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The emergence and maintenance of cooperation has attracted intensive scholarly interest and has been analysed within the framework of evolutionary game theory. The role of innovation, which introduces novel strategies into the population, is a relatively understudied aspect of evolutionary game theory. Here, we investigate the effects of two sources of innovation —mutation and heterogeneous updating rules. These mechanisms allow agents to adopt strategies that do not rely on the imitation of other individuals. The model introduces —in addition to canonical imitation-based strategy updating—aspiration-based updating, whereby agents switch their strategy by referring solely to the performance of their own strategy; mutation also introduces novel strategies into the population. Our simulation results show that the introduction of aspiration-based rules into a population of imitators leads to the deterioration of cooperation. In addition, mutation, in combination with heterogeneous updating rules, also diminishes cooperators. This phenomenon is prominent when a large proportion of the population consists of imitators rather than adopters of aspiration-based updating. Nevertheless, a high mutation rate, in combination with a low aspiration level, has positive nonlinear effects, and a heterogeneous population achieves a higher level of cooperation than the weighted average of homogeneous populations. Our results demonstrate the profound role of innovation in the evolution of cooperation. [ABSTRACT FROM AUTHOR]

Punishment and partner switching are two well-studied mechanisms that support the evolution of cooperation. Observation of human behaviour suggests that the extent to which punishment is adopted depends on the usage of alternative mechanisms, including partner switching. In this study, we investigate the combined effect of punishment and partner switching in evolutionary prisoner's dilemma games conducted on a network. In the model, agents are located on the network and participate in the prisoner's dilemma games with punishment. In addition, they can opportunistically switch interaction partners to improve their payoff. Our Monte Carlo simulation showed that a large frequency of punishers is required to suppress defectors when the frequency of partner switching is low. In contrast, cooperation is the most abundant strategy when the frequency of partner switching is high regardless of the strength of punishment. Interestingly, cooperators become abundant not because they avoid the cost of inflicting punishment and earn a larger average payoff per game but rather because they have more numerous opportunities to be referred to as a role agent by defectors. Our results imply that the fluidity of social relationships has a profound effect on the adopted strategy in maintaining cooperation. [ABSTRACT FROM AUTHOR]

The lung airways exhibit distinct features with long, wide proximal branches and short, thin distal branches, crucial for optimal respiratory function. In this study, we investigated the mechanism behind this hierarchical structure through experiments and modeling, focusing on the regulation of branch length and width during the pseudoglandular stage. To evaluate the response of mouse lung epithelium to fibroblast growth factor 10 (FGF10), we monitored the activity of extracellular signal-regulated kinase (ERK). ERK activity exhibited an increase dependent on the curvature of the epithelial tissue, which gradually decreased with the progression of development. We then constructed a computational model that incorporates curvature-dependent growth to predict its impact on branch formation. It was demonstrated that branch length is determined by the curvature dependence of growth. Next, in exploring branch width regulation, we considered the effect of apical constriction, a mechanism we had previously proposed to be regulated by Wnt signaling. Analysis of a mathematical model representing apical constriction showed that branch width is determined by cell shape. Finally, we constructed an integrated computational model that includes curvature-dependent growth and cell shape controls, confirming their coordination in regulating branch formation. This study proposed that changes in the autonomous property of the epithelium may be responsible for the progressive branch morphology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Takigawa-Imamura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In human celiac disease (CeD) HLA-DQ2.5 presents gluten peptides to antigen-specific CD4 + T cells, thereby instigating immune activation and enteropathy. Targeting HLA-DQ2.5 with neutralizing antibody for treating CeD may be plausible, yet using pan-HLA-DQ antibody risks affecting systemic immunity, while targeting selected gluten peptide:HLA-DQ2.5 complex (pHLA-DQ2.5) may be insufficient. Here we generate a TCR-like, neutralizing antibody (DONQ52) that broadly recognizes more than twenty-five distinct gluten pHLA-DQ2.5 through rabbit immunization with multi-epitope gluten pHLA-DQ2.5 and multidimensional optimization. Structural analyses show that the proline-rich and glutamine-rich motif of gluten epitopes critical for pathogenesis is flexibly recognized by multiple tyrosine residues present in the antibody paratope, implicating the mechanisms for the broad reactivity. In HLA-DQ2.5 transgenic mice, DONQ52 demonstrates favorable pharmacokinetics with high subcutaneous bioavailability, and blocks immunity to gluten while not affecting systemic immunity. Our results thus provide a rationale for clinical testing of DONQ52 in CeD., (© 2023. The Author(s).)

