responses of the implants. Natural frequencies of the tested implants were recorded under various clamping forces and clamping levels. RESULTS: Natural frequencies of the tested implants were concentrated from 8 to 19 kHz under different boundary conditions. On the other hand, the natural frequency values decreased when boundary levels and boundary force were reduced. Linear relationships (P <.005) were found between response frequencies and the degree of implant stability. CONCLUSIONS: Our results show that the boundary status of an implant can be monitored by detecting its natural frequency. A noncontact transducer used in this study can also serve as a useful tool for future clinical investigations.

Dental Implants↗

Developmental stability in the mouse vertebral column.

The effects of six mutant genes (Sd, T, vt, Sp, un, Ph) on the axial skeleton of the mouse were studied both alone and in combination with 24 hours starvation on Day 8 of gestation. Normal controls showed a craniocaudal gradient of size variation and relatively low variability towards the boundaries of the cervical, thoracic and lumbar vertebral classes. Gene-induced craniocaudal gradients of abnormality were observed in response to Sd and T, and to Ph, which have direct and indirect effects respectively on the primitive streak and/or notochord. By contrast, vt, which influences the paraxial mesoderm, and Sp and un, which act later, during somite formation and sclerotome differentiation respectively, did not produce craniocaudal gradients of abnormality. For all genes there were indications of relative resistance to their effects towards the vertebral class boundaries. Starvation did not materially influence these patterns of abnormality. The division of the axial skeleton of the mouse into its morphologically distinct classes of vertebrae thus appears to originate at the earliest stage of axial development, even before somite formation, with the positions of the future vertebral class boundaries established both axially and paraxially as regions of relative stability that persist into later stages of development. The primary craniocaudal gradient associated with the advancing primitive streak, from which the vertebral class boundary positions may be derived, appears to be restricted to the axial structures themselves and to be lost after the somites appear.

Animals↗

Porous silicon formation and electropolishing.

Electrochemical etching of silicon in hydrofluoride containing electrolytes leads to pore formation for low and to electropolishing for high applied current. The transition between pore formation and polishing is accompanied by a change of the valence of the electrochemical dissolution reaction. The local etching rate at the interface between the semiconductor and the electrolyte is determined by the local current density. We model the transport of reactants and reaction products and thus the current density in both, the semiconductor and the electrolyte. Basic features of the chemical reaction at the interface are summarized in the law of mass-action-type boundary conditions for the transport equations at the interface. We investigate the linear stability of a planar and flat interface. Upon increasing the current density the stability flips either through a change of the valence of the dissolution reaction or by a nonlinear boundary condition at the interface.

Journal Article↗

Correlation between thermal stability maps and genetic maps of double-stranded DNAs.

The positional correlation of boundaries of cooperatively melting regions with boundaries of genes and with cleavage sites of restriction enzymes are statistically examined for phiX174, G4, fd, SV40, BKV, and polyoma DNAs. A statistically significant correlation does exist in the case of gene boundaries, but none is detected for cleavage sites.

Base Composition↗

Stereoelectronic tuning of the structure and stability of the trp cage miniprotein.

Proline residues are critical structural elements in proteins, defining turns, loops, secondary structure boundaries, and polyproline helices. Control of proline conformation therefore may be used to define protein structure and stability. 4-Substituted proline derivatives may be used to control proline ring pucker, which correlates with protein main chain conformation. To examine the use of proline conformational restriction to tune globular protein stability, a series of peptides derived from the trp cage miniprotein was synthesized. Proline at residue 12 of the trp cage miniprotein, which adopts a Cgamma-exo ring pucker in the NMR structure, was replaced with 4-substituted proline derivatives, including 4R derivatives favoring a Cgamma-exo ring pucker and 4S derivatives favoring a Cgamma-endo ring pucker. Eight trp cage peptides were synthesized, five of which included residues that are not commercially available, without requiring any solution phase chemistry. Analysis of the trp cage peptides by circular dichroism and NMR indicated that the structure and stability of the trp cage miniprotein was controllable based on the conformational bias of the proline derivative. Replacement of Pro12 with 4S-substituted proline derivatives that favor the Cgamma-endo ring pucker destabilized the trp cage, while replacement of Pro12 with 4R-substituted proline derivatives that favor a Cgamma-exo ring pucker resulted in increased alpha-helicity and thermal stability of the trp cage. The most stable trp cage derivatives contained benzoates of 4R-hydroxyproline, which also exhibited the most pronounced stereoelectronic effects in TYProxN model peptides. Overall, the stability of the trp cage was tunable by over 50 degrees C depending on the identity of the proline side chain at residue 12.

