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The immunological synapse is a patterned collection of different types of receptors and ligands that forms in the intercellular junction between T Cells and antigen presenting cells (APCs) during recognition. The synapse is implicated in information transfer between cells, and is characterized by different spatial patterns of receptors at different stages in the life cycle of T cells. We obtain a minimalist model that captures this experimentally observed phenomenology. A functional RG analysis provides further insights., Comment: 6 pages, 3 figures, submitted for publication

The curvature stress of DNA packed inside a phage is balanced against its electrostatic self-interaction. The DNA density is supposed nonuniform and as a result the Donnan effect is also inhomogeneous. The coarse-grained DNA density is a nonlinear function of the DNA radius of curvature at a given position inside the bacteriophage. It turns out that a region (or regions) exists totally free from DNA. The size of such holes is computed., Comment: 11 pages, 2 figures, submitted to J. Phys. Chem. B (special Polyelectrolytes issue)

We study a model of directed percolation (DP) with immunization, i.e. with different probabilities for the first infection and subsequent infections. The immunization effect leads to an additional non-Markovian term in the corresponding field theoretical action. We consider immunization as a small perturbation around the DP fixed point in d<6, where the non-Markovian term is relevant. The immunization causes the system to be driven away from the neighbourhood of the DP critical point. In order to investigate the dynamical critical behaviour of the model, we consider the limits of low and high first infection rate, while the second infection rate remains constant at the DP critical value. Scaling arguments are applied to obtain an expression for the survival probability in both limits. The corresponding exponents are written in terms of the critical exponents for ordinary DP and DP with a wall. We find that the survival probability does not obey a power law behaviour, decaying instead as a stretched exponential in the low first infection probability limit and to a constant in the high first infection probability limit. The theoretical predictions are confirmed by optimized numerical simulations in 1+1 dimensions., Comment: 12 pages, 11 figures. v.2: minor corrections

In the framework of the Poland Scheraga model of DNA denaturation, we derive a recursion relation for the partition function of double stranded DNA, allowing for mismatches between the two strands. This relation is studied numerically using standard parameters for the stacking energies and loop entropies. For complementary strands (of length 1000), we find that mismatches are significant only when the cooperativity parameter $\sigma$ is of order one. Since $\sigma \sim O(10^{-5})$ in DNA, entropic gains from mismatches are overwhelmed by the energetic cost of opening a loop: mismatches are therefore irrelevant (and molecular recognition of the strands is perfect). Generating random mutations with probability $p$ on one strand, we find that large values of $\sigma$ are rather tolerant to mutations. For realistic (small) values of $\sigma$, the two strands do not recombine, even for small mutation fractions. Thus, molecular recognition is extremely selective., Comment: 7 pages, uses epl.cls (included), a few typos corrected

A dynamic model of a society is studied where each person is an uncorrelated and non-interacting random walker. A dynamical random graph represents the acquaintance network of the society whose nodes are the individuals and links are the pairs of mutual friendships. This network exhibits a novel percolation like phase transition in all dimensions. On introducing simultaneous death and birth rates in the population we show that the friendship network shows the six degrees of separation for ever after where the precise value of the network diameter depends on the death/birth rate. A SIS type model of disease spreading shows that this society remains always healthy if the population density is less than certain threshold value., Comment: 4 pages, 4 figures

We address theoretically aggregation of DNA segments by multivalent polyamines such as spermine and spermidine. In experiments, the aggregation occurs above a certain threshold concentration of multivalent ions. We demonstrate that the dependence of this threshold on the concentration of DNA has a simple form. When the DNA concentration c_DNA is smaller than the monovalent salt concentration, the threshold multivalent ion concentration depends linearly on c_DNA, having the form alpha c_DNA + beta. The coefficients alpha and beta are related to the density profile of multivalent counterions around isolated DNA chains, at the onset of their aggregation. This analysis agrees extremely well with recent detailed measurements on DNA aggregation in the presence of spermine. From the fit to the experimental data, the number of condensed multivalent counterions per DNA chain can be deduced. A few other conclusions can then be reached: i) the number of condensed spermine ions at the onset of aggregation decreases with the addition of monovalent salt; ii) the Poisson-Boltzmann theory over-estimates the number of condensed multivalent ions at high monovalent salt concentrations; iii) our analysis of the data indicates that the DNA charge is not over-compensated by spermine at the onset of aggregation., Comment: 12 pages, 8 figures. Biophysical Journal 2003, in press

