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01.
arXiv (CS.LG) 2026-06-12

A Unified Latent Space Disentanglement VAE Framework with Robust Disentanglement Effectiveness Evaluation

arXiv:2603.11242v2 Announce Type: replace-cross Abstract: Evaluating and interpreting latent representations, such as variational autoencoders (VAEs), remains a significant challenge for diverse data types, especially when ground-truth generative factors are unknown. To address this, we unify several state-of-the-art disentangled VAE approaches for latent space disentanglement into one framework – bfVAE. To assess the effectiveness of a disentangled VAE model and enhance latent space interpretability, we propose Feature Variance Heterogeneity via Latent Traversal (FVH-LT) and Dirty Block Sparse Regression in Latent Space (DBSR-LS). To ensure robust interpretability of learned latent space, we develop a greedy alignment strategy (GAS) that mitigates label switching and aligns latent dimensions across runs to set the foundation of result aggregation. We also introduce a convenient scalar latent space separation index (LSSI) based on the GAS-aligned outputs of FVH-LT and DBSR-LS to summarize the overall latent structural separation without knowledge of the ground-truth generative factors. We compare bfVAE to five VAE models and validate the effectiveness FVH-LT, DBSR-LS, and LSSI in on seven tabular and image datasets. Under our examined experimental settings, bfVAE provides a more flexible disentanglement framework achieves more favorable overall trade-off between disentanglement and reconstruction than the benchmark VAE models; FVH-LT and DBSR-LS reliably uncover semantically meaningful and domain-relevant latent structures and generally yield consistent results; and LSSI makes an effective quantitative summary of latent structural separation.

02.
arXiv (CS.AI) 2026-06-11

Are Frontier LLMs Ready for Cybersecurity? Evidence for Vertical Foundation Models from Dual-Mode Vulnerability Benchmarks

arXiv:2605.23243v2 Announce Type: replace-cross Abstract: We evaluate whether frontier LLMs are ready for cybersecurity through a dual-mode benchmark: white-box function-level vulnerability detection (VulnLLM-R, across C/Java/Python) and black-box web application security testing (five production-style applications with 118 ground-truth vulnerabilities across 20+ CWE families, which we will open-source). We test six frontier models (GPT-5.4, Codex~5.3, Claude Opus~4.6, Sonnet~4.6, Gemini~3.1~Pro and Gemini~3~Flash) and two domain-specialized models across four testing paradigms. Our findings are sobering: (1)~every frontier model produces 10-50% false positive rates in white-box detection, systematically over-predicting vulnerabilities; (2)~in black-box testing, frontier models achieve only 4-8% ground-truth coverage, improving to just 10-19% even with external security tools (Playwright MCP, Burp Suite MCP); (3)~structured penetration-testing methodology encoded in domain-specialized agents raises per-family detection above 50%, demonstrating that methodology, not scale, is the primary lever; and (4)~a domain-specialized defense model achieves the highest precision (0.904) and lowest false positive rate (9.7%) among all models, on a single GPU. We identify the absence of structured security testing traces end-to-end request/response sequences, failure-heavy data, and multi-step attack chains as the fundamental training data bottleneck, and propose self-play security testing as a data generation strategy. Our results make the case for vertical foundation models purpose-built for cybersecurity.

03.
medRxiv (Medicine) 2026-06-11

A Global Health Quality Improvement Project: Enhancing Cervical Cancer Awareness and screening in Nigeria

Background Cervical cancer remains a significant global public health challenge, ranking as the fourth most common cancer among women worldwide. According to The World Health Organization (WHO) 604,000 women were diagnosed with cervical cancer globally in 2020, with over 342,000 deaths amongst this group [1]. Despite its high mortality, cervical cancer is largely preventable through early detection and vaccination against human papillomavirus (HPV), which causes nearly all cases of cervical cancer [1,2] In Nigeria, it is the second most common cancer among women in Nigeria and a leading cause of cancer-related deaths, with low screening rates exacerbating late diagnoses and poor outcomes [1]. Despite global commitments to elimination with Pap smear screening and HPV vaccination, less than 10% of women in Nigeria have undergone screening due to misconceptions, stigma, and limited awareness. Educational interventions may improve awareness and promote screening behaviors. This global health quality improvement (QI) project aimed to enhance cervical cancer awareness and increase Pap smear uptake at the Central Bank of Nigeria (CBN) Clinic in Abuja, Nigeria. Methods In November 2024, we conducted a health education intervention at the Central Bank of Nigeria (CBN) through a structured educational session for male and female CBN staff members. The session focused on cervical cancer prevention, risk factors, and screening guidelines. Additionally, cervical cancer awareness was raised via email, social media, and electronic bulletin board. Participants completed pre and post-interventions surveys assessing cervical cancer knowledge across 10 key items and demographic characteristics. Pap smear uptake was assessed using the CBN clinic records for three months before and after the intervention. Institutional approval was obtained from CBN and external institutional review board approval was not required. Results 188 participants attended the health education session with 124 survey responses (70 pre-event, 54 post-event). Participants were mostly women aged 30-39. Post-intervention, eight of ten survey questions showed improved knowledge, with five demonstrating statistically significant gains: understanding Pap smear frequency (p

