Mapping behavioral specifications to model parameters in synthetic biology

With recent improvements of protocols for the assembly of transcriptional parts, synthetic biological devices can now more reliably be assembled according to a given design. The standardization of parts open up the way for in silico design tools that improve the construct and optimize devices with respect to given formal design specifications. The simplest such optimization is the selection of kinetic parameters and protein abundances such that the specified design constraints are robustly satisfied. In this work we address the problem of determining parameter values that fulfill specifications expressed in terms of a functional on the trajectories of a dynamical model. We solve this inverse problem by linearizing the forward operator that maps parameter sets to specifications, and then inverting it locally. This approach has two advantages over brute-force random sampling. First, the linearization approach allows us to map back intervals instead of points and second, every obtained value in the parameter region is satisfying the specifications by construction. The method is general and can hence be incorporated in a pipeline for the rational forward design of arbitrary devices in synthetic biology

Mapping behavioral specifications to model parameters in synthetic biology

With recent improvements of protocols for the assembly of transcriptional parts, synthetic biological devices can now more reliably be assembled according to a given design. The standardization of parts open up the way for in silico design tools that improve the construct and optimize devices with respect to given formal design specifications. The simplest such optimization is the selection of kinetic parameters and protein abundances such that the specified design constraints are robustly satisfied. In this work we address the problem of determining parameter values that fulfill specifications expressed in terms of a functional on the trajectories of a dynamical model. We solve this inverse problem by linearizing the forward operator that maps parameter sets to specifications, and then inverting it locally. This approach has two advantages over brute-force random sampling. First, the linearization approach allows us to map back intervals instead of points and second, every obtained value in the parameter region is satisfying the specifications by construction. The method is general and can hence be incorporated in a pipeline for the rational forward design of arbitrary devices in synthetic biology

Synthetic in vitro transcriptional oscillators

The construction of synthetic biochemical circuits from simple components illuminates how complex behaviors can arise in chemistry and builds a foundation for future biological technologies. A simplified analog of genetic regulatory networks, in vitro transcriptional circuits, provides a modular platform for the systematic construction of arbitrary circuits and requires only two essential enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In this study, we design and experimentally demonstrate three transcriptional oscillators in vitro. First, a negative feedback oscillator comprising two switches, regulated by excitatory and inhibitory RNA signals, showed up to five complete cycles. To demonstrate modularity and to explore the design space further, a positive-feedback loop was added that modulates and extends the oscillatory regime. Finally, a three-switch ring oscillator was constructed and analyzed. Mathematical modeling guided the design process, identified experimental conditions likely to yield oscillations, and explained the system's robust response to interference by short degradation products. Synthetic transcriptional oscillators could prove valuable for systematic exploration of biochemical circuit design principles and for controlling nanoscale devices and orchestrating processes within artificial cells

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

Towards Learning ‘Self’ and Emotional Knowledge in Social and Cultural Human-Agent Interactions

Original article can be found at: http://www.igi-global.com/articles/details.asp?ID=35052 Copyright IGI. Posted by permission of the publisher.This article presents research towards the development of a virtual learning environment (VLE) inhabited by intelligent virtual agents (IVAs) and modeling a scenario of inter-cultural interactions. The ultimate aim of this VLE is to allow users to reflect upon and learn about intercultural communication and collaboration. Rather than predefining the interactions among the virtual agents and scripting the possible interactions afforded by this environment, we pursue a bottomup approach whereby inter-cultural communication emerges from interactions with and among autonomous agents and the user(s). The intelligent virtual agents that are inhabiting this environment are expected to be able to broaden their knowledge about the world and other agents, which may be of different cultural backgrounds, through interactions. This work is part of a collaborative effort within a European research project called eCIRCUS. Specifically, this article focuses on our continuing research concerned with emotional knowledge learning in autobiographic social agents.Peer reviewe

Toward guiding simulation experiments

To face the variety of simulation experiment methods, tools are needed that allow their seamless integration, guide the user through the steps of an experiment, and support him in selecting the most suitable method for the task at hand. This work presents techniques for facing such challenges. To guide users through the experiment process, six typical tasks have been identified for structuring the experiment workflow. The M&S framework JAMES II and its plug-in system is exploited to integrate various methods. Finally, an approach for automatic selection and use of such methods is realized

A Formal Methods Approach to Pattern Synthesis in Reaction Diffusion Systems

We propose a technique to detect and generate patterns in a network of locally interacting dynamical systems. Central to our approach is a novel spatial superposition logic, whose semantics is defined over the quad-tree of a partitioned image. We show that formulas in this logic can be efficiently learned from positive and negative examples of several types of patterns. We also demonstrate that pattern detection, which is implemented as a model checking algorithm, performs very well for test data sets different from the learning sets. We define a quantitative semantics for the logic and integrate the model checking algorithm with particle swarm optimization in a computational framework for synthesis of parameters leading to desired patterns in reaction-diffusion systems