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01.
arXiv (CS.LG) 2026-06-24

Multi-agent imitation learning with function approximation: Linear Markov games and beyond

arXiv:2602.22810v2 Announce Type: replace Abstract: In this work, we present the first theoretical analysis of multi-agent imitation learning (MAIL) in linear Markov games where both the transition dynamics and each agent's reward function are linear in some given features. We demonstrate that by leveraging this structure, it is possible to replace the state-action level "all policy deviation concentrability coefficient" (Freihaut et al., arXiv:2510.09325) with a concentrability coefficient defined at the feature level which can be much smaller than the state-action analog when the features are informative about states' similarity. Furthermore, to circumvent the need for any concentrability coefficient, we turn to the interactive setting. We provide the first, computationally efficient, interactive MAIL algorithm for linear Markov games and show that its sample complexity depends only on the dimension of the feature map $d$. Building on these theoretical findings, we propose a deep MAIL interactive algorithm which clearly outperforms BC on games such as Tic-Tac-Toe and Connect4.

02.
arXiv (CS.AI) 2026-06-16

EMS: Multi-Agent Voting via Efficient Majority-then-Stopping

arXiv:2604.02863v2 Announce Type: replace Abstract: Majority voting is the standard for aggregating multi-agent responses into a final decision. However, traditional methods typically require all agents to complete their reasoning before aggregation begins, leading to significant computational overhead, as many responses become redundant once a majority consensus is achieved. In this work, we formulate efficient multi-agent voting as a reliability-aware agent scheduling problem and propose Efficient Majority-then-Stopping (EMS) to improve reasoning efficiency. EMS first estimates a Task-Conditioned Reliability Ordering (TCRO) for each agent by retrieving its historical consensus evidence on semantically similar queries, and then invoking agents in descending reliability order. Next, Adaptive Incremental Voting (AIV) terminates the process once the current leading answer cannot be overturned by any possible votes from the remaining agents, and returns this answer. Finally, Reliability History Updating (RHU) updates only the invoked agents according to their consensus with the final decision. Extensive evaluations across five benchmarks show that EMS preserves the accuracy of Majority Voting while reducing the average number of invoked agents by 35% and token consumption by 44%, respectively. The code is available at https://github.com/fuyu66/EMS.

03.
Nature (Science) 2026-06-15

Daily briefing: Iron-Age human bones were made into tools before interment

Authors:

Newly uncovered bones hint at how Iron Age Britons treated their dead. Plus, AI models have failed to beat human mathematicians at research-level problems and the everyday items that make great scientific tools. Newly uncovered bones hint at how Iron Age Britons treated their dead. Plus, AI models have failed to beat human mathematicians at research-level problems and the everyday items that make great scientific tools.

04.
arXiv (CS.LG) 2026-06-17

BioArtlas: Computational Clustering of Multi-Dimensional Complexity in Bioart

Authors:

arXiv:2511.19162v3 Announce Type: replace-cross Abstract: Bioart brings living material into artistic practice, where a single work can be at once an aesthetic object, a scientific instrument, and an ethical provocation. Traditional categories sort such works along one axis at a time, which flattens the very hybridity that defines the field and leaves curators no way to compare works across many dimensions together. I introduce BioArtlas, a computational atlas that represents each bioartwork along many curated dimensions at once and organizes the field by conceptual similarity rather than by medium or chronology. My method embeds the keywords of all 81 works on each of thirteen interpretive axes, groups related concepts into a shared codebook that tames inconsistent terminology, and then searches systematically for a clustering that is both statistically clean and interpretable. Among the methods that place every work on the map, agglomerative clustering separates the field far more cleanly than the usual k-means baseline (silhouette 0.664 versus 0.483), whereas density-based methods reach higher scores only by discarding most of the corpus as noise. By separating rigorous analysis from public storytelling, BioArtlas turns the tangled complexity of bioart into a navigable landscape, openly available as an interactive interface (https://www.bioartlas.com) and dataset (https://github.com/joonhyungbae/BioArtlas).

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

The Linguistics Olympiads: Towards a New Corpus for Linguistics Research?

