20 research outputs found
A field-theoretic approach to the Wiener Sausage
The Wiener Sausage, the volume traced out by a sphere attached to a Brownian
particle, is a classical problem in statistics and mathematical physics.
Initially motivated by a range of field-theoretic, technical questions, we
present a single loop renormalised perturbation theory of a stochastic process
closely related to the Wiener Sausage, which, however, proves to be exact for
the exponents and some amplitudes. The field-theoretic approach is particularly
elegant and very enjoyable to see at work on such a classic problem. While we
recover a number of known, classical results, the field-theoretic techniques
deployed provide a particularly versatile framework, which allows easy
calculation with different boundary conditions even of higher momenta and more
complicated correlation functions. At the same time, we provide a highly
instructive, non-trivial example for some of the technical particularities of
the field-theoretic description of stochastic processes, such as excluded
volume, lack of translational invariance and immobile particles. The aim of the
present work is not to improve upon the well-established results for the Wiener
Sausage, but to provide a field-theoretic approach to it, in order to gain a
better understanding of the field-theoretic obstacles to overcome.Comment: 45 pages, 3 Figures, Springer styl
Integrin Clustering Is Driven by Mechanical Resistance from the Glycocalyx and the Substrate
Integrins have emerged as key sensory molecules that translate chemical and physical cues from the extracellular matrix (ECM) into biochemical signals that regulate cell behavior. Integrins function by clustering into adhesion plaques, but the molecular mechanisms that drive integrin clustering in response to interaction with the ECM remain unclear. To explore how deformations in the cell-ECM interface influence integrin clustering, we developed a spatial-temporal simulation that integrates the micro-mechanics of the cell, glycocalyx, and ECM with a simple chemical model of integrin activation and ligand interaction. Due to mechanical coupling, we find that integrin-ligand interactions are highly cooperative, and this cooperativity is sufficient to drive integrin clustering even in the absence of cytoskeletal crosslinking or homotypic integrin-integrin interactions. The glycocalyx largely mediates this cooperativity and hence may be a key regulator of integrin function. Remarkably, integrin clustering in the model is naturally responsive to the chemical and physical properties of the ECM, including ligand density, matrix rigidity, and the chemical affinity of ligand for receptor. Consistent with experimental observations, we find that integrin clustering is robust on rigid substrates with high ligand density, but is impaired on substrates that are highly compliant or have low ligand density. We thus demonstrate how integrins themselves could function as sensory molecules that begin sensing matrix properties even before large multi-molecular adhesion complexes are assembled
Teachers’ Work: Institutional Isomorphism and Cultural Variation in the U.S., Germany, and Japan
Optimal pooling designs with error detection
Consider a collection of objects, some of which may be `bad', and a test
which determines whether or not a given sub-collection contains no bad
objects. The non-adaptive pooling (or group testing) problem involves
identifying the bad objects using the least number of tests applied in
parallel. The `hypergeometric' case occurs when an upper bound on the number
of bad objects is known {\em a priori}. Here, practical considerations lead us
to impose the additional requirement of {\em a posteriori} confirmation that
the bound is satisfied. A generalization of the problem in which occasional
errors in the test outcomes can occur is also considered. Optimal solutions to
the general problem are shown to be equivalent to maximum-size collections of
subsets of a finite set satisfying a union condition which generalizes that
considered by Erd\"os \etal \cite{erd}. Lower bounds on the number of tests
required are derived when the number of bad objects is believed to be either 1
or 2. Steiner systems are shown to be optimal solutions in some cases
EFFICIENT POOLING DESIGNS FOR LIBRARY SCREENING
We describe efficient methods for screening clone libraries, based on pooling schemes that we call "random k-sets designs." In these designs, the pools in which any clone occurs are equally likely to be any possible selection of k from the v pools. The values of k and v can be chosen to optimize desirable properties. Random k-sets designs have substantial advantages over alternative pooling schemes: they are efficient, flexible, and easy to specify, require fewer pools, and have error-correcting and error-detecting capabilities. In addition, screening can often be achieved in only one pass, thus facilitating automation. For design comparison, we assume a binomial distribution for the number of "positive" clones, with parameters n, the number of clones, and c, the coverage. We propose the expected number of resolved positive clones--clones that are definitely positive based upon the pool assays--as a criterion for the efficiency of a pooling design. We determine the value of k that is optimal, with respect to this criterion, as a function of v, n, and c. We also describe superior k-sets designs called k-sets packing designs. As an illustration, we discuss a robotically implemented design for a 2.5-fold-coverage, human chromosome 16 YAC library of n = 1298 clones. We also estimate the probability that each clone is positive, given the pool-assay data and a model for experimental errors