Minimal Phenomenal Experiences (MPEs) are states of consciousness in which wakefulness is preserved but phenomenal content is low or absent. The Entropic Brain Hypothesis (EBH) is a model of conscious processes that regards the entropy of spontaneous brain activity as a marker of 'phenomenal richness', exemplified by high-content psychedelic experiences (HCPEs). Yet recent human neuroimaging studies of MPEs induced by meditation -- and possibly 5-MeO-DMT -- suggest that these states, defined by their phenomenological simplicity, also show signs of increased neurophysiological entropy. This presents a conundrum for the EBH: brain entropy is elevated with increased and decreased richness of the phenomenal experience. Here, we put forward the Complex Brain Hypothesis (CBH), which proposes that the richness of experience differentiating MPEs from HCPEs is better indexed by complexity than by entropy. We argue that brain complexity is modulated by the grain of inference through which the brain resolves uncertainty: some HCPEs exemplify a fine-grained regime, in which loosened constraints amplify fluctuations into proliferating content, whereas some MPEs exemplify a coarse-grained regime, in which a simpler model dissolves variety into an experience of 'contentless' awareness. Both regimes can be associated with elevated brain entropy, but they diverge in phenomenology and perturbational signatures. By resolving the entropy-content conundrum, the CBH refines the EBH and highlights MPEs as an important test case for computational theories of consciousness.

Predicting drug-induced cellular state changes at single-cell resolution remains a central challenge in virtual cell modeling, particularly under out-of-distribution (OOD) conditions. Current approaches predominantly rely on RNA-based assays, which often fail to adequately capture the diverse cellular states underlying drug responses. Moreover, conditional distribution shifts and low signal-to-noise ratios frequently cause models to learn spurious correlations rather than genuine state transitions. To address these limitations, we introduce StateXDiff, a cell State-contextualized multimodal (X) Diffusion framework for predicting single-cell responses to drug perturbations. The framework operates sequentially: first, it learns a disentangled, multimodal representation of cellular state by integrating transcriptomic profiles with inferred protein features; second, it employs a conditional diffusion model to generate perturbation-specific changes. Our approach introduces a Virtual Multimodal Cell State, which augments RNA-based representations with protein-level context, and a Mechanism-aware Drug-Gene Template, which consolidates multi-source biological knowledge for accurate drug representation. Generation is driven by a latent-space diffusion Transformer, regularized through quality-aware triplet constraints, including positive drug-protein pairs or protein-drug mismatched pairs, and explicit protein-reliability weighting. Extensive evaluation demonstrates that StateXDiff consistently enhances generalization performance across three challenging settings: unseen cell lines, unseen drugs, and combinatorial perturbations.

We study the onset of spatial instabilities in reaction networks where the spatially homogeneous system admits a steady state parameterization. We formulate a sufficient condition -- based on the signs of the constant and leading coefficients of the characteristic polynomial of the linearized Jacobian scaled by the diffusion coefficients -- that guarantees a Turing-like instability to spatially inhomogeneous solutions on appropriately chosen domains $Ω$. We also present a specific condition on the domain size $|Ω|$ required to trigger this instability. As a consequence of employing a monomial parameterization, these conditions take the form of algebraic polynomial inequalities involving only rate constants and diffusion coefficients. We apply these ideas to a network describing the sequential and distributive (de-)phosphorylation of a protein at two binding sites, ultimately deriving a condition involving only the four catalytic constants of the enzymes and the diffusion coefficients of the four enzyme-substrate complexes that guarantees a Turing-like instability.

Extreme heat events are increasing in frequency and intensity under climate change, but the socio-behavioral mechanisms that shape community resilience remain insufficiently understood. This study uses a Large Language Model-enhanced agent-based model to simulate responses to a prolonged heatwave in a virtual society. One hundred heterogeneous agents were assigned a Heat Vulnerability Index based on demographic risk factors and observed over 13 simulated days covering baseline, heatwave, and recovery periods. The simulation shows that heat-related impacts are primarily psychosocial and unequally distributed. Agents with higher vulnerability experienced larger declines in perceived safety and social connection than agents with lower vulnerability. Vulnerability also shaped adaptive capacity. More resilient agents maintained routine self-care and protective behaviors, whereas highly vulnerable agents showed behavioral constriction, marked by reduced engagement in protective actions. At the collective level, risk-information diffusion followed a pattern of complex contagion, with adoption driven more by repeated social reinforcement within cohesive networks than by broad exposure alone. These findings suggest that LLM-enhanced simulation can help identify behavioral and social mechanisms of climate resilience and inform heat-risk interventions that combine targeted support for vulnerable groups with community-based information pathways.

