Evolution of Heterogeneous Cellular Automata in Fluctuating Environments

The importance of environmental fluctuations in the evolution of living organisms by natural selection has been widely noted by biologists and linked to many important characteristics of life such as modularity, plasticity, genotype size, mutation rate, learning, or epigenetic adaptations. In artificial-life simulations, however, environmental fluctuations are usually seen as a nuisance rather than an essential characteristic of evolution. HetCA is a heterogeneous cellular automata characterized by its ability to generate open-ended long-term evolution and “evolutionary progress”. In this paper, we propose to measure the impact of different types of environmental fluctuations in HetCA. Our results indicate that environmental changes induce mechanisms analogous to epigenetic adaptation or multilevel selection. This is particularly prevalent in two of the tested fluctuation schemes, which involve a round-robin inhibition of certain cell types, where phenotypic selection seems to occur.Funding for this work was provided by the Science Foundation Ireland and the ERC Advanced Grant EPNet #340828. Some of the simulations were run on the MareNostrum supercomputer of the Barcelona Supercomputing Center.Postprint (author's final draft

A New Wave: A Dynamic Approach to Genetic Programming

Wave is a novel form of semantic genetic programming which operates by optimising the residual errors of a succession of short genetic programming runs, and then producing a cumulative solution. These short genetic programming runs are called periods, and they have heterogeneous parameters. In this paper we leverage the potential of Wave's heterogeneity to simulate a dynamic evolutionary environment by incorporating self adaptive parameters together with an innovative approach to population renewal. We conduct an empirical study comparing this new approach with multiple linear regression~(MLR) as well as several evolutionary computation~(EC) methods including the well known geometric semantic genetic programming~(GSGP) together with several other optimised Wave techniques. The results of our investigation show that the dynamic Wave algorithm delivers consistently equal or better performance than Standard GP (both with or without linear scaling), achieves testing fitness equal or better than multiple linear regression, and performs significantly better than GSGP on five of the six problems studied

Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Importance: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. Objective: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. Interventions: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). Main Outcomes and Measures: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. Results: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (O

A hybrid approach to the problem of class imbalance

In Machine Learning classification tasks, the class imbalance problem is an important one which has received a lot of attention in the last few years. In binary classification, class imbalance occurs when there are significantly fewer examples of one class than the other. A variety of strategies have been applied to the problem with varying degrees of success. Typically previous approaches have involved attacking the problem either algorithmically or by manipulating the data in order to mitigate the imbalance. We propose a hybrid approach which combines Proportional Individualised Random Sampling(PIRS) with two different fitness functions designed to improve performance on imbalanced classification problems in Genetic Programming. We investigate the efficacy of the proposed methods together with that of five different algorithmic GP solutions, two of which are taken from the recent literature. We conclude that the PIRS approach combined with either average accuracy or Matthews Correlation Coefficient, delivers superior results in terms of AUC score when applied to either balanced or imbalanced datasets

Selection bias and generalisation error in genetic programming

There have been many studies undertaken to determine the efficacy of parameters and algorithmic components of Genetic Programming, but historically, generalization considerations have not been of central importance in such investigations. Recent contributions have stressed the importance of generalisation to the future development of the field. In this paper we investigate aspects of selection bias as a component of generalisation error, where selection bias refers to the method used by the learning system to select one hypothesis over another. Sources of potential bias include the replacement strategy chosen and the means of applying selection pressure. We investigate the effects on generalisation of two replacement strategies, together with tournament selection with a range of tournament sizes. Our results suggest that larger tournaments are more prone to overfitting than smaller ones, and that a small tournament combined with a generational replacement strategy produces relatively small solutions and is least likely to over-fit

Wave: A Heterogeneous Genetic Programming Approach to Divide and Conquer

This work introduces Wave, a divide and conquer approach to GP whereby a sequence of short, and dependent but potentially heterogeneous GP runs provides a collective solution; the sequence akins a wave such that each short GP run is a period of the wave. Heterogeneity across periods results from varying settings of system parameters, such as population size or number of generations, and also by alternating use of the popular GP technique known as linear scaling

Wave: Incremental Erosion of Residual Error

Typically, Genetic Programming (GP) attempts to solve a problem by evolving solutions over a large, and usually pre-determined number of generations. However, overwhelming evidence shows that not only does the rate of performance improvement drop considerably after a few early generations, but that further improvement also comes at a considerable cost (bloat). Furthermore, each simulation (a GP run), is typically independent yet homogeneous: it does not re-use solutions from a previous run and retains the same experimental settings. Some recent research on symbolic regression divides work across GP runs where the subsequent runs optimise the residuals from a previous run and thus produce a cumulative solution; however, all such subsequent runs (or iterations) still remain homogeneous thus using a pre-set, large number of generations (50 or more). This work introduces Wave, a divide and conquer approach to GP whereby a sequence of short but sharp, and dependent yet potentially heterogeneous GP runs provides a collective solution; the sequence is akin to a wave such that each member of the sequence (that is, a short GP run) is a period of the wave. Heterogeneity across periods results from varying settings of system parameters, such as population size or number of generations, and also by alternating use of the popular GP technique known as linear scaling. The results show that Wave trains faster and better than both standard GP and multiple linear regression, can prolong discovery through constant restarts (which as a side effect also reduces bloat), can innovatively leverage a learning aid, that is, linear scaling at various stages instead of using it constantly regardless of whether it helps and performs reasonably even with a tiny population size (25) which bodes well for real time or data intensive training

Evolution of Heterogeneous Cellular Automata in Fluctuating Environments

The importance of environmental fluctuations in the evolution of living organisms by natural selection has been widely noted by biologists and linked to many important characteristics of life such as modularity, plasticity, genotype size, mutation rate, learning, or epigenetic adaptations. In artificial-life simulations, however, environmental fluctuations are usually seen as a nuisance rather than an essential characteristic of evolution. HetCA is a heterogeneous cellular automata characterized by its ability to generate open-ended long-term evolution and “evolutionary progress”. In this paper, we propose to measure the impact of different types of environmental fluctuations in HetCA. Our results indicate that environmental changes induce mechanisms analogous to epigenetic adaptation or multilevel selection. This is particularly prevalent in two of the tested fluctuation schemes, which involve a round-robin inhibition of certain cell types, where phenotypic selection seems to occur.Funding for this work was provided by the Science Foundation Ireland and the ERC Advanced Grant EPNet #340828. Some of the simulations were run on the MareNostrum supercomputer of the Barcelona Supercomputing Center

Structure of a Leu3-DNA Complex: Recognition of Everted CGG Half-Sites by a Zn2Cys6 Binuclear Cluster Protein

SummaryGal4 is the prototypical Zn2Cys6 binuclear cluster transcriptional regulator that binds as a homodimer to DNA containing inverted CGG half-sites. Leu3, a member of this protein family, binds to everted (opposite polarity to inverted) CGG half-sites, and an H50C mutation within the Leu3 Zn2Cys6 binuclear motif abolishes its transcriptional repression function without impairing DNA binding. We report the X-ray crystal structures of DNA complexes with Leu3 and Leu3(H50C) and solution DNA binding studies of selected Leu3 mutant proteins. These studies reveal the molecular details of everted CGG half-site recognition, and suggest a role for the H50C mutation in transcriptional repression. Comparison with the Gal4-DNA complex shows an unexpected conservation in the DNA recognition mode of inverted and everted CGG half-sites, and points to a critical function of a linker region between the Zn2Cys6 binuclear cluster and dimerization regions in DNA binding specificity. Broader implications of these findings are discussed