We have analyzed dynamics on the complex free energy landscape of protein folding in the FOLD-X model, by calculating for each state of the system the mean first passage time to the folded state. The resulting kinetic map of the folding process shows that it proceeds in jumps between well-defined, local free energy minima. Closer analysis of the different local minima allows us to reveal secondary, parallel pathways as well as dead ends., Comment: 7 pages

Using a model for rodent population dynamics, we study outbreaks of Hantavirus infection induced by the alternation of seasons. Neither season by itself satisfies the environmental requirements for propagation of the disease. This result can be explained in terms of the seasonal interruption of the relaxation process of the mouse population toward equilibrium, and may shed light on the reported connection between climate variations and outbreaks of the dise ase., Comment: Submitted to PRE

We investigate a map-based model of paced cardiac muscle in the presence of closed-loop feedback control. The model relates the duration of an action potential to the preceding diastolic interval as well as the preceding action potential duration and thus has some amount of `memory.' We find that the domain of control depends on this memory, independently of the specific functional form of the map. The memory-dependent domain of control can encompass large feedback gains, thus providing the first possible explanation of the recent experimental results of Hall et al. [Phys. Rev. Lett, 88, 198102 (2002)] on controlling alternans in small pieces of rapidly-paced cardiac muscle., Comment: 10 pages, 2 figures, submitted to Phys. Rev. Lett

The spreading of infectious diseases with and without immunization of individuals can be modeled by stochastic processes that exhibit a transition between an active phase of epidemic spreading and an absorbing phase, where the disease dies out. In nature, however, the transmitted pathogen may also mutate, weakening the effect of immunization. In order to study the influence of mutations, we introduce a model that mimics epidemic spreading with immunization and mutations. The model exhibits a line of continuous phase transitions and includes the general epidemic process (GEP) and directed percolation (DP) as special cases. Restricting to perfect immunization in two spatial dimensions we analyze the phase diagram and study the scaling behavior along the phase transition line as well as in the vicinity of the GEP point. We show that mutations lead generically to a crossover from the GEP to DP. Using standard scaling arguments we also predict the form of the phase transition line close to the GEP point. It turns out that the protection gained by immunization is vitally decreased by the occurrence of mutations., Comment: 9 pages, 13 figures

We investigate the isometric transient response of muscle using a quantitative stochastic model of the actomyosin cycle based on the swinging lever-arm hypothesis. We first consider a single pair of filaments, and show that when values of parameters such as the lever-arm displacement and the crossbridge elasticity are chosen to provide effective energy transduction, the T2 curve (the tension recovered immediately after a step displacement) displays a region of negative slope. If filament compliance and the discrete nature of the binding sites are taken into account, the negative slope is diminished, but not eliminated. This implies that there is an instability in the dynamics of individual half-sarcomeres. However, when the symmetric nature of whole sarcomeres is taken into account, filament rearrangement becomes important during the transient: as tension is recovered, some half-sarcomeres lengthen while others shorten. This leads to a flat T2 curve, as observed experimentally. In addition, we investigate the isotonic transient response and show that for a range of parameter values the model displays damped oscillations, as recently observed in experiments on single muscle fibers. We conclude that it is essential to consider the collective dynamics of many sarcomeres, rather than the dynamics of a single pair of filaments, when interpreting the transient response of muscle., Comment: 11 pages, 11 figures, Submitted to Biophysical Journal

A natural similarity in body dimensions of terrestrial animals noticed by ancient philosophers remains the main key to the problem of mammalian skeletal evolution with body mass explored in theoretical and experimental biology and tested by comparative zoologists. We discuss the long-standing problem of mammalian bone allometry commonly studied in terms of the so-called ''geometric'', ''elastic'', and ''static stress'' similarities by McMahon (1973, 1975a, 1975b). We revise the fundamental assumptions underlying these similarities and give new physical insights into geometric-shape and elastic-force constraints imposed on spatial evolution of mammalian long bones., Comment: 15 pages, 1 figure