Subcellular protein complexes and organelles exhibit diverse dynamic behaviors that reflect the mechanical constraints and organization of the intracellular environment. Although some structures follow classical Brownian motion, many display anomalous dynamics. The transitions between these regimes are increasingly recognized as critical for subcellular organization, yet how they influence pattern formation remains unclear. Here, we investigate the spatial arrangement of cilia on the apical surface of multiciliated cells (MCCs) in developing Xenopus laevis embryos, where coordinated ciliary beating depends on the precise organization of hundreds of centriole-derived basal bodies (BBs). Using quantitative confocal, high-resolution and high-speed TIRF imaging together with theoretical modeling, we show that BB trajectories undergo time-resolved transitions between diffusive and anomalous motion, with distinct regimes that correlate with apical surface expansion. During the early stages, actin remodeling facilitates the dispersal of BBs by providing a permissive, low-confinement environment. As development progresses, the actin network becomes increasingly cross-linked that constrains BB movement and promotes uniform spacing across the apical domain. Disruption of $α$-actinin-1, a major actin cross-linking protein, impairs the integrity of the apical actin meshwork, weakens BB confinement, and disrupts regular spatial patterning, ultimately compromising the arrangement of BBs required for proper cilia alignment. Together, we show that progressive apical actin cross-linking coordinates BB positioning and regulates their dynamic state, guiding the shift from diffusive to confined motion. This transition in dynamics enables the emergence of a uniform BB pattern, which in turn ensures the aligned deployment of motile cilia necessary for effective directional fluid flow.

Adaptive biomechanical systems may show similar observable gait performance while differing in latent organization and longitudinal behavior. This study examines whether an observed longitudinal transformation of gait organization can be approximated within a predictive latent-space framework, without claiming clinical prediction or causal occlusal effects. Using an exploratory single-subject design in a Parkinsonian participant, gait was recorded with instrumented insoles during two sessions separated by eleven weeks. Six occlusal observational probes were tested: natural occlusion, open-mouth disengagement, strong clenching, two vertical-dimension increases in centric relation, and one vertical-dimension increase with mandibular protrusion. Principal Component Analysis was used to construct a PC1--PC2 latent representation. A simplified supervised machine-learning model, implemented as a feed-forward neural network, was trained to approximate the observed M1--M2 transformation. The primary analysis focused on the three centric-relation conditions and tested whether the displacement hierarchy could be reproduced. The model preserved the ordering OC3 < ONL < OC2.5. The extended six-probe analysis also preserved the global structure of the exploratory displacement pattern, with OC3 and OC3P closely grouped and the highest displacements associated with OC2.5 and open-mouth disengagement. Held-out M2 and leave-condition-out analyses showed condition-dependent approximation variability. These findings do not establish generalizable prediction, therapeutic superiority, causal occlusal effects, or clinical viability forecasting. They support only the restricted conclusion that observed longitudinal latent transformations can be internally approximated within this single-subject dataset, providing a methodological bridge toward future multi-subject predictive viability models.

Turing patterns are a cornerstone of biological self-organization, yet their emergence typically requires finely tuned parameters occupying narrow regions of high-dimensional space. This poses a fundamental challenge: how can evolving biological systems reliably find and exploit such rare conditions? In this work, we propose that common biochemical limit cycles, such as those arising from genetic feedback loops, can act as natural explorers of Turing space. By coupling a reaction-diffusion system to an orbit that modulates some of its parameters, we show that the system can dynamically sweep through Turing-permissive regimes and generate transient spatial patterns. We use an entropy-based measure in Fourier space to quantify pattern formation and demonstrate how cycles enhance the detectability and robustness of Turing islands. We further explore how coupling to positional gradients increases reproducibility, suggesting a route from oscillatory dynamics to stable developmental programs. Our results highlight a powerful mechanism by which nature might bootstrap complex spatial structure from simple temporal motifs.