A coherent XY machine (CXYM) is a physical spin simulator that can simulate the XY model by mapping XY spins onto the continuous phases of non-degenerate optical parametric oscillators (NOPOs). Here, we demonstrated a large-scale CXYM with >47,000 spins by generating 10-GHz-clock time-multiplexed NOPO pulses via four-wave mixing in a highly nonlinear fiber inside a fiber ring cavity. By implementing a unidirectional coupling from the ith pulse to the (i + 1)th pulse with a variable 1-pulse delay planar lightwave circuit interferometer, we successfully controlled the effective temperature of a one-dimensional XY spin network within two orders of magnitude.

Computers based on physical systems are increasingly anticipated to overcome the impending limitations on digital computer performance. One such computer is a coherent Ising machine (CIM) for solving combinatorial optimization problems. Here, we report a CIM with 100,512 degenerate optical parametric oscillator pulses working as the Ising spins. We show that the CIM delivers fine solutions to maximum cut problems of 100,000-node graphs drastically faster than standard simulated annealing. Moreover, the CIM, when operated near the phase transition point, provides some extremely good solutions and a very broad distribution. This characteristic will be useful for applications that require fast random sampling such as machine learning.

Nonlinear dynamics of spiking neural networks have recently attracted much interest as an approach to understand possible information processing in the brain and apply it to artificial intelligence. Since information can be processed by collective spiking dynamics of neurons, the fine control of spiking dynamics is desirable for neuromorphic devices. Here we show that photonic spiking neurons implemented with paired nonlinear optical oscillators can be controlled to generate two modes of bio-realistic spiking dynamics by changing optical-pump amplitude. When the photonic neurons are coupled in a network, the interaction between them induces an effective change in the pump amplitude depending on the order parameter that characterizes synchronization. The experimental results show that the effective change causes spontaneous modification of the spiking modes and firing rates of clustered neurons, and such collective dynamics can be utilized to realize efficient heuristics for solving NP-hard combinatorial optimization problems.

Evaluation of the binding and uptake of an antibody in liver non-parenchymal cells (NPC), including liver sinusoidal endothelial cells, is important for revealing its pharmacokinetic (PK) behavior, since NPC has important roles in eliminating an antibody from the blood via the Fc fragment of IgG receptor IIB (FcγRIIB). However, there is currently no in vitro quantitative assay using NPC. This study reports on the development of a cell-based assay for evaluating the binding and uptake of such an antibody using liver NPC of mice and monkeys. In mice, the FcγRIIB-expressing cells were identified in the CD146-positive and CD45-negative fraction by flow cytometry. A titration assay was performed to determine the PK parameters, and the obtained parameter was comparable to that determined by the fitting of the in vivo PK. This approach was also extended to NPC from monkeys. The concentration-dependent binding and uptake was measured to determine the PK parameters using monkey NPC, the FcγRIIB-expressing fraction of which was identified by CD31 and CD45. The findings presented herein demonstrate that the in vitro liver NPC assay using flow cytometry is a useful tool to determine the binding and uptake of biologics and to predict the PK.

Quantum random numbers distinguish themselves from others by their intrinsic unpredictability arising from the principles of quantum mechanics. As such they are extremely useful in many scientific and real-world applications with considerable efforts going into their realizations. Most demonstrations focus on high asymptotic generation rates. For this goal, a large number of repeated trials are required to accumulate a significant store of certifiable randomness, resulting in a high latency between the initial request and the delivery of the requested random bits. Here we demonstrate low-latency real-time certifiable randomness generation from measurements on photonic time-bin states. For this, we develop methods to certify randomness taking into account adversarial imperfections in both the state preparation and the measurement apparatus. Every 0.12 s we generate a block of 8192 random bits which are certifiable against all quantum adversaries with an error bounded by 2 -64 . Our quantum random number generator is thus well suited for realizing a continuously-operating, high-security and high-speed quantum randomness beacon.

Human pharmacokinetics (PK) profiles of monoclonal antibodies (mAbs) are usually predicted using non-human primates (NHP), but this comes with drawbacks in terms of cost and throughput. Therefore, we established a human PK profile prediction method using human neonatal Fc receptor (hFcRn) transgenic mice (TgM). We administered launched 13 mAbs to hFcRn TgM and measured the concentration in plasma using electro-chemiluminescence immunoassay. This was then used to calculate PK parameters and predict human PK profiles. The mAbs showed a bi-phased elimination pattern, and clearance (CL) (mL/d/kg) and distribution volume at steady state (V dss ) (mL/kg) ranges were 11.0 to 131 and 110 to 285, respectively. There was a correlation in half-life at elimination phase (t 1/2β ) between hFcRn TgM and humans for 10 mAbs showing CL of more than 80% in the elimination phase (R 2  = 0.714). Human t 1/2β was predicted using hFcRn TgM t 1/2β ; 9 out of 10 mAbs were within 2-fold the actual values, and all mAbs were within 3-fold. Regarding the predicted CL values, 7 out of 10 mAbs were within 2-fold the human values and all mAbs were within 3-fold. Furthermore, even on day 7 the predicted CL values of 8 out of 10 mAbs were within 2-fold the observed value, with all mAbs within 3-fold. These results suggest human PK profiles can be predicted using hFcRn TgM data. These methods can accelerate the development of antibody drugs while also reducing cost and improving throughput.

