Hybrid Life: Integrating biological, artificial, and cognitive systems.

Artificial life is a research field studying what processes and properties define life, based on a multidisciplinary approach spanning the physical, natural, and computational sciences. Artificial life aims to foster a comprehensive study of life beyond "life as we know it" and toward "life as it could be," with theoretical, synthetic, and empirical models of the fundamental properties of living systems. While still a relatively young field, artificial life has flourished as an environment for researchers with different backgrounds, welcoming ideas, and contributions from a wide range of subjects. Hybrid Life brings our attention to some of the most recent developments within the artificial life community, rooted in more traditional artificial life studies but looking at new challenges emerging from interactions with other fields. Hybrid Life aims to cover studies that can lead to an understanding, from first principles, of what systems are and how biological and artificial systems can interact and integrate to form new kinds of hybrid (living) systems, individuals, and societies. To do so, it focuses on three complementary perspectives: theories of systems and agents, hybrid augmentation, and hybrid interaction. Theories of systems and agents are used to define systems, how they differ (e.g., biological or artificial, autonomous, or nonautonomous), and how multiple systems relate in order to form new hybrid systems. Hybrid augmentation focuses on implementations of systems so tightly connected that they act as a single, integrated one. Hybrid interaction is centered around interactions within a heterogeneous group of distinct living and nonliving systems. After discussing some of the major sources of inspiration for these themes, we will focus on an overview of the works that appeared in Hybrid Life special sessions, hosted by the annual Artificial Life Conference between 2018 and 2022. This article is categorized under: Neuroscience > Cognition Philosophy > Artificial Intelligence Computer Science and Robotics > Robotics.

Prediction of Protein Function from Tertiary Structure of the Active Site in Heme Proteins by Convolutional Neural Network.

Structure-function relationships in proteins have been one of the crucial scientific topics in recent research. Heme proteins have diverse and pivotal biological functions. Therefore, clarifying their structure-function correlation is significant to understand their functional mechanism and is informative for various fields of science. In this study, we constructed convolutional neural network models for predicting protein functions from the tertiary structures of heme-binding sites (active sites) of heme proteins to examine the structure-function correlation. As a result, we succeeded in the classification of oxygen-binding protein (OB), oxidoreductase (OR), proteins with both functions (OB-OR), and electron transport protein (ET) with high accuracy. Although the misclassification rate for OR and ET was high, the rates between OB and ET and between OB and OR were almost zero, indicating that the prediction model works well between protein groups with quite different functions. However, predicting the function of proteins modified with amino acid mutation(s) remains a challenge. Our findings indicate a structure-function correlation in the active site of heme proteins. This study is expected to be applied to the prediction of more detailed protein functions such as catalytic reactions.

Elucidation of the Correlation between Heme Distortion and Tertiary Structure of the Heme-Binding Pocket Using a Convolutional Neural Network.

Heme proteins serve diverse and pivotal biological functions. Therefore, clarifying the mechanisms of these diverse functions of heme is a crucial scientific topic. Distortion of heme porphyrin is one of the key factors regulating the chemical properties of heme. Here, we constructed convolutional neural network models for predicting heme distortion from the tertiary structure of the heme-binding pocket to examine their correlation. For saddling, ruffling, doming, and waving distortions, the experimental structure and predicted values were closely correlated. Furthermore, we assessed the correlation between the cavity shape and molecular structure of heme and demonstrated that hemes in protein pockets with similar structures exhibit near-identical structures, indicating the regulation of heme distortion through the protein environment. These findings indicate that the tertiary structure of the heme-binding pocket is one of the factors regulating the distortion of heme porphyrin, thereby controlling the chemical properties of heme relevant to the protein function; this implies a structure-function correlation in heme proteins.

Superposition mechanism as a neural basis for understanding others.

Social cognition has received much attention in fields such as neuroscience, psychology, cognitive science, and philosophy. Theory-theory (TT) and simulation theory (ST) provide the dominant theoretical frameworks for research on social cognition. However, neither theory addresses the matter of how the concepts of "self" and "other" are acquired through the development of human and nonhuman agents. Here, we show that the internal representations of "self" and "other" can be developed in an artificial agent only through the simple predictive learning achieved by deep neural networks with the superposition mechanism we herein propose. That is, social cognition can be achieved without a pre-given (or innate) framework of self and other; this is not assumed (or is at least unclear) in TT and ST. We demonstrate that the agent with the proposed model can acquire basic abilities of social cognition such as shared spatial representations of self and other, perspective-taking, and mirror-neuron-like activities of the agent's neural network. The result indicates that the superposition mechanism we propose is a necessary condition for the development of the concepts of "self" and "other" and, hence, for the development of social cognition in general.

