Quasi-steady state reduction of molecular motor-based models of directed intermittent search

We present a quasi–steady state reduction of a linear reaction–hyperbolic master equation describing the directed intermittent search for a hidden target by a motor–driven particle moving on a one–dimensional filament track. The particle is injected at one end of the track and randomly switches between stationary search phases and mobile, non-search phases that are biased in the anterograde direction. There is a finite possibility that the particle fails to find the target due to an absorbing boundary at the other end of the track. Such a scenario is exemplified by the motor–driven transport of vesicular cargo to synaptic targets located on the axon or dendrites of a neuron. The reduced model is described by a scalar Fokker–Planck (FP) equation, which has an additional inhomogeneous decay term that takes into account absorption by the target. The FP equation is used to compute the probability of finding the hidden target (hitting probability) and the corresponding conditional mean first passage time (MFPT) in terms of the effective drift velocity V , diffusivity D and target absorption rate λ of the random search. The quasi–steady state reduction determines V, D and λ in terms of the various biophysical parameters of the underlying motor transport model. We first apply our analysis to a simple 3–state model and show that our quasi–steady state reduction yields results that are in excellent agreement with Monte Carlo simulations of the full system under physiologically reasonable conditions. We then consider a more complex multiple motor model of bidirectional transport, in which opposing motors compete in a “tug-of-war,” and use this to explore how ATP concentration might regulate the delivery of cargo to synaptic targets

Random intermittent search and the tug-of-war model of motor-driven transport

We formulate the tug-of-war model of microtubule cargo transport by multiple molecular motors as an intermittent random search for a hidden target. A motor-complex consisting of multiple molecular motors with opposing directional preference is modeled using a discrete Markov process. The motors randomly pull each other off of the microtubule so that the state of the motor-complex is determined by the number of bound motors. The tug-of-war model prescribes the state transition rates and corresponding cargo velocities in terms of experimentally measured physical parameters. We add space to the resulting Chapman-Kolmogorov (CK) equation so that we can consider delivery of the cargo to a hidden target somewhere on the microtubule track. Using a quasi-steady state (QSS) reduction technique we calculate analytical approximations of the mean first passage time (MFPT) to find the target. We show that there exists an optimal adenosine triphosphate (ATP)concentration that minimizes the MFPT for two different cases: (i) the motor complex is composed of equal numbers of kinesin motors bound to two different microtubules (symmetric tug-of-war model), and (ii) the motor complex is composed of different numbers of kinesin and dynein motors bound to a single microtubule(asymmetric tug-of-war model)

Sign rank versus VC dimension

This work studies the maximum possible sign rank of $N \times N$ sign matrices with a given VC dimension $d$. For $d=1$, this maximum is {three}. For $d=2$, this maximum is $\tilde{\Theta}(N^{1/2})$. For $d >2$, similar but slightly less accurate statements hold. {The lower bounds improve over previous ones by Ben-David et al., and the upper bounds are novel.} The lower bounds are obtained by probabilistic constructions, using a theorem of Warren in real algebraic topology. The upper bounds are obtained using a result of Welzl about spanning trees with low stabbing number, and using the moment curve. The upper bound technique is also used to: (i) provide estimates on the number of classes of a given VC dimension, and the number of maximum classes of a given VC dimension -- answering a question of Frankl from '89, and (ii) design an efficient algorithm that provides an $O(N/\log(N))$ multiplicative approximation for the sign rank. We also observe a general connection between sign rank and spectral gaps which is based on Forster's argument. Consider the $N \times N$ adjacency matrix of a $\Delta$ regular graph with a second eigenvalue of absolute value $\lambda$ and $\Delta \leq N/2$. We show that the sign rank of the signed version of this matrix is at least $\Delta/\lambda$. We use this connection to prove the existence of a maximum class $C\subseteq\{\pm 1\}^N$ with VC dimension $2$ and sign rank $\tilde{\Theta}(N^{1/2})$. This answers a question of Ben-David et al.~regarding the sign rank of large VC classes. We also describe limitations of this approach, in the spirit of the Alon-Boppana theorem. We further describe connections to communication complexity, geometry, learning theory, and combinatorics.Comment: 33 pages. This is a revised version of the paper "Sign rank versus VC dimension". Additional results in this version: (i) Estimates on the number of maximum VC classes (answering a question of Frankl from '89). (ii) Estimates on the sign rank of large VC classes (answering a question of Ben-David et al. from '03). (iii) A discussion on the computational complexity of computing the sign-ran

Output-Sensitive Tools for Range Searching in Higher Dimensions

Let $P$ be a set of $n$ points in ${\mathbb R}^{d}$. A point $p \in P$ is $k$\emph{-shallow} if it lies in a halfspace which contains at most $k$ points of $P$ (including $p$). We show that if all points of $P$ are $k$-shallow, then $P$ can be partitioned into $\Theta(n/k)$ subsets, so that any hyperplane crosses at most $O((n/k)^{1-1/(d-1)} \log^{2/(d-1)}(n/k))$ subsets. Given such a partition, we can apply the standard construction of a spanning tree with small crossing number within each subset, to obtain a spanning tree for the point set $P$, with crossing number $O(n^{1-1/(d-1)}k^{1/d(d-1)} \log^{2/(d-1)}(n/k))$. This allows us to extend the construction of Har-Peled and Sharir \cite{hs11} to three and higher dimensions, to obtain, for any set of $n$ points in ${\mathbb R}^{d}$ (without the shallowness assumption), a spanning tree $T$ with {\em small relative crossing number}. That is, any hyperplane which contains $w \leq n/2$ points of $P$ on one side, crosses $O(n^{1-1/(d-1)}w^{1/d(d-1)} \log^{2/(d-1)}(n/w))$ edges of $T$. Using a similar mechanism, we also obtain a data structure for halfspace range counting, which uses $O(n \log \log n)$ space (and somewhat higher preprocessing cost), and answers a query in time $O(n^{1-1/(d-1)}k^{1/d(d-1)} (\log (n/k))^{O(1)})$, where $k$ is the output size

Spectral properties of incommensurate charge-density wave systems

The concept of frustrated phase separation is applied to investigate its consequences for the electronic structure of the high T_c cuprates. The resulting incommensurate charge density wave (CDW) scattering is most effective in creating local gaps in k-space when the scattering vector connects states with equal energy. Starting from an open Fermi surface we find that the resulting CDW is oriented along the (10)- and (or) (01)-direction which allows for a purely one-dimensional or a two-dimensional ``eggbox type'' charge modulation. In both cases the van Hove singularities are substantially enhanced, and the spectral weight of Fermi surface states near the M-points, tends to be suppressed. Remarkably, a leading edge gap arises near these points, which, in the eggbox case, leaves finite arcs of the Fermi surface gapless. We discuss our results with repect to possible consequences for photoemission experiments