04.
arXiv (CS.LG) 2026-06-15

Contract-Based Compositional Shielding for Safe Multi-Agent Reinforcement Learning

arXiv:2606.14130v1 Announce Type: new Abstract: Safe coordination problems surface in multi-agent reinforcement learning when global safety cannot be enforced by any agent unilaterally: the admissibility of one agent's action may depend on the dynamics of other agents. Decentralised shields can enforce safety at runtime, but purely factorised permissions often exclude optimal team behaviour that is safe only through coordination. We study deterministic safety guarantees for agents trained and deployed under decentralised execution, recovering team-optimal safe behaviour without centralised runtime control. Agents have a shared global specification $\phi$ in the safety fragment of Linear Temporal Logic ($\mathsf{LTL}_{\mathsf{safe}}$ ), and select among tuples of local $\mathsf{LTL}_{\mathsf{safe}}$ obligations whose conjunction implies the global specification $\phi$. Each agent may rely on the other agents' local obligations as assumptions because the whole contract tuple is certified simultaneously and allows projection into local action masks. At learning time, a non-stationary multi-armed bandit chooses among a library of local $\mathsf{LTL}_{\mathsf{safe}}$ obligations to select the tuple that optimises team reward, all without forgoing end-to-end safety. We evaluate the approach across 6 environments and 15 algorithmic variants.

05.
arXiv (CS.AI) 2026-06-15

A Comparative Study of Deep Learning Architectures for Multi-Horizon Behavioural Forecasting for Mobile Health

arXiv:2606.14604v1 Announce Type: cross Abstract: Wearable devices and smartphones generate rich behavioural time series that can support proactive health interventions, yet systematic comparisons of modern forecasting architectures for these data are lacking. In particular, it remains unclear how models generalise across populations, how different architectures respond to participant-level fine-tuning and how forecasting accuracy degrades across multi-day horizons. We benchmark six deep learning architectures, two zero-shot Foundation Models (FM) and statistical baselines on three public datasets encompassing over 800 participants, reporting per-feature metrics for step counts, screen time and sleep duration across 1-8 day horizons. We further conduct a per-feature personalisation study across all six architectures and assess FM transferability across dataset sizes and temporal granularities. Our key findings are: (i) no single architecture dominates, PatchTST leads among trained models while the three runners-up (TCN, MLP, Transformer) show no meaningful performance difference; (ii) the FM TimesFM matches or exceeds trained models zero-shot, especially in low-data regimes and (iii) participant-level fine-tuning reduces per-feature RMSE by 16-60\%, with sleep benefiting most and step counts least. These results provide practical guidance on architecture selection, FM applicability and personalisation strategies for mobile health forecasting. To the best of our knowledge, this is the first study to jointly evaluate modern deep learning, FMs and personalisation for multi-horizon behavioural forecasting from wearables.

06.
arXiv (quant-ph) 2026-06-16

Fully Quantum Algorithm for the 1-dimensional linear Lattice Boltzmann Method

arXiv:2606.16514v1 Announce Type: new Abstract: A fully quantum algorithm for solving the one-dimensional linear advection-diffusion equation using the Lattice Boltzmann method as a numerical procedure is presented in this work. We start by presenting a state of the art of the current usage of quantum algorithms for solving ordinary and partial differential equations. We then describe two algorithms for the one-dimensional Lattice Boltzmann method with two degrees of freedom. The first one is an existing hybrid quantum-classical algorithm with measurements at each time step, and the second one is our improved version, viz. a fully quantum algorithm where only one measurement is needed at the end of the algorithm. The fully quantum algorithm is first executed on a quantum simulator and then compared with a classical approach. Subsequently, the fully quantum algorithm is run on a quantum system with 133 qubits to investigate the effect of noise and the depth of the circuit on the output state. We find fluctuations in the final result due to the decoherence noise of the qubits.

