Social dilemma in foraging behavior and evolution of cooperation by learning.

We consider foraging behaviors in a two-dimensional continuum space and show that a cooperative chasing strategy can emerge in a social dilemma. Predators can use two different chasing strategies: A direct chasing strategy (DCS) and a group chasing strategy (GCS). The DCS is a selfish strategy with which a chaser moves straight toward the nearest prey, and the GCS is a cooperative strategy in the sense that the chaser chooses the chasing direction for the group at a cost of its own speed. A prey flees away from the nearest hazard, either a chaser or the boundary, within its recognition range. We check the capturing activities of each strategy and find a social dilemma between the two strategies because the GCS is more efficient for the group whereas the DCS is better individually. Using a series of numerical simulations, we further show that the cooperative strategy can proliferate when a learning process of nearby successful strategies is introduced.

Safety tests and clinical research on buccal and nasal microneedle swabs for genomic analysis.

Conventional swabs have been used as a non-invasive method to obtain samples for DNA analysis from the buccal and the nasal mucosa. However, swabs may not always collect pure enough genetic material. In this study, buccal and nasal microneedle swab is developed to improve the accuracy and reliability of genomic analysis. A cytotoxicity test, a skin sensitivity test, and a skin irritation test are conducted with microneedle swabs. Polymer microneedle swabs meet the safety requirements for clinical research and commercial use. When buccal and nasal microneedle swabs are used, the amount of genetic material obtained is greater than that from commercially available swabs, and DNA purity is also high. The comparatively short microneedle swab (250 µm long) cause almost no pain to all 25 participants. All participants also report that the microneedle swabs are very easy to use. When genotypes are compared at five SNP loci from blood of a participant and from that person's buccal or nasal microneedle swab, the buccal and nasal microneedle swabs show 100% concordance for all five SNP genotypes. Microneedle swabs can be effectively used for genomic analysis and prevention through genomic analysis, so the utilization of microneedle swabs is expected to be high.

Grouping promotes both partnership and rivalry with long memory in direct reciprocity.

Biological and social scientists have long been interested in understanding how to reconcile individual and collective interests in the iterated Prisoner's Dilemma. Many effective strategies have been proposed, and they are often categorized into one of two classes, 'partners' and 'rivals.' More recently, another class, 'friendly rivals,' has been identified in longer-memory strategy spaces. Friendly rivals qualify as both partners and rivals: They fully cooperate with themselves, like partners, but never allow their co-players to earn higher payoffs, like rivals. Although they have appealing theoretical properties, it is unclear whether they would emerge in an evolving population because most previous works focus on the memory-one strategy space, where no friendly rival strategy exists. To investigate this issue, we have conducted evolutionary simulations in well-mixed and group-structured populations and compared the evolutionary dynamics between memory-one and longer-memory strategy spaces. In a well-mixed population, the memory length does not make a major difference, and the key factors are the population size and the benefit of cooperation. Friendly rivals play a minor role because being a partner or a rival is often good enough in a given environment. It is in a group-structured population that memory length makes a stark difference: When longer-memory strategies are available, friendly rivals become dominant, and the cooperation level nearly reaches a maximum, even when the benefit of cooperation is so low that cooperation would not be achieved in a well-mixed population. This result highlights the important interaction between group structure and memory lengths that drive the evolution of cooperation.

Evolution of direct reciprocity in group-structured populations.

People tend to have their social interactions with members of their own community. Such group-structured interactions can have a profound impact on the behaviors that evolve. Group structure affects the way people cooperate, and how they reciprocate each other's cooperative actions. Past work has shown that population structure and reciprocity can both promote the evolution of cooperation. Yet the impact of these mechanisms has been typically studied in isolation. In this work, we study how the two mechanisms interact. Using a game-theoretic model, we explore how people engage in reciprocal cooperation in group-structured populations, compared to well-mixed populations of equal size. In this model, the population is subdivided into groups. Individuals engage in pairwise interactions within groups while they also have chances to imitate strategies outside the groups. To derive analytical results, we focus on two scenarios. In the first scenario, we assume a complete separation of time scales. Mutations are rare compared to between-group comparisons, which themselves are rare compared to within-group comparisons. In the second scenario, there is a partial separation of time scales, where mutations and between-group comparisons occur at a comparable rate. In both scenarios, we find that the effect of population structure depends on the benefit of cooperation. When this benefit is small, group-structured populations are more cooperative. But when the benefit is large, well-mixed populations result in more cooperation. Overall, our results reveal how group structure can sometimes enhance and sometimes suppress the evolution of cooperation.

