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

A Model of Cooperative Threads

We develop a model of concurrent imperative programming with threads. We focus on a small imperative language with cooperative threads which execute without interruption until they terminate or explicitly yield control. We define and study a trace-based denotational semantics for this language; this semantics is fully abstract but mathematically elementary. We also give an equational theory for the computational effects that underlie the language, including thread spawning. We then analyze threads in terms of the free algebra monad for this theory.Comment: 39 pages, 5 figure

Comparing hierarchies of total functionals

In this paper we consider two hierarchies of hereditarily total and continuous functionals over the reals based on one extensional and one intensional representation of real numbers, and we discuss under which asumptions these hierarchies coincide. This coincidense problem is equivalent to a statement about the topology of the Kleene-Kreisel continuous functionals. As a tool of independent interest, we show that the Kleene-Kreisel functionals may be embedded into both these hierarchies.Comment: 28 page

Online Admission Control and Embedding of Service Chains

The virtualization and softwarization of modern computer networks enables the definition and fast deployment of novel network services called service chains: sequences of virtualized network functions (e.g., firewalls, caches, traffic optimizers) through which traffic is routed between source and destination. This paper attends to the problem of admitting and embedding a maximum number of service chains, i.e., a maximum number of source-destination pairs which are routed via a sequence of to-be-allocated, capacitated network functions. We consider an Online variant of this maximum Service Chain Embedding Problem, short OSCEP, where requests arrive over time, in a worst-case manner. Our main contribution is a deterministic O(log L)-competitive online algorithm, under the assumption that capacities are at least logarithmic in L. We show that this is asymptotically optimal within the class of deterministic and randomized online algorithms. We also explore lower bounds for offline approximation algorithms, and prove that the offline problem is APX-hard for unit capacities and small L > 2, and even Poly-APX-hard in general, when there is no bound on L. These approximation lower bounds may be of independent interest, as they also extend to other problems such as Virtual Circuit Routing. Finally, we present an exact algorithm based on 0-1 programming, implying that the general offline SCEP is in NP and by the above hardness results it is NP-complete for constant L.Comment: early version of SIROCCO 2015 pape

Leveraging Semantic Web Service Descriptions for Validation by Automated Functional Testing

Recent years have seen the utilisation of Semantic Web Service descriptions for automating a wide range of service-related activities, with a primary focus on service discovery, composition, execution and mediation. An important area which so far has received less attention is service validation, whereby advertised services are proven to conform to required behavioural specifications. This paper proposes a method for validation of service-oriented systems through automated functional testing. The method leverages ontology-based and rule-based descriptions of service inputs, outputs, preconditions and effects (IOPE) for constructing a stateful EFSM specification. The specification is subsequently utilised for functional testing and validation using the proven Stream X-machine (SXM) testing methodology. Complete functional test sets are generated automatically at an abstract level and are then applied to concrete Web services, using test drivers created from the Web service descriptions. The testing method comes with completeness guarantees and provides a strong method for validating the behaviour of Web services

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

Proof Relevant Corecursive Resolution

Resolution lies at the foundation of both logic programming and type class context reduction in functional languages. Terminating derivations by resolution have well-defined inductive meaning, whereas some non-terminating derivations can be understood coinductively. Cycle detection is a popular method to capture a small subset of such derivations. We show that in fact cycle detection is a restricted form of coinductive proof, in which the atomic formula forming the cycle plays the role of coinductive hypothesis. This paper introduces a heuristic method for obtaining richer coinductive hypotheses in the form of Horn formulas. Our approach subsumes cycle detection and gives coinductive meaning to a larger class of derivations. For this purpose we extend resolution with Horn formula resolvents and corecursive evidence generation. We illustrate our method on non-terminating type class resolution problems.Comment: 23 pages, with appendices in FLOPS 201

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

On Probabilistic Applicative Bisimulation and Call-by-Value λ\lambda-Calculi (Long Version)

Probabilistic applicative bisimulation is a recently introduced coinductive methodology for program equivalence in a probabilistic, higher-order, setting. In this paper, the technique is applied to a typed, call-by-value, lambda-calculus. Surprisingly, the obtained relation coincides with context equivalence, contrary to what happens when call-by-name evaluation is considered. Even more surprisingly, full-abstraction only holds in a symmetric setting.Comment: 30 page