Amino Acid Sequence↗

Evolutionary protein stabilization in comparison with computational design.

Two major strategies are currently used for stabilizing proteins: in vitro evolution and computational design. Here, we used gene libraries of the beta1 domain of the streptococcal protein G (Gbeta1) and Proside, an in vitro selection method, to identify stabilized variants of this protein. In the Gbeta1 libraries, the codons for the four boundary positions 16, 18, 25, and 29 were randomized. Many Gbeta1 variants with strongly increased thermal stabilities were found in 11 selections performed with five independent libraries. Previously, Mayo and co-workers used computational design to stabilize Gbeta1 by sequence optimization at the same positions. Their best variant ranked third within the panel of the selected variants. None of the ten computed sequences was found in the Proside selections, because several computed residues for positions 18 and 29 were not optimal for stability.

Bacterial Proteins↗

Desynchronization of chaos in coupled logistic maps.

When identical chaotic oscillators interact, a state of complete or partial synchronization may be attained in which the motion is restricted to an invariant manifold of lower dimension than the full phase space. Riddling of the basin of attraction arises when particular orbits embedded in the synchronized chaotic state become transversely unstable while the state remains attracting on the average. Considering a system of two coupled logistic maps, we show that the transition to riddling will be soft or hard, depending on whether the first orbit to lose its transverse stability undergoes a supercritical or subcritical bifurcation. A subcritical bifurcation can lead directly to global riddling of the basin of attraction for the synchronized chaotic state. A supercritical bifurcation, on the other hand, is associated with the formation of a so-called mixed absorbing area that stretches along the synchronized chaotic state, and from which trajectories cannot escape. This gives rise to locally riddled basins of attraction. We present three different scenarios for the onset of riddling and for the subsequent transformations of the basins of attraction. Each scenario is described by following the type and location of the relevant asynchronous cycles, and determining their stable and unstable invariant manifolds. One scenario involves a contact bifurcation between the boundary of the basin of attraction and the absorbing area. Another scenario involves a long and interesting series of bifurcations starting with the stabilization of the asynchronous cycle produced in the riddling bifurcation and ending in a boundary crisis where the stability of an asynchronous chaotic state is destroyed. Finally, a phase diagram is presented to illustrate the parameter values at which the various transitions occur.

Journal Article↗

The effect of migration on metapopulation stability is qualitatively unaffected by demographic and spatial heterogeneity.

Coupled map lattices (CMLs), using two coupled logistic equations, have been extensively used to model the dynamics of two-patch ecological systems. Such studies have revealed that migration rate plays an important role in determining the dynamics of the system, particularly when the two maps differ in their intrinsic growth rate parameter, r. However, under more realistic assumptions, a metapopulation can be expected to consist of more than two subpopulations, each with its own demographic parameters, which will in part be a function of the environment of that patch. The role of the spatial arrangement of heterogeneous (i.e. with different r values) subpopulations in shaping the dynamics of such a metapopulation has rarely been investigated. Here, we study the effect of demographic and spatial heterogeneity on the stability of one- and two-dimensional systems of 64 coupled Ricker maps with different r values, under periodic and absorbing boundary conditions. We show that the effects of migration rate on metapopulation stability do not depend upon either the precise spatial arrangement of the subpopulations in the lattice, or on the presence of a moderate proportion of vacant (uninhabitable) patches in the lattice. The results, thus, suggest that metapopulation models are robust to variation in spatial arrangement of patch quality and, hence, of demographic parameters. We also show that for any given arrangement of the patches, maximum stability of the metapopulation occurs when the migration levels are intermediate, a result that agrees well with previous studies on two-map CML systems.

Animals↗

Influence of boundary slip on the optimal excitations in thermocapillary driven spreading.

