We derive a Riemannian metric on three-dimensional color space from the Fisher information of neural population codes in the visual pathway. Photoreceptor adaptation, retinal opponent channels, and cortical population encoding each map onto a geometric construction, producing a metric tensor whose components correspond to measurable neural quantities. The resulting 17-parameter model is fitted jointly to four independent threshold datasets: MacAdam's (1942) chromaticity ellipses, the Koenderink et al. (2026) three-dimensional ellipsoids, Wright's (1941) wavelength discrimination function, and the Huang et al. (2012) threshold color difference ellipses, covering 96 independently measured discrimination conditions across varied chromaticities and luminances. The joint fit achieves STRESS of 23.9 on MacAdam, 20.8 on Koenderink et al., 30.1 on Wright, and 30.8 on Huang et al.

The use of ad-hoc engineered viruses in the fight against tumours is one of the greatest ideas in cancer therapeutics within the last three decades. Together with other strategies such as immunotherapies, nanoparticles and adjunct therapies, the use of viral vectors in clinical trials and in the clinics has been and is still widely studied and pursued. The ability of those vectors to infiltrate and infect tumours represents one of the key attributes that regulates the success of such a strategy. Although some remarkable successes have been obtained, it is still not entirely clear how to achieve reliable protocols that can be routinely employed with confidence on a significant range of tumours. In this work, we thus concentrate on the study of different mathematical descriptions of virotherapy with the aim of better understanding the role of viral infectivity and viral dynamics in positive therapeutic outcomes. In particular, we compare probabilistic, individual approaches with continuous, spatially inhomogeneous models and investigate the importance of different tumour motility and different mathematical representations of viral infectivity. These formulations also allow us to arrive at better analytical characterisation of how waves of viral infections arise and propagate in tumours, providing interesting insights into therapy dynamics. Similarly to previous studies, oscillatory behaviours, stochasticity and cancers' diffusivities are all central to the eradication or the escape of tumours under virotherapy. Here, though, our results also show that the ability of viruses to infect tumours seems, in certain cases, more important to a final positive outcome than tumours' motility or even reproducibility. This could hopefully represent a first step into better insights into viral dynamics that may help clinicians to achieve consistently better outcomes.

People make strategic decisions many times a day - during negotiations, when coordinating actions with others, or when choosing partners for cooperation. The resulting dynamics can be studied with learning theory and evolutionary game theory. These frameworks explore how people adapt their decisions over time, in light of how effective their strategies have been. The outcomes of such learning processes depend on how sensitive individuals are to the performance of their strategies. When they are more sensitive, they systematically favor strategies they deem more successful. When they are less sensitive, their learning process is noisier and more erratic. Traditionally, most models treat this sensitivity as a fixed parameter - like the "selection strength" parameter in evolutionary models. Instead, we study how strategies and sensitivities co-evolve. We find that the co-evolutionary endpoints depend on both the type of strategic interaction and the learning rule employed. In prisoner's dilemmas, we often observe sensitivities to increase indefinitely. But in snowdrift and stag-hunt games, sensitivities often converge to a finite value, or we observe evolutionary branching altogether. These results shed light on how evolution might shape learning mechanisms for social behavior. They suggest that noisy learning does not need to be a by-product of cognitive constraints. Instead, it can serve as a means to gain strategic advantages.

How do humans move? Advances in reinforcement learning (RL) have produced impressive results in capturing human motion using physics-based humanoid control. However, torque-controlled humanoids fail to model key aspects of human motor control such as biomechanical joint constraints & non-linear and overactuated musculotendon control. We present KINESIS, a model-free motion imitation framework that tackles these challenges. KINESIS is trained on 1.8 hours of locomotion data and achieves strong motion imitation performance on unseen trajectories. Through a negative mining approach, KINESIS learns robust locomotion priors that we leverage to deploy the policy on several downstream tasks such as text-to-control, target point reaching, and football penalty kicks. Importantly, KINESIS learns to generate muscle activity patterns that correlate well with human EMG activity. We show that these results scale seamlessly across biomechanical model complexity, demonstrating control of up to 290 muscles. Overall, the physiological plausibility makes KINESIS a promising model for tackling challenging problems in human motor control. Code, videos and benchmarks are available at https://github.com/amathislab/Kinesis.

