Dichotomous Feedback: A Signal Sequestration-based Feedback Mechanism for Biocontroller Design

We introduce a new design framework for implementing negative feedback regulation in Synthetic Biology, which we term "dichotomous feedback". Our approach is different from current methods, in that it sequesters existing fluxes in the process to be controlled, and in this way takes advantage of the process's architecture to design the control law. This signal sequestration mechanism appears in many natural biological systems and can potentially be easier to realise than 'molecular sequestration' and other comparison motifs that are nowadays common in biomolecular feedback control design. The loop is closed by linking the strength of signal sequestration to the process output. Our feedback regulation mechanism is motivated by two-component signalling systems, where we introduce a second response regulator competing with the natural response regulator thus sequestering kinase activity. Here, dichotomous feedback is established by increasing the concentration of the second response regulator as the level of the output of the natural process increases. Extensive analysis demonstrates how this type of feedback shapes the signal response, attenuates intrinsic noise while increasing robustness and reducing crosstalk.

AGUSTIN DE BETANCOURT AS CREATOR OF OPTICAL TELEGRAPH MACHINE USED ON THE FIRST EUROPEAN RAILWAY LINES AND PRECURSOR OF RAILWAY SIGNALLING SYSTEMS

The origin of signalling principles, their purpose and development since the 4th century BC are described. Claude Chappe' s research on the peculiarities of human vision and the rationale for the choice of colors for the optical telegraph are presented. These principles are used in modern rail and road signaling systems with slight modifi cations to refl ect the development of technology. The transmission apparatus and the Claude Chappe alphabet are presented, documentary examples of its use in France are proposed, and the main disadvantages of this principle of data transmission are indicated. Further in the article, an alternative principle of data transmission using a single semaphore wing in an optical telegraph is presented. It was developed and introduced in 1798 between Madrid and Cadiz (Spain) by Agustin de Betancourt. The article shows the diagrams of the optical telegraph apparatus of Agustin de Betancourt, and also gives its comparison with fi rst mechanical signals used in railway transport. With references to historical documents and evidence, the evolution of the optical telegraph by Agustin de Betancourt from data transmission systems between cities to systems for the exchange of information between neighboring railway posts and stations on the fi rst railway lines is presented. The evolution of the telegraph from mechanical devices announcing the train approach to the railway post to the signals for train drivers thanks to the change of wing position is shown. As a transitional stage from mechanical to electrical signals in railway transport, the principle of operation of semaphores with kerosene lamps lit at night with light fi lters mechanically connected to the position of the wing is explained. Based on development of mechanical signals, the historical reasons for signal aspect with two lamps in diff erent modern signalling systems are presented. The article opens a new, previously little-known page of the activities by Agustin de Betancourt, who was not only the fi rst rector of the fi rst transport high school in Russia but also one of developers of data transmission systems used optical telegraph. His inventions such as mechanical signal with one wing are using in improved form in railway signalling systems up today.

A refinement-based development of a distributed signalling system

The decentralised railway signalling systems have a potential to increase capacity, availability and reduce maintenance costs of railway networks. However, given the safety-critical nature of railway signalling and the complexity of novel distributed signalling solutions, their safety should be guaranteed by using thorough system validation methods. To achieve such a high-level of safety assurance of these complex signalling systems, scenario-based testing methods are far from being sufficient despite that they are still widely used in the industry. Formal verification is an alternative approach which provides a rigorous approach to verifying complex systems and has been successfully used in the railway domain. Despite the successes, little work has been done in applying formal methods for distributed railway systems. In our research we are working towards a multifaceted formal development methodology of complex railway signalling systems. The methodology is based on the Event-B modelling language which provides an expressive modelling language, a stepwise development and a proof-based model verification. In this paper, we present the application of the methodology for the development and verification of a distributed protocol for reservation of railway sections. The main challenge of this work is developing a distributed protocol which ensures safety and liveness of the distributed railway system when message delays are allowed in the model.

Parental control: ecology drives plasticity in parental response to offspring signals

Different bird species have completely different parent-offspring interactions. When food is plentiful, the chicks that are begging the loudest are fed the most. When food is scarce, bird species instead feed the largest offspring. While this variation could be due to parents responding to signalling differently based on food availability, it could equally be due to offspring adjusting their behaviour, or to variation in information availability. We tested between these competing explanations experimentally, by manipulating food availability in a population of wild great tits, Parus major, while standardising offspring behaviour and size. We found that when food was more plentiful, parents were: (1) more likely to preferentially feed the chicks that were begging the most; and (2) less likely to preferentially feed larger chicks. In addition, we consistently found these same patterns, in a meta-analysis across 57 bird species. Overall, our results suggest that parents have more control over food distribution than offspring do, and that they flexibly adjust how they respond to both offspring signals and cues of offspring quality in response to food availability. Consequently, depending upon environmental conditions, predictably different signalling systems are favoured.