Why sex evolved and it prevails in nature remains one of the great puzzles of evolution. Most biologists would explain that it promotes genetic variability, however this explanation suffers from several difficulties. What advantages might sex confer? The present communication aims at certain investigations related to this question, in this way we introduce sexual recombination on the H\"otzel model (with males and females) and we compare these results with those from asexual reproduction without recombination., Comment: 10 pages, 6 figures

Extracellular local field potentials (LFP) are usually modeled as arising from a set of current sources embedded in a homogeneous extracellular medium. Although this formalism can successfully model several properties of LFPs, it does not account for their frequency-dependent attenuation with distance, a property essential to correctly model extracellular spikes. Here we derive expressions for the extracellular potential that include this frequency-dependent attenuation. We first show that, if the extracellular conductivity is non-homogeneous, there is induction of non-homogeneous charge densities which may result in a low-pass filter. We next derive a simplified model consisting of a punctual (or spherical) current source with spherically-symmetric conductivity/permittivity gradients around the source. We analyze the effect of different radial profiles of conductivity and permittivity on the frequency-filtering behavior of this model. We show that this simple model generally displays low-pass filtering behavior, in which fast electrical events (such as Na$^+$-mediated action potentials) attenuate very steeply with distance, while slower (K$^+$-mediated) events propagate over larger distances in extracellular space, in qualitative agreement with experimental observations. This simple model can be used to obtain frequency-dependent extracellular field potentials without taking into account explicitly the complex folding of extracellular space., Comment: text (LaTeX), 6 figs. (ps)

A general model for the ontogenetic growth of living organisms has been recently proposed. Here we investigate the extension of this model to the growth of solid malignant tumors. A variety of in vitro and in vivo data are analyzed and compared with the prediction of a 'universal' law, relating properly rescaled tumor masses and tumor growth times. The results support the notion that tumor growth follows such a universal law. Several important implications of this finding are discussed, including its relevance for tumor metastasis and recurrence, cell turnover rates, angiogenesis and invasion.

A lattice model of RNA denaturation which fully accounts for the excluded volume effects among nucleotides is proposed. A numerical study shows that interactions forming pseudoknots must be included in order to get a sharp continuous transition. Otherwise a smooth crossover occurs from the swollen linear polymer behavior to highly ramified, almost compact conformations with secondary structures. In the latter scenario, which is appropriate when these structures are much more stable than pseudoknot links, probability distributions for the lengths of both loops and main branches obey scaling with nonclassical exponents., Comment: 4 pages 3 figures

We present a game of interacting agents which mimics the complex dynamics found in many natural and social systems. These agents modify their strategies periodically, depending on their performances using genetic crossover mechanisms, inspired by biology. We study the performances of the agents under different conditions, and how they adapt themselves. In addition the dynamics of the game is investigated., Comment: 4 pages including 6 figures. Uses REVTeX4. Submitted for Conference Proceedings of the "Unconventional Applications of Statistical Physics", Kolkata

The electrodynamic response of DNA in the millimeter wave range is investigated. By performing measurements under a wide range of humidity conditions and comparing the response of single strand DNA and double strand DNA, we show that the appreciable AC conductivity of DNA is not due to photon activated hopping between localized states, but instead due to dissipation from dipole motion in the surrounding water helix. Such a result, where the conductivity is due to the constrained motion of overdamped dipoles, reconciles the vanishing DC conductivity of DNA with the considerable AC response., Comment: 4 pages, 3 figures

Why is the genetic code the way it is? The most successful theory states that the codon assignments minimise the effects of errors arising in primordial living systems. Here a transversion is reported that leaves invariant degeneracy in the genetic code. A model was established to address the question: How should sets of synonymous codons be chosen to minimise the deleterious effects of non synonymous substitutions? It is shown that the arithmetic theory of quadratic forms provides the framework for degeneracy in the genetic code., Comment: 8 pages, 2 figures, modified title, added introduction and references, added paragraph with further concept, extended conclusion, acknowledgements and figure legends