A code-modulated motion visual evoked potential (c-MVEP) for brain-computer interfacing (BCI) is presented in this study. This paradigm uses pseudo-random sequences to visually stimulate objects using motion as an alternative to flickering. In an offline experiment of this study, EEG data were recorded and compared during sequential stimulation of a single object under four conditions: c-MVEP, code-modulated visual evoked potential (c-VEP), steady-state motion visual evoked potential (SSMVEP), and steady-state visual evoked potential (SSVEP). c-MVEP showed similar time-domain characteristics as c-VEP, and also in the frequency domain c-MVEP evoked a broadband response similar to c-VEP, with a comparable signal-to-noise ratio (SNR), albeit more focused in the lower frequency range. Both SSMVEP and SSVEP showed clear oscillatory responses at the stimulation frequency and harmonics, with a higher SNR for SSVEP than SSMVEP. The spatial distribution of c-MVEP showed the main activation at Oz and spread across multiple electrodes, whereas c-VEP showed less spreading and was more focused at Oz. Similar observations were made for SSMVEP and SSVEP. From subjective ratings, there was no clear preference for the motion-based stimulation of SSMVEP or c-MVEP over flicker-based stimulation of SSVEP or c-VEP. The online experiment of this study, evaluated a 4-class BCI with the same four conditions, testing the practical feasibility of the c-MVEP paradigm. The c-MVEP BCI reached a mean accuracy of 85.67% with an average selection time of 2.61s, which was significantly lower than c-VEP (97.81%; 1.15s) and SSVEP (93.42%; 1.94s), but significantly higher than SSMVEP (64.91%; 4.18s). Overall, this study shows the great potential of the newly proposed c-MVEP paradigm using motion stimulation for BCI applications, providing a valuable alternative to the c-VEP paradigm using flickering stimulation.

The replication dynamics (differential equation system) is the foundation of evolutionary game theory. When n=2, there are four possible types of replication dynamics. When n=3, there are 49 possible types of replication dynamics. However, when n>3, the classification of replication dynamics has not been solved. In this article, the sufficient and necessary conditions of the replication dynamics equation with a unique fixed point in the interior of simplex $S_n$(Int$S_n$) for $n\geq 2$ are presented. Furthermore, the different types of replication dynamics equations with a unique fixed point in IntSn is discussed.

For a phenomenon $\boldsymbol{f}$ that is a function of $n$ factors, defined on a finite abelian group $G$, we derive its population statistics solely from its Fourier transform $\hat{\boldsymbol{f}}$. Our main result is an $m$-Coefficient/Index Annihilation Theorem: the $m$th moment of $\boldsymbol{f}$ becomes a series of terms, each with precisely $m$ Fourier coefficients --- and surprisingly, the coefficient indices in each term sum to zero under group addition. This condition acts like a filter, limiting which terms appear in the Fourier domain, and can reveal deeper relationships between the variables driving $\boldsymbol{f}$. These techniques can also be used as an analytical/design tool, or as a feasibility constraint in search algorithms. For functions defined on $\mathbb{Z}_2^n$, we show how the skew, kurtosis, etc. of a binomial distribution can be derived from the Fourier domain. Several other examples are presented.

The Petz recovery map (1986) provably reverses a noisy quantum channel on a reference state, but its algorithmic relevance to real, dissipation-dominated platforms has remained unclear. Using the open-source \texttt{organic-qc-bench} simulation package, we benchmark a Petz-style covariant-purification quantum error correction (CQEC) protocol across four engineered organic qubit platforms operated \emph{without any magnetic field}: a flavin-nitroxide radical-pair reservoir (P1); perchlorotriphenylmethyl radicals in a covalent organic framework (P2); the SVILC qubit [Wakaura2017] on $κ$-(BEDT-TTF)$_2$Cu[N(CN)$_2$]Br (P3, conditional on SVILC confirmation); and a Su-Schrieffer-Heeger soliton on \emph{trans}-polyacetylene (P4). Across five quantum algorithms (QKAN, qDRIFT, control-free QPE, Shor-Regev, Bernstein-Vazirani) and two ML tasks, CQEC gains are significant ($p\!<\!10^{-5}$; Wilcoxon, Bonferroni $α\!=\!0.05/44$) for all sixteen path$\times$algorithm pairs. The central finding is the \emph{$γ_c$-peak}: the fidelity gain $ΔF$ is maximised \emph{at} the entanglement-breaking threshold $γ_c$, with $ΔF_{\rm max}\!=\!+0.303$ at $d\!=\!64$ and a linear $\log_2 d$ scaling over $d=2$-$64$ -- algorithmically confirming the prediction [Wakaura2026LQBH] that Petz recovery preserves coherence beyond this threshold. Bernstein-Vazirani also yields a $7.6$-$31\times$ provable quantum advantage at $n\!=\!3$-$5$, diarylethene-photoswitch CZ fidelities reach $F_{CZ}\!\ge\!0.987$ for P2-P4, and projected manufacturing costs are 10-40$\times$ lower with 10-200$\times$ less operating power than superconducting platforms. The $γ_c$-peak establishes Petz-style recovery as a practically relevant primitive at the dissipation-coherence boundary and identifies PTM-COF (P2) as the highest-priority experimental target.