We develop a novel ultrasound nasogastric tube (UNGT) dataset to address the lack of public nasogastric tube datasets. The UNGT dataset includes 493 images gathered from 110 patients with an average image resolution of approximately 879 $\times$ 583. Four structures, encompassing the liver, stomach, tube, and pancreas, are precisely annotated. Besides, we propose a semi-supervised adaptive-weighting aggregation medical segmenter to address data limitation and imbalance concurrently. The introduced adaptive weighting approach tackles the severe unbalanced challenge by regulating the loss across varying categories as training proceeds. The presented multiscale attention aggregation block bolsters the feature representation by integrating local and global contextual information. With these, the proposed AAMS can emphasize sparse or small structures and feature enhanced representation ability. We perform extensive segmentation experiments on our UNGT dataset, and the results show that AAMS outperforms existing state-of-the-art approaches to varying extents. In addition, we conduct comprehensive classification experiments across varying state-of-the-art methods and compare their performance. The dataset and code will be available upon publication at https://github.com/NUS-Tim/UNGT.

The tragedy of the commons illustrates a fundamental social dilemma where individual rational actions lead to collectively undesired outcomes, threatening the sustainability of shared resources. Strategies to escape this dilemma, however, are in short supply. In this study, we explore how artificial intelligence (AI) agents can be leveraged to enhance cooperation in public goods games, moving beyond traditional regulatory approaches to using AI as facilitators of cooperation. We investigate three scenarios: (1) Mandatory Cooperation Policy for AI Agents, where AI agents are institutionally mandated always to cooperate; (2) Player-Controlled Agent Cooperation Policy, where players evolve control over AI agents' likelihood to cooperate; and (3) Agents Mimic Players, where AI agents copy the behavior of players. Using a computational evolutionary model with a population of agents playing public goods games, we find that only when AI agents mimic player behavior does the critical synergy threshold for cooperation decrease, effectively resolving the dilemma. This suggests that we can leverage AI to promote collective well-being in societal dilemmas by designing AI agents to mimic human players.

The effectiveness of oncolytic virotherapy is significantly affected by several elements of the tumour microenvironment, which reduce the ability of the virus to infect cancer cells. In this work, we focus on the influence of hypoxia on this therapy and develop a novel continuous mathematical model that considers both the spatial and epigenetic heterogeneity of the tumour. We investigate how oxygen gradients within tumours affect the spatial distribution and replication of both the tumour and oncolytic viruses, focusing on regions of severe hypoxia versus normoxic areas. Additionally, we analyse the evolutionary dynamics of tumour cells under hypoxic conditions and their influence on susceptibility to viral infection. Our findings show that the reduced metabolic activity of hypoxic cells may significantly impact the virotherapy effectiveness; the knowledge of the tumour's oxygenation could, therefore, suggest the most suitable type of virus to optimise the outcome. The combination of numerical simulations and theoretical results for the model equilibrium values allows us to elucidate the complex interplay between viruses, tumour evolution and oxygen dynamics, ultimately contributing to developing more effective and personalised cancer treatments.

Understanding how animals move through heterogeneous landscapes is central to ecology and conservation. In this context, step selection functions (SSFs) have emerged as the main statistical framework to analyze how biotic and abiotic predictors influence movement paths observed by radio tracking, GPS tags, or similar sensors. A traditional SSF consists of a generalized linear model (GLM) that infers the animal's habitat preferences (selection coefficients) by comparing each observed movement step to random steps. Such GLM-SSFs, however, cannot flexibly consider non-linear or interacting effects, unless those have been specified a priori. To address this problem, generalized additive models have been integrated in the SSF framework, but those GAM-SSFs are still limited in their ability to represent complex habitat preferences and inter-individual variability. Here we explore the utility of deep neural networks (DNNs) to overcome these limitations. We find that DNN-SSFs, coupled with explainable AI to extract selection coefficients, offer many advantages for analyzing movement data. In the case of linear effects, they effectively retrieve the same effect sizes and p-values as conventional GLMs. At the same time, however, they can automatically detect complex interaction effects, nonlinear responses, and inter-individual variability if those are present in the data. We conclude that DNN-SSFs are a promising extension of traditional SSF. Our analysis extends previous research on DNN-SSF by exploring differences and similarities of GLM, GAM and DNN-based SSF models in more depth, in particular regarding the validity of statistical indicators that are derived from the DNN. We also propose new DNN structures to capture inter-individual effects that can be viewed as a nonlinear random effect. All methods used in this paper are available via the 'citoMove' R package.

