Optimisation in ‘Self-modelling’ Complex Adaptive Systems

When a dynamical system with multiple point attractors is released from an arbitrary initial condition it will relax into a configuration that locally resolves the constraints or opposing forces between interdependent state variables. However, when there are many conflicting interdependencies between variables, finding a configuration that globally optimises these constraints by this method is unlikely, or may take many attempts. Here we show that a simple distributed mechanism can incrementally alter a dynamical system such that it finds lower energy configurations, more reliably and more quickly. Specifically, when Hebbian learning is applied to the connections of a simple dynamical system undergoing repeated relaxation, the system will develop an associative memory that amplifies a subset of its own attractor states. This modifies the dynamics of the system such that its ability to find configurations that minimise total system energy, and globally resolve conflicts between interdependent variables, is enhanced. Moreover, we show that the system is not merely ‘recalling’ low energy states that have been previously visited but ‘predicting’ their location by generalising over local attractor states that have already been visited. This ‘self-modelling’ framework, i.e. a system that augments its behaviour with an associative memory of its own attractors, helps us better-understand the conditions under which a simple locally-mediated mechanism of self-organisation can promote significantly enhanced global resolution of conflicts between the components of a complex adaptive system. We illustrate this process in random and modular network constraint problems equivalent to graph colouring and distributed task allocation problems

How Do Gestures Influence Thinking and Speaking? The Gesture-for-Conceptualization Hypothesis.

Peer reviewedPostprin

Managing in conflict: How actors distribute conflict in an industrial network

IMP researchers have examined conflict as a threat to established business relationships and commercial exchanges, drawing on theories and concepts developed in organization studies. We examine cases of conflict in relationships from the oil and gas industry's service sector, focusing on conflicts of interest and resources, and conflict as experienced by actors. Through a comparative case study design, we propose an explanation of how actors manage conflict and manage in conflict given that they tend to value and maintain relationships beyond episodes of exchange. We consider conflicts in relationships from a network perspective, showing that actors experienced these while adapting to changes in their business setting, modifying their roles in that network. By identifying conflict with the organizing forms of relationship and network, we show how actors formulate conflict through pursuing and combining a number of strategies, distributing the conflict across an enlarged network

High-throughput screening in larval zebrafish identifies novel potent sedative-hypnotics

BACKGROUND: Many general anesthetics were discovered empirically, but primary screens to find new sedative-hypnotics in drug libraries have not used animals, limiting the types of drugs discovered. The authors hypothesized that a sedative-hypnotic screening approach using zebrafish larvae responses to sensory stimuli would perform comparably to standard assays, and efficiently identify new active compounds. METHODS: The authors developed a binary outcome photomotor response assay for zebrafish larvae using a computerized system that tracked individual motions of up to 96 animals simultaneously. The assay was validated against tadpole loss of righting reflexes, using sedative-hypnotics of widely varying potencies that affect various molecular targets. A total of 374 representative compounds from a larger library were screened in zebrafish larvae for hypnotic activity at 10 µM. Molecular mechanisms of hits were explored in anesthetic-sensitive ion channels using electrophysiology, or in zebrafish using a specific reversal agent. RESULTS: Zebrafish larvae assays required far less drug, time, and effort than tadpoles. In validation experiments, zebrafish and tadpole screening for hypnotic activity agreed 100% (n = 11; P = 0.002), and potencies were very similar (Pearson correlation, r > 0.999). Two reversible and potent sedative-hypnotics were discovered in the library subset. CMLD003237 (EC50, ~11 µM) weakly modulated γ-aminobutyric acid type A receptors and inhibited neuronal nicotinic receptors. CMLD006025 (EC50, ~13 µM) inhibited both N-methyl-D-aspartate and neuronal nicotinic receptors. CONCLUSIONS: Photomotor response assays in zebrafish larvae are a mechanism-independent platform for high-throughput screening to identify novel sedative-hypnotics. The variety of chemotypes producing hypnosis is likely much larger than currently known.This work was supported by grants from Shanghai Jiaotong University School of Medicine, Shanghai, China, and the Chinese Medical Association, Beijing, China (both to Dr. Yang). The Department of Anesthesia, Critical Care and Pain Medicine of Massachusetts General Hospital, Boston, Massachusetts, supported this work through a Research Scholars Award and an Innovation Grant (both to Dr. Forman). Contributions to this research from the Boston University Center for Molecular Discovery, Boston, Massachusetts (to Drs. Porco, Brown, Schaus, and Xu, and to Mr. Trilles), were supported by a grant from the National Institutes of Health, Bethesda, Maryland (grant No. R24 GM111625). (Shanghai Jiaotong University School of Medicine, Shanghai, China; Chinese Medical Association, Beijing, China; Department of Anesthesia, Critical Care and Pain Medicine of Massachusetts General Hospital, Boston, Massachusetts; R24 GM111625 - National Institutes of Health, Bethesda, Maryland)Accepted manuscript2019-09-0

Salt intake and regulation in two passerine nectar drinkers: white-bellied sunbirds and New Holland honeyeaters

Avian nectarivores face the dilemma of having to conserve salts while consuming large volumes of a dilute, electrolyte-deficient diet. This study evaluates the responses to salt solutions and the regulation of salt intake in white-bellied sunbirds (Cinnyris talatala) and New Holland honeyeaters (Phylidonyris novaehollandiae). Birds were first offered a choice of four sucrose diets, containing no salt or 25, 50 or 75 mM NaCl. The experiment was repeated using five sucrose concentrations (0.075-0.63 M) as the base solution. Both species ingested similar amounts of all diets when fed the concentrated base solutions. However, when birds had to increase their intake to obtain enough energy on the dilute sucrose diets, there was a general avoidance of the higher salt concentrations. Through this diet switching, birds maintained constant intakes of both sucrose and sodium; the latter may contribute to absorption of their sugar diets. A second, no-choice experiment was designed to elucidate the renal concentrating abilities of these two nectarivores, by feeding them 0.63 M sucrose containing 5-200 mM NaCl over a 4-h trial. In both species, cloacal fluid osmolalities increased with diet NaCl concentration, but honeyeaters tended to retain ingested Na+, while sunbirds excreted it. Comparison of Na+ and K+ concentrations in ureteral urine and cloacal fluid showed that K+, but not Na+, was reabsorbed in the lower intestine of both species. The kidneys of sunbirds and honeyeaters, like those of hummingbirds, are well suited to diluting urine; however, they also appear to concentrate urine efficiently when necessary