The minimum requirements for an optical reservoir computer, a recent paradigm for computation using simple algorithms, are nonlinearity and internal interactions. A promising optical system satisfying these requirements is a platform based on coupled degenerate optical parametric oscillators (DOPOs) in a fiber ring cavity. We can expect advantages using DOPOs for reservoir computing with respect to scalability and reduction of excess noise; however, the continuous stabilization required for reservoir computing has not yet been demonstrated. Here, we report the continuous and long-term stabilization of an optical system by introducing periodical phase modulation patterns for DOPOs and a local oscillator. We observed that the Allan variance of the optical phase up to 100 ms was suppressed and that the homodyne measurement signal had a relative standard deviation of 1.4% over 62,500 round trips. The proposed methods represent important technical bases for realizing stable computation on large-scale optical hybrid computers.

We generated time-multiplexed degenerate optical parametric oscillator (DOPO) pulses using a nonlinear fiber Sagnac loop as a phase-sensitive amplifier (PSA), where the pump and amplified light in pump-signal-idler degenerate four-wave mixing can be spatially separated. By placing the PSA in a fiber cavity, we successfully generated more than 5000 time-multiplexed DOPO pulses. We confirmed the bifurcation of pulse phases to 0 or π relative to the pump phase, which makes them useful for representing Ising spins in an Ising model solver based on coherent optical oscillator networks. We also confirmed inherent randomness of the DOPO phases using the National Institute of Standards and Technology random number test.

Physical annealing systems provide heuristic approaches to solving combinatorial optimization problems. Here, we benchmark two types of annealing machines-a quantum annealer built by D-Wave Systems and measurement-feedback coherent Ising machines (CIMs) based on optical parametric oscillators-on two problem classes, the Sherrington-Kirkpatrick (SK) model and MAX-CUT. The D-Wave quantum annealer outperforms the CIMs on MAX-CUT on cubic graphs. On denser problems, however, we observe an exponential penalty for the quantum annealer [exp(-α DW N 2 )] relative to CIMs [exp(-α CIM N )] for fixed anneal times, both on the SK model and on 50% edge density MAX-CUT. This leads to a several orders of magnitude time-to-solution difference for instances with over 50 vertices. An optimal-annealing time analysis is also consistent with a substantial projected performance difference. The difference in performance between the sparsely connected D-Wave machine and the fully-connected CIMs provides strong experimental support for efforts to increase the connectivity of quantum annealers.

Many problems in mathematics, statistical mechanics, and computer science are computationally hard but can often be mapped onto a ground-state-search problem of the Ising model and approximately solved by artificial spin-networks of coupled degenerate optical parametric oscillators (DOPOs) in coherent Ising machines. To better understand their working principle and optimize their performance, we analyze the dynamics during the ground state search of 2D Ising models with up to 1936 mutually coupled DOPOs. For regular as well as frustrated and disordered 2D lattices, the machine finds the correct solution within just a few milliseconds. We determine that calculation performance is limited by freeze-out effects and can be improved by controlling the DOPO dynamics, which allows to optimize performance of coherent Ising machines in various tasks. Comparisons with Monte Carlo simulations reveal that coherent Ising machines behave like low temperature spin systems, thus making them suitable for optimization tasks.

Sudden death associated with patients with severe motor and intellectual disabilities (SMID) have been thought to be caused in part by venous thromboembolism (VTE), but actual situation of VTE in SMID is not clear. We examined the prevalence and location of deep venous thrombosis (DVT), and the relation of the development of crural veins in 16 patients with SMID, using ultrasonography. The maximum diameter of soleal vein was 1.6±0.5 mm. In most cases, DVT was found in the femoral veins. We could not detect thrombus in the soleal veins. In the present study, the detection ratio of DVT was high in patients with SMID who had restricted mobility capability and were bedridden, and we found the veins centrally from popliteal veins in DVT in SMID, not soleal veins, as the initial sites of the DVT. In the literature, the mean diameter of soleal veins, in healthy adults is 6.7±1.8 mm, that in contrast in SMID being smaller. Underdevelopment of intramuscular veins is possibly related to the mechanism of DVT in SMID. In the current guidelines for the management of VTE, there is limited in scope of ambulatory adults and no application cases who exhibit to SMID restricted mobility of the lower extremities and are bedridden associated with cerebral palsy and developmental motor disabilities, and such patients have associated high risk of the complications of DVT. According to our present study, it is necessary to provide appropriate guidelines for DVT in SMID considering characteristic features. (This is a translation of Jpn J Phlebol 2017; 28: 29-34.).