Understanding how the brain processes linguistic constructions is a central challenge in cognitive neuroscience and linguistics. Recent computational studies show that artificial neural language models spontaneously develop differentiated representations of Argument Structure Constructions (ASCs), generating predictions about when and how construction-level information emerges during processing. The present study tests these predictions in human neural activity using electroencephalography (EEG). Ten native English speakers listened to 200 synthetically generated sentences across four construction types (transitive, ditransitive, caused-motion, resultative) while neural responses were recorded. Analyses using time-frequency methods, feature extraction, and machine learning classification revealed construction-specific neural signatures emerging primarily at sentence-final positions, where argument structure becomes fully disambiguated, and most prominently in the alpha band. Pairwise classification showed reliable differentiation, especially between ditransitive and resultative constructions, while other pairs overlapped. Crucially, the temporal emergence and similarity structure of these effects mirror patterns in recurrent and transformer-based language models, where constructional representations arise during integrative processing stages. These findings support the view that linguistic constructions are neurally encoded as distinct form-meaning mappings, in line with Construction Grammar, and suggest convergence between biological and artificial systems on similar representational solutions. More broadly, this convergence is consistent with the idea that learning systems discover stable regions within an underlying representational landscape - recently termed a Platonic representational space - that constrains the emergence of efficient linguistic abstractions.

Brain foundation models have achieved remarkable advances across a wide range of neuroscience tasks. However, most existing models are limited to a single functional modality, restricting their ability to exploit complementary spatiotemporal dynamics and the collective data scale across different neuroimaging techniques. This limitation largely arises from severe semantic heterogeneity and resolution discrepancies among modalities. To address these challenges, we propose Brain-OF, an omnifunctional brain foundation model jointly pretrained on fMRI, EEG and MEG, capable of handling both unimodal and multimodal inputs within a unified framework. To reconcile heterogeneous spatiotemporal resolutions, we introduce the Any-Resolution Neural Signal Sampler, which projects diverse brain signals into a shared semantic space. To further manage semantic shifts, the Brain-OF backbone integrates DINT attention with a Sparse Mixture of Experts, where shared experts capture modality-invariant representations and routed experts specialize in modality-specific semantics. Furthermore, to explicitly internalize the characteristics of neural activity through self-supervised learning, we propose Masked Temporal-Frequency Modeling, a dual-domain pretraining objective that jointly reconstructs brain signals in both the time and frequency domains. Brain-OF is pretrained on a large-scale corpus comprising around 40 datasets and demonstrates superior performance across diverse downstream tasks, highlighting the benefits of joint multimodal integration and dual-domain pretraining.

Protein function is driven by cohesive substructures, such as catalytic triads, binding pockets, and structural motifs, that occupy only a small fraction of a protein's residues. Yet existing pipelines built on protein encoders do not model proteins at the substructure level, leaving the central biological question unanswered: which substructure of a protein is responsible for its function? We introduce BioBlobs, an encoder-agnostic, end-to-end differentiable framework that compresses a protein into a small set of cohesive substructures (blobs) and predicts function from these blobs alone, so that each blob corresponds to a candidate functional region. Across diverse protein function prediction tasks and multiple sequence- and structure-based encoders, BioBlobs matches or exceeds strong baselines while operating on only a small fraction of residues. The discovered blobs adapt their spatial scale to the task, ranging from local catalytic sites to entire structural domains. Trained only on protein-level labels, BioBlobs recovers experimentally annotated catalytic sites in the M-CSA database, demonstrating unsupervised functional substructure discovery and opening a path to large-scale functional site discovery across the unannotated proteome.