Linguistics olympiad problems (LOPs) are a category of self-sufficient puzzles consisting of a scaled-down corpus representative of certain linguistic phenomena, from which the solver must deduce a primitive set of rules of the language and then translate a new set of elements. The linguistics olympiads (LOs) have become a worldwide phenomenon with 43 different territories taking part in the International Linguistics Olympiad (IOL) 2025. While the typology and solving strategies of LOPs have been analysed, their scientific facet and connections to academic linguistics have yet to be explored. LOPs are directly connected to many linguistic fields, e.g., linguistic typology, linguistic relativity, and linguistics fieldwork. Recently, LOPs have become a research focus as benchmarks for large language models, thus highlighting their usefulness in computational linguistics. Nevertheless, they have not yet been integrated into mainstream linguistics research. This paper attempts to open new directions of including this particular type of puzzle in academic research by offering a structured evaluation of LOPs as linguistic data sources and proposes criteria for their responsible use in academic research. Starting from a set of over 1800 LOPs, this study critically examines the potential of LOPs as a novel corpus for linguistics research by discussing their strengths and limitations as tools, as well as the areas of linguistics into which these problems could fit. This work forms the foundation for a broader initiative aimed at bridging the gap between LOs and academic linguistics, by establishing a robust theoretical framework for LOPs.

06.
arXiv (CS.CV) 2026-06-24

SER: Learning to Ground Video Reasoning with Semantic Evidence Rewards

Video MLLMs often struggle with fine-grained spatio-temporal reasoning, sometimes generating correct answers based on irrelevant frames or objects. Although outputting spatio-temporal evidence during reasoning is a promising direction, existing RL frameworks typically rely on geometry-only (IoU) rewards, which can be sensitive to boundary perturbations and overlook semantic alignment. To address this, we propose Semantic Evidence Reward (SER), which reformulates spatio-temporal evidence grounding as a constrained verification task. Instead of computing pixel-level overlap, SER uses a referee VLM as a local checker to evaluate model-generated evidence claims across two dimensions: relevance and localization quality, combined with a temporal penalty. This design reduces the reliance on dense box annotations and enables training directly on standard video QA data. On the V-STAR benchmark, SER achieves 49.6% mLGM, improving by 3.0 points over the strong evidence-grounded baseline Open-o3-Video, demonstrating its potential in enhancing both answer accuracy and evidence grounding.

07.
arXiv (CS.CL) 2026-06-24

Bilevel Data Curation for LLM Fine-tuning: Offline Selection and Online Self-Refining Generation

Supervised fine-tuning (SFT) datasets are critical to the downstream performance of large language models, yet they often contain low-quality or harmful question-response pairs. To improve SFT data quality, we develop a unified bilevel framework that combines offline data selection with the online self-refining generation. In the offline setting, bilevel data selection (BDS) selects question-response pairs from the offline SFT dataset to maximize the validation performance. We theoretically show that the optimal model given by BDS outperforms direct data mixing approach in useful data coverage. Moreover, we provide a global convergence analysis for gradient-based BDS approach for one-layer Transformer, showing that the epsilon-global optimum of offline BDS is achievable in finite time. Although efficient, offline BDS discards potentially harmful questions together with responses, thereby reducing question diversity. We address this limitation by refining the responses to selected questions using online self-refining generation framework. However, BDS is inefficient to update the response weights when responses are regenerated online. To address this issue, we introduce bilevel multi-objective optimization (BMO) for response-level weighting. We show that BMO recovers the same validation-aligned solution as BDS, but admits a closed-form importance-ratio weight that adapts to regenerated responses. Experiments on LLM quality enhancement and safety-aware fine-tuning demonstrate that the proposed framework consistently improves both data quality and downstream fine-tuning performance.

08.
arXiv (CS.CL) 2026-06-15

CacheRL:Multi-Turn Tool-Calling Agents via Cached Rollouts and Hybrid Reward

We present CacheRL, a system for training small agent foundation models that achieves 92 percent process accuracy on multi-step tool-calling tasks, approaching GPT-5's 94 percent while requiring 100 times less compute. Our approach addresses three challenges in practical agent training: transferring tool-calling knowledge from large models at scale, enabling reinforcement learning without costly live tool execution, and learning robustly from noisy cached environments. CacheRL introduces three key innovations. First, a hybrid thinking trajectory pipeline augments agent trajectories with LLM-generated reasoning traces, producing training examples that teach models not only what tools to call but also why. Second, the CacheAgentLoop eliminates live execution costs through a three-tier fuzzy cache while preserving trajectory fidelity using token-level masking. Third, a cache-tier-aware reward dynamically adjusts answer-quality weights to avoid penalizing models for cache-induced limitations. Through iterative supervised fine-tuning (SFT) and Group Relative Policy Optimization (GRPO), CacheRL improves Qwen3-4B-Thinking's validation reward from 0.43 to 0.78. On public agentic tool-calling benchmarks, our model achieves competitive performance against frontier models such as GPT-5. Ablation studies show that removing knowledge transfer reduces performance by 41 percent, while cache-aware rewards contribute a 17 percent improvement. Interestingly, reinforcement learning improves training stability but yields limited gains beyond strong supervised fine-tuning, suggesting that data quality and reward design play a more important role than complex optimization methods in building practical small agent models.

