Biomedical subjects

H E Stanley

Publications and source records attributed to H E Stanley.

At least 19 recordsLinked to original sources

PubMed2006

Glass transition in biomolecules and the liquid-liquid critical point of water.

Using molecular dynamics simulations, we investigate the relation between the dynamic transitions of biomolecules (lysozyme and DNA) and the dynamic and thermodynamic properties of hydration water. We find that the dynamic transition of the macromolecules, sometimes called a "protein glass transition," occurs at the temperature of dynamic crossover in the diffusivity of hydration water and also coincides with the maxima of the isobaric specific heat C_{P} and the temperature derivative of the orientational order parameter. We relate these findings to the hypothesis of a liquid-liquid critical point in water. Our simulations are consistent with the possibility that the protein glass transition results from crossing the Widom line, which is defined as the locus of correlation length maxima emanating from the hypothesized second critical point of water.

Computer Simulation↗

PubMed2005

Relation between the Widom line and the dynamic crossover in systems with a liquid-liquid phase transition.

We investigate, for two water models displaying a liquid-liquid critical point, the relation between changes in dynamic and thermodynamic anomalies arising from the presence of the liquid-liquid critical point. We find a correlation between the dynamic crossover and the locus of specific heat maxima C(P)(max) ("Widom line") emanating from the critical point. Our findings are consistent with a possible relation between the previously hypothesized liquid-liquid phase transition and the transition in the dynamics recently observed in neutron scattering experiments on confined water. More generally, we argue that this connection between C(P)(max) and dynamic crossover is not limited to the case of water, a hydrogen bond network-forming liquid, but is a more general feature of crossing the Widom line. Specifically, we also study the Jagla potential, a spherically symmetric two-scale potential known to possess a liquid-liquid critical point, in which the competition between two liquid structures is generated by repulsive and attractive ramp interactions.

Journal Article↗

PubMed2005

Optimization of network robustness to waves of targeted and random attacks.

We study the robustness of complex networks to multiple waves of simultaneous (i) targeted attacks in which the highest degree nodes are removed and (ii) random attacks (or failures) in which fractions p(t) and p(r) , respectively, of the nodes are removed until the network collapses. We find that the network design which optimizes network robustness has a bimodal degree distribution, with a fraction r of the nodes having degree k2 = ((k)-1+r)/r and the remainder of the nodes having degree k1=1, where k is the average degree of all the nodes. We find that the optimal value of r is of the order of p(t)/p(r) for p(t)/p(r) << 1.

Journal Article↗

PubMed2005

A statistically based density map method for identification and quantification of regional differences in microcolumnarity in the monkey brain.

We present a statistical density map method derived from condensed matter physics to quantify microcolumns, the fundamental computational unit of the cerebral cortex. This method provides measures for microcolumnar strength, width, spacing, length, and periodicity. We applied this method to Nissl-stained 30 microm thick frozen sections from areas 46, TE, and TL of rhesus monkey brains, areas that differ visually in microcolumnarity and are associated with different cognitive functions. Our results indicate that microcolumns in these areas are similar in width, spacing, and periodicity, but are stronger (possess a higher neuronal density) in area TE, as compared to areas TL and 46. We modeled the effect of section orientation on microcolumnar spacing and demonstrated that this method provides an adequate estimate of spacing. We also modeled disruption of microcolumnarity by performing simulations that randomly displace neurons and demonstrated that displacements of only one neuronal diameter effectively eliminate microcolumnar organization. These results indicate that our density map method is sensitive enough to detect and quantify subtle differences in microcolumnar organization that may occur in the context of development, aging, and neuropathology, as well as between areas and species.

Animals↗

PubMed2004

In silico study of amyloid beta-protein folding and oligomerization.

Experimental findings suggest that oligomeric forms of the amyloid beta protein (Abeta) play a critical role in Alzheimer's disease. Thus, elucidating their structure and the mechanisms of their formation is critical for developing therapeutic agents. We use discrete molecular dynamics simulations and a four-bead protein model to study oligomerization of two predominant alloforms, Abeta40 and Abeta42, at the atomic level. The four-bead model incorporates backbone hydrogen-bond interactions and amino acid-specific interactions mediated through hydrophobic and hydrophilic elements of the side chains. During the simulations we observe monomer folding and aggregation of monomers into oligomers of variable sizes. Abeta40 forms significantly more dimers than Abeta42, whereas pentamers are significantly more abundant in Abeta42 relative to Abeta40. Structure analysis reveals a turn centered at Gly-37-Gly-38 that is present in a folded Abeta42 monomer but not in a folded Abeta40 monomer and is associated with the first contacts that form during monomer folding. Our results suggest that this turn plays an important role in Abeta42 pentamer formation. Abeta pentamers have a globular structure comprising hydrophobic residues within the pentamer's core and hydrophilic N-terminal residues at the surface of the pentamer. The N termini of Abeta40 pentamers are more spatially restricted than Abeta42 pentamers. Abeta40 pentamers form a beta-strand structure involving Ala-2-Phe-4, which is absent in Abeta42 pentamers. These structural differences imply a different degree of hydrophobic core exposure between pentamers of the two alloforms, with the hydrophobic core of the Abeta42 pentamer being more exposed and thus more prone to form larger oligomers.