Thin liquid films driven to spread on homogeneous surfaces by thermocapillarity can undergo frontal breakup and parallel rivulet formation with well-defined wavelength. Previous modal analyses have relieved the well-known divergence in stress that occurs at a moving contact line by matching the front region to a precursor film. Because the linearized disturbance operator is non-normal, a generalized, nonmodal analysis is required to probe film stability at all times. The effect of the contact line model on nonmodal stability has not been previously investigated. This work examines the influence of boundary slip on thermocapillary driven spreading using a transient stability analysis, which recovers the conventional modal results in the long-time limit. In combination with earlier work on thermocapillary driven spreading, this study verifies that the dynamics and stability of this system are rather insensitive to the choice of contact line model and that the leading eigenvalue is physically determinant, thereby assuring results that agree with the eigenspectrum. Modal results for the flat precursor film model are reproduced with appropriate choice of slip coefficient and contact line slope.

Journal Article↗

Nonlinear Stability of an Electrified Interface Supporting Surface Charges between Two Viscous Fluids.

The charged boundary between two viscous fluid media is taken to be under the influence of a vertical constant electric field producing surface charges. We illustrate the solution of the nonlinear perturbation using the method of multiple scales. In the neutral stability the relation between surface charge density and surface viscous force is obtained. Because the viscosity ratio has the same value as the dielectric constant ratio a singularity in the nonlinear coefficient of Schrödinger equation is observed and gradually creates a growth in the instability. Previous works have failed to recognize this singularity by not including the effects of viscosity. The absence of surface viscous force leads to decay in the surface charge density and a growth in the stability occurs. Global stability and local instability are observed in the stability diagrams. The duality mechanism is observed for the electric field, the surface charge density, and the stratified kinematic viscosity. Further, the behavior away from neutral stability is explained by examination of the dynamical system. It is observed that the stabilizing or destabilizing role for the surface charge density has been related to the destabilizing or stabilizing role of the density influence. Copyright 1999 Academic Press.

Journal Article↗

Stability distribution in the phage lambda-DNA double helix: a correlation between physical and genetic structure.

Statistical analyses on the positional correlation of physical-stability and base-sequence distribution maps with genetic map are made for the whole DNA (48502 bases) of lambda-phage. The susceptibility to a double-helix unfolding perturbation and the fraction of the transient opening of a particular region of the double helix are adopted to define this physical stability. The principal features obtained are: A) The DNA double strand of protein coding regions is found to have homostabilizing propensity around a defined stability which is characteristic to each individual gene. B) The stability of the double helix in non-protein coding region fluctuates, on average over the whole region, more than that in protein coding region. C) Boundary regions of protein coding and non-protein coding regions are regions of high stability-fluctuation. Stability especially fluctuates at the protein-coding-region side of the boundary. Contrary to the quiet feature of the interior part of protein coding region rather noisy part exists at its edge. D) One frequently opening region coincides with the attaching site for the site specific recombination between phage and bacterial DNA. There are two possible ways to explain the noisy feature in the stability distribution in non-protein coding regions: 1) The region has been used as the locus of recombination as evolution took place. Thus DNAs which were homostabilized around a different value characteristic to each individual DNA, have been joined there many times, so that the noise has accumulated as a remnant of evolutional history; and/or 2) the base-composition homogenizing or double-helix homostabilizing mechanism does not work in unneeded region such as non-protein coding region or introns. Since corresponding characteristics have been found in our previous analyses on other viral and globin-gene DNAs, the rules mentioned above may be comprehensively extended to other DNAs.

Bacteriophage lambda↗

Surface-directed boundary flow in microfluidic channels.

Channel geometry combined with surface chemistry enables a stable liquid boundary flow to be attained along the surfaces of a 12 microm diameter hydrophilic glass fiber in a closed semi-elliptical channel. Surface free energies and triangular corners formed by PDMS/glass fiber or OTS/glass fiber surfaces are shown to be responsible for the experimentally observed wetting phenomena and formation of liquid boundary layers that are 20-50 microm wide and 12 microm high. Viewing this stream through a 20 microm slit results in a virtual optical window with a 5 pL liquid volume suitable for cell counting and pathogen detection. The geometry that leads to the boundary layer is a closed channel that forms triangular corners where glass fiber and the OTS coated glass slide or PDMS touch. The contact angles and surfaces direct positioning of the fluid next to the fiber. Preferential wetting of corner regions initiates the boundary flow, while the elliptical cross-section of the channel stabilizes the microfluidic flow. The Young-Laplace equation, solved using fluid dynamic simulation software, shows contact angles that exceed 105 degrees will direct the aqueous fluid to a boundary layer next to a hydrophilic fiber with a contact angle of 5 degrees. We believe this is the first time that an explanation has been offered for the case of a boundary layer formation in a closed channel directed by a triangular geometry with two hydrophobic wetting edges adjacent to a hydrophilic surface.