09.
arXiv (CS.CL) 2026-06-16

Bridging Passive and Active: Enhancing Conversation Starter Recommendation via Active Expression Modeling

Large Language Model (LLM)-driven conversational search is shifting information retrieval from reactive keyword matching to proactive, open-ended dialogues. In this context, Conversation Starters are widely deployed to provide personalized query recommendations that help users initiate dialogues. Conventionally, recommending these starters relies on a closed "exposure-click" loop. Yet, this feedback loop mechanism traps the system in an echo chamber where, compounded by data sparsity, it fails to capture the dynamic nature of conversational search intents shaped by the open world. As a result, the system skews towards popular but generic suggestions. In this work, we uncover an untapped paradigm shift to shatter this harmful feedback loop: harnessing user "free will" through active user expressions. Unlike traditional recommendations, conversational search empowers users to bypass menus entirely through manually typed queries. The open-world intents in active queries hold the key to breaking this loop. However, incorporating them is non-trivial: (1) there exists an inherent distribution shift between active queries and formulated starters. (2) Furthermore, the "non-ID-able" nature of open text renders traditional item-based popularity statistics ineffective for large-scale industrial streaming training. To this end, we propose Passive-Active Bridge (PA-Bridge), a novel framework that employs an adversarial distribution aligner to bridge the distributional gap between passively recommended starters and active expressions. Moreover, we introduce a semantic discretizer to enable the deployment of popularity debiasing algorithms. Online A/B tests on our platform, demonstrate that PA-Bridge significantly boosts the Feature Penetration Rate by 0.54% and User Active Days by 0.04%.

10.
arXiv (CS.LG) 2026-06-12

EPM-JEPA: Operator-Side Experience Modulation in JEPA-Family World Models

Authors:

arXiv:2606.12979v1 Announce Type: new Abstract: JEPA-family world models use a static predictor whose weights do not adapt when test-time dynamics diverge from training. We compare two mechanisms for incorporating accumulated experience into a JEPA predictor under distribution shift: operand-side injection, where a compressed experience representation is added as a residual to the predictor's hidden state (EI-JEPA), and operator-side modulation, where the same representation generates low-rank weight deltas via LoRA applied to the predictor's weights (EPM-JEPA). On a pre-registered comparison (Moving MNIST, gravity shift), EPM-JEPA (D_shift^{n=50} = 0.7848 +/- 0.0078, three seeds) differs from EI-JEPA (0.8238) by delta = 4.74% - Outcome C: a null result - by our stated criterion, a valid outcome. As a secondary, non-pre-registered observation, EPM-JEPA improves 1.90% over a no-memory baseline (0.8000), consistently across seeds, while EI-JEPA underperforms the baseline, indicating the benefit is specific to weight-level modulation. Our primary contribution is a mechanism analysis: the D_shift^{n=50} trajectory reflects three independent dynamical processes - buffer cycling, EMA target drift, and an intrinsic LoRA settling transient of +0.021 - rather than convergence to equilibrium. These findings motivate PEM-JEPA, a physics-grounded successor addressing this dynamical-peak limitation.

11.
arXiv (CS.CL) 2026-06-17

Correct When Paired, Wrong When Split: Decoupling and Editing Modality-Specific Neurons in MLLMs

Although Knowledge Editing provides an efficient mechanism for updating the knowledge of Multimodal Large Language Models (MLLMs), we find that current paradigms still suffer from an important yet remain underexplored issue : editing decoupling failure, where entity-related knowledge can be updated when the model is triggered by multimodal inputs (text–image query pairs), however, it often reverts to outdated pre-edit facts when the paired inputs are split into unimodal ones. Our in-depth empirical analysis reveals that the entity knowledge in MLLMs is not stored as a unified representation, but is instead distributed across disentangled modality-specific pathways. As a result, updates biased toward multimodal queries fail to propagate effectively to unimodal circuits. To bridge this gap, we propose DECODE, which explicitly disentangles and localizes modality-specific neuron groups for targeted knowledge. Extensive experiments demonstrate that DECODE consistently achieves effective knowledge updates under different modality triggers, thereby mitigating editing decoupling failures.