Human heart rate fluctuates in a complex and non-stationary manner. Elaborating efficient and adequate tools for the analysis of such signals has been a great challenge for the researchers during last decades. Here, an overview of the main research results in this field is given. The following question are addressed: (a) what are the intrinsic features of the heart rate variability signal; (b) what are the most promising non-linear measures, bearing in mind clinical diagnostic and prognostic applications., Comment: 23 pages

We propose and solve exactly a model of a network that has both a tunable degree distribution and a tunable clustering coefficient. Among other things, our results indicate that increased clustering leads to a decrease in the size of the giant component of the network. We also study SIR-type epidemic processes within the model and find that clustering decreases the size of epidemics, but also decreases the epidemic threshold, making it easier for diseases to spread. In addition, clustering causes epidemics to saturate sooner, meaning that they infect a near-maximal fraction of the network for quite low transmission rates., Comment: 7 pages, 2 figures, 1 table

A sound stimulus entering the inner ear excites a deformation of the basilar membrane which travels along the cochlea towards the apex. It is well established that this wave-like disturbance is amplified by an active system. Recently, it has been proposed that the active system consists of a set of self-tuned critical oscillators which automatically operate at an oscillatory instability. Here, we show how the concepts of a traveling wave and of self-tuned critical oscillators can be combined to describe the nonlinear wave in the cochlea., Comment: 5 pages, 2 figures

We analyse growing networks ranging from collaboration graphs of scientists to the network of similarities defined among the various transcriptional profiles of living cells. For the explicit demonstration of the scale-free nature and hierarchical organization of these graphs, a deterministic construction is also used. We demonstrate the use of determining the eigenvalue spectra of sparse random graph models for the categorization of small measured networks., Comment: 12 pages, 5 figures, last figure color

We introduce an approach for performing "very long" computer simulations of the dynamics of simplified, folded proteins. Using an alpha-carbon protein model and a fine grid to mimic continuum computations at increased speed, we perform unbiased simulations which exhibit many large-scale conformational transitions at low cost. In the case of the 72-residue N-terminal domain of calmodulin, the approach yields structural transitions between the calcium-free and calcium-bound structures at a rate of roughly one per day on a single Intel processor. Stable intermediates can be clearly characterized. The model employs Go-like interactions to stabilize two (or more) experimentally-determined structures. The approach is trivially parallelizable and readily generalizes to more complex potentials at minimal cost.

We study the relation between different social behaviors and the onset of epidemics in a model for the dynamics of sexual transmitted diseases. The model considers the society as a system of individual sexuated agents that can be organized in couples and interact with each other. The different social behaviors are incorporated assigning what we call a promiscuity value to each individual agent. The individual promiscuity is taken from a distributions and represents the daily probability of going out to look for a sexual partner, abandoning its eventual mate. In terms of this parameter we find a threshold for the epidemic which is much lower than the classical fully mixed model prediction, i.e. $R_0$ (basic reproductive number) $= 1$. Different forms for the distribution of the population promiscuity are considered showing that the threshold is weakly sensitive to them. We study the homosexual and the heterosexual case as well., Comment: 6 pages, 4 figures

It is shown that the scaling analysis presented in Phys. Rev. Lett. 85, 4988 (2000) is valid for finite chains of lengths relevant to experiments, in contrast to a recent claim made by A. Hanke and R. Metzler in cond-mat/0110164.

We study an off-lattice protein toy model with two species of monomers interacting through modified Lennard-Jones interactions. Low energy configurations are optimized using the pruned-enriched-Rosenbluth method (PERM), hitherto employed to native state searches only for off lattice models. For 2 dimensions we found states with lower energy than previously proposed putative ground states, for all chain lengths $\ge 13$. This indicates that PERM has the potential to produce native states also for more realistic protein models. For $d=3$, where no published ground states exist, we present some putative lowest energy states for future comparison with other methods., Comment: 4 pages, 2 figures

Poland-Scheraga models were introduced to describe the DNA denaturation transition. We give a rigorous and refined discussion of a family of these models. We derive possible scaling functions in the neighborhood of the phase transition point and review common examples. We introduce a self-avoiding Poland-Scheraga model displaying a first order phase transition in two and three dimensions. We also discuss exactly solvable directed examples. This complements recent suggestions as to how the Poland-Scheraga class might be extended in order to display a first order transition, which is observed experimentally., Comment: 23 pages, 4 figures; v2: new section 2.4, changes in introduction and conclusion; v3: major changes, version as published