Dimethylpolysiloxanes↗

A range of spin-crossover temperature T1/2>300 K results from out-of-sphere anion exchange in a series of ferrous materials based on the 4-(4-imidazolylmethyl)-2-(2-imidazolylmethyl)imidazole (trim) ligand, [Fe(trim)2]X2 (X=F, Cl, Br, I): comparison of experimental results with those derived from density functional theory calculations.

The synthesis and characterization of [FeII(trim)2]Cl2 (2), [FeII(trim)2]Br2MeOH (3), and [FeII(trim)2]I2MeOH (4), including the X-ray crystal structure determinations of 2 (50 and 293 K) and 4 (293 K), have been performed and their properties have been examined. In agreement with the magnetic susceptibility results, the Mössbauer data show the presence of high-spin (HS) to low-spin (LS) crossover with a range of T1/2 larger than 300 K (from approximately 20 K for [FeII(trim)2]F2 (1) to approximately 380 K for 4). All complexes in this series include the same [Fe(trim)2]2+ complex cation: the ligand field comprises a constant contribution from the trim ligands and a variable one originating from the out-of-sphere anions, which is transmitted to the metal center by the connecting imidazole rings and hydrogen bonds. The impressive variation in the intrinsic characteristics of the spin-crossover (SCO) phenomenon in this series is then interpreted as an inductive effect of the anions transmitted to the nitrogen donors through the hydrogen bonds. Based on this qualitative analysis, an increased inductive effect of the out-of-sphere anion corresponds to a decreased SCO temperature T1/2, in agreement with the experimental results. Electronic structure calculations with periodic boundary conditions have been performed that show the importance of intermolecular effects in tuning the ligand field, and thus in determining the transition temperature. Starting with the geometries obtained from the X-ray studies, the [FeII(trim)2]X2 complex molecules 1-4 have been investigated both for the single molecules and the crystal lattices with the local density approximation of density functional theory. The bulk geometries of the complex cations deduced from the X-ray studies and those calculated are in fair agreement for both approaches. However, the trend observed for the transition temperatures of 1-4 disagrees with the trend for the spin-state splittings ES (difference EHS-ELS between the energy of the HS and LS isomers) calculated for the isolated molecules, whereas it agrees with the trend for ES calculated with periodic boundary conditions. The latter calculations predict the strongest stabilization of the HS state for the fluoride complex, which actually is essentially HS above T=50 K, while the most pronounced stabilization of the LS state is predicted for 4, in line with the experimental results.

Journal Article↗

Molecular analysis of the transferrin gene in a patient with hereditary hypotransferrinemia.

We previously reported a patient with hereditary hypotransferrinemia who suffered from severe anemia and growth retardation and was diagnosed on the basis of an extremely low level of serum transferrin (TF). By an isoelectric focusing analysis, we found that the patient and his father shared a variant TF protein with an abnormal isoelectric point. The study suggested that the patient was a compound heterozygote with a variant allele, encoding the mutant TF, of paternal origin and a null allele of maternal origin. In the present study, we investigated the TF gene of the patient and his family. We showed that the patient and his father shared a variant TF gene bearing a GAA to AAA transition at codon 394. This nucleotide substitution causes a nonconservative amino acid change from glutamate to lysine in amino acid residue 375 of the TF protein. This single amino acid mutation is predicted to cause a conformational change in the coiled region of the carboxyl-terminal iron-binding lobe. As for the maternal null allele, no mutation was found in either the coding region or the exon-intron boundaries, suggesting an abnormality in the transcription or stability of mRNA of maternal allele origin.

Amino Acid Substitution↗

Magnetic domains and stripes in a spin-fermion model for cuprates

Monte Carlo simulations applied to a model of interacting fermions and classical spins show the existence of antiferromagnetic spin domains and charge stripes upon hole doping. The stripes have a filling of approximately 1/2 hole per site, and they separate spin domains with a pi phase shift among them. The observed stripes run either along the x or y axes. No particular boundary conditions or external fields are needed to stabilize these structures. When magnetic incommensurate peaks are observed at momentum pi(1,1-delta), charge incommensurate peaks appear at (0,2delta). The charge fluctuations responsible for the stripe formation also induce a pseudogap in the density of states.

Journal Article↗