Amyloid beta-Peptides↗

PubMed2004

Age-related reduction in microcolumnar structure in area 46 of the rhesus monkey correlates with behavioral decline.

Many age-related declines in cognitive function are attributed to the prefrontal cortex, area 46 being especially critical. Yet in normal aging, studies indicate that neurons are not lost in area 46, suggesting that impairments result from more subtle processes. One cortical feature that is functionally important, but that has not been examined in normal aging because of a lack of efficient quantitative methods, is the vertical arrangement of neurons into microcolumns, a fundamental computational unit of the cortex. By using a density-map method derived from condensed-matter physics, we quantified microcolumns in area 46 of seven young and seven aged rhesus monkeys that had been cognitively tested. This analysis demonstrated that there is no age-related reduction in total neuronal density or in microcolumn width, length, or periodicity. There was, however, a statistically significant decrease in the strength of microcolumns, indicating microcolumnar disorganization. This reduction in strength was significantly correlated with age-related cognitive decline on tests of spatial working memory and recognition memory independent of the effect of age. Modeling demonstrated that random neuron displacements of approximately 30% of a neuronal diameter (<3 mum) produced the observed reduction in strength. Hence, it is possible that, with changes in dendrites and myelinated axons, subtle displacements of neurons occur that alter microcolumnar structure and correlate with age-induced dysfunction. Therefore, quantitative measurement of microcolumnar structure may provide a sensitive morphological method to assay microcolumnar function in aging and other conditions.

Aging↗

PubMed2004

Liquid-liquid phase transitions for soft-core attractive potentials.

Using event-driven molecular dynamics simulations, we study a three-dimensional one-component system of spherical particles interacting via a discontinuous potential combining a repulsive square soft core and an attractive square well. In the case of a narrow attractive well, it has been shown that this potential has two metastable gas-liquid critical points. Here we systematically investigate how the changes of the parameters of this potential affect the phase diagram of the system. We find a broad range of potential parameters for which the system has both a gas-liquid critical point C1 and a liquid-liquid critical point C2. For the liquid-gas critical point we find that the derivatives of the critical temperature and pressure, with respect to the parameters of the potential, have the same signs: they are positive for increasing width of the attractive well and negative for increasing width and repulsive energy of the soft core. This result resembles the behavior of the liquid-gas critical point for standard liquids. In contrast, for the liquid-liquid critical point the critical pressure decreases as the critical temperature increases. As a consequence, the liquid-liquid critical point exists at positive pressures only in a finite range of parameters. We present a modified van der Waals equation which qualitatively reproduces the behavior of both critical points within some range of parameters, and gives us insight on the mechanisms ruling the dependence of the two critical points on the potential's parameters. The soft-core potential studied here resembles model potentials used for colloids, proteins, and potentials that have been related to liquid metals, raising an interesting possibility that a liquid-liquid phase transition may be present in some systems where it has not yet been observed.

Journal Article↗

PubMed2004

Discrete molecular dynamics simulations of peptide aggregation.

We study the aggregation of peptides using the discrete molecular dynamics simulations. Specifically, at temperatures above the alpha-helix melting temperature of a single peptide, the model peptides aggregate into a multilayer parallel beta-sheet structure. This structure has an interstrand distance of 4.8 A and an intersheet distance of 10 A, which agree with experimental observations. Our model explains these results as follows: hydrogen-bond interactions give rise to the interstrand spacing in beta sheets, while Gō interactions between side chains make beta strands parallel to each other and allow beta sheets to pack into layers. An important feature of our results is that the aggregates contain free edges, which may allow for further aggregation of model peptides to form elongated fibrils.

Amyloid beta-Peptides↗

PubMed2004

Analysis of clusters formed by the moving average of a long-range correlated time series.

We analyze the stochastic function C(n)(i) identical with y(i)-y(n)(i), where y(i) is a long-range correlated time series of length N(max) and y(n)(i) identical with (1/n) Sigma(n-1)(k=0)y(i-k) is the moving average with window n. We argue that C(n)(i) generates a stationary sequence of self-affine clusters C with length l, lifetime tau, and area s. The length and the area are related to the lifetime by the relationships l approximately tau(psi(l)) and s approximately tau(psi(s)), where psi(l)=1 and psi(s)=1+H. We also find that l, tau, and s are power law distributed with exponents depending on H: P(l) approximately l(-alpha), P(tau) approximately tau(-beta), and P(s) approximately s(-gamma), with alpha=beta=2-H and gamma=2/(1+H). These predictions are tested by extensive simulations on series generated by the midpoint displacement algorithm of assigned Hurst exponent H (ranging from 0.05 to 0.95) of length up to N(max)=2(21) and n up to 2(13).