Filtered glucose is mostly reabsorbed by sodium-glucose cotransporter 2 (SGLT2) in the proximal tubules. SGLT2 is predominantly expressed in the human kidney. However, the regulatory mechanisms for SGLT2 gene expression in the human kidney remain unclear. We in this work elucidated the transcriptional regulatory mechanisms for the SGLT2 gene by nucleosome occupancy in the SGLT2 promoter region. Expressions of SGLT2 mRNA and protein were markedly weaker in human kidney-derived HK-2 cells than the human kidney. The nucleosome occupancy level in the SGLT2 promoter region was low in the kidney, but high in HK-2 cells. A treatment with a histone deacetylase inhibitor trichostatin A (TSA) decreased nucleosome occupancy in the promoter region and increased SGLT2 expression levels in HK-2 cells. The upregulation of SGLT2 expression by histone acetylation was accompanied by a higher binding frequency of hepatocyte nuclear factor (HNF) 1 α , a transcriptional modulator of SGLT2 in the human kidney, to the promoter region. The transfection of a HNF1 α expression plasmid into HK-2 cells resulted in the upregulation of SGLT2 mRNA expression in the presence of TSA, but not in the treatment of dimethylsulfoxide as a control. Nucleosome occupancy in the promoter region was markedly higher in the liver and small intestine than the kidney. Our results indicate that tissue-specific nucleosome occupancy plays an important role in the regulation of SGLT2 gene expression via HNF1 α binding at the SGLT2 promoter region., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)

Coupled cavities have been used previously to realize on-chip low-dispersion slow-light waveguides, but the bandwidth was usually narrower than 10 nm and the total length was much shorter than 1 mm. Here we report long (0.05-2.5 mm) slow-light coupled cavity waveguides formed by using 50, 200, and 1,000 L3 photonic crystal nanocavities with an optical volume smaller than (λ/n) 3 , slanted from Γ-K orientation. We demonstrate experimentally the formation of a single-mode wideband coupled cavity mode with a bandwidth of up to 32nm (4THz) in telecom C-band, generated from the ultra-narrow-band (~300 MHz) fundamental mode of each L3 nanocavity, by controlling the cavity array orientation. Thanks to the ultrahigh-Q nanocavity design, coupled cavity waveguides longer than 1 mm exhibited low loss and allowed time-of-flight dispersion measurement over a bandwidth up to 22 nm by propagating a short pulse over 1,000 coupled L3 nanocavities. The highly-dense slanted array of L3 nanocavity demonstrated unprecedentedly high cavity coupling among the nanocavities. The scheme we describe provides controllable planar dispersion-managed waveguides as an alternative to W1-based waveguides on a photonic crystal chip.

High-dimensional quantum entanglement can enrich the functionality of quantum information processing. For example, it can enhance the channel capacity for linear optic superdense coding and decrease the error rate threshold of quantum key distribution. Long-distance distribution of a high-dimensional entanglement is essential for such advanced quantum communications over a communications network. Here, we show a long-distance distribution of a four-dimensional entanglement. We employ time-bin entanglement, which is suitable for a fibre transmission, and implement scalable measurements for the high-dimensional entanglement using cascaded Mach-Zehnder interferometers. We observe that a pair of time-bin entangled photons has more than 1 bit of secure information capacity over 100 km. Our work constitutes an important step towards secure and dense quantum communications in a large Hilbert space.

In the pursuance of equality, behavioural scientists disagree about distinct motivators, that is, consideration of others and prospective calculation for oneself. However, accumulating data suggest that these motivators may share a common process in the brain whereby perspectives and events that did not arise in the immediate environment are conceived. To examine this, we devised a game imitating a real decision-making situation regarding redistribution among income classes in a welfare state. The neural correlates of redistributive decisions were examined under contrasting conditions, with and without uncertainty, which affects support for equality in society. The dorsal anterior cingulate cortex (dACC) and the caudate nucleus were activated by equality decisions with uncertainty but by selfless decisions without uncertainty. Activation was also correlated with subjective values. Activation in both the dACC and the caudate nucleus was associated with the attitude to prefer accordance with others, whereas activation in the caudate nucleus reflected that the expected reward involved the prospective calculation of relative income. The neural correlates suggest that consideration of others and prospective calculation for oneself may underlie the support for equality. Projecting oneself into the perspective of others and into prospective future situations may underpin the pursuance of equality.

