Positive Feedback Regulation Results in Spatial Clustering and Fast Spreading of Active Signaling Molecules on a Cell Membrane

Positive feedback regulation is ubiquitous in cell signaling networks, often leading to binary outcomes in response to graded stimuli. However, the role of such feedbacks in clustering, and in spatial spreading of activated molecules, has come to be appreciated only recently. We focus on the latter, using a simple model developed in the context of Ras activation with competing negative and positive feedback mechanisms. We find that positive feedback, in the presence of slow diffusion, results in clustering of activated molecules on the plasma membrane, and rapid spatial spreading as the front of the cluster propagates with a constant velocity (dependent on the feedback strength). The advancing fronts of the clusters of the activated species are rough, with scaling consistent with the Kardar-Parisi-Zhang (KPZ) equation in one dimension. Our minimal model is general enough to describe signal transduction in a wide variety of biological networks where activity in the membrane-proximal region is subject to feedback regulation.Comment: 37 pages, 8 figures. Journal of Chemical Physics (in press

Probability distributions for polymer translocation

We study the passage (translocation) of a self-avoiding polymer through a membrane pore in two dimensions. In particular, we numerically measure the probability distribution Q(T) of the translocation time T, and the distribution P(s,t) of the translocation coordinate s at various times t. When scaled with the mean translocation time , Q(T) becomes independent of polymer length, and decays exponentially for large T. The probability P(s,t) is well described by a Gaussian at short times, with a variance that grows sub-diffusively as t^{\alpha} with \alpha~0.8. For times exceeding , P(s,t) of the polymers that have not yet finished their translocation has a non-trivial stable shape.Comment: 5 pages, 4 figure

QProber: A System for Automatic Classification of Hidden-Web Resources

The contents of many valuable web-accessible databases are only available through search interfaces and are hence invisible to traditional web "crawlers." Recently, commercial web sites have started to manually organize web-accessible databases into Yahoo!-like hierarchical classification schemes. Here, we introduce QProber, a modular system that automates this classification process by using a small number of query probes, generated by document classifiers. QProber can use a variety of types of classifiers to generate the probes. To classify a database, QProber does not retrieve or inspect any documents or pages from the database, but rather just exploits the number of matches that each query probe generates at the database in question. We have conducted an extensive experimental evaluation of QProber over collections of real documents, experimenting with different types of document classifiers and retrieval models. We have also tested our system with over one hundred web-accessible databases. Our experiments show that our system has low overhead and achieves high classification accuracy across a variety of databases

Material dependence of Casimir forces: gradient expansion beyond proximity

A widely used method for estimating Casimir interactions [H. B. G. Casimir, Proc. K. Ned. Akad. Wet. 51, 793 (1948)] between gently curved material surfaces at short distances is the proximity force approximation (PFA). While this approximation is asymptotically exact at vanishing separations, quantifying corrections to PFA has been notoriously difficult. Here we use a derivative expansion to compute the leading curvature correction to PFA for metals (gold) and insulators (SiO$_2$) at room temperature. We derive an explicit expression for the amplitude $\hat\theta_1$ of the PFA correction to the force gradient for axially symmetric surfaces. In the non-retarded limit, the corrections to the Casimir free energy are found to scale logarithmically with distance. For gold, $\hat\theta_1$ has an unusually large temperature dependence.Comment: 4 pages, 2 figure

Apex Exponents for Polymer--Probe Interactions

We consider self-avoiding polymers attached to the tip of an impenetrable probe. The scaling exponents $\gamma_1$ and $\gamma_2$, characterizing the number of configurations for the attachment of the polymer by one end, or at its midpoint, vary continuously with the tip's angle. These apex exponents are calculated analytically by $\epsilon$-expansion, and numerically by simulations in three dimensions. We find that when the polymer can move through the attachment point, it typically slides to one end; the apex exponents quantify the entropic barrier to threading the eye of the probe

First Passage Distributions in a Collective Model of Anomalous Diffusion with Tunable Exponent

We consider a model system in which anomalous diffusion is generated by superposition of underlying linear modes with a broad range of relaxation times. In the language of Gaussian polymers, our model corresponds to Rouse (Fourier) modes whose friction coefficients scale as wavenumber to the power $2-z$. A single (tagged) monomer then executes subdiffusion over a broad range of time scales, and its mean square displacement increases as $t^\alpha$ with $\alpha=1/z$. To demonstrate non-trivial aspects of the model, we numerically study the absorption of the tagged particle in one dimension near an absorbing boundary or in the interval between two such boundaries. We obtain absorption probability densities as a function of time, as well as the position-dependent distribution for unabsorbed particles, at several values of $\alpha$. Each of these properties has features characterized by exponents that depend on $\alpha$. Characteristic distributions found for different values of $\alpha$ have similar qualitative features, but are not simply related quantitatively. Comparison of the motion of translocation coordinate of a polymer moving through a pore in a membrane with the diffusing tagged monomer with identical $\alpha$ also reveals quantitative differences.Comment: LaTeX, 10 pages, 8 eps figure

The Unusual Universality of Branching Interfaces in Random Media

We study the criticality of a Potts interface by introducing a {\it froth} model which, unlike its SOS Ising counterpart, incorporates bubbles of different phases. The interface is fractal at the phase transition of a pure system. However, a position space approximation suggests that the probability of loop formation vanishes marginally at a transition dominated by {\it strong random bond disorder}. This implies a linear critical interface, and provides a mechanism for the conjectured equivalence of critical random Potts and Ising models.Comment: REVTEX, 13 pages, 3 Postscript figures appended using uufile

Casimir Force at a Knife's Edge

The Casimir force has been computed exactly for only a few simple geometries, such as infinite plates, cylinders, and spheres. We show that a parabolic cylinder, for which analytic solutions to the Helmholtz equation are available, is another case where such a calculation is possible. We compute the interaction energy of a parabolic cylinder and an infinite plate (both perfect mirrors), as a function of their separation and inclination, $H$ and $\theta$, and the cylinder's parabolic radius $R$. As $H/R\to 0$, the proximity force approximation becomes exact. The opposite limit of $R/H\to 0$ corresponds to a semi-infinite plate, where the effects of edge and inclination can be probed.Comment: 5 pages, 3 figures, uses RevTeX; v2: expanded conclusions; v3: fixed missing factor in Eq. (3) and incorrect diagram label (no changes to results); v4: fix similar factor in Eq. (16) (again no changes to results