Biophysics↗

PubMed2004

Molecular dynamics simulation of amyloid beta dimer formation.

Recent experiments with amyloid beta (Abeta) peptide indicate that formation of toxic oligomers may be an important contribution to the onset of Alzheimer's disease. The toxicity of Abeta oligomers depends on their structure, which is governed by assembly dynamics. Due to limitations of current experimental techniques, a detailed knowledge of oligomer structure at the atomic level is missing. We introduce a molecular dynamics approach to study Abeta dimer formation. 1), We use discrete molecular dynamics simulations of a coarse-grained model to identify a variety of dimer conformations; and 2), we employ all-atom molecular mechanics simulations to estimate thermodynamic stability of all dimer conformations. Our simulations of a coarse-grained Abeta peptide model predicts 10 different planar beta-strand dimer conformations. We then estimate the free energies of all dimer conformations in all-atom molecular mechanics simulations with explicit water. We compare the free energies of Abeta(1-42) and Abeta(1-40) dimers. We find that 1), dimer conformations have higher free energies compared to their corresponding monomeric states; and 2), the free-energy difference between the Abeta(1-42) and the corresponding Abeta(1-40) dimer conformation is not significant. Our results suggest that Abeta oligomerization is not accompanied by the formation of thermodynamically stable planar beta-strand dimers.

Amyloid beta-Peptides↗

PubMed2003

Neuron recognition by parallel Potts segmentation.

Identifying neurons and their spatial coordinates in images of the cerebral cortex is a necessary step in the quantitative analysis of spatial organization in the brain. This is especially important in the study of Alzheimer's disease (AD), in which spatial neuronal organization and relationships are highly disrupted because of neuronal loss. To automate neuron recognition by using high-resolution confocal microscope images from human brain tissue, we propose a recognition method based on statistical physics that consists of image preprocessing, parallel image segmentation, and cluster selection on the basis of shape, optical density, and size. We segment a preprocessed digital image into clusters by applying Monte Carlo simulations of a q-state inhomogeneous Potts model. We then select the range of Potts segmentation parameters to yield an ideal recognition of simplified objects in the test image. We apply our parallel segmentation method to control individuals and to AD patients and achieve recognition of 98% (for a control) and 93% (for an AD patient), with at most 3% false clusters.

Alzheimer Disease↗

PubMed2002

Metastable liquid-liquid phase transition in a single-component system with only one crystal phase and no density anomaly.

We investigate the phase behavior of a single-component system in three dimensions with spherically-symmetric, pairwise-additive, soft-core interactions with an attractive well at a long distance, a repulsive soft-core shoulder at an intermediate distance, and a hard-core repulsion at a short distance, similar to potentials used to describe liquid systems such as colloids, protein solutions, or liquid metals. We showed [Nature (London) 409, 692 (2001)] that, even with no evidence of the density anomaly, the phase diagram has two first-order fluid-fluid phase transitions, one ending in a gas-low-density-liquid (LDL) critical point, and the other in a gas-high-density-liquid (HDL) critical point, with a LDL-HDL phase transition at low temperatures. Here we use integral equation calculations to explore the three-parameter space of the soft-core potential and perform molecular dynamics simulations in the interesting region of parameters. For the equilibrium phase diagram, we analyze the structure of the crystal phase and find that, within the considered range of densities, the structure is independent of the density. Then, we analyze in detail the fluid metastable phases and, by explicit thermodynamic calculation in the supercooled phase, we show the absence of the density anomaly. We suggest that this absence is related to the presence of only one stable crystal structure.

Journal Article↗

PubMed2002

Traveling length and minimal traveling time for flow through percolation networks with long-range spatial correlations.

We study the distributions of traveling length l and minimal traveling time t(min) through two-dimensional percolation porous media characterized by long-range spatial correlations. We model the dynamics of fluid displacement by the convective movement of tracer particles driven by a pressure difference between two fixed sites ("wells") separated by Euclidean distance r. For strongly correlated pore networks at criticality, we find that the probability distribution functions P(l) and P(t(min)) follow the same scaling ansatz originally proposed for the uncorrelated case, but with quite different scaling exponents. We relate these changes in dynamical behavior to the main morphological difference between correlated and uncorrelated clusters, namely, the compactness of their backbones. Our simulations reveal that the dynamical scaling exponents d(l) and d(t) for correlated geometries take values intermediate between the uncorrelated and homogeneous limiting cases, where l(*) approximately r(d(l)) and t(*)(min) approximately r(d(t)), and l(*) and t(*)(min) are the most probable values of l and t(min), respectively.