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

From Uncertain Judgments to Calibrated Rankings: Conformal Elo Estimation for LLM Evaluation

arXiv:2606.13221v1 Announce Type: new Abstract: Evaluating new large language models typically requires costly human annotation campaigns at scale. LLM-as-a-judge offers a cheaper alternative, but judge scores carry systematic errors - such as position bias, self-preference, or intransitivity - that can strongly miscalibrate the resulting rankings. We quantify the resulting judge-human disagreement at two complementary levels. At the local level, we estimate per-battle uncertainty from the judge's own score differences by propagating calibrated win probabilities rather than hard labels into the Bradley-Terry procedure. This alone provides a drastic improvement to Elo estimation accuracy, bringing LLM-derived ratings within 17.9 Elo MAE of human-derived ones when averaged over 55 held-out models on LMArena. At the global level, we apply split conformal prediction to the residual gap between LLM-derived and human-derived Elo ratings across held-out models, producing prediction intervals with distribution-free marginal coverage guarantees that account for irreducible LLM-human disagreement. Together, these two layers yield a low-cost evaluation tool that provides developers with calibrated Elo estimates and honest uncertainty bounds, without access to large-scale human annotations.To facilitate reproducibility, we release our code at https://github.com/kargibora/SoftElo .

13.
arXiv (CS.LG) 2026-06-16

Decoupling Inference from State Updates in Low-Latency Feature Engines via Probabilistic Thinning

arXiv:2606.16981v1 Announce Type: cross Abstract: Streaming data systems increasingly underpin Machine Learning workflows that maintain large numbers of continuously updated aggregations. In production settings, each incoming event typically triggers read-modify-write operations to persistent storage, making high-frequency state updates a dominant source of latency, contention, and operational cost. In this work, we decouple inference from state persistence in streaming Machine Learning pipelines via probabilistic thinning: every event is scored, but durable state updates are selectively triggered by informative events. Unlike approaches that shed input or state, we show that persistence-path control is achievable without a high-frequency in-memory control plane or cross-worker coordination, relying exclusively on approximate statistics retrieved from disk-backed key-value stores. We model the resulting stochastic processes, derive bounds on filtering rates, and prove that common time-based aggregations remain unbiased under variance-aware formulations, preventing systemic error accumulation. We evaluate the approach in a controlled setting that isolates per-event costs, demonstrating substantial reductions in storage Input/Output and serialization overhead. Across experiments, up to 90% of events are excluded from the persistence path while preserving and in some cases improving downstream utility.

14.
arXiv (CS.AI) 2026-06-12

A Three-Layer Framework for AI in Scientific Discovery

Authors:

arXiv:2606.13566v1 Announce Type: new Abstract: Current discussions of AI in scientific discovery are often dominated by two visible capabilities: search over existing knowledge and execution through optimization, simulation, and automation. Both are important, but neither fully captures the central act of discovery: the formation and evolution of models. This paper proposes a three-layer view of AI in discovery. Layer 1 is search and retrieval by large language models. Layer 2, as the main innovation of this paper, is model formation through qualitative reasoning: the capacity to recognize when a current framework is structurally inadequate and to understand the problem within a broader representational space, not through trial and error, but through structural insight into what is missing and where it can be found. Layer 3 is execution, optimization, and refinement. The main claim is that Layer 2 is both the most important and the least developed. Search without model formation remains confined to inherited frameworks, while execution without conceptual revision only amplifies an existing formulation. We illustrate Layer 2 reasoning through three case studies: S. S. Chern's intrinsic proof of the Gauss-Bonnet theorem, the resolution of the Nesterov Accelerated Gradient convergence problem via Lyapunov functions, and the autonomous disproof of the Erdos unit distance conjecture by OpenAI in 2026. Each case exhibits the same structural signature: a framework that had become inadequate, a missing conceptual object, and a resolution found in an unexpected neighboring field.