Corrigendum: Development of a microneedle swab for acquisition of genomic DNA from buccal cells.

[This corrects the article DOI: 10.3389/fbioe.2022.829648.].

Preparation of particle-attached microneedles using a dry coating process.

The standard process for manufacturing microneedles containing API requires a way to process the API, including dissolving the API in a co-solvent and a drying process. In this study, the authors introduce a novel microneedle system that involves physically attaching API particles to the biocompatible adhesive surface of the microneedles. To manufacture particle-attached microneedles, an adhesive surface was prepared by coating polydimethylsiloxane (PDMS) mixed with an elastomer base and a curing agent at a ratio of 40:1 (PDMS40) onto polylactic acid microneedles (PLA), and then attaching ovalbumin (OVA) particles with a mean diameter of 10 µm to the PDMS adhesive layer. The OVA particles were delivered for 5 min into porcine skin with a delivery efficiency of 93% ex vivo and into mouse skin with a delivery efficiency of over 90% in vivo. Finally, mouse experiments with OVA particle-attached microneedles showed a value of OVA antibody titer similar to that produced by intramuscular administration. Particle-attached microneedles are a novel microneedle system with a dry coating process and rapid API delivery into the skin. Particle-attached microneedles can provide a wide range of applications for administering drugs and vaccines.

A second-order stability analysis for the continuous model of indirect reciprocity.

Reputation is one of key mechanisms to maintain human cooperation, but its analysis gets complicated if we consider the possibility that reputation does not reach consensus because of erroneous assessment. The difficulty is alleviated if we assume that reputation and cooperation do not take binary values but have continuous spectra so that disagreement over reputation can be analysed in a perturbative way. In this work, we carry out the analysis by expanding the dynamics of reputation to the second order of perturbation under the assumption that everyone initially cooperates with good reputation. The second-order theory clarifies the difference between Image Scoring and Simple Standing in that punishment for defection against a well-reputed player should be regarded as good for maintaining cooperation. Moreover, comparison among the leading eight shows that the stabilizing effect of justified punishment weakens if cooperation between two ill-reputed players is regarded as bad. Our analysis thus explains how Simple Standing achieves a high level of stability by permitting justified punishment and also by disregarding irrelevant information in assessing cooperation. This observation suggests which factors affect the stability of a social norm when reputation can be perturbed by noise.

Development of a Microneedle Swab for Acquisition of Genomic DNA From Buccal Cells.

A swab is a tool for obtaining buccal DNA from buccal mucus for biological analysis. The acquisition of a sufficient amount and high quality of DNA is an important factor in determining the accuracy of a diagnosis. A microneedle swab (MN swab) was developed to obtain more oral mucosal tissues non-invasively. Eight types of MN swabs were prepared with varying combinations of patterns (zigzag or straight), number of MNs, intervals of MNs, and sharpness of tips. When MN swab was applied up to 10 times, the tissue amount and DNA yield increased compared to commercial swabs. A zigzag pattern of microneedles was found to be more efficient than a straight pattern and increasing the number of microneedles in an array increased the DNA yield. The MN swab collected about twice the DNA compared to the commercial swab. In an in vivo test using mini pigs, the lower cycle threshold values of mucosal samples collected with MN swabs compared to samples collected with commercial swabs indicated that a greater amount of DNA was collected for SNP genotyping. A polymer MN swab is easy to manufacture by a single molding process, and it has a greater sampling capacity than existing commercial swabs.

Social norms in indirect reciprocity with ternary reputations.

Indirect reciprocity is a key mechanism that promotes cooperation in social dilemmas by means of reputation. Although it has been a common practice to represent reputations by binary values, either 'good' or 'bad', such a dichotomy is a crude approximation considering the complexity of reality. In this work, we studied norms with three different reputations, i.e., 'good', 'neutral', and 'bad'. Through massive supercomputing for handling more than thirty billion possibilities, we fully identified which norms achieve cooperation and possess evolutionary stability against behavioural mutants. By systematically categorizing all these norms according to their behaviours, we found similarities and dissimilarities to their binary-reputation counterpart, the leading eight. We obtained four rules that should be satisfied by the successful norms, and the behaviour of the leading eight can be understood as a special case of these rules. A couple of norms that show counter-intuitive behaviours are also presented. We believe the findings are also useful for designing successful norms with more general reputation systems.