To examine associations between screen time and anxiety, depression, behavior or conduct problems, and ADHD among children and adolescents during the pandemic, and to assess whether physical activity, sleep duration, and bedtime regularity mediate these associations. Data from 50231 US children and adolescents aged 6 to 17 years in the 2020 to 2021 National Survey of Childrens Health were analyzed. Exact natural effect models and structural equation modeling assessed mediation by physical activity, short sleep duration, and irregular bedtime. We found that daily screen time equal or more than 4 hours was linked to higher risks of anxiety (aOR = 1.45, 95% CI 1.32, 1.58), depression (aOR = 1.65, 95% CI 1.41, 1.93), behavior or conduct problems (aOR = 1.17, 95% CI 1.05, 1.30), and ADHD (aOR = 1.21, 95% CI 1.11, 1.33). Physical activity accounted for 30.2% to 39.3% of the association, irregular bedtime for 18.2% to 25.7%, and short sleep duration for 2.77% to 7.34%. Excessive screen time was associated with poorer mental health and ADHD, partly explained by reduced physical activity, irregular bedtime, and insufficient sleep. Interventions should promote physical activity, regular sleep routines, and adequate sleep duration to effectively mitigate mental health issues and ADHD among children and adolescents.

The Syncytial Mesh Model introduces a three-layered framework for large-scale brain dynamics integrating local neural circuitry, macrostructural connectivity, and a slow mesoscale control-field substrate associated with astrocytic syncytial organization. Rather than directly generating electrophysiological activity, the proposed syncytial layer modulates neuronal excitability, coherence structure, and metastable coordination across spatial scales. The framework is formulated as a phenomenological effective theory combining neural-mass dynamics, connectome-scale coupling, and continuous-field interactions. Within this architecture, the model provides a candidate explanation for large-scale traveling-wave organization, low-frequency coherence structure, and distributed plasticity phenomena that are not straightforwardly reducible to direct local synaptic connectivity alone. Numerical simulations of the effective field dynamics generate stable traveling-wave propagation, smooth phase-gradient organization, and low-frequency modal structure qualitatively resembling experimentally reported infra-slow and delta/theta coordination patterns. An analytic mesoscale coherence model further illustrates how scale-dependent synchronization probabilities may emerge from slow-field modulation and damping dynamics without requiring globally phase-locked neuronal oscillations.

Online patient inquiries are often informal, incomplete, and written before professional assessment, yet they must still be routed to an appropriate level of clinical follow-up. We study this as a four-class actionable triage task -- self-care, schedule-visit, urgent-clinician-review, or emergency-referral, and ask whether prompted large language models (LLMs) can support such routing under low-resource labeling conditions. Using the public HealthCareMagic-100K corpus, we construct a 300-example human calibrated gold evaluation set, a 700-example auto-labeled silver training set, and a 40-example few-shot pool. We compare Term Frequency-Inverse Document Frequency (TF-IDF) and Bidirectional Encoder Representations from Transformers for Biomedical Text Mining (BioBERT) baselines train on silver labels against six prompted LLMs under 0-shot, 4-shot, and 12-shot conditions respectively. Accordingly, we evaluate with macro-$F_1$ alongside safety-aware metrics, including emergency-recall, under-triage rate, and severe under-triage rate. The strongest LLM (Claude Haiku 4.5, 12-shot) reaches macro-$F_1$ 0.475, exceeding the best supervised baseline (BioBERT, 0.378) on point estimate, with overlapping confidence intervals. Few-shot prompting and two-model agreement help in label-dependent ways: self-care agreement is reliable, urgent-clinician-review is not. We conclude that LLMs can support triage prioritization and selective human review, but not autonomous deployment.