Spatial patterning and synchronization are pervasive features of plankton communities, yet the mechanisms that allow such patterns to persist coherently under environmental noise remain unresolved. In vertically structured aquatic ecosystems, plankton populations are often organized into distinct layers, raising the question of how interactions between layers shape both spatial self-organization and robustness. Here, we develop a spatiotemporal ecosystem model of a two-layer plankton community to examine the role of passive diffusive coupling under stochastic environmental fluctuations. We show that interlayer diffusion induces a sharp transition from independent, layer-specific Turing patterns to fully synchronized spatial patterns once the coupling strength exceeds a critical threshold. Importantly, the same coupling mechanism markedly enhances the stability of spatial patterns against environmental noise, extending their persistence far beyond that of non-coupled layers. Moreover, we uncover a trophic hierarchy in noise sensitivity, with zooplankton exhibiting substantially greater vulnerability than phytoplankton. Together, these results identify passive diffusive coupling as a unifying mechanism that simultaneously promotes spatial synchronization and robustness, providing a mechanistic explanation for the persistence of coherent plankton patterns in fluctuating aquatic environments.

A major barrier to decentralized, near-patient diagnostics is the lack of a signal transduction modality that is both analytically precise and accessible at the point of care. Optical readouts remain instrument-dependent and difficult to miniaturize, while compact electrochemical readouts are prone to matrix-derived signal distortion, limiting their biomarker coverage in real clinical settings. Here, we define interfacial potential transduction as a standardized electrical modality for portable, clinical-grade diagnostics across diverse assay formats. A mechanistic framework identifying key sample matrix parameters within the interfacial potentials transduction system enables control of biofluid-derived interference, and is demonstrated in a widely accessible lateral flow immunoassay format through quantitative detection of estradiol, progesterone, and luteinizing hormone in human plasma with high correlation (r2 > 0.97) to clinical analyzers. Broader applicability across representative diagnostic sectors is further demonstrated through exceptional performance including glucose quantification for biochemical analysis with limit of detection (LOD) of 0.92 ug/dL, HIV p24 capsid protein under an immunomagnetic separation workflow (LOD = 44.8 fg/mL), and hepatitis B virus detection within 5 min via loop-mediated isothermal amplification for molecular diagnostics. Together, these results establish interfacial potentials transduction as a unified diagnostic paradigm for near-patient deployment beyond optical and electrochemical approaches.

The accurate prediction of protein-RNA binding affinity remains an unsolved problem in structural biology, limiting opportunities in understanding gene regulation and designing RNA-targeting therapeutics. A central obstacle is the structural flexibility of RNA, as, unlike proteins, RNA molecules exist as dynamic conformational ensembles. Thus, committing to a single predicted structure discards information relevant to binding. Here, we show that this obstacle can be addressed by extracting pre-structural embeddings, which are intermediate representations from a biomolecular foundation model captured before the structure decoding step. Pre-structural embeddings implicitly encode conformational ensemble information without requiring predicted structures. We build ZeroFold, a transformer-based model that combines pre-structural embeddings from Boltz-2 for both protein and RNA molecules through a cross-modal attention mechanism to predict binding affinity directly from sequence. To support training and evaluation, we construct PRADB, a curated dataset of 2,621 unique protein-RNA pairs with experimentally measured affinities drawn from four complementary databases. On a held-out test set constructed with 40% sequence identity thresholds, ZeroFold achieves a Spearman correlation of 0.65, a value approaching the ceiling imposed by experimental measurement noise. Under progressively fairer evaluation conditions that control for training-set overlap, ZeroFold compares favourably with respect to leading structure-based and leading sequence-based predictors, with the performance gap widening as sequence similarity to competitor training data is reduced. These results illustrate how pre-structural embeddings offer a representation strategy for flexible biomolecules, opening a route to affinity prediction for protein-RNA pairs for which no structural data exist.

Addressing both natural and societal challenges requires collective cooperation. Studies on collective-risk social dilemmas have shown that individual decisions are influenced by the perceived risk of collective failure. However, existing feedback evolving game models often focus on a single feedback mechanism, such as the coupling between cooperation and risk or between cooperation and cost. In many real-world scenarios, however, the level of cooperation, the cost of cooperating, and the collective risk are dynamically interlinked. Here, we present an evolutionary game model that considers the interplay of these three variables. Our analysis shows that the worst-case scenario, characterized by full defection, maximum risk, and the highest cost of cooperation, remains a stable evolutionary attractor. Nevertheless, cooperation can emerge and persist because the system also supports stable equilibria with non-zero cooperation. The system exhibits multistability, meaning that different initial conditions lead to either sustained cooperation or a tragedy of the commons. These findings highlight that initial levels of cooperation, cost, and risk collectively determine whether a population can avert a tragic outcome.