Intuitive control of mobile robots: an architecture for autonomous adaptive dynamic behaviour integration.

In this paper, we present a novel approach to human-robot control. Taking inspiration from behaviour-based robotics and self-organisation principles, we present an interfacing mechanism, with the ability to adapt both towards the user and the robotic morphology. The aim is for a transparent mechanism connecting user and robot, allowing for a seamless integration of control signals and robot behaviours. Instead of the user adapting to the interface and control paradigm, the proposed architecture allows the user to shape the control motifs in their way of preference, moving away from the case where the user has to read and understand an operation manual, or it has to learn to operate a specific device. Starting from a tabula rasa basis, the architecture is able to identify control patterns (behaviours) for the given robotic morphology and successfully merge them with control signals from the user, regardless of the input device used. The structural components of the interface are presented and assessed both individually and as a whole. Inherent properties of the architecture are presented and explained. At the same time, emergent properties are presented and investigated. As a whole, this paradigm of control is found to highlight the potential for a change in the paradigm of robotic control, and a new level in the taxonomy of human in the loop systems.

A Sensorimotor Signature of the Transition to Conscious Social Perception: Co-regulation of Active and Passive Touch.

It is not yet well understood how we become conscious of the presence of other people as being other subjects in their own right. Developmental and phenomenological approaches are converging on a relational hypothesis: my perception of a "you" is primarily constituted by another subject's attention being directed toward "me." This is particularly the case when my body is being physically explored in an intentional manner. We set out to characterize the sensorimotor signature of the transition to being aware of the other by re-analyzing time series of embodied interactions between pairs of adults (recorded during a "perceptual crossing" experiment). Measures of turn-taking and movement synchrony were used to quantify social coordination, and transfer entropy was used to quantify direction of influence. We found that the transition leading to one's conscious perception of the other's presence was indeed characterized by a significant increase in one's passive reception of the other's tactile stimulations. Unexpectedly, one's clear experience of such passive touch was consistently followed by a switch to active touching of the other, while the other correspondingly became more passive, which suggests that this intersubjective experience was reciprocally co-regulated by both participants.

Unconscious improvement in foreign language learning using mismatch negativity neurofeedback: A preliminary study.

When people learn foreign languages, they find it difficult to perceive speech sounds that are nonexistent in their native language, and extensive training is consequently necessary. Our previous studies have shown that by using neurofeedback based on the mismatch negativity event-related brain potential, participants could unconsciously achieve learning in the auditory discrimination of pure tones that could not be consciously discriminated without the neurofeedback. Here, we examined whether mismatch negativity neurofeedback is effective for helping someone to perceive new speech sounds in foreign language learning. We developed a task for training native Japanese speakers to discriminate between 'l' and 'r' sounds in English, as they usually cannot discriminate between these two sounds. Without participants attending to auditory stimuli or being aware of the nature of the experiment, neurofeedback training helped them to achieve significant improvement in unconscious auditory discrimination and recognition of the target words 'light' and 'right'. There was also improvement in the recognition of other words containing 'l' and 'r' (e.g., 'blight' and 'bright'), even though these words had not been presented during training. This method could be used to facilitate foreign language learning and can be extended to other fields of auditory and clinical research and even other senses.

Four-pole galvanic vestibular stimulation causes body sway about three axes.

Galvanic vestibular stimulation (GVS) can be applied to induce the feeling of directional virtual head motion by stimulating the vestibular organs electrically. Conventional studies used a two-pole GVS, in which electrodes are placed behind each ear, or a three-pole GVS, in which an additional electrode is placed on the forehead. These stimulation methods can be used to induce virtual head roll and pitch motions when a subject is looking upright. Here, we proved our hypothesis that there are current paths between the forehead and mastoids in the head and show that our invented GVS system using four electrodes succeeded in inducing directional virtual head motion around three perpendicular axes containing yaw rotation by applying different current patterns. Our novel method produced subjective virtual head yaw motions and evoked yaw rotational body sway in participants. These results support the existence of three isolated current paths located between the mastoids, and between the left and right mastoids and the forehead. Our findings show that by using these current paths, the generation of an additional virtual head yaw motion is possible.