07.
arXiv (CS.LG) 2026-06-19

Computational Methods and Challenges in Cell-Free DNA Analysis for Multi-Cancer Early Detection

arXiv:2606.20174v1 Announce Type: new Abstract: Cell-free DNA (cfDNA) is a promising avenue for non-invasive multicancer early detection (MCED), in that, it can enable multiple cancer detection simultaneously from a single blood draw, with particular sensitivity to cancers that currently lack established screening programs. Here we review the computational methods developed between 2022 and 2025 for cfDNA-based MCED. We focus on how fragmentomics and epigenetic features are extracted and analyzed to detect cancer at early stages. We first briefly outline the biological basis of cfDNA signals, then review classical statistical and machine learning approaches alongside deep learning frameworks including autoencoder-based models. For each method we discuss biological interpretability, validation strategy, and readiness for clinical integration. Furthermore, we categorize the current challenges into technical, computational, and methodological while outlining open problems in the field. This review shows that multimodal ensemble approaches have the strongest promise for clinical integration and the highest readiness. However, for better assessment of future work and side-by-side comparison, standardization of evaluation protocols and reporting results will be crucial.

08.
arXiv (CS.AI) 2026-06-12

A Theory of Training Profit-Optimal LLMs

arXiv:2605.16430v3 Announce Type: replace-cross Abstract: Scaling LLMs requires tremendous computational resources, and recent advances in AI have gone hand in hand with massive amounts of capital expenditure. While it is established that scaling up LLMs reliably increases model quality (quantified in terms of loss or downstream evaluations), it is unclear how these quality improvements translate to potential revenue, and whether revenue increases would offset costs of larger-scale training and inference. In this work, we develop an economic model for characterizing the rational behavior of an LLM training firm by combining scaling laws with microeconomic theory. Under our model of firm behavior, LLM quality can be increased with more parameters and training tokens, leading to more potential adoption by consumers, who each have a quality threshold for using the LLM. On the other hand, additional parameters and training tokens both incur additional costs. We analyze the profit maximization problem for this model under compute-bound and data-bound regimes. In the compute-bound regime, optimal model size and token budget track hardware efficiency $E$ (FLOPs/\$) at a near-linear rate; total training cost then scales sub-quadratically in $E$. Data efficiency improvements incentivize larger models and training expenditure. When we are limited to $D$ data, profit-optimal training expenditure scales as $D^2/E$, i.e, increase with data and decreases with hardware efficiency (as well as data efficiency). Finally, we analyze practical trends in training expenditure: current trends are consistent with our most permissive model variants in the compute-bound regime, but are not profit-optimal in the data-bound regime or assuming hardware advances will stall. Overall, our results provide a theory of profit-optimal LLM training, providing a foundation for engaging critically with industry statements and supporting long-term economic decision making.

09.
arXiv (CS.AI) 2026-06-12

EpiBench: Verifiable Evaluation of AI Agents on Epigenomics Analysis

arXiv:2606.13602v1 Announce Type: new Abstract: We introduce EpiBench, a verifiable benchmark for short-horizon epigenomics analysis. EpiBench evaluates whether agents can make well-defined analysis decisions from realistic workflow states and return deterministically gradable answers. The benchmark includes 106 evaluations across CUT\&Tag/CUT\&RUN, ATAC-seq, ChIP-seq, and DNA methylation workflows. Across 5,088 valid trajectories from 16 model-harness pairs, no system passed a majority of attempts: GPT-5.5 / Pi led at 45.0\% (143/318 attempts; 95\% confidence interval (CI), 36.3–53.7), followed by GPT-5.5 / OpenAI Codex at 39.9\% (127/318 attempts; 95\% CI, 31.6–48.3). Claude Opus 4.8 Max / Pi and GPT-5.4 / Pi each passed 39.0\% (124/318 attempts; 95\% CI, 30.2–47.8 and 31.0–47.0, respectively). Performance varies across assay types, and many failed runs still contain parts of the correct answer. Agents often found the right files and computed useful intermediate results, but failed when the task required deeper, assay-specific scientific judgment.