The growth of an actin network against an obstacle that stimulates branching locally is studied using several variants of a kinetic rate model based on the orientation-dependent number density of filaments. The model emphasizes the effects of branching and capping on the density of free filament ends. The variants differ in their treatment of side vs. end branching and dimensionality, and assume that new branches are generated by existing branches (autocatalytic behavior) or independently of existing branches (nucleation behavior). In autocatalytic models, the network growth velocity is rigorously independent of the opposing force exerted by the obstacle, and the network density is proportional to the force. The dependence of the growth velocity on the branching and capping rates is evaluated by a numerical solution of the rate equations. In side-branching models, the growth velocity drops gradually to zero with decreasing branching rate, while in end-branching models the drop is abrupt. As the capping rate goes to zero, it is found that the behavior of the velocity is sensitive to the thickness of the branching region. Experiments are proposed for using these results to shed light on the nature of the branching process., Comment: 6 figures

Protein representation and potential function are essential ingredients for studying proteins folding and protein prediction. We introduce a novel geometric representation of contact interactions using the edge simplices from alpha shape of protein structure. This representation can eliminate implausible neighbors not in physical contact, and can avoid spurious contact between two residues when a third residue is between them. We develop statistical alpha contact potential. A studentized bootstrap method is then introduced for assessing the 95% confidence intervals for each of the 210 parameters. We found with confidence that there is significant long range propensity (>30 residues apart) for hydrophobic interactions. We test alpha contact potential for native structure discrimination using several decoy sets, and found it often has comparable performance with atom-based potentials requiring more parameters. We also show that alpha contact potential has better performance than potential defined by cut-off distance between geometric centers of side chains. Clustering of alpha contact potentials reveals natural grouping of residues. To explore the relationship between shape representation and physicochemical representation, we test the minimum alphabet size for structure discrimination. We found that there is no significant difference in discrimination when alphabet size varies from 7 to 20, if geometry is represented accurately by alpha simplicial edges. This result suggests that the geometry of packing plays an important role, but the specific residue types are often interchangeable., Comment: 18 pages, 7 figures, and 6 tables. Accepted by Proteins

Transmissible spongiform encephalopathies like the bovine spongiform encephalopathy (BSE) and the Creutzfeldt-Jakob disease (CJD) in humans are neurodegenerative diseases for which prions are the attributed pathogenic agents. A widely accepted theory assumes that prion replication is due to a direct interaction between the pathologic (PrPsc) form and the host encoded (PrPc) conformation, in a kind of an autocatalytic process. Here we show that the overall features of the incubation time of prion diseases are readily obtained if the prion reaction is described by a simple mean-field model. An analytical expression for the incubation time distribution then follows by associating the rate constant to a stochastic variable log normally distributed. The incubation time distribution is then also shown to be log normal and fits the observed BSE data very well. The basic ideas of the theoretical model are then incorporated in a cellular automata model. The computer simulation results yield the correct BSE incubation time distribution at low densities of the host encoded protein.

We consider a model for population dynamics such as for the evolution of bacterial colonies which is of the Fisher type but where the competitive interaction among individuals is non-local, and show that spatial structures with interesting features emerge. These features depend on the nature of the competitive interaction as well as on its range, specifically on the presence or absence of tails in, and the central curvature of, the influence function of the interaction., Comment: 4 Pages, 6 Figures included

We developed a non-parametric method of Information Decomposition (ID) of a content of any symbolical sequence. The method is based on the calculation of Shannon mutual information between analyzed and artificial symbolical sequences, and allows the revealing of latent periodicity in any symbolical sequence. We show the stability of the ID method in the case of a large number of random letter changes in an analyzed symbolic sequence. We demonstrate the possibilities of the method, analyzing both poems, and DNA and protein sequences. In DNA and protein sequences we show the existence of many DNA and amino acid sequences with different types and lengths of latent periodicity. The possible origin of latent periodicity for different symbolical sequences is discussed., Comment: 18 pages, 8 figures