Biofilms, bacteria cells surrounded by a self-produced polymeric matrix, are common on medical devices and lead to many hospital infections. The biofilm lifecycle includes disassembly and dispersion, where bacteria clusters detach from the biofilm, circulate in the bloodstream, and potentially colonize secondary infection sites. Existing models often simplify detachment to a function of biofilm thickness or extracellular polymeric substance (EPS) density, without tracking properties of detached clusters that impact their biological fate, including cluster size and morphology. Addressing this gap, our detachment model accounts for drag and adhesion in tagged sections of the biofilm determined by the cluster geometry and local arrangement of bacteria and EPS. A stickiness parameter controls local EPS adhesion strength, which is modulated to disrupt (or compromise) EPS biomass. We specifically model the detachment of clusters from a Staphylococcus epidermidis biofilm grown for 24 hours. Experimental data for biofilm microstructural features are utilized to benchmark the simulated biofilm, which is then subjected to different EPS disruption levels. We examine parameters that influence detached biofilm cell cluster frequency, size, and shape, providing mechanistic insights into how compromised EPS influences detachment dynamics. This integrated modeling framework is a significant advance in the predictive capabilities for biofilm detachment processes.

Inferring the structure of directed acyclic graphs (DAGs) from data is a central challenge in causal discovery, particularly in modern high-dimensional settings where large-scale interventional data are increasingly available. While interventional data can improve identifiability, existing methods remain limited by soft acyclicity constraints, leading to optimization over invalid cyclic graphs, numerical instability, and reduced scalability. We introduce PACER (Perturbation-driven Acyclic Causal Edge Recovery), a scalable framework for causal discovery that guarantees acyclicity by construction. PACER parameterizes a distribution over DAGs through a joint model of variable permutations and edge probabilities, enabling direct optimization over valid causal structures without surrogate penalties. The framework supports a unified likelihood-based treatment of observational and interventional data, flexible conditional density models, and the incorporation of structural prior knowledge. For linear-Gaussian mechanisms, we derive closed-form expressions for the expected interventional log-likelihood and its gradients, yielding substantial computational gains. Empirically, PACER matches or exceeds state-of-the-art methods on protein signaling and large-scale genetic perturbation benchmarks, while scaling efficiently to networks with thousands of variables and achieving up to two orders of magnitude speedups over penalty-based differentiable approaches. These results demonstrate that exact and scalable causal discovery from high-dimensional perturbation data is achievable through principled search space design.

When reliable target structures are unavailable at scale or phenotypes arise from dysregulated pathways, transcriptomic perturbations provide a system-level functional readout for drug action. In this work, we formalize \emph{Transcriptome-based Drug Design (TBDD)} as a generative inverse problem: designing drug molecules conditioned on desired transcriptomic state transitions. We analyze the inherently ill-posed nature of this task, which is further complicated by the profound domain gap between biology and chemistry and by the sparsity of transcriptomic signals. To address these challenges, we propose \textbf{\themodel{}} (A \textbf{C}ell\textbf{U}lar \textbf{R}esponse \textbf{E}ngine), a multi-resolution transcriptome-guided diffusion framework. \themodel{} features a specialized \textbf{Transcriptome Perturbation Functional Feature Extractor (TFE)} that (1) distills function-oriented perturbation embeddings from pre/post states, (2) aligns these signatures to dual chemical views to bridge the cross-modal gap, and (3) performs heterogeneity-aware aggregation to extract robust state-specific signals from noisy transcriptomic data. Extensive evaluations on both standard benchmarks and rigorous out-of-distribution protocols demonstrate that \themodel{} consistently outperforms strong baselines in structural quality and functional consistency. Furthermore, we validate its practical utility via a zero-shot gene-inhibitor design task, highlighting the potential of phenotype-driven generative discovery.

Biologically-inspired AI agent frameworks claim reliability benefits through structural guarantees adapted from gene regulatory networks, immune systems, and metabolic control. These claims are rarely tested empirically against simpler alternatives. We present three deep benchmarks: metabolic priority gating, autoinducer-based quorum sensing, and Bayesian stagnation detection, each comparing a biologically-grounded implementation against a naive non-biological alternative and an ablated control, across 1,000 trials per seed and 10 seeds (10M+ data points total).