10.
arXiv (CS.AI) 2026-06-15

ANSR-DT: A Neuro-Symbolic Framework for Adaptive and Explainable Digital Twins

arXiv:2501.08561v4 Announce Type: replace Abstract: Digital twins are increasingly used to monitor and optimize industrial systems, yet many existing frameworks remain difficult to interpret, slow to adapt, and limited in their ability to incorporate explicit domain knowledge. This paper presents ANSR-DT, an adaptive neuro-symbolic framework that unifies temporal anomaly detection, symbolic reasoning, and reinforcement-learning-based decision support within a single digital twin pipeline. ANSR-DT combines a CNN-LSTM model for multivariate pattern recognition with Prolog-based reasoning that converts learned signals into explicit rules, enabling transparent diagnoses and traceable decision paths. A PPO-based adaptation layer further refines operational responses under changing conditions while preserving interpretability. Experiments against 8 baselines show that ANSR-DT delivers competitive predictive performance together with stable rule extraction, scalable symbolic reasoning, and actionable explanations. Additional validation on the Skoltech Anomaly Benchmark (SKAB) further indicates that the framework transfers beyond synthetic settings. These findings position ANSR-DT as a practical foundation for trustworthy, adaptive, and explainable industrial digital twins.

11.
arXiv (CS.AI) 2026-06-15

COGNITION: From Evaluation to Defense against Multimodal LLM CAPTCHA Solvers

arXiv:2512.02318v4 Announce Type: replace-cross Abstract: This paper studies how multimodal large language models (MLLMs) undermine the security guarantees of visual CAPTCHA. We identify the attack surface where an adversary can cheaply automate CAPTCHA solving using off-the-shelf models. We evaluate 7 representative MLLMs on 18 real-world CAPTCHA task types, measuring single-shot accuracy, success under limited retries, end-to-end latency, and per-solve cost. We further validate our findings through a supplemental external dataset and an adaptive-attacker setting with session memory, while also analyzing the impact of task-specific prompt engineering and few-shot demonstrations on solver effectiveness. We reveal that MLLMs can reliably solve recognition-oriented and low-interaction CAPTCHA tasks at human-like cost and latency, whereas tasks requiring fine-grained localization, multi-step spatial reasoning, or cross-frame consistency remain significantly harder for current models. By examining the reasoning traces of such MLLMs, we investigate the underlying mechanisms of why models succeed/fail on specific CAPTCHA puzzles and use these insights to derive defense-oriented guidelines for selecting and strengthening CAPTCHA tasks. To validate these principles, we present a proof-of-concept by hardening a vulnerable CAPTCHA type using our guidelines. We demonstrate that incorporating fine-grained localization and implicit counting reduces the success rate of state-of-the-art MLLMs from over 95\% to 0\%, confirming that structural changes can effectively mitigate the threat. We conclude by emphasizing the urgent need for CAPTCHA redesign as MLLM capabilities increasingly threaten existing defenses. Code Availability (https://doi.org/10.5281/zenodo.20406852).

12.
arXiv (CS.AI) 2026-06-18

Structured Cognitive Loop for Behavioral Intelligence in Large Language Model Agents (Extended Revision: From Behavioral Architecture to Epistemic Accountability)

Authors:

arXiv:2510.05107v5 Announce Type: replace Abstract: The central challenge for AI agents is not only performance but accountability. Agents that act through opaque prompt sequences may produce correct outputs, but they provide little basis for verifying why an action was permitted, where an error occurred, or how responsibility should be assigned. This paper presents the Structured Cognitive Loop as an architecture for accountable behavior in large language model agents. SCL separates cognition, memory, control, and action into distinct modules. The language model proposes. External memory preserves verified state. A lightweight controller checks preconditions, prevents redundant actions, and authorizes execution before tools are used. We evaluate SCL against ReAct and common LangChain agent variants across travel planning, conditional email drafting, and constraint guided image generation. Across 360 episodes, SCL achieves 86.3 percent task success compared with 70.5 to 76.8 percent for prompt based baselines. It also improves goal fidelity, reduces redundant tool calls, increases reuse of intermediate state, and lowers unsupported assertions. This extended revision situates SCL within a broader architecture of epistemic accountability. Subsequent extensions integrate context aware Human in the Loop control, Pool Gated Retrieval, and the Horizon Warrant Commitment framework. Together these components define an agent architecture in which the model proposes, structure decides, evidence is warranted before use, and human judgment is embedded in the trace rather than imposed after the fact. The result is a foundation for AI agents whose decisions are not only effective but also authorized, inspectable, and accountable.