The merit-based equity norm is a widely observed principle of fairness in resource distribution, in which the resources acquired by each individual are expected to be proportional to the contribution. Despite the empirical significance of this principle, theoretical progress in evolutionary explanations of the fairness norm has been limited to an egalitarian norm. In this study, we examined the effect of partner selection on the evolution of the merit-based equity norm in a simple bargaining game. Our agent-based model demonstrates that the merit-based equity norm emerges when the agent can choose to continue the current partnership based on the bargaining result, whereas the egalitarian norm arises in a random matching situation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Drug transporters are expressed in a number of tissues such as the intestine, liver, and kidney, and play key roles in drug absorption, distribution, and excretion. Variations in drug transporter gene expression significantly contribute to interindividual differences in drug responses. Epigenetic regulation of drug transporter genes has recently emerged as an important mechanism. Epigenetic regulation alters the expression of genes without changing DNA sequences. Epigenetic control mechanisms are associated with DNA methylation, histone modifications, and microRNAs. Herein we discuss recent advances in the study of the transcriptional and post-transcriptional mechanisms of drug transporters with a focus on epigenetic regulation. Areas covered: This review summarizes recent research on the epigenetic regulation of drug transporter genes, and highlights the importance of identifying novel biomarkers based on epigenetics for use in individualized drug therapy. Expert opinion: Researchers are actively attempting to elucidate the epigenetic mechanisms that control the expression of drug transporters, which affect the pharmacokinetics of drugs. Current evidence suggests that epigenetic changes play an important role in drug transporter function. A clearer understanding of epigenetic regulation in drug transporter genes will provide an insight into novel approaches to individualized drug therapy.

Unconventional, special-purpose machines may aid in accelerating the solution of some of the hardest problems in computing, such as large-scale combinatorial optimizations, by exploiting different operating mechanisms than those of standard digital computers. We present a scalable optical processor with electronic feedback that can be realized at large scale with room-temperature technology. Our prototype machine is able to find exact solutions of, or sample good approximate solutions to, a variety of hard instances of Ising problems with up to 100 spins and 10,000 spin-spin connections., (Copyright © 2016, American Association for the Advancement of Science.)

The analysis and optimization of complex systems can be reduced to mathematical problems collectively known as combinatorial optimization. Many such problems can be mapped onto ground-state search problems of the Ising model, and various artificial spin systems are now emerging as promising approaches. However, physical Ising machines have suffered from limited numbers of spin-spin couplings because of implementations based on localized spins, resulting in severe scalability problems. We report a 2000-spin network with all-to-all spin-spin couplings. Using a measurement and feedback scheme, we coupled time-multiplexed degenerate optical parametric oscillators to implement maximum cut problems on arbitrary graph topologies with up to 2000 nodes. Our coherent Ising machine outperformed simulated annealing in terms of accuracy and computation time for a 2000-node complete graph., (Copyright © 2016, American Association for the Advancement of Science.)

A coherent Ising machine based on degenerate optical parametric oscillators (DOPOs) is drawing attention as a way to find a solution to the ground-state search problem of the Ising model. Here we report the generation of time-multiplexed DOPOs at a 10 GHz clock frequency. We successfully generated >50,000 DOPOs using dual-pump four-wave mixing in a highly nonlinear fiber that formed a 1 km cavity, and observed phase bifurcation of the DOPOs, which suggests that the DOPOs can be used as stable artificial spins. In addition, we demonstrated the generation of more than 1 million DOPOs by extending the cavity length to 21 km. We also confirmed that the binary numbers obtained from the DOPO phase-difference measurement passed the NIST random number test, which suggests that we can obtain unbiased artificial spins.

The dark-count rate (DCR) is a key parameter of single-photon detectors. By introducing a bulk optical band-pass filter mounted on a fiber-to-fiber optical bench cooled at 3 K and blocking down to 5 μm, we suppressed the DCR of a superconducting nanowire single-photon detector by more than three orders of magnitude. The DCR is limited by the blackbody radiation through a signal passband of 20-nm bandwidth. The figure of merit, system detection efficiency, and DCR were 2.7×10(11), 2.3%, and 10(-3)  Hz, respectively. Narrowing the bandwidth to 100 GHz suppresses the DCR to 10(-4)  Hz, and the figure of merit increases to 1.8×10(12).