Unconscious learning of auditory discrimination using mismatch negativity (MMN) neurofeedback.

Neurofeedback is a strong direct training method for brain function, wherein brain activity patterns are measured and displayed as feedback, and trainees try to stabilize the feedback signal onto certain desirable states to regulate their own mental states. Here, we introduce a novel neurofeedback method, using the mismatch negativity (MMN) responses elicited by similar sounds that cannot be consciously discriminated. Through neurofeedback training, without participants' attention to the auditory stimuli or awareness of what was to be learned, we found that the participants could unconsciously achieve a significant improvement in the auditory discrimination of the applied stimuli. Our method has great potential to provide effortless auditory perceptual training. Based on this method, participants do not need to make an effort to discriminate auditory stimuli, and can choose tasks of interest without boredom due to training. In particular, it could be used to train people to recognize speech sounds that do not exist in their native language and thereby facilitate foreign language learning.

Using minimal human-computer interfaces for studying the interactive development of social awareness.

According to the enactive approach to cognitive science, perception is essentially a skillful engagement with the world. Learning how to engage via a human-computer interface (HCI) can therefore be taken as an instance of developing a new mode of experiencing. Similarly, social perception is theorized to be primarily constituted by skillful engagement between people, which implies that it is possible to investigate the origins and development of social awareness using multi-user HCIs. We analyzed the trial-by-trial objective and subjective changes in sociality that took place during a perceptual crossing experiment in which embodied interaction between pairs of adults was mediated over a minimalist haptic HCI. Since that study required participants to implicitly relearn how to mutually engage so as to perceive each other's presence, we hypothesized that there would be indications that the initial developmental stages of social awareness were recapitulated. Preliminary results reveal that, despite the lack of explicit feedback about task performance, there was a trend for the clarity of social awareness to increase over time. We discuss the methodological challenges involved in evaluating whether this trend was characterized by distinct developmental stages of objective behavior and subjective experience.

Alternating images of congruent and incongruent movement creates the illusion of agency.

We report a novel illusion whereby people perceive both congruent and incongruent hand motions as a united, single, and continuous motion of one's own hand (i.e. a sense of agency). This arises when individuals watch congruent and incongruent hand motions alternately from a first person perspective. Despite an individual knowing that s/he is not performing the motion, this illusion still can arise. Although a sense of agency might require congruency between predicted and actual movements, united motion is incongruent with predicted movement because the motion contains oscillating movement which results from switching hand movement images. This illusion offers new insights into the integration mechanism of predicted and observed movements on agency judgment. We investigated this illusion from a subjective experience point of view and from a motion response point of view.

Embodied social interaction constitutes social cognition in pairs of humans: a minimalist virtual reality experiment.

Scientists have traditionally limited the mechanisms of social cognition to one brain, but recent approaches claim that interaction also realizes cognitive work. Experiments under constrained virtual settings revealed that interaction dynamics implicitly guide social cognition. Here we show that embodied social interaction can be constitutive of agency detection and of experiencing another's presence. Pairs of participants moved their "avatars" along an invisible virtual line and could make haptic contact with three identical objects, two of which embodied the other's motions, but only one, the other's avatar, also embodied the other's contact sensor and thereby enabled responsive interaction. Co-regulated interactions were significantly correlated with identifications of the other's avatar and reports of the clearest awareness of the other's presence. These results challenge folk psychological notions about the boundaries of mind, but make sense from evolutionary and developmental perspectives: an extendible mind can offload cognitive work into its environment.

From synthetic modeling of social interaction to dynamic theories of brain-body-environment-body-brain systems.

Synthetic approaches to social interaction support the development of a second-person neuroscience. Agent-based models and psychological experiments can be related in a mutually informing manner. Models have the advantage of making the nonlinear brain-body-environment-body-brain system as a whole accessible to analysis by dynamical systems theory. We highlight some general principles of how social interaction can partially constitute an individual's behavior.