Cooperating to show that you care: costly helping as an honest signal of fitness interdependence

Social organisms often need to know how much to trust others to cooperate. Organisms can expect cooperation from another organism that depends on them (i.e. stake or fitness interdependence), but how do individuals assess fitness interdependence? Here, we extend fitness interdependence into a signalling context: costly helping behaviour can honestly signal one's stake in others, such that those who help are trusted more. We present a mathematical model in which agents help others based on their stake in the recipient's welfare, and recipients use that information to assess whom to trust. At equilibrium, helping is a costly signal of stake: helping is worthwhile for those who value the recipient (and thus will repay any trust), but is not worthwhile for those who do not value the recipient (and thus will betray the trust). Recipients demand signals when they value the signallers less and when the cost of betrayed trust is higher; signal costs are higher when signallers have more incentive to defect. Signalling systems are more likely when the trust games resemble Prisoner's Dilemmas, Stag Hunts or Harmony Games, and are less likely in Snowdrift Games. Furthermore, we find that honest signals need not benefit recipients and can even occur between hostile parties. By signalling their interdependence, organisms benefit from increased trust, even when no future interactions will occur. This article is part of the theme issue ‘The language of cooperation: reputation and honest signalling’.

High-Speed Railway

Union Internationale des Chemins (UIC) defines the high-speed railway (HSR) as a high-speed railway system that contains the infrastructure and the rolling stock. The infrastructure can be newly built dedicated lines enabled for trains to travel with speed above 250 km/h or upgraded conventional lines with a speed up to 200 or even 220 km/h. HSR requires specially built trains with increased power to weight ratio and must have an in-cab signalling system as traditional signalling systems are incapable of above 200 km/h.

Reliability and Inspection Modelling of Railway Signalling Systems

The railway is one of the most prominent models of transportation across the globe and it carries a large number of people, thus requiring high reliability, maintainability and safety. The reliability of railways mostly depends on an effective signalling system, making it one of the critical parts of railway operation. A signalling system is part of a large array of systems with interconnected components and subcomponents. Therefore, there is a need to make the signalling system more reliable and optimised with enhanced fault detection. Proper inspection and maintenance are required to make the signalling system reliable and safe. In this study, different inspection modelling techniques are applied to find the reliability of the signalling system. The signalling system has been divided into subsystems (signal unit, track unit, point-and-point machine) considering their importance and their effects on the failure rate of the entire signalling system. Inspection modelling of each subsystem has been conducted to provide the basis for the entire signalling system. A case study has been investigated to validate the model developed in one of the busiest tracks in eastern India. The obtained data thus are used to analyse the inspection pattern of signalling subsystems. Special attention to maintenance for inspection activities and logistics support has been taken into consideration, which is required to improve the reliability and maintainability of signalling subsystems and systems to make the railway signalling system sustainable in the long run.

Smoke signalling resistance: Aboriginal use of long-distance communication during Australia’s frontier wars

This essay reconstructs defensive/offensive mechanisms of Aboriginal communication networks and presents historical examples of their application as a means of resistance during Australia’s frontier wars. The principal focus is on smoke-signalling systems, especially in Queensland.

Mechanisms of microbe-immune system dialogue within the skin

The prevalence and severity of dermatological conditions such as atopic dermatitis have increased dramatically during recent decades. Many of the factors associated with an altered risk of developing inflammatory skin disorders have also been shown to alter the composition and diversity of non-pathogenic microbial communities that inhabit the human host. While the most densely microbial populated organ is the gut, culture and non-culture-based technologies have revealed a dynamic community of bacteria, fungi, viruses and mites that exist on healthy human skin, which change during disease. In this review, we highlight some of the recent findings on the mechanisms through which microbes interact with each other on the skin and the signalling systems that mediate communication between the immune system and skin-associated microbes. In addition, we summarize the ongoing clinical studies that are targeting the microbiome in patients with skin disorders. While significant efforts are still required to decipher the mechanisms underpinning host-microbe communication relevant to skin health, it is likely that disease-related microbial communities, or Dermatypes, will help identify personalized treatments and appropriate microbial reconstitution strategies.