S+Net: extending functional coordination with extra-functional semantics

This technical report introduces S+Net, a compositional coordination language for streaming networks with extra-functional semantics. Compositionality simplifies the specification of complex parallel and distributed applications; extra-functional semantics allow the application designer to reason about and control resource usage, performance and fault handling. The key feature of S+Net is that functional and extra-functional semantics are defined orthogonally from each other. S+Net can be seen as a simultaneous simplification and extension of the existing coordination language S-Net, that gives control of extra-functional behavior to the S-Net programmer. S+Net can also be seen as a transitional research step between S-Net and AstraKahn, another coordination language currently being designed at the University of Hertfordshire. In contrast with AstraKahn which constitutes a re-design from the ground up, S+Net preserves the basic operational semantics of S-Net and thus provides an incremental introduction of extra-functional control in an existing language.Comment: 34 pages, 11 figures, 3 table

Using Links to prototype a Database Wiki

Both relational databases and wikis have strengths that make them attractive for use in collaborative applications. In the last decade, database-backed Web applications have been used extensively to develop valuable shared biological references called curated databases. Databases offer many advantages such as scalability, query optimization and concurrency control, but are not easy to use and lack other features needed for collaboration. Wikis have become very popular for early-stage biocuration projects because they are easy to use, encourage sharing and collaboration, and provide built-in support for archiving, history-tracking and annotation. However, curation projects often outgrow the limited capabilities of wikis for structuring and efficiently querying data at scale, necessitating a painful phase transition to a database-backed Web application. We perceive a need for a new class of general-purpose system, which we call a Database Wiki, that combines flexible wiki-like support for collaboration with robust database-like capabilities for structuring and querying data. This paper presents DBWiki, a design prototype for such a system written in the Web programming language Links. We present the architecture, typical use, and wiki markup language design for DBWiki and discuss features of Links that provided unique advantages for rapid Web/database application prototyping

Design Environments for Complex Systems

The paper describes an approach for modeling complex systems by hiding as much formal details as possible from the user, still allowing verification and simulation of the model. The interface is based on UML to make the environment available to the largest audience. To carry out analysis, verification and simulation we automatically extract process algebras specifications from UML models. The results of the analysis is then reflected back in the UML model by annotating diagrams. The formal model includes stochastic information to handle quantitative parameters. We present here the stochastic -calculus and we discuss the implementation of its probabilistic support that allows simulation of processes. We exploit the benefits of our approach in two applicative domains: global computing and systems biology

Beating the reaction limits of biosensor sensitivity with dynamic tracking of single binding events

The clinical need for ultrasensitive molecular analysis has motivated the development of several endpoint-assay technologies capable of single-molecule readout. These endpoint assays are now primarily limited by the affinity and specificity of the molecular-recognition agents for the analyte of interest. In contrast, a kinetic assay with single-molecule readout could distinguish between low-abundance, high-affinity (specific analyte) and high-abundance, low-affinity (nonspecific background) binding by measuring the duration of individual binding events at equilibrium. Here, we describe such a kinetic assay, in which individual binding events are detected and monitored during sample incubation. This method uses plasmonic gold nanorods and interferometric reflectance imaging to detect thousands of individual binding events across a multiplex solid-phase sensor with a large area approaching that of leading bead-based endpoint-assay technologies. A dynamic tracking procedure is used to measure the duration of each event. From this, the total rates of binding and debinding as well as the distribution of binding-event durations are determined. We observe a limit of detection of 19 fM for a proof-of-concept synthetic DNA analyte in a 12-plex assay format.First author draf

A formal support to business and architectural design for service-oriented systems

Architectural Design Rewriting (ADR) is an approach for the design of software architectures developed within Sensoria by reconciling graph transformation and process calculi techniques. The key feature that makes ADR a suitable and expressive framework is the algebraic handling of structured graphs, which improves the support for specification, analysis and verification of service-oriented architectures and applications. We show how ADR is used as a formal ground for high-level modelling languages and approaches developed within Sensoria

Dynamic multifactor hubs interact transiently with sites of active transcription in Drosophila embryos.

The regulation of transcription requires the coordination of numerous activities on DNA, yet how transcription factors mediate these activities remains poorly understood. Here, we use lattice light-sheet microscopy to integrate single-molecule and high-speed 4D imaging in developing Drosophila embryos to study the nuclear organization and interactions of the key transcription factors Zelda and Bicoid. In contrast to previous studies suggesting stable, cooperative binding, we show that both factors interact with DNA with surprisingly high off-rates. We find that both factors form dynamic subnuclear hubs, and that Bicoid binding is enriched within Zelda hubs. Remarkably, these hubs are both short lived and interact only transiently with sites of active Bicoid-dependent transcription. Based on our observations, we hypothesize that, beyond simply forming bridges between DNA and the transcription machinery, transcription factors can organize other proteins into hubs that transiently drive multiple activities at their gene targets.Editorial noteThis article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter)

C++ Templates as Partial Evaluation

This paper explores the relationship between C++ templates and partial evaluation. Templates were designed to support generic programming, but unintentionally provided the ability to perform compile-time computations and code generation. These features are completely accidental, and as a result their syntax is awkward. By recasting these features in terms of partial evaluation, a much simpler syntax can be achieved. C++ may be regarded as a two-level language in which types are first-class values. Template instantiation resembles an offline partial evaluator. This paper describes preliminary work toward a single mechanism based on Partial Evaluation which unifies generic programming, compile-time computation and code generation. The language Catat is introduced to illustrate these ideas.Comment: 13 page

Myosin II filament dynamics in actin networks revealed with interferometric scattering microscopy

The plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood due to difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering (iSCAT) microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer membrane. Using the magnitude of the interferometric contrast, which is proportional to molecular mass, and fast acquisition rates, we detect, and image individual membrane attached actin filaments diffusing within the acto-myosin network and follow individual myosin II filament dynamics. We quantify myosin II filament dwell times and processivity as functions of ATP concentration, providing experimental evidence for the predicted ensemble behavior of myosin head domains. Our results show how decreasing ATP concentrations lead to both increasing dwell times of individual myosin II filaments and a global change from a remodeling to a contractile state of the acto-myosin network