15.
arXiv (CS.AI) 2026-06-16

MADAR: An Address-Free Processor

arXiv:2606.15535v1 Announce Type: cross Abstract: In a modern processor, computing is the cheap part. Most of its area and energy go to addressing – moving operands to and from a register file and cache, and running the tags, ports, miss queues, and bypass networks that find a value where it was left. MADAR deletes that machinery by abolishing the address. All state circulates in rings of slots that advance one position per clock; instructions and data ride in the same slots; a value is named by its place in an orbit – a \rp{} coordinate – not by an address; a fixed station computes when a circulating instruction sweeps past its operands, on a schedule set at compile time; and a hierarchy of rings of increasing period replaces the cache hierarchy, movement between them scheduled rather than triggered by a miss. No prior circulating-store, dataflow, or statically scheduled machine combines all four of these. We define the execution model, validate it in a cycle-accurate register-transfer-level implementation, show it compilable – a constructive scheduler emits programs cross-checked against the implementation – and price it with a first-order energy model. The payoff is clearest for AI acceleration: the multiply-accumulate at the heart of every matmul and convolution compiles to a streaming form whose energy per operation stays flat as the reduction grows, and the operand reuse that makes matrix multiplication efficient is carried by the ring-period hierarchy – the memory hierarchy doing by rotation what a cache does by tags. MADAR is a new design point for any computation whose data movement is known before the program runs.

16.
bioRxiv (Bioinfo) 2026-06-12

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.

17.
medRxiv (Medicine) 2026-06-18

Age as a moderator of a brief alcohol intervention among injury patients in Northern Tanzania

Background: Alcohol use is a leading modifiable risk factor for injury in sub-Saharan Africa. In Tanzania, young people ([≤]24 years) experience greater alcohol-related harm despite drinking less frequently than adults. Punguza Pombe kwa Afya Yako (PPKAY) is a culturally adapted, brief intervention for injury patients in Tanzania. This study examined whether age moderates its effectiveness. Methods: We conducted an exploratory secondary analysis of baseline and 3-month data from the PPKAY randomized trial among injury patients aged [≥]18 years at Kilimanjaro Christian Medical Centre, Tanzania. Eligible participants reporting alcohol use before injury, AUDIT [≥]8, or positive breathalyzer were randomized to usual care or PPKAY with SMS boosters. The primary outcome was binge drinking days. Count outcomes were analyzed using negative binomial regression with robust SEs and continuous outcomes using mixed-effects models. Effect modification was assessed using a three-way interaction (Time x intervention x Age). Results: Among 543 participants (mean age 36.8 years; 16.2% aged 18–24), age moderated the intervention effect for drinking days (IRR = 0.27, 95% CI 0.07 – 0.98; p = 0.046) and drinks consumed (IRR = 0.17, 95% CI 0.04 – 0.77; p = 0.021). The intervention reduced 4 drinking days (95% CI -7.1 to -0.8) and 27.5 drinks (95% CI -42.8 to -12.2) among young people, while adults showed reductions in both arms, without intervention-specific effect. Conclusion: The effects of ED-based brief alcohol interventions are not uniform, varying across both age groups and alcohol-related outcomes. We found a greater responsiveness in drinking frequency and quantity reported among young people.

18.
arXiv (CS.AI) 2026-06-17

TRACE: Learning to Compute on Circuit Graphs

arXiv:2509.21886v3 Announce Type: replace Abstract: Learning to compute, the ability to model the functional behavior of a circuit graph, is a fundamental challenge for graph representation learning. Yet, the dominant paradigm is architecturally mismatched for this task. This flawed assumption, central to mainstream message passing neural networks (MPNNs) and their conventional Transformer-based counterparts, prevents models from capturing the position-aware, hierarchical nature of computation. To resolve this, we introduce TRACE, a new paradigm built on an architecturally sound backbone and a principled learning objective. First, TRACE employs a Hierarchical Transformer that mirrors the step-by-step flow of computation, providing a faithful architectural backbone that replaces the flawed permutation-invariant aggregation. Second, we introduce function shift learning, a novel objective that decouples the learning problem. Instead of predicting the complex global function directly, our model is trained to predict only the function shift, the discrepancy between the true global function and a simple local approximation that assumes input independence. We validate this paradigm on various circuits modalities, including Register Transfer Level graphs, And-Inverter Graphs and post-mapping netlists. Across a comprehensive suite of benchmarks, TRACE substantially outperforms all prior architectures. These results demonstrate that our architecturally-aligned backbone and decoupled learning objective form a more robust paradigm for the fundamental challenge of learning the functional behavior of a circuit graph.