13.
arXiv (CS.CL) 2026-06-17

Scaling Enterprise Agent Routing: Degradation, Diagnosis, and Recovery

Production LLM assistants route user requests to growing libraries of specialized tools, but how does routing accuracy degrade as the catalog scales? We study single-step routing on a 110-agent, 584-tool catalog from a deployed enterprise productivity assistant, evaluating three frontier models from 10 to 110 agents. Routing F1 on under-specified requests drops 16–23 percentage points across models. An oracle analysis decomposes the degradation into a retrieval gap (the model cannot surface the right tool) and a confusion gap (even with perfect retrieval, the oracle ceiling drops 10pp). Embedding-based shortlisting recovers +10–11pp F1 at full scale across all three models and two providers. A production annotation study (1,435 human-labeled utterances, three annotators) confirms the recovery on real traffic at +10–17pp despite 10–15pp lower absolute performance.

14.
arXiv (CS.LG) 2026-06-15

Optimal Hidden-Target Learning for Online Inventory Optimization on General Convex Sets

arXiv:2606.14679v1 Announce Type: new Abstract: Online inventory optimization (OIO) is online convex optimization with physical memory: inventory carryover makes the feasible action set depend on the past. A natural principle, used in stochastic inventory learning and recently in OIO under a single linear capacity constraint, is to maintain a hidden target chosen by an online learner and implement its projection onto the currently feasible order-up-to set. We prove that this simple principle is optimal for OIO on arbitrary bounded convex capacity sets. With online gradient descent as the base learner, the method improves the best known regret guarantee for OIO on general convex sets from inverse to inverse-square-root dependence on the common-demand probability, and we prove a matching lower bound. The same principle gives the first polylogarithmic regret guarantee for strongly convex losses and the first dynamic regret guarantee adapting to Euclidean path variation on general convex capacity sets. The analysis introduces a norm alignment principle: the right state variable is the distance from the hidden target to the feasible set, measured in the same norm as the projection. Under norm alignment, this distance evolves pathwise as a scalar queue, with target movement as arrival and common demand as service. This reduction to one-dimensional queue control resolves the state dependence and extends the guarantees to general convex capacity sets, beyond the reach of prior productwise approaches. Experiments on synthetic and real-world inventory data corroborate the theory.

15.
arXiv (CS.AI) 2026-06-18

Signals of Provenance: Practices & Challenges of Navigating Indicators in AI-Generated Media for Sighted and Blind Individuals

arXiv:2505.16057v2 Announce Type: replace-cross Abstract: AI-Generated (AIG) content has become increasingly widespread by recent advances in generative models and the easy-to-use tools that have significantly lowered the technical barriers for producing highly realistic audio, images, and videos through simple natural language prompts. In response, platforms are adopting provable provenance with platforms recommending AIG to be self-disclosed and signaled to users. However, these indicators may be often missed, especially when they rely solely on visual cues and make them ineffective to users with different sensory abilities. To address the gap, we conducted semi-structured interviews (N=28) with 15 sighted and 13 BLV participants to examine their interaction with AIG content through self-disclosed AI indicators. Our findings reveal diverse mental models and practices, highlighting different strengths and weaknesses of content-based (e.g., title, description) and menu-aided (e.g., AI labels) indicators. While sighted participants leveraged visual and audio cues, BLV participants primarily relied on audio and existing assistive tools, limiting their ability to identify AIG. Across both groups, they frequently overlooked menu-aided indicators deployed by platforms and rather interacted with content-based indicators such as title and comments. We uncovered usability challenges stemming from inconsistent indicator placement, unclear metadata, and cognitive overload. These issues were especially critical for BLV individuals due to the insufficient accessibility of interface elements. We provide practical recommendations and design implications for future AIG indicators across several dimensions.

16.
arXiv (CS.AI) 2026-06-17

Physics-Informed Attention Mechanism and Generalization Capability of Deep Learning-Based Grain Growth Evolution Prediction