Local stability of cooperation in a continuous model of indirect reciprocity.

Reputation is a powerful mechanism to enforce cooperation among unrelated individuals through indirect reciprocity, but it suffers from disagreement originating from private assessment, noise, and incomplete information. In this work, we investigate stability of cooperation in the donation game by regarding each player's reputation and behaviour as continuous variables. Through perturbative calculation, we derive a condition that a social norm should satisfy to give penalties to its close variants, provided that everyone initially cooperates with a good reputation, and this result is supported by numerical simulation. A crucial factor of the condition is whether a well-reputed player's donation to an ill-reputed co-player is appreciated by other members of the society, and the condition can be reduced to a threshold for the benefit-cost ratio of cooperation which depends on the reputational sensitivity to a donor's behaviour as well as on the behavioural sensitivity to a recipient's reputation. Our continuum formulation suggests how indirect reciprocity can work beyond the dichotomy between good and bad even in the presence of inhomogeneity, noise, and incomplete information.

Win-Stay-Lose-Shift as a self-confirming equilibrium in the iterated Prisoner's Dilemma.

Evolutionary game theory assumes that players replicate a highly scored player's strategy through genetic inheritance. However, when learning occurs culturally, it is often difficult to recognize someone's strategy just by observing the behaviour. In this work, we consider players with memory-one stochastic strategies in the iterated Prisoner's Dilemma, with an assumption that they cannot directly access each other's strategy but only observe the actual moves for a certain number of rounds. Based on the observation, the observer has to infer the resident strategy in a Bayesian way and chooses his or her own strategy accordingly. By examining the best-response relations, we argue that players can escape from full defection into a cooperative equilibrium supported by Win-Stay-Lose-Shift in a self-confirming manner, provided that the cost of cooperation is low and the observational learning supplies sufficiently large uncertainty.

Epicutaneous Allergen Administration with Microneedles as a Novel Method of Immunotherapy for House Dust Mite (HDM) Allergic Rhinitis.

PURPOSE: Epicutaneous immunotherapy (EPIT) is being studied as a method for treating allergic rhinitis because of skin immunology, user convenience and enhanced patient compliance. However, the use of EPIT is limited because of the very low skin permeability of the allergen. In this study, the limitations of EPIT were overcome by using sophisticated delivery with microneedles. The immunological efficacy of this method was studied in a murine model of house dust mite (HDM) allergic rhinitis. METHODS: The length of the microneedles was 400 µm, and the coating formulation containing HDM was locally distributed near the end of the microneedle tips. The change of distribution of FITC-dextran in porcine skin in vitro was observed over time using a confocal microscope. The effect of immunotherapy in the allergic rhinitis model, sensitized by HDM-coated microneedles (HDM MNs), was observed according to the amount of HDM applied. RESULTS: The microneedles delivered the coating formulation with precision into the porcine skin layer, and the coated formulation on the microneedles was all dissolved in the porcine skin in vitro within 20 min of administration and then gradually diffused into the skin layer. When HDM MNs were administered to mice, a 0.1-µg dose of HDM provided the most effective immunization, and improved efficacy was shown between 0.1- and 0.5- µg doses of HDM. CONCLUSIONS: Effective immunotherapy can be achieved by precision delivery of the allergen into the skin layer, and microneedles can provide effective immunological therapy by delivering the appropriate amount of allergen.

Assortative clustering in a one-dimensional population with replication strategies.

In a geographically distributed population, assortative clustering plays an important role in evolution by modifying local environments. To examine its effects in a linear habitat, we consider a one-dimensional grid of cells, where each cell is either empty or occupied by an organism whose replication strategy is genetically inherited to offspring. The strategy determines whether to have offspring in surrounding cells, as a function of the neighborhood configuration. If more than one offspring compete for a cell, then they can be all exterminated due to the cost of conflict depending on environmental conditions. We find that the system is more densely populated in an unfavorable environment than in a favorable one because only the latter has to pay the cost of conflict. This observation agrees reasonably well with a mean-field analysis which takes assortative clustering of strategies into consideration. Our finding suggests a possibility of intrinsic nonlinearity between environmental conditions and population density when an evolutionary process is involved.

Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling.

Although smallpox has been eradicated globally, the potential use of the smallpox virus in bioterrorism indicates the importance of stockpiling smallpox vaccines. Considering the advantages of microneedle-based vaccination over conventional needle injections, in this study, we examined the feasibility of microneedle-based smallpox vaccination as an alternative approach for stockpiling smallpox vaccines. We prepared polylactic acid (PLA) microneedle array patches by micromolding and loaded a second-generation smallpox vaccine on the microneedle tips via dip coating. We evaluated the effect of excipients and drying conditions on vaccine stability in vitro and examined immune responses in female BALB/c mice by measuring neutralizing antibodies and interferon (IFN)-γ-secreting cells. Approximately 40% of the virus titer was reduced during the vaccine-coating process, with or without excipients. At -20 °C, the smallpox vaccine coated on the microneedles was stable up to 6 months. Compared to natural evaporation, vacuum drying was more efficient in improving the smallpox vaccine stability. Microneedle-based vaccination of the mice elicited neutralizing antibodies beginning 3 weeks after immunization; the levels were maintained for 12 weeks. It significantly increased IFN-γ-secreting cells 12 weeks after priming, indicating the induction of cellular immune responses. The smallpox-vaccine-coated microneedles could serve as an alternative delivery system for vaccination and stockpiling.

Friendly-rivalry solution to the iterated n-person public-goods game.

Repeated interaction promotes cooperation among rational individuals under the shadow of future, but it is hard to maintain cooperation when a large number of error-prone individuals are involved. One way to construct a cooperative Nash equilibrium is to find a 'friendly-rivalry' strategy, which aims at full cooperation but never allows the co-players to be better off. Recently it has been shown that for the iterated Prisoner's Dilemma in the presence of error, a friendly rival can be designed with the following five rules: Cooperate if everyone did, accept punishment for your own mistake, punish defection, recover cooperation if you find a chance, and defect in all the other circumstances. In this work, we construct such a friendly-rivalry strategy for the iterated n-person public-goods game by generalizing those five rules. The resulting strategy makes a decision with referring to the previous m = 2n - 1 rounds. A friendly-rivalry strategy for n = 2 inherently has evolutionary robustness in the sense that no mutant strategy has higher fixation probability in this population than that of a neutral mutant. Our evolutionary simulation indeed shows excellent performance of the proposed strategy in a broad range of environmental conditions when n = 2 and 3.

Progress in microneedle array patch (MAP) for vaccine delivery.

A microneedle array patch (MAP) has been developed as a new delivery system for vaccines. Preclinical and clinical trials with a vaccine MAP showed improved stability, safety, and immunological efficacy compared to conventional vaccine administration. Various vaccines can be delivered with a MAP. Currently, microneedle manufacturers can mass-produce pharmaceutical MAP and cosmetic MAP and this mass-production system can be adapted to produce a vaccine MAP. Clinical trials with a vaccine MAP have shown comparable efficacy with conventional administration, and discussions about regulations for a vaccine MAP are underway. However, there are concerns of reasonable cost, mass production, efficacy, and safety standards that meet FDA approval, as well as the need for feedback regarding the best method of administration. Currently, microneedles have been studied for the delivery of many kinds of vaccines, and preclinical and clinical studies of vaccine microneedles are in progress. For the foreseeable future, some vaccines will continue to be administered with syringes and needles while the use of a vaccine MAP continues to be improved because of the advantages of less pain, self-administration, improved stability, convenience, and safety.

Five rules for friendly rivalry in direct reciprocity.

Direct reciprocity is one of the key mechanisms accounting for cooperation in our social life. According to recent understanding, most of classical strategies for direct reciprocity fall into one of two classes, 'partners' or 'rivals'. A 'partner' is a generous strategy achieving mutual cooperation, and a 'rival' never lets the co-player become better off. They have different working conditions: For example, partners show good performance in a large population, whereas rivals do in head-to-head matches. By means of exhaustive enumeration, we demonstrate the existence of strategies that act as both partners and rivals. Among them, we focus on a human-interpretable strategy, named 'CAPRI' after its five characteristic ingredients, i.e., cooperate, accept, punish, recover, and defect otherwise. Our evolutionary simulation shows excellent performance of CAPRI in a broad range of environmental conditions.

