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.

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.

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.

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.

Seven rules to avoid the tragedy of the commons.

Cooperation among self-interested players in a social dilemma is fragile and easily interrupted by mistakes. In this work, we study the repeated n-person public-goods game and search for a strategy that forms a cooperative Nash equilibrium in the presence of implementation error with a guarantee that the resulting payoff will be no less than any of the co-players'. By enumerating strategic possibilities for n=3, we show that such a strategy indeed exists when its memory length m equals three. It means that a deterministic strategy can be publicly employed to stabilize cooperation against error with avoiding the risk of being exploited. We furthermore show that, for general n-person public-goods game, m ≥ n is necessary to satisfy the above criteria.

Duality between cooperation and defection in the presence of tit-for-tat in replicator dynamics.

The prisoner's dilemma describes a conflict between a pair of players, in which defection is a dominant strategy whereas cooperation is collectively optimal. The iterated version of the dilemma has been extensively studied to understand the emergence of cooperation. In the evolutionary context, the iterated prisoner's dilemma is often combined with population dynamics, in which a more successful strategy replicates itself with a higher growth rate. Here, we investigate the replicator dynamics of three representative strategies, i.e., unconditional cooperation, unconditional defection, and tit-for-tat, which prescribes reciprocal cooperation by mimicking the opponent's previous move. Our finding is that the dynamics is self-dual in the sense that it remains invariant when we apply time reversal and exchange the fractions of unconditional cooperators and defectors in the population. The duality implies that the fractions can be equalized by tit-for-tat players, although unconditional cooperation is still dominated by defection. Furthermore, we find that mutation among the strategies breaks the exact duality in such a way that cooperation is more favored than defection, as long as the cost-to-benefit ratio of cooperation is small.

Combination with anti-tit-for-tat remedies problems of tit-for-tat.

One of the most important questions in game theory concerns how mutual cooperation can be achieved and maintained in a social dilemma. In Axelrod's tournaments of the iterated prisoner's dilemma, Tit-for-Tat (TFT) demonstrated the role of reciprocity in the emergence of cooperation. However, the stability of TFT does not hold in the presence of implementation error, and a TFT population is prone to neutral drift to unconditional cooperation, which eventually invites defectors. We argue that a combination of TFT and anti-TFT (ATFT) overcomes these difficulties in a noisy environment, provided that ATFT is defined as choosing the opposite to the opponent's last move. According to this TFT-ATFT strategy, a player normally uses TFT; turns to ATFT upon recognizing his or her own error; returns to TFT either when mutual cooperation is recovered or when the opponent unilaterally defects twice in a row. The proposed strategy provides simple and deterministic behavioral rules for correcting implementation error in a way that cannot be exploited by the opponent, and suppresses the neutral drift to unconditional cooperation.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Wireless induction heating in a microfluidic device for cell lysis.

A wireless induction heating system in a microfluidic device was devised for cell lysis to extract DNA and RNA from Escherichia coli. The thermal responses of nickel, iron and copper heating units were studied by applying an alternating magnetic field as a function of geometry of unit, strength of magnetic field, and kind of metal. Heating units were prepared by cutting metal film using a fiber laser, and the units were integrated into a microchannel system using a soft lithographic process. Variation and distribution of temperature on the surface of the heating units was observed using a thermographic camera and temperature labels. The amount of protein released from E. coli by thermal lysis was determined by protein concentration measurement. Hemoglobin released from red blood cells was observed using colorimetric intensity measurement. Extracted DNA was quantified by real-time polymerase chain reaction, and the profile was compared with that of a positive control of ultrasonically disrupted E. coli. The stability of RNA extracted by induction heating was quantified by the measurement of 23S/16S rRNA ratio and comparison with that by normal RNA extraction kit as a gold standard. A solid-shaped nickel structure was selected as the induction heating element in the microfluidic device because of the relatively small influence of geometries and faster thermal response.The amount of protein extracted from E. coli and hemoglobin released from red blood cells by induction heating of the nickel unit in the microfluidic device was proportional to the strength of the applied magnetic field. The lysis of E. coli by induction heating was as effective as lysis of DNA by the ultrasonication method because the threshold cycle values of the sample were compatible with those of the positive control as measured by ultrasonication. Thermal lysis of E. coli by induction heating represents a reasonable alternative to a commercial RNA extraction method as shown by the comparative ratio of 23S/16S obtained. In this study, wireless induction heating in a microfluidic device achieved convenience, portability, and economic efficiency by wireless operation, easy fabrication, disposability, and treatment of a large number of cells.