Experimental study on co-evolution of categorical perception and communication systems in humans.

In this paper, we present an experiment that integrates a semiotic investigation with a dynamical perspective on embodied social interactions. The primary objective is to study the emergence of a communication system between two interacting individuals, where no dedicated communication modalities are predefined and the only possible interaction is very simple, non-directional, and embodied. Throughout the experiment, we observe the following three phenomena: (1) the spontaneous emergence of turn-taking behaviour that allows communication in non-directional environments; (2) the development of an association between behaviours and perceptive categories; (3) the acquisition of novel meaning by exploiting the notion of complementary set theory.

Phenotype and genotype characteristics of age-related macular degeneration in a Japanese population.

PURPOSE: To describe phenotype and genotype characteristics of age-related macular degeneration (AMD) in Japanese patients. DESIGN: A case-control study. PARTICIPANTS: A total of 550 case-control samples composed of 408 consecutive AMD cases and 142 controls. METHODS: Clinical information assessing age, gender, affected eyes, fundus features, and fluorescein/indocyanine green angiograms were systematically evaluated. Four single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the complement factor H (CFH) gene, 1 SNP (rs11200638) in the high-temperature requirement factor A1 (HTRA1) gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were assessed using TaqMan technology. MAIN OUTCOME MEASURES: The clinical phenotype information and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms. RESULTS: Of Japanese patients with neovascular AMD (nAMD), 219 (58.7%) had typical nAMD and 154 (41.3%) had polypoidal choroidal vasculopathy (PCV). The frequency of bilateral exudative involvement was similar between typical nAMD (15.5%) and PCV (13.6%) (P = 0.613). Significant soft drusen were observed in the fellow eyes of 88 (47.6%) of 185 patients with unilateral typical nAMD and in 25 (18.8%) of 133 patients with unilateral PCV (P = 1.24x10(-7)). A serous pigment epithelium detachment was seen in 55 (25.1%) of 219 patients with typical nAMD and in 64 (41.6%) of 154 patients with PCV. A significant association was noted in CFH-rs800292, CFH-rs1410996, CFH-rs2274700, and HTRA1-rs11200638 with AMD development (P = 2.36x10(-5), 7.18x10(-5), 7.18x10(-5), 2.70x10(-7), respectively; population attributable risk = 57.3%, 57.8%, 57.8%, and 58.9%, respectively). We estimated the highest-risk group to have an approximately 70-fold greater risk of nAMD compared with the lowest-risk group when analyzing a combination of 4 SNPs in the CFH and HTRA1 genes. CONCLUSIONS: The Japanese AMD phenotype is characterized by a higher frequency of PCV, male predominance, and lower frequency of bilateral presentation compared with Caucasian AMD. Genotype analyses demonstrate a significant population attributable risk for SNPs in the CFH and HTRA1 genes and demonstrate joint effects for both genes. Gene variants in both CFH and HTRA1 contribute significantly to the AMD phenotype in a Japanese population.

Association of type 1 diabetes with two Loci on 12q13 and 16p13 and the influence coexisting thyroid autoimmunity in Japanese.

CONTEXT: Recent genome-wide association studies have identified several novel type 1 diabetes (T1D) loci in white populations. OBJECTIVE: In line with recent findings, we conducted a replication study of two loci on chromosome 12p13 and 16p13 and assessed their potential associations with thyroid autoimmunity in a Japanese population. SUBJECTS AND METHODS: Two single-nucleotide polymorphisms (SNPs), rs2292399 in ERBB3 on 12q13 and rs2903692 in CLEC16A (or KIAA0350) on 16p13, were analyzed in Japanese subjects consisting of 735 T1D patients, 330 patients with autoimmune thyroid disease (AITD), and 621 control subjects. RESULTS: According to a case-control study and logistic regression adjusting for sex and age, we observed that these SNPs in ERBB3 and CLEC16A were both significantly associated with T1D, with the risk alleles being consistent with those in white populations [adjusting odds ratio by multiplicative model: 1.37 (1.13-1.67), P = 0.001; and 1.28 (1.02-1.60), P = 0.030, respectively]. In both SNPs, the association was suggested to be stronger in T1D complicated with AITD (Graves' disease, Hashimoto's thyroiditis, or thyroid autoantibodies). Furthermore, a joint analysis, with the INS and CTLA4 SNPs, revealed that CTLA4 rs3087243, ERBB3 rs2292399, and CLEC16A rs2903692, but not INS rs689, were significant risk factors for the cooccurrence of AITD in Japanese T1D. CONCLUSION: We confirmed two loci on 12q13 and 16p13 that were identified by the independent genome-wide association studies in white populations, thus suggesting that these loci contribute to T1D susceptibility across different ethnic groups. In addition, these loci may also be associated with the cooccurrence of thyroid autoimmunity in T1D.