Journal Article↗

PubMed2002

Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's disease.

Despite extensive deposition of putatively neurotoxic amyloid-beta (Abeta) protein in the brain, it has not been possible to demonstrate an association of Abeta deposits with neuronal loss in Alzheimer's disease (AD), and neuronal loss is minimal in transgenic mouse models of AD. Using triple immunostaining confocal microscopy and analyzing the images with the cross-correlation density map method from statistical physics, we directly compared Abeta deposition, Abeta morphology, and neuronal architecture. We found dramatic, focal neuronal toxicity associated primarily with thioflavin S-positive fibrillar Abeta deposits in both AD and PSAPP mice. These results, along with computer simulations, suggest that Abeta develops neurotoxic properties in vivo when it adopts a fibrillar beta-pleated sheet conformation.

Alzheimer Disease↗

PubMed2002

Dynamics and configurational entropy in the Lewis-Wahnström model for supercooled orthoterphenyl.

We study thermodynamic and dynamic properties of a rigid model of the fragile glass-forming liquid orthoterphenyl. This model, introduced by Lewis and Wahnström in 1993, collapses each phenyl ring to a single interaction site; the intermolecular site-site interactions are described by the Lennard-Jones potential whose parameters have been selected to reproduce some bulk properties of the orthoterphenyl molecule. A system of N=343 molecules is considered in a wide range of densities and temperatures, reaching simulation times up to 1 micros. Such long trajectories allow us to equilibrate the system at temperatures below the mode coupling temperature T(c) at which the diffusion constant reaches values of order 10(-10) cm(2)/s and thereby to sample in a significant way the potential energy landscape in the entire temperature range. Working within the inherent structures thermodynamic formalism, we present results for the temperature and density dependence of the number, depth and shape of the basins of the potential energy surface. We evaluate the total entropy of the system by thermodynamic integration from the ideal-noninteracting-gas state and the vibrational entropy approximating the basin free energy with the free energy of 6N-3 harmonic oscillators. We evaluate the configurational part of the entropy as a difference between these two contributions. We study the connection between thermodynamical and dynamical properties of the system. We confirm that the temperature dependence of the configurational entropy and of the diffusion constant, as well as the inverse of the characteristic structural relaxation time, are strongly connected in supercooled states; we demonstrate that this connection is well represented by the Adam-Gibbs relation, stating a linear relation between logD and the quantity 1/TS(c). This relation is found to hold both above and below the critical temperature T(c)-as previously found in the case of silica-supporting the hypothesis that a connection exists between the number of basins and the connectivity properties of the potential energy surface.

Journal Article↗

PubMed2002

Self-organized complexity in economics and finance.

This article discusses some of the similarities between work being done by economists and by physicists seeking to contribute to economics. We also mention some of the differences in the approaches taken and seek to justify these different approaches by developing the argument that by approaching the same problem from different points of view, new results might emerge. In particular, we review two newly discovered scaling results that appear to be universal, in the sense that they hold for widely different economies as well as for different time periods: (i) the fluctuation of price changes of any stock market is characterized by a probability density function, which is a simple power law with exponent -4 extending over 10(2) SDs (a factor of 10(8) on the y axis); this result is analogous to the Gutenberg--Richter power law describing the histogram of earthquakes of a given strength; and (ii) for a wide range of economic organizations, the histogram shows how size of organization is inversely correlated to fluctuations in size with an exponent approximately 0.2. Neither of these two new empirical laws has a firm theoretical foundation. We also discuss results that are reminiscent of phase transitions in spin systems, where the divergent behavior of the response function at the critical point (zero magnetic field) leads to large fluctuations.

Journal Article↗

PubMed2002

Water and its energy landscape.

We present an overview of the recent studies on the properties of the potential energy surface for a simple model of water. We emphasize the relations between PES properties and dynamics in supercooled states for the model and discuss possible future application of the PES studies.

Journal Article↗

PubMed2001

When human walking becomes random walking: fractal analysis and modeling of gait rhythm fluctuations.

We present a random walk, fractal analysis of the stride-to-stride fluctuations in the human gait rhythm. The gait of healthy young adults is scale-free with long-range correlations extending over hundreds of strides. This fractal scaling changes characteristically with maturation in children and older adults and becomes almost completely uncorrelated with certain neurologic diseases. Stochastic modeling of the gait rhythm dynamics, based on transitions between different "neural centers", reproduces distinctive statistical properties of the gait pattern. By tuning one model parameter, the hopping (transition) range, the model can describe alterations in gait dynamics from childhood to adulthood including a decrease in the correlation and volatility exponents with maturation.

Adolescent↗