Bio-logic: gene expression and the laws of combinatorial logic

Original article can be found at: http://www.mitpressjournals.org/ Copyright MIT Press DOI: 10.1162/artl.2008.14.1.121At the heart of the development of fertilized eggs into fully formed organisms and the adaptation of cells to changed conditions are genetic regulatory networks (GRNs). In higher multi-cellular organisms, signal selection and multiplexing is performed at the cis-regulatory domains of genes, where combinations of transcription factors (TFs) regulate the rates at which the genes are transcribed into mRNA. To be able to act as activators or repressors of gene transcription, TFs must first bind to target sequences on the regulatory domains. Two TFs that act in concert may bind entirely independently of each other, but more often binding of the first one will alter the affinity of the other for its binding site. This paper presents a systematic investigation into the effect of TF binding dependencies on the predicted regulatory function of this “bio-logic”. Four extreme scenarios, commonly used to classify enzyme activation and inhibition patterns, for the binding of two TFs were explored: independent (the TFs bind without affecting each other’s affinities), competitive (the TFs compete for the same binding site), ordered (the TFs bind in a compulsory order), and joint binding (the TFs either bind as a preformed complex, or binding of one is virtually impossible in the absence of the other). The conclusions are: 1) the laws of combinatorial logic hold only for systems with independently binding TFs; 2) systems formed according to the other scenarios can mimic the functions of their Boolean logical counterparts, but cannot be combined or decomposed in the same way; and 3) the continuously scaled output of systems consisting of competitively binding activators and repressors can be more robustly controlled than that of single TF or (quasi-) logical multi-TF systems. Keywords: Transcription regulation, Genetic regulatory networks, Enzyme kinetics, Combinatorial logic, Non-Boolean continuous logic, Modelling.Peer reviewe

Close encounters : spatial distances between people and a robot of mechanistic appearance

Peer reviewe

Measuring Time with Minimal Clocks

© 2019 Massachusetts Institute of Technology. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1162/artl_a_00303Being able to measure time, whether directly or indirectly, is a significant advantage for an organism. It allows for timely reaction to regular or predicted events, reducing the pressure for fast processing of sensory input. Thus, clocks are ubiquitous in biology. In the present article, we consider minimal abstract pure clocks in different configurations and investigate their characteristic dynamics. We are especially interested in optimally time-resolving clocks. Among these, we find fundamentally diametral clock characteristics, such as oscillatory behavior for purely local time measurement or decay-based clocks measuring time periods on a scale global to the problem. We include also sets of independent clocks (clock bags), sequential cascades of clocks, and composite clocks with controlled dependence. Clock cascades show a condensation effect, and the composite clock shows various regimes of markedly different dynamics.Peer reviewe

Scaling laws in bacterial genomes: A side-effect of selection of mutational robustness?

In the past few years, numerous research projects have focused on identifying and understanding scaling properties in the gene content of prokaryote genomes and the intricacy of their regulation networks. Yet, and despite the increasing amount of data available, the origins of these scalings remain an open question. The RAevol model, a digital genetics model, provides us with an insight into the mechanisms involved in an evolutionary process. The results we present here show that (i) our model reproduces qualitatively these scaling laws and that (ii) these laws are not due to differences in lifestyles but to differences in the spontaneous rates of mutations and rearrangements. We argue that this is due to an indirect selective pressure for robustness that constrains the genome size

EEG microstates: Functional significance and short-term test-retest reliability

Appendix A: Supplementary data to this article can be found online at https://doi. org/10.1016/j.ynirp.2022.100089.Copyright /© 2022 The Authors. EEG signal power, may have clinical relevance; however, their functional significance and test-retest reliability remain unclear. To investigate the functional significance of the canonical EEG microstate classes and their pairwise transitions, and to establish their within-session test-retest reliability, we recorded 36-channel EEGs in 20 healthy volunteers during three eyes-closed conditions: mind-wandering, verbalization (silently repeating the word ‘square’ every 2 s), and visualization (visualizing a square every 2 s). Each condition lasted 3 min and the sequence of three conditions was repeated four times (two runs of two sequence repetitions). The participants' alertness and their sense of effort during the experiment were rated using visual-analogue scales. The EEG data were 2–20 Hz bandpass-filtered and analysed into the four canonical microstate classes: A, B, C, and D. EEG microstate classes C and D were persistently more dominant than classes A and B in all conditions. Of the first-order microstate parameters, average microstate duration was most reliable. The duration of class D microstate was longer during mind-wandering (106.8 ms) than verbalization (102.2 ms) or visualization (99.8 ms), with a concomitantly higher coverage (36.4% vs. 34.7% and 35.2%), but otherwise there was no clear association of the four microstate classes to particular mental states. The test-retest reliability was higher at the beginning of each run, together with higher average alpha power and subjective ratings of alertness. Only the transitions between classes C and D (from C to D in particular) were significantly higher than what would be expected from the respective microstates' occurrences. The transition probabilities, however, did not distinguish between conditions, and their test-retest reliability was overall lower than that of the first-order parameters such as duration and coverage. Further studies are needed to establish the functional significance of the canonical EEG microstate classes. This might be more fruitfully achieved by looking at their complex syntax beyond pairwise transitions. To ensure greater test-retest reliability of microstate parameters, study designs should allow for shorter experimental runs with regular breaks, particularly when using EEG microstates as clinical biomarkers.BIAL Foundation (grant number: 183/16)

Embodied imitation-enhanced reinforcement learning in multi-agent systems

Imitation is an example of social learning in which an individual observes and copies another's actions. This paper presents a new method for using imitation as a way of enhancing the learning speed of individual agents that employ a well-known reinforcement learning algorithm, namely Q-learning. Compared with other research that uses imitation with reinforcement learning, our method uses imitation of purely observed behaviours to enhance learning, with no internal state access or sharing of experiences between agents. The paper evaluates our imitation-enhanced reinforcement learning approach in both simulation and with real robots in continuous space. Both simulation and real robot experimental results show that the learning speed of the group is improved. © The Author(s) 2013

Embodied language learning and cognitive bootstrapping: methods and design principles

Co-development of action, conceptualization and social interaction mutually scaffold and support each other within a virtuous feedback cycle in the development of human language in children. Within this framework, the purpose of this article is to bring together diverse but complementary accounts of research methods that jointly contribute to our understanding of cognitive development and in particular, language acquisition in robots. Thus, we include research pertaining to developmental robotics, cognitive science, psychology, linguistics and neuroscience, as well as practical computer science and engineering. The different studies are not at this stage all connected into a cohesive whole; rather, they are presented to illuminate the need for multiple different approaches that complement each other in the pursuit of understanding cognitive development in robots. Extensive experiments involving the humanoid robot iCub are reported, while human learning relevant to developmental robotics has also contributed useful results. Disparate approaches are brought together via common underlying design principles. Without claiming to model human language acquisition directly, we are nonetheless inspired by analogous development in humans and consequently, our investigations include the parallel co-development of action, conceptualization and social interaction. Though these different approaches need to ultimately be integrated into a coherent, unified body of knowledge, progress is currently also being made by pursuing individual methods

A guided tour of asynchronous cellular automata

Research on asynchronous cellular automata has received a great amount of attention these last years and has turned to a thriving field. We survey the recent research that has been carried out on this topic and present a wide state of the art where computing and modelling issues are both represented.Comment: To appear in the Journal of Cellular Automat