arXiv:2606.17235v1 Announce Type: cross Abstract: Machine Learning (ML) models for grain growth prediction are typically trained on idealized synthetic data, yet practical applications require generalization to conditions outside the training distribution. This study evaluated the Out-Of-Distribution (OOD) generalization capability of the trained model from our previous study across three test cases, including experimental microstructures, microstructures characterized by a bimodal grain size distribution, and abnormal grain growth. To further probe whether physics-informed architectural design could improve robustness under these different conditions, a boundary-masked attention mechanism was proposed specifically for grain growth, constraining attention to grain boundary pixels. Both the baseline and the proposed physics-informed attention model were evaluated without retraining or fine-tuning on the OOD data. Both models successfully generalized to all three test cases, yet the boundary-masked attention mechanism provided substantial improvements, with the most notable gains for microstructures characterized by a bimodal grain size distribution, where Structural Similarity Index Measure (SSIM) improved from \num{0.6221} to \num{0.7609} and mean grain size ($\overline{R}$) error decreased from \operatorname{SI}{8.75}{\percent} to \operatorname{SI}{3.57}{\percent}. The attention heatmap analysis revealed that the boundary-masked attention model learned to concentrate attention on large grain boundaries in a manner consistent with curvature-driven grain growth physics, emerging from training without being explicitly encoded into the architecture. These results indicate that models trained on synthetic data can generalize to diverse OOD conditions without retraining, and that physics-informed attention may improve accuracy when the boundary morphology matches the training domain.

17.
arXiv (CS.CL) 2026-06-16

CHILLGuard: Towards Fine-Grained Chinese LLM Safety Guardrail with Scalable Data Construction and Model-aware Preference Alignment

Malicious content generated from large language models (LLMs) could pose severe safety risks and ethical concerns. While existing LLM safety guardrails excel in English or multilingual settings, they lack adaptation to Chinese-specific regulatory policies, cultural context and linguistic nuances, failing to support fine-grained risk classification for diverse deployment needs. In this paper, we introduce a 5-macro, 31-micro category fine-grained risk taxonomy for Chinese scenarios, and build CHILLGuard: a dedicated Chinese LLM content safety guardrail. To address the critical scarcity of high-quality annotated Chinese safety data, we propose a scalable multi-stage data construction pipeline: we expand multi-source corpus via retrieval-augmented generation, generate implicit harmful samples through prompt engineering rewriting, and refine high-quality data via multi-model voting-based label calibration. Based on this, we build CHILLGuardTrain, a large-scale training set with 405,007 samples, and CHILLGuardTest, a rigorously curated annotated test set with 51,745 samples. We then train CHILLGuard on CHILLGuardTrain under a generator-classifier collaborative framework via Model-aware Direct Preference Optimization. Extensive experiments under multiple settings demonstrate the state-of-the-art performance of CHILLGuard, e.g., a 15.92% improvement of F1 score over Qwen3Guard-8B-Strict on our benchmark. We will release our resources at https://github.com/cswbyu/CHILLGuard.

18.
arXiv (CS.LG) 2026-06-18

Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot with Thermodynamics-Driven Machine Learning

arXiv:2604.14906v3 Announce Type: replace-cross Abstract: The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through $-$1 programmed ribosomal frameshifting ($-1$ PRF), a mechanism that allows the virus to generate both structural and non-structural proteins from overlapping reading frames. This pseudoknot exhibits both threaded and unthreaded long-lived topologies. The influence of ligand binding on its folding is a process critical for the development of $-$1 PRF small-molecule inhibitors. Understanding this process through unbiased molecular dynamics (MD) simulations can be facilitated by introducing collective variables (CVs) that capture the corresponding slowest dynamical modes. Here, we use spectral map (SM), a thermodynamics-driven machine learning technique, to learn such CVs directly from all-atom MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the $-$1 PRF inhibitor merafloxacin and its two structural analogs in neutral and ionized forms. Free-energy landscapes (FELs) derived from the learned CVs indicate that ligand-induced destabilization is topology-selective. In the threaded pseudoknot, the inhibitors destabilize the S2 stem, while in the unthreaded pseudoknot, destabilization occurs in the S1 and S3 stems. Furthermore, the extent to which each ligand reshapes the FEL matches experimentally reported antiviral potency, whereas the protonation state qualitatively alters dynamics within the same RNA topology. Overall, our results show how pseudoknot topology, ligand type, and protonation state collectively influence the slow conformational dynamics of viral RNA and establish physiological protonation as a critical factor for modeling RNA-targeted drug action.