Automata representation of successful strategies for social dilemmas.

In a social dilemma, cooperation is collectively optimal, yet individually each group member prefers to defect. A class of successful strategies of direct reciprocity were recently found for the iterated prisoner's dilemma and for the iterated three-person public-goods game: By a successful strategy, we mean that it constitutes a cooperative Nash equilibrium under implementation error, with assuring that the long-term payoff never becomes less than the co-players' regardless of their strategies, when the error rate is small. Although we have a list of actions prescribed by each successful strategy, the rationale behind them has not been fully understood for the iterated public-goods game because the list has hundreds of entries to deal with every relevant history of previous interactions. In this paper, we propose a method to convert such history-based representation into an automaton with a minimal number of states. Our main finding is that a successful strategy for the iterated three-person public-goods game can be represented as a 10-state automaton by this method. In this automaton, each state can be interpreted as the player's internal judgement of the situation, such as trustworthiness of the co-players and the need to redeem oneself after defection. This result thus suggests a comprehensible way to choose an appropriate action at each step towards cooperation based on a situational judgement, which is mapped from the history of interactions.

Patchless administration of canine influenza vaccine on dog's ear using insertion-responsive microneedles (IRMN) without removal of hair and its in vivo efficacy evaluation.

Microneedles provide the advantages of convenience and compliance by avoiding the pain and fear of needles that animals often experience. Insertion-responsive microneedles (IRMN) were used for administration to a hairy dog without removing the dog's hair. Canine H3N2 vaccine was administered with IRMN attached to the dog's ears ex vivo and the conventional microneedle system (MN) was administered for 15 min to compare puncture performance and delivery efficiency. The vaccine was also administered to compare antibody formation using IRMN with the use of intramuscular injection. The veterinarian observed the behavior of the dog during the course of the administration and compared the response to IRMN with that of intramuscular administration. The tips of IRMN were separated from the base and delivered into the hairy skin successfully. Puncture performance of IRMN were the same as that of coated microneedles (95%), but delivery efficiency of IRMN were 95% compared to less than 1% for coated microneedles. The H3N2 vaccine inoculated into the dog's ears showed the same antibody formation as the intramuscular injection. The dog appeared to be more comfortable with IRMN administration compared to syringe administration. IRMN are the first microneedle system to deliver a canine vaccine successfully into a hairy dog without removal of the dog's hair. The use of IRMN can provide both convenience and compliance for both the dog and the owner.

Preclinical study of influenza bivalent vaccine delivered with a two compartmental microneedle array.

Multiple vaccines can be mixed into a single combination to be a single product. However, combination vaccines have problems of complexity. In this study, microneedles were utilized in a compartmental microneedle array (CMA) to deliver two influenza vaccine strains without mixing. In this study, the CMA had two compartments, and two rectangular structures were attached to each end of the array to enable integration of the compartments with the coating equipment. The coating solution, which contained influenza vaccines for B/Yamagata (B-Y) and B/Victoria (B-V), was filled into the two reservoirs of the container. The CMA was aligned with the container for dipping the first compartment of the array into the first reservoir and the second compartment into the second reservoir. The CMA containing B-Y and B-V separately was administered to mice, and weight change and survival were compared with other groups of mice administered (a) combination vaccines with microneedles, (b) two monovalent vaccines with microneedles, (c) intramuscularly with a combination vaccine, and (d) intramuscularly with two monovalent vaccines. Plaque reduction neutralization tests were also performed to compare the CMA group with the other groups. The CMA showed a relative standard error of less than 7% between samples in dose uniformity. It also showed comparable antibody-forming efficacy compared to other groups, especially by B/Yamagata virus challenge. The CMA mice group showed better survival and weight change than mice that received intramuscular (IM) injection of the combination vaccine. In the neutralizing antibody experiment, all microneedle groups showed a higher neutralizing antibody than the IM groups. Vaccines were administered without mixing by a single administration using a CMA, and the CMA showed comparable efficacy with IM administration of the combination vaccine. Multivalent vaccines can be delivered without mixing as a single product by using a CMA.