Simple two-state folding kinetics of many small single-domain proteins are characterized by chevron plots with linear folding and unfolding arms consistent with a two-state description of equilibrium thermodynamics. This phenomenon is hereby recognized as a nontrivial heteropolymer property capable of providing fundamental insight into protein energetics. Many current protein chain models, including common lattice and continuum G\=o models with explicit native biases, fail to reproduce this generic protein property. Here we show that simple two-state kinetics is obtainable from models with a cooperative interplay between core burial and local conformational propensities or an extra strongly favorable energy for the native structure. These predictions suggest that intramolecular recognition in real two-state proteins is more specific than that envisioned by common G\=o-like constructs with pairwise additive energies. The many-body interactions in the present kinetically two-state models lead to high thermodynamic cooperativity as measured by their van't Hoff to calorimetric enthalpy ratios, implying that the native and denatured conformational populations are well separated in enthalpy by a high free energy barrier. Consistent with experiments, comparison among the present models with extra native favorabilities indicate that their folding rate at a given interaction strength decreases with increasing native contact order, although the dependence is weaker than the corresponding trend in real proteins. It has been observed experimentally that deviations from Arrhenius behavior are often more severe for folding than for unfolding. This asymmetry may be rationalized by one ..., Comment: 30 pages, 8 Postscript figures (will appear in Proteins)

Chevron rollovers of some proteins imply that their logarithmic folding rates are nonlinear in native stability. This is predicted by lattice and continuum G\=o models to arise from diminished accessibilities of the ground state from transiently populated compact conformations under strongly native conditions. Despite these models' native-centric interactions, the slowdown is due partly to kinetic trapping caused by some of the folding intermediates' nonnative topologies. Notably, simple two-state folding kinetics of small single-domain proteins are not reproduced by common G\=o-like schemes., Comment: 10 pages, 4 Postscript figures (will appear on PRL)

In this work, we revisit the basic reproduction rate $\mathcal{R}_{0}$ definition for analysis of epidemic-non-epidemic phases describing the dynamics of the discrete stochastic version of the epidemic $SIR$ model based on the Master Equation formalism. One shows that it is a very precise and efficient way to determine the epidemic threshold; using its most primitive concept, we can find exact results., Comment: Submitted to PRL

An important issue in theoretical epidemiology is the epidemic threshold phenomenon, which specify the conditions for an epidemic to grow or die out. In standard (mean-field-like) compartmental models the concept of the basic reproductive number, R0, has been systematically employed as a predictor for epidemic spread and as an analytical tool to study the threshold conditions. Despite the importance of this quantity, there are no general formulation of R0 when one considers the spread of a disease in a generic finite population, involving, for instance, arbitrary topology of inter-individual interactions and heterogeneous mixing of susceptible and immune individuals. The goal of this work is to study this concept in a generalized stochastic system described in terms of global and local variables. In particular, the dependence of R0 on the space of parameters that define the model is investigated; it is found that near of the ``classical'' epidemic threshold transition the uncertainty about the strength of the epidemic process still is significantly large. The forecasting attributes of R0 for a discrete finite system is discussed and generalized; in particular, it is shown that, for a discrete finite system, the pretentious predictive power of R0 is significantly reduced., Comment: To appear in "Journal of Biological Physics" - March 2003

We calculate the induced elastic-interaction between pointwise membrane inclusions that locally interact up to quadratic order with the membrane curvature tensor. For isotropic inclusions, we recover the usual interaction proportional to the inverse fourth power of the separation, however with a prefactor showing a non-trivial dependence on the rigidity $\Gamma$ of the quadratic potential. In the large $\Gamma$ limit, corresponding to ``hard'' inclusions, we recover the standard prefactor first obtained by Goulian et al. [Europhys. Lett. \textbf{22}, 145 (1993)]. In the small $\Gamma$ limit, corresponding to "soft" inclusions, we recover the recent result of Marchenko and Misbah [Eur. Phys. J. E \textbf{8}, 477 (2002)]. This shows that the latter result bears no fundamental discrepancy with previous works, but simply corresponds to the limit of soft inclusions. We discuss how the same inclusion can be depicted as hard or soft according to the degree of coarse-graining of the pointwise description. Finally, we argue that conical transmembrane proteins should be fundamentally considered as hard inclusions., Comment: 6 pages