We present a new solution concept called evolutionarily stable Stackelberg equilibrium (SESS). We study the Stackelberg evolutionary game setting in which there is a single leading player and a symmetric population of followers. The leader selects an optimal mixed strategy, anticipating that the follower population plays an evolutionarily stable strategy (ESS) in the induced subgame and may satisfy additional ecological conditions. We consider both leader-optimal and follower-optimal selection among ESSs, which arise as special cases of our framework. Prior approaches to Stackelberg evolutionary games either define the follower response via evolutionary dynamics or assume rational best-response behavior, without explicitly enforcing stability against invasion by mutations. We present algorithms for computing SESS in discrete and continuous games, and validate the latter empirically. Our model applies naturally to biological settings; for example, in cancer treatment the leader represents the physician and the followers correspond to competing cancer cell phenotypes.

Fossil DNA preservation varies with depositional environments and diagenesis, producing fragments of heterogeneous origins and degradation states. We use first-principles biomolecular analysis to classify fossil molecular environments into four system types, distinguished by three orthogonal indicators: origin (H/h: host/heterologous), deamination status (D/d), and similarity ratio (S/s). Conventional aDNA pipelines assume a binary mix of endogenous host DNA and modern contaminants, overlooking multisource complexity from multiple species and time-averaged deposits. This leads to bias: authentic signals suppressed during enrichment, alignment, or damage filtering, and exogenous/ancient admixed fragments misassigned as endogenous, particularly in open systems. We introduce the HSF (Host/Species-specific Fragment) posterior traceability framework to address this. It treats fragments as primary units, maximizes source diversity, detects isolated sequences, defers lineage assignment to preserve uncertainty, and applies phylogenetic consistency to discriminate origins. Combined with preservation characterization (e.g., 3D imaging and volumetric openness assessment), it improves authenticity evaluation and reduces misassignment in mixed-signal samples. Case studies identify novel fossil DNA patterns (CRSRR and SRRA) and demonstrate superior performance compared with conventional methods. The HSF framework enhances aDNA reliability, extends molecular archaeology to challenging contexts, and aids genome evolution and lineage reconstruction.

The NBSS (normalized biomass size spectrum) is a common, intuitive approach for the study of natural ecosystems. However, very few studies have been dedicated to verifying possible flaws and paradoxes in this widely used method. Evident points of concern of the NBSS method are 1.) the loss of variability due to binning and 2.) the use of intriguing non-biomass units (such as abundance units) on biomass spectra. The main objectives of this study were to verify, test and analyze the procedures involved in transformations that lead to the NBSS plot, and to check for the correctness of currently used units, while testing the hypothesis that NBSS indeed represents biomass, not abundance or biomass flux (dB/dM), while developing i.) a new conceptual framework, ii.) new terminology, iii.) a novel back-transformation method, iv.) high-resolution kernel density estimation (KDE) plots of the density distribution shape, and v.) a new calculation method for numerical values, dimensions, and units. Extensive tests with in situ and synthetic (simulated) data were used to compare the original biomass distributions with binned outputs. Original biomass units and dimensions are retained in the proposed robust 'bootstrapped, backtransformed, and normalized biomass spectrum' (bNBS). The combination of quantitative binning and non-parametric KDE intends to address the importance of intuitive, high-resolution, simple plotting methods and the relevance of avoiding binning artifacts and oversimplifications. If a standardized binning vector and units are used, the proposed bNBS may allow for a new approach of robust size spectra science, that allows for quantitative inter-comparisons of biomass across regions and time periods.

Determining the binding pose of a ligand to a protein, known as molecular docking, is a fundamental task in drug discovery. Generative approaches promise faster, improved, and more diverse pose sampling than physics-based methods, but are often hindered by chemically implausible outputs, poor generalisability, and high computational cost. To address these challenges, we introduce a novel fragmentation scheme, leveraging inductive biases from structural chemistry, to decompose ligands into rigid-body fragments. Building on this decomposition, we present SigmaDock, an SE(3) Riemannian diffusion model that generates poses by learning to reassemble these rigid bodies within the binding pocket. By operating at the level of fragments in SE(3), SigmaDock exploits well-established geometric priors while avoiding overly complex diffusion processes and unstable training dynamics. Experimentally, we show SigmaDock achieves state-of-the-art performance, reaching Top-1 success rates (RMSD<2 & PB-valid) above 79.9% on the PoseBusters set, compared to 12.7-30.8% reported by recent deep learning approaches, whilst demonstrating consistent generalisation to unseen proteins. SigmaDock is the first deep learning approach to surpass classical physics-based docking under the PB train-test split, marking a significant leap forward in the reliability and feasibility of deep learning for molecular modelling.