NMR relaxation experiments have shown that there are small but measurable changes in the native state dynamics of the Fyn SH3 domain associated with the substitution by other amino acids of a phenylalanine residue (F20) in the hydrophobic core. We have here used experimental values of NMR order parameters for the wild type protein and two mutational variants (F20L and F20V) as restraints in molecular dynamics simulations. This approach is highly sensitive and provides an atomistic description of the subtle perturbations in native state fluctuations accompanying the mutations. The structural ensembles that we have determined using this method allow the changes in the native state entropy of the protein caused by each of the mutations to be estimated. These entropy changes correspond to free energy variations of several kcal/mol and therefore represent sizable contributions to the overall changes in stability that are associated with the amino acid mutations.

Emerging foundation models (FMs) in electroencephalography (EEG) promise a path to scale deep learning in diagnostics and brain-computer interfaces despite data scarcity, yet their opaque nature remains a barrier to wider adoption. We investigate attention-aware Layer-wise relevance propagation (LRP) as a post-hoc attribution method for EEG-FMs, extending LRP's use on convolutional neural network (CNN)-based EEG models to the Transformer architectures that current FMs are based on. We find that LRP can both verify EEG-FM decisions and surface novel, biologically plausible hypotheses from them. In motor imagery, it unmasks 'Clever Hans' behavior where models prioritize task correlated ocular signals over the intended motor correlates. In a naturalistic paradigm for affect prediction, it reveals a recurring reliance on a central electrode cluster, suggesting a candidate sensorimotor signature of arousal. Though heatmap interpretation remains ambiguous in this complex domain, the results position LRP as a tool for both verification and exploration of EEG-FMs, a role that will grow in both importance and discovery potential as the underlying models mature.

Stochastic models of diffusion are routinely used to study dispersal of populations, including populations of animals, plants, seeds and cells. Advances in imaging and field measurement technologies mean that data are often collected across a range of scales, including count data collected across a series of fixed sampling regions to characterize population-level dispersal, as well as individual trajectory data to examine at the motion of individuals within a diffusive population. In this work we consider a lattice-based random walk model and examine the extent to which model parameters can be determined by collecting count data and/or trajectory data. Our analysis combines agent-based stochastic simulations, mean-field partial differential equation approximations, likelihood-based estimation, identifiability analysis, and model-based prediction. These combined tools reveal that working with count data alone can sometimes lead to challenges involving structural non-identifiability that can be alleviated by collecting trajectory data. Furthermore, these tools allow us to explore how different experimental designs impact inferential precision by comparing how different trajectory data collection protocols affects practical identifiability. Open source implementations of all algorithms used in this work are available on GitHub.

Diverse scientific and engineering research areas deal with discrete, time-stamped changes in large systems of interacting delay differential equations. Simulating such complex systems at scale on high-performance computing clusters demands efficient management of communication and memory. Inspired by the human cerebral cortex -- a sparsely connected network of $\mathcal{O}(10^{10})$ neurons, each forming $\mathcal{O}(10^{3})$--$\mathcal{O}(10^{4})$ synapses and communicating via short electrical pulses called spikes -- we study the simulation of large-scale spiking neural networks for computational neuroscience research. This work presents a novel network construction method for multi-GPU clusters and upcoming exascale supercomputers using the Message Passing Interface (MPI), where each process builds its local connectivity and prepares the data structures for efficient spike exchange across the cluster during state propagation. We demonstrate scaling performance of two cortical models using point-to-point and collective communication, respectively.

Codon usage bias has a crucial impact on the translation efficiency and co-translational folding of proteins, necessitating the algorithmic development of codon optimization/harmonization methods, particularly for heterologous recombinant protein expression. Codon harmonization is especially valuable for proteins sensitive to translation rates, because it can potentially replicate native translation speeds, preserving proper folding and maintaining protein activity. This work proposes a Monte Carlo-based codon harmonization algorithm, MOSAIC (Monte Carlo-based Simulated Annealing for Linked Codons), for the harmonization of a set of linked codons, which differs from conventional codon harmonization, by focusing on the codon sets rather than individual ones. Our MOSAIC demonstrates robust computational performance on ribosomal proteins (S18, S15, S10, and L11) as model systems. Among them, the harmonized gene of RP S18 was expressed and compared with the expression of the wild-type gene. The harmonized gene clearly yielded a larger quantity of the protein, from which the amount of the soluble protein was also significant. These results underscored the potential of the linked codon harmonization approach to enhance the expression and functionality of sensitive proteins, setting the stage for more efficient production of recombinant proteins in various biotechnological and pharmaceutical applications.