We study the spontaneous ''sliding'' of histone spools (nucleosomes) along DNA as a result of thermally activated single base pair twist defects. To this end we map the system onto a suitably extended Frenkel-Kontorova model. Combining results from several recent experiments we are able to estimate the nucleosome mobility without adjustable parameters. Our model shows also how the local mobility is intimately linked to the underlying base pair sequence., Comment: 4 pages, 2 figures

Single molecule studies, at constant force, of the separation of double-stranded DNA into two separated single strands may provide information relevant to the dynamics of DNA replication. At constant applied force, theory predicts that the unzipped length as a function of time is characterized by jumps during which the strands separate rapidly, followed by long pauses where the number of separated base pairs remains constant. Here, we report previously uncharacterized observations of this striking behavior carried out on a number of identical single molecules simultaneously. When several single lphage molecules are subject to the same applied force, the pause positions are reproducible in each. This reproducibility shows that the positions and durations of the pauses in unzipping provide a sequence-dependent molecular fingerprint. For small forces, the DNA remains in a partially unzipped state for at least several hours. For larger forces, the separation is still characterized by jumps and pauses, but the double-stranded DNA will completely unzip in less than 30 min.

We propose an assembly algorithm {\sc Barnacle} for sequences generated by the clone-based approach. We illustrate our approach by assembling the human genome. Our novel method abandons the original physical-mapping-first framework. As we show, {\sc Barnacle} more effectively resolves conflicts due to repeated sequences. The latter is the main difficulty of the sequence assembly problem. Inaddition, we are able to detect inconsistencies in the underlying data. We present and compare our results on the December 2001 freeze of the public working draft of the human genome with NCBI's assembly (Build 28). The assembly of December 2001 freeze of the public working draft generated by {\sc Barnacle} and the source code of {\sc Barnacle} are available at (http://www.cs.rutgers.edu/~vchoi)., Comment: 13 pages, 10 figures

DNA denaturation, wetting in two dimensions, depinning of a flux line, and other problems map onto a phase transition with effective long range interaction. It yields giant non-universal critical indexes, arbitrarily large macroscopic correlation length and fluctuations at a finite distance from the critical temperature. In the vicinity of this region the Gibbs distribution is invalid, and thermodynamics must be calculated from the first principles. There are no fluctuations above the critical temperature., Comment: 9 pages, no figures, an improved presentation of cond-mat/0212175

Biological approximations, which are universal for diverse species, are well known. With no other experimental data, their invariance to transformations from one species to another yields exact conservation (with respect to biological diversity and evolutionary history) laws, which are inconsistent with known physics and unique for self-organized live systems. The laws predict two and only two universal ways of biological diversity and evolution; their singularities; a new kind of rapid (compared to lifespan) adaptation and reversible mortality, which may be directed. Predictions agree with experimental data, and call for new concepts, insights, and microscopic theory., Comment: 15 pages, no figures, a generalization of cond-mat/0212174

Potential functions are critical for computational studies of protein structure prediction, folding, and sequence design. A class of widely used potentials for coarse grained models of proteins are contact potentials in the form of weighted linear sum of pairwise contacts. However, these potentials have been shown to be unsuitable choices because they cannot stabilize native proteins against a large number of decoys generated by gapless threading. We develop an alternative framework for designing protein potential. We describe how finding optimal protein potential can be understood from two geometric viewpoints, and we derive nonlinear potentials using mixture of Gaussian kernel functions for folding and design. The optimization criterion for obtaining parameters of the potential is to minimize bounds on the generalization error of discriminating protein structures and decoys not used in training. In our experiment we use a training set of 440 protein structures repre senting a major portion of all known protein structures, and about 14 million structure decoys and sequence decoys obtained by gapless threading. We succeeded in obtaining nonlinear potential with perfect discrimination of the 440 native structures and native sequences. For the more challenging task of sequence design when decoys are obtained by gapless threading, we show that there is no linear potential with perfect discrimination of all 440 native sequences. Results on an independent test set of 194 proteins also showed that nonlinear kernel potential performs well., Comment: 22 pages, 7 figures, and 5 tables

A toy model of a neural network in which both Hebbian learning and reinforcement learning occur is studied. The problem of `path interference', which makes that the neural net quickly forgets previously learned input-output relations is tackled by adding a Hebbian term (proportional to the learning rate $\eta$) to the reinforcement term (proportional to $\rho$) in the learning rule. It is shown that the number of learning steps is reduced considerably if $1/4 < \eta/\rho < 1/2$, i.e., if the Hebbian term is neither too small nor too large compared to the reinforcement term.