We investigate traveling wave solutions in the two-species reaction-diffusion Lotka-Volterra competition system under weak competition. For the strict weak competition regime $(b<a<1/c,\,d>0)$, we construct refined upper and lower solutions combined with the Schauder fixed point theorem to establish the existence of traveling waves for all wave speeds $s\geq s^*:=\max\{2,2\sqrt{ad}\}$, and provide verifiable sufficient conditions for the emergence of non-monotone waves. Such conditions for non-monotonic waves have not been explicitly addressed in previous studies. It is interesting to point out that our result for non-monotone waves also hold for the critical speed case $s=s^*$. In addition, in the critical weak competition case $(b<a=1/c,\,d>0)$, we rigorously prove, for the first time, the existence of front-pulse traveling waves.

Boolean networks are a widely used modeling framework in systems biology for studying gene regulation, signal transduction, and cellular decision-making. Empirical studies indicate that biological Boolean networks exhibit a high degree of canalization, a structural property of Boolean update rules that stabilizes dynamics and constrains state transitions. Despite its central role, existing software packages provide limited support for the systematic generation of Boolean functions and networks with prescribed canalization properties. We present BoolForge, a Python toolbox for the random generation and analysis of Boolean functions and networks, with a particular focus on canalization. BoolForge enables users to (i) generate random Boolean functions with specified canalizing depth, layer structure, and related constraints; (ii) construct Boolean networks with tunable topological and functional properties; and (iii) analyze structural and dynamical features including canalization measures, robustness, modularity, and attractor structure. By enabling controlled generation alongside analysis, BoolForge facilitates ensemble-based investigations of structure-dynamics relationships, benchmarking of theoretical predictions, and construction of biologically informed null models for Boolean network studies. Availability and Implementation: BoolForge is implemented in Python ($\geq$3.10) and can be installed via \texttt{pip install boolforge}. Source code and documentation are available at https://github.com/ckadelka/BoolForge. A PDF tutorial compendium is provided as Supplementary Material.

Drug combinations are essential in cancer therapy, leveraging synergistic drug-drug interactions (DDI) to enhance efficacy and combat resistance. However, the vast combinatorial space makes experimental screening impractical, and existing computational models struggle to capture the complex, bidirectional nature of DDIs, often relying on independent drug encoding or simplistic fusion strategies that miss fine-grained inter-molecular dynamics. Moreover, state-of-the-art graph-based approaches suffer from high computational costs, limiting scalability for real-world drug discovery. To address this, we propose DPASyn, a novel drug synergy prediction framework featuring a dual-attention mechanism and Precision-Aware Quantization (PAQ). The dual-attention architecture jointly models intra-drug structures and inter-drug interactions via shared projections and cross-drug attention, enabling fine-grained, biologically plausible synergy modeling. While this enhanced expressiveness brings increased computational resource consumption, our proposed PAQ strategy complements it by dynamically optimizing numerical precision during training based on feature sensitivity-reducing memory usage by 40% and accelerating training threefold without sacrificing accuracy. With LayerNorm-stabilized residual connections for training stability, DPASyn outperforms seven state-of-the-art methods on the O'Neil dataset (13,243 combinations) and supports full-batch processing of up to 256 graphs on a single GPU, setting a new standard for efficient and expressive drug synergy prediction.

Species complexes are groups of closely related populations exchanging genes through dispersal. We study the dynamics of the structure of species complexes in a class of metapopulation models where demes can exchange genetic material through migration and diverge through the accumulation of new mutations. Importantly, we model the ecological feedback of differentiation on gene flow by assuming that the success of migrations decreases with genetic distance, through a specific function $h$. We investigate the effects of metapopulation size on the coherence of species structures, depending on some mathematical characteristics of the feedback function $h$. Our results suggest that with larger metapopulation sizes, species form increasingly coherent, transitive, and uniform entities. We conclude that the initiation of speciation events in large species requires the existence of idiosyncratic geographic or selective restrictions on gene flow.