19.
arXiv (CS.CL) 2026-06-16

When Do LLMs Reason? A Dynamical Systems View via Entropy Phase Transitions

Chain-of-thought (CoT) reasoning has become the default strategy for enhancing LLM capabilities, yet its application raises a fundamental question: when is explicit reasoning actually beneficial? Empirical evidence reveals a striking paradox: CoT often provides marginal or even negative gains on factual and open-ended tasks while multiplying token consumption. In this work, we show that LLM reasoning is not a static property of tasks or models, but a dynamic decoding state that emerges during generation. Through systematic analysis, we find early-stage entropy dynamics provide a reliable signal of this state: tasks benefiting from CoT exhibit consistent entropy reduction, while others display unstable or increasing patterns. This behavior can be interpreted as a phase-transition-like shift from a high-entropy exploratory regime to a low-entropy structured reasoning regime. Based on these insights, we propose EDRM (Entropy Dynamics-based Reasoning Manifold), a lightweight and training-free routing framework that leverages early decoding entropy to adaptively select inference strategies. EDRM embeds entropy trajectories into a compact and interpretable manifold representation, enabling both zero-shot deployment and fine-grained instance-level adaptation. Across 15 benchmarks and 4 LLMs of varying scales and architectures, EDRM consistently outperforms static baselines. At the dataset level, EDRM achieves 41–55\% token reduction while improving accuracy with as few as 50 calibration samples. At the instance level, it further improves accuracy by up to 4.7\% while maintaining 27–45\% token savings. These results suggest that reasoning should be invoked selectively rather than by default, and demonstrate the effectiveness of entropy-driven decoding control for efficient and adaptive LLM inference.

20.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

21.
medRxiv (Medicine) 2026-06-10

Towards the Virtual Amyotrophic Lateral Sclerosis Patient: Inferring Cortical Excitability through Whole-Brain Dynamical Modeling

Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem neurodegenerative disorder in which motor-neuron degeneration is accompanied by widespread alterations in cortical dynamics. Among its most reproducible neurophysiological signatures is cortical hyperexcitability, yet how this local excitability imbalance shapes distributed whole-brain activity remains poorly understood. Here, we combined source-reconstructed resting-state MEG data, tractography-informed whole-brain modeling, and simulation-based inference to investigate whether ALS-related alterations in large-scale brain dynamics can be mechanistically explained by changes in cortical excitability. First, we characterized empirical brain dynamics using complementary features spanning regional activity amplitude and variability, functional connectivity, and avalanche-based metrics. These analyses revealed significant alterations in ALS patients relative to healthy controls, as well as associations with clinical impairment and disease staging. To mechanistically interpret these changes, we employed a reduced Wong-Wang whole-brain model in which local recurrent excitation modulates emergent large-scale neural dynamics. Simulations showed that increasing excitability systematically reproduced the empirical dynamical signatures observed in ALS. We then applied a simulation-based inference framework to estimate latent excitability parameters directly from empirical observations. Whole-brain model inversion revealed increased excitability in ALS patients compared with controls. The recovered excitability parameter was associated with disease staging, supporting its clinical relevance as a model-derived descriptor of ALS progression. Finally, by extending the model to estimate frontal and non-frontal excitability separately, we found that ALS-related alterations were predominantly associated with increased frontal excitability, whereas non-frontal regions appeared comparatively less affected. The recovered parameters related to disease staging. Together, these findings provide a mechanistic framework linking altered large-scale brain dynamics in ALS to selective cortical hyperexcitability, explaining how local excitability changes can give rise to global network reorganization. More broadly, they show how computational model inversion can recover latent multiscale pathophysiological processes from empirical neural recordings, offering a non-perturbative alternative to complex experimental paradigms typically required to causally probe local-to-global mechanisms.

22.
arXiv (CS.LG) 2026-06-11

How Low Can You Go? Active Learning for Sparse Model Discovery in the Ultra-Low-Data Limit

arXiv:2606.12182v1 Announce Type: new Abstract: Identifying the governing equations of complex dynamical systems remains a fundamental challenge across science and engineering. While early approaches relied on empirical data and heuristics, modern data-driven methods offer greater flexibility and fewer assumptions. However, data acquisition in real-world settings is often expensive. This work addresses this challenge by introducing an active learning strategy for dynamics discovery in the ultra-low data limit. Rather than sampling randomly, our method iteratively prioritizes regions that are most informative for model identification. This approach builds on Sparse Identification of Nonlinear Dynamics (SINDy), and utilizes an ensemble extension, E-SINDy, to estimate epistemic uncertainty and guide the sampling for both ordinary and partial differential equations (ODEs/PDEs). For ODEs, an exhaustive analysis is conducted on the Lorenz system across varying data budgets and noise levels. For PDEs, two systems with contrasting dynamical characteristics are examined: the Burgers' equation, where a sharp shock front creates a distinction between informative and uninformative regions, and the Kuramoto-Sivashinsky equation, which presents a more spatially complex sampling landscape. Across all scenarios, the proposed method accurately identifies the governing dynamics with significantly fewer data samples than random sampling.

