Transcriptional errors and the drift barrier

Population genetics predicts that the balance between natural selection and genetic drift is determined by the population size. Species with large population sizes are predicted to have properties governed mainly by selective forces; whereas species with small population sizes should exhibit features governed by mutational processes alone. This “drift-barrier hypothesis” has been successful in explaining extensive variation in genome size, mutation rate, transposable element abundance, and other molecular features across diverse taxa (1⇓–3). However, in PNAS Traverse and Ochman (4) report a striking exception to this theory by showing that transcriptional error rates are nearly equal across several bacterial species with very different population sizes

Designing an international policy and legal framework for the control of emerging infectious diseases: first steps.

As the pace of emergence and reemergence of infectious diseases quickens, the International Health Regulations, which have served as the legal and policy framework of epidemic control for 45 years, are being revised by the World Health Organization (WHO). In this article, we review the recent history, legal construction, and application of these regulations and related international treaty-based sanitary measures, especially the General Agreement on Tariffs and Trade and the Agreement on the Application of Sanitary and Phytosanitary Measures, and the history of applying the regulations in the maritime and aviation industries. This review indicates that revision efforts should address 1) the limited scope of disease syndromes (and reporters of these syndromes) now in the regulations and 2) the mismatch between multisectoral factors causing disease emergence and the single agency (WHO) administering the regulations. The revised regulations should expand the scope of reporting and simultaneously broaden international agency coordination

Sound and complete axiomatizations of coalgebraic language equivalence

Coalgebras provide a uniform framework to study dynamical systems, including several types of automata. In this paper, we make use of the coalgebraic view on systems to investigate, in a uniform way, under which conditions calculi that are sound and complete with respect to behavioral equivalence can be extended to a coarser coalgebraic language equivalence, which arises from a generalised powerset construction that determinises coalgebras. We show that soundness and completeness are established by proving that expressions modulo axioms of a calculus form the rational fixpoint of the given type functor. Our main result is that the rational fixpoint of the functor $FT$, where $T$ is a monad describing the branching of the systems (e.g. non-determinism, weights, probability etc.), has as a quotient the rational fixpoint of the "determinised" type functor $\bar F$, a lifting of $F$ to the category of $T$-algebras. We apply our framework to the concrete example of weighted automata, for which we present a new sound and complete calculus for weighted language equivalence. As a special case, we obtain non-deterministic automata, where we recover Rabinovich's sound and complete calculus for language equivalence.Comment: Corrected version of published journal articl

Non-Markovian Configurational Diffusion and Reaction Coordinates for Protein Folding

The non-Markovian nature of polymer motions is accounted for in folding kinetics, using frequency-dependent friction. Folding, like many other problems in the physics of disordered systems, involves barrier crossing on a correlated energy landscape. A variational transition state theory (VTST) that reduces to the usual Bryngelson-Wolynes Kramers approach when the non-Markovian aspects are neglected is used to obtain the rate, without making any assumptions regarding the size of the barrier, or the memory time of the friction. The transformation to collective variables dependent on the dynamics of the system allows the theory to address the controversial issue of what are ``good'' reaction coordinates for folding.Comment: 9 pages RevTeX, 3 eps-figures included, submitted to PR

Syntax for free: representing syntax with binding using parametricity

We show that, in a parametric model of polymorphism, the type ∀ α. ((α → α) → α) → (α → α → α) → α is isomorphic to closed de Bruijn terms. That is, the type of closed higher-order abstract syntax terms is isomorphic to a concrete representation. To demonstrate the proof we have constructed a model of parametric polymorphism inside the Coq proof assistant. The proof of the theorem requires parametricity over Kripke relations. We also investigate some variants of this representation

Evaluating the performance of model transformation styles in Maude

Rule-based programming has been shown to be very successful in many application areas. Two prominent examples are the specification of model transformations in model driven development approaches and the definition of structured operational semantics of formal languages. General rewriting frameworks such as Maude are flexible enough to allow the programmer to adopt and mix various rule styles. The choice between styles can be biased by the programmer’s background. For instance, experts in visual formalisms might prefer graph-rewriting styles, while experts in semantics might prefer structurally inductive rules. This paper evaluates the performance of different rule styles on a significant benchmark taken from the literature on model transformation. Depending on the actual transformation being carried out, our results show that different rule styles can offer drastically different performances. We point out the situations from which each rule style benefits to offer a valuable set of hints for choosing one style over the other

Protein folding rates correlate with heterogeneity of folding mechanism

By observing trends in the folding kinetics of experimental 2-state proteins at their transition midpoints, and by observing trends in the barrier heights of numerous simulations of coarse grained, C-alpha model, Go proteins, we show that folding rates correlate with the degree of heterogeneity in the formation of native contacts. Statistically significant correlations are observed between folding rates and measures of heterogeneity inherent in the native topology, as well as between rates and the variance in the distribution of either experimentally measured or simulated phi-values.Comment: 11 pages, 3 figures, 1 tabl

On the Number of Iterations for Dantzig-Wolfe Optimization and Packing-Covering Approximation Algorithms

We give a lower bound on the iteration complexity of a natural class of Lagrangean-relaxation algorithms for approximately solving packing/covering linear programs. We show that, given an input with $m$ random 0/1-constraints on $n$ variables, with high probability, any such algorithm requires $\Omega(\rho \log(m)/\epsilon^2)$ iterations to compute a $(1+\epsilon)$-approximate solution, where $\rho$ is the width of the input. The bound is tight for a range of the parameters $(m,n,\rho,\epsilon)$. The algorithms in the class include Dantzig-Wolfe decomposition, Benders' decomposition, Lagrangean relaxation as developed by Held and Karp [1971] for lower-bounding TSP, and many others (e.g. by Plotkin, Shmoys, and Tardos [1988] and Grigoriadis and Khachiyan [1996]). To prove the bound, we use a discrepancy argument to show an analogous lower bound on the support size of $(1+\epsilon)$-approximate mixed strategies for random two-player zero-sum 0/1-matrix games

Call-by-value non-determinism in a linear logic type discipline

We consider the call-by-value lambda-calculus extended with a may-convergent non-deterministic choice and a must-convergent parallel composition. Inspired by recent works on the relational semantics of linear logic and non-idempotent intersection types, we endow this calculus with a type system based on the so-called Girard's second translation of intuitionistic logic into linear logic. We prove that a term is typable if and only if it is converging, and that its typing tree carries enough information to give a bound on the length of its lazy call-by-value reduction. Moreover, when the typing tree is minimal, such a bound becomes the exact length of the reduction