Deep learning, particularly with the advancement of Large Language Models, has transformed biomolecular modeling, with protein language models such as ESM inspiring emerging RNA language models such as RiNALMo. Recent work has begun applying sparse autoencoders (SAEs) to protein language model representations, exploring representation-level interpretability in biomolecular models. Here, we explore whether SAEs can provide interpretable feature decompositions of RNA language model representations, while also examining their limitations in this setting. We present SAE-RNA, interpretability model that analyzes RiNALMo representations and maps them to known human-level biological features. Rather than claiming definitive biological concept discovery, our study frames SAE-based analysis as a representation-level probe for characterizing how RNA language models organize biological information internally. More broadly, SAE-RNA provides a feature-level framework for comparing RNA groups and identifying sparse representation components associated with RNA family identity or structural context.

We introduce Genome-Factory, the first integrated Python library for tuning, deploying, and interpreting genomic foundation models. Our core contribution is to simplify and unify the workflow for genomic model development: data collection, model tuning, inference, benchmarking, and interpretability. For data collection, Genome-Factory offers an automated pipeline to download genomic sequences and preprocess them. For model tuning, Genome-Factory supports both full and parameter-efficient fine-tuning across diverse genomic models. For inference, Genome-Factory enables both embedding extraction and DNA sequence generation. For benchmarking, we include two existing benchmarks and provide a flexible interface to incorporate additional benchmarks. For interpretability, Genome-Factory introduces an open-source biological interpreter based on a sparse auto-encoder. We validate the utility of Genome-Factory across three dimensions: (i) Compatibility with diverse models and fine-tuning methods; (ii) Benchmarking downstream performance using two open-source benchmarks; (iii) Biological interpretation of learned representations with DNABERT-2. These results highlight its practical value for real-world genomic analysis. GitHub: https://github.com/WeiminWu2000/Genome_Factory.

As neuroscientific theories of consciousness continue to proliferate, the need to assess their similarities and differences - as well as their predictive and explanatory power - becomes ever more pressing. Recently, a number of structured adversarial collaborations have been devised to test the competing predictions of several candidate theories of consciousness. In this review, we compare and contrast three theories being investigated in one such adversarial collaboration: Integrated Information Theory, Neurorepresentationalism, and Active Inference. We begin by presenting the core claims of each theory, before comparing them in terms of the phenomena they seek to explain, the sorts of explanations they avail, and the methodological strategies they endorse. We then consider some of the inherent challenges of theory-testing, and how adversarial collaboration addresses some of these difficulties. The stage is then set for the empirical work to come: first, we outline the key hypotheses to be tested across a series of multi-site experiments; second, we discuss the kinds of observations that would support or challenge each theory; third, we consider how these theories might assimilate or accommodate such observations. Finally, we show how data harvested across disparate experiments (and their replicates) may be formally integrated to provide a quantitative measure of the evidential support accrued under each theory. Besides orienting the reader to the theoretical foundations of our collaboration, this review aims to provide valuable meta-scientific insights into the mechanics of adversarial collaboration and theory-testing in general - including the way theories may be evaluated in terms of the scientific progress they deliver.

All intelligence is collective intelligence, in the sense that it is made of parts which must align with respect to system-level goals. Understanding the dynamics which facilitate or limit navigation of problem spaces by aligned parts thus impacts many fields ranging across life sciences and engineering. To that end, consider a system on the vertices of a planar graph, with pairwise interactions prescribed by the edges of the graph. Such systems can sometimes exhibit long-range order, distinguishing one phase of macroscopic behaviour from another. In networks of interacting systems we may view spontaneous ordering as a form of self-organisation, modelling neural and basal forms of cognition. Here, we discuss necessary conditions on the topology of the graph for an ordered phase to exist, with an eye towards finding constraints on the ability of a system with local interactions to maintain an ordered target state. By studying the scaling of free energy under the formation of domain walls in three model systems -- the Potts model, autoregressive models, and hierarchical networks -- we show how the combinatorics of interactions on a graph prevent or allow spontaneous ordering. As an application we are able to analyse why multiscale systems like those prevalent in biology are capable of organising into complex patterns, whereas rudimentary language models are challenged by long sequences of outputs.