How (not) to model autonomous behaviour.

Autonomous systems are the result of self-sustaining processes of constitution of an identity under precarious circumstances. They may transit through different modes of dynamical engagement with their environment, from committed ongoing coping to open susceptibility to external demands. This paper discusses these two statements and presents examples of models of autonomous behaviour using methods in evolutionary robotics. A model of an agent capable of issuing self-instructions demonstrates the fragility of modelling autonomy as a function rather than as a property of a system's organization. An alternative model of behavioural preference based on homeostatic adaptation avoids this problem by establishing a mutual constraining between lower-level processes (neural dynamics and sensorimotor interaction) and higher-level metadynamics (experience-dependent, homeostatic triggering of local plasticity and re-organization). The results of these models are lessons about how strong autonomy should be approached: neither as a function, nor as a matter of external vs. internal determination.

Coding and noncoding variants in the CFH gene and cigarette smoking influence the risk of age-related macular degeneration in a Japanese population.

PURPOSE: Ethnic variation has been reported in age-related macular degeneration (AMD)-associated Y402H polymorphism in complement factor H (CFH). This variation is evident in the Japanese population. Recently a strong association between a novel single-nucleotide polymorphism (SNP; rs1410996) in the CFH gene and AMD has been identified in Caucasian patients. The present study was undertaken to investigate whether four coding and noncoding variants of the CFH gene, including rs1410996, are associated with AMD in native, unrelated Japanese patients. METHODS: A total of 188 patients with AMD and 139 control subjects without AMD were recruited for the study. Four SNPs (rs800292, rs1061170, rs1410996, and rs2274700) in the CFH gene were assessed by genotyping assay. The information regarding systemic conditions and lifestyle including smoking were documented in each subject by standardized questionnaire. RESULTS: The intronic SNP (rs1410996) and the synonymous SNP (rs2274700) were associated with a significant risk of AMD (P = 2.37 x 10(-5) and 3.52 x 10(-5), respectively). A significant association was also noted between a coding variant (rs800292, I62V) and AMD (P = 8.63 x 10(-6)). In contrast, the Y402H variant showed no significant association with AMD (P = 0.101). Two common haplotypes also demonstrated significant association with AMD (P = 1.08 x 10(-3) and 2.00 x 10(-5)). Among the environmental factors, smoking alone had a significant association with AMD (P = 1.17 x 10(-4)). CONCLUSIONS: Although the Y402H variant was not significantly associated with AMD, other coding and noncoding variants in the CFH gene including rs1410996 and smoking moderately influenced the risk of AMD in a Japanese population.

Promoter polymorphisms of the pigment epithelium-derived factor gene are associated with diabetic retinopathy.

Pigment epithelium-derived factor (PEDF or SERPINF1), a neuroprotective and anti-angiogenic factor, may play an important role in the pathogenesis of diabetic retinopathy (DR). In 416 patients with type 2 diabetes, four polymorphisms in the PEDF SNPs were identified, rs12150053 and rs12948385 in the promoter region, rs9913583 in the 5'-untranslated region, and rs1136287 (Met72Thr) in exon 3. Based on case-control studies, rs12150053 and rs12948385, but not rs9913583 and rs1136287, were significantly associated with DR. A logistic regression analysis revealed that the TC or CC genotype of rs12150053 was a significant risk factor for DR (odds ratio 2.40, p=0.0004). The GA or AA genotype of rs12948385 was also a significant risk factor for DR. In addition, a significant interaction between the vascular endothelial growth factor (VEGF) and PEDF SNPs in the susceptibility to DR was found. These results demonstrate that the PEDF gene, in cooperation with the VEGF gene, may contribute to the development of DR.