The results of minimal model calculations suggest that the stability and the kinetic accessibility of the native state of small globular proteins are controlled by few "hot" sites. By mean of molecular dynamics simulations around the native conformation, which simulate the protein and the surrounding solvent at full--atom level, we generate an energetic map of the equilibrium state of the protein and simplify it with an Eigenvalue decomposition. The components of the Eigenvector associated with the lowest Eigenvalue indicate which are the "hot" sites responsible for the stability and for the fast folding of the protein. Comparison of these predictions with the results of mutatgenesis experiments, performed for five small proteins, provide an excellent agreement.

Interictal spikes and sharp waves in human EEG are characteristic signatures of epilepsy. These potentials originate as a result of synchronous, pathological discharge of many neurons. The reliable detection of such potentials has been the long standing problem in EEG analysis, especially after long-term monitoring became common in investigation of epileptic patients. The traditional definition of a spike is based on its amplitude, duration, sharpness, and emergence from its background. However, spike detection systems built solely around this definition are not reliable due to the presence of numerous transients and artifacts. We use wavelet transform to analyze the properties of EEG manifestations of epilepsy. We demonstrate that the behavior of wavelet transform of epileptic spikes across scales can constitute the foundation of a relatively simple yet effective detection algorithm., Comment: 4 pages, 3 figures

We study the middle cerebral artery blood flow velocity (MCAfv) in humans using transcranial Doppler ultrasonography (TCD). Scaling properties of time series of the axial flow velocity averaged over a cardiac beat interval may be characterized by two exponents. The short time scaling exponent (STSE) determines the statistical properties of fluctuations of blood flow velocities in short-time intervals while the Hurst exponent describes the long-term fractal properties. In many migraineurs the value of the STSE is significantly reduced and may approach that of the Hurst exponent. This change in dynamical properties reflects the significant loss of short-term adaptability and the overall hyperexcitability of the underlying cerebral blood flow control system. We call this effect fractal rigidity., Comment: 4 pages, 6 figures

The translocation of a macromolecule through a nanometer-sized pore is an interesting process with important applications in the development of biosensors for single--molecule analysis and in drug delivery and gene therapy. We have carried out a molecular dynamics simulation study of electrophoretic translocation of a charged polymer through an artificial nanopore to explore the feasibility of semiconductor--based nanopore devices for ultra--fast DNA sequencing. The polymer is represented by a simple bead--spring model designed to yield an appropriate coarse-grained description of the phosphate backbone of DNA in salt--free aqueous solution. A detailed analysis of single translocation event is presented to assess whether the passage of individual ions through the pore can be detected by a nanoscale field--effect transistor by measuring variations in electrostatic potential during polymer translocation. We find that it is possible to identify single events corresponding to the passage of counterions through the pore, but that discrimination of individual ions on the polymer chain based on variations in electrostatic potential is problematic. Several distinct stages in the translocation process are identified, characterized by changes in polymer conformation and by variations in the magnitude and direction of the internal electric field induced by the fluctuating charge distribution. The dependence of the condensed fraction of counterions on Bjerrum length leads to significant changes in polymer conformation, which profoundly affect the dynamics of electrophoresis and translocation., Comment: 37 pages Revtex, 11 postscript figures

The coding sequence in DNA molecule is considered as a message to be transferred to receiver, the proteins, through a noisy information channel and each nucleotide is assigned a respective information weight. With the help of the nucleotide substitution matrix we estimated the lower bound of the amount of information carried out by nucleotides which is not subject of mutations. We used the calculated weights to reconstruct k-oligomers of genes from the Borrelia burgdorferi genome. We showed, that to this aim there is sufficient a simple rule, that the number of bits of the carried information cannot exceed some threshold value. The method introduced by us is general and applies to every genome., Comment: 8 pages, 7 figures, submitted for publication