23.
PLOS Computational Biology 2026-06-08

Assessing the inference of single-cell phylogenies and population dynamics from CRISPR lineage recordings

by Julia Pilarski, Tanja Stadler, Sophie Seidel Multicellular organisms develop from a single cell by repeated rounds of cell division, differentiation, and death, which can be represented as a single-cell phylogenetic tree. Genetic lineage tracing allows us to investigate this development by tracking the ancestry of individual cells as populations grow and change over time. However, accurate reconstruction of the cell phylogeny and quantification of the corresponding phylodynamic parameters – cell division, differentiation, and death rates – from this tracking data remains challenging and needs to be systematically evaluated. We perform simulations and assess, using the Bayesian framework, the joint inference of time-scaled cell phylogenies and phylodynamic parameters from CRISPR lineage recordings with random or sequential edits. Principally, we characterize the inference improvements as the recorder capacity increases. We observe more accurate phylogenetic reconstruction from sequential compared to random recordings, but no substantial improvement in phylodynamic inference when using the additional information contained in the order of edits. Overall, we find that CRISPR lineage recordings carry a strong signal on the rates of cell division when appropriate models are used. However, we detect biases in the inferred rates of cell division and death under phylodynamic model misspecification, i.e., when fitting classic memoryless birth-death processes to synchronous cell divisions. Moreover, for scenarios when cells differentiate into distinct types, we demonstrate that Bayesian phylodynamic analysis of sparse end-point measurements can resolve these cell differentiation trajectories by lineage and time. Under prototypical dynamics, we recover cell type-specific division and death rates, and cell type transition rates in over 80% of simulations. Overall, this simulation study explores how much information on cellular development can be extracted from state-of-the-art genetic lineage tracing data using phylogenetic and phylodynamic methodology.

24.
arXiv (CS.LG) 2026-06-17

Delta-Based Target Reformulation for Short-Term Electricity Load Forecasting Using LSTM and Transformer Models

Authors:

arXiv:2606.17692v1 Announce Type: new Abstract: Accurate short-term electricity load forecasting is critical for the reliable and economic operation of modern power systems, under non-stationarity arising from weather variability, calendar effects, and evolving consumption patterns. While deep learning models such as LSTMs and Transformers show promising performance, most existing studies focus on direct absolute load prediction without explicitly addressing target non-stationarity. Motivated by classical time-series differencing techniques in ARIMA models, this paper investigates a delta-based target reformulation for short-term electricity load forecasting using deep learning. Instead of directly predicting absolute load values, the proposed formulation trains models to predict the change in load between consecutive time steps, with final forecasts reconstructed using the last observed load. This aims to stabilize the learning target and reduce forecasting difficulty. Using multi-year, hourly real-world electricity load data from India, augmented with meteorological variables from the NASA POWER project and calendar features, this study evaluates LSTM and Transformer models under both formulations, benchmarking them against LightGBM. Experiments are conducted for hour-ahead and day-ahead horizons, assessing performance via Mean Absolute Error (MAE) and Mean Absolute Percentage Error (MAPE). Results show that delta-based reformulation consistently improves forecasting accuracy for hour-ahead prediction across all evaluated models, yielding MAPE reductions of over 50% compared to absolute formulations. For day-ahead forecasting, delta targets specifically benefit deep sequence models (LSTM and Transformer), while LightGBM remains competitive under the absolute formulation. These findings indicate that while delta reformulation is a powerful inductive bias for neural networks, its efficacy is model- and horizon-dependent.

25.
arXiv (CS.AI) 2026-06-16

Beyond Weights and Gradients: A Taxonomy of Federated Learning Messages

arXiv:2606.16891v1 Announce Type: cross Abstract: Federated Learning is rapidly evolving beyond the exchange of traditional model weights and gradients, yet existing definitions fail to capture the full scope of modern payloads like synthetic data and federated analytics. This paper addresses the gap by proposing a formal mathematical definition of a federated message that accounts for both utility and privacy. We introduce a taxonomy that organizes these exchanges into three categories: model structures, statistical summaries, and data-conditioned representations. By evaluating these groups based on computational demands, communication costs, and privacy risks, we provide a clearer understanding of the trade-offs involved in decentralized training. Our review of 202 recent publications highlights a significant shift since 2021 toward diverse messaging paradigms, signaling a move away from standard deep learning updates toward more specialized information sharing. This framework provides a structured path for future research to optimize federated systems for varying hardware and security requirements.