19.
arXiv (math.PR) 2026-06-16

Layerwise Terminal Discrepancy in Chen's Reverse-Heat Coupling on the Boolean Cube

arXiv:2606.04573v2 Announce Type: replace-cross Abstract: Recently, Chen [Chen2026] proved that Talagrand's Boolean convolution conjecture holds up to the dimension-free factor \((\log\log\eta)^{3/2}\), namely for every fixed \(\tau>0\), \[ \mu\{P_\tau f>\eta\|f\|_1\} \le C_\tau \frac{(\log\log\eta)^{3/2}}{\eta\sqrt{\log\eta}}, \qquad \eta>e^3. \] We revisit the terminal testing-discrepancy step in Chen's perturbed reverse-heat coupling. Chen estimates this discrepancy globally in terms of the remaining gap to the terminal level. We keep the same coupling and the same reverse-heat formulations, but localize the terminal discrepancy on each remaining-gap layer before summing the layers. This changes the fixed-time anti-concentration cost from order \((\log L)^{3/2}/\sqrt L\) to order \((\log L)/\sqrt L\), where \(L=\log\eta\). Consequently, we obtain a \((\log\log\eta)^{1/2}\) improvement as \[ \mu\{P_\tau f>\eta\|f\|_1\} \le C_\tau \frac{\log\log\eta}{\eta\sqrt{\log\eta}}, \qquad \eta>e^3. \]

20.
bioRxiv (Bioinfo) 2026-06-20

MIRATS framework: Normative multiscale characterization of brain regulatory systems across sex and age using multimodal MRI

Authors:

Deep brain systems involved in arousal, autonomic regulation, sensory integration, and homeostatic control remain underrepresented in conventional whole-brain neuroimaging frameworks. In particular, diencephalic and brainstem nuclei are often insufficiently represented in cortex-centered analyses, limiting the normative references needed to interpret systems-level variation in health and disease. To address this gap, we developed a unified multiscale framework with explicit representation of deep nuclei. By integrating cerebral, cerebellar, diencephalic, and brainstem atlases in standard space, we constructed a 220-region whole-brain parcellation and extracted complementary features at three analytical scales: nodal properties, edge-wise connectivity, and persistent-homology-based topological descriptors. We applied this framework to healthy adults from the Human Connectome Project-Aging cohort to characterize normative multiscale organization and test sex- and age-related variation. Applied to this cohort, our framework revealed pronounced heterogeneity across anatomical systems. Brainstem and diencephalic nuclei showed multiscale feature profiles distinct from those of cerebral and cerebellar regions across nodal, edge-wise, and higher-order topological scales. Sex comparisons identified selective differences across different scales, whereas age modeling revealed widespread but feature- and system-dependent variation across adulthood. Together, these findings show that normative whole-brain organization in this deep-system-aware space is structured by system-specific rather than globally uniform patterns. These findings establish a normative multiscale framework for characterizing brainstem-diencephalic-cerebellar-cerebral organization in healthy adults and provide a quantitative reference for future translational studies of disease-related abnormalities in deep regulatory systems.

21.
arXiv (CS.LG) 2026-06-16

The limits of interpretability in multiple linear regression

arXiv:2606.16013v1 Announce Type: cross Abstract: Interpreting machine-learning models has attracted increasing attention, particularly in the physical sciences, where one often seeks to understand the underlying mechanisms rather than merely make predictions. Multiple linear regression is often regarded as an interpretable alternative to more complex models, such as deep neural networks, because its predictions are expressed as explicit weighted sums of input features. However, when input features are strongly correlated, namely in the presence of multicollinearity, the learned weights can exhibit large dataset-to-dataset fluctuations and oscillatory behavior across physically similar features, making their interpretation difficult or even impossible. Although the instability of the weights under multicollinearity is well known in statistics, its consequences for physical interpretation, in particular its connection to oscillatory weights across physically similar features, have not been systematically clarified. Here, we theoretically discuss the mechanism behind this loss of interpretability by analyzing the eigenmodes of the feature correlation matrix. We show that small-eigenvalue modes associated with multicollinearity amplify fluctuations in the weights and generate oscillatory patterns that do not necessarily reflect meaningful contributions. We test this theoretical picture numerically on physics datasets and show that Ridge regularization suppresses these unstable modes, although the resulting weights must still be interpreted with caution. We further confirm the generality of our findings beyond physics by analyzing a diverse collection of publicly available datasets. Our results clarify why, in the presence of multicollinearity, physical interpretation can remain difficult even for linear regression models.

22.
bioRxiv (Bioinfo) 2026-06-11

EditorForge: An Active-Site-Aware Framework for Inverse-Folding-Based Protein Redesign

Inverse-folding models can rapidly generate protein sequences compatible with a supplied backbone, but unconstrained redesign is poorly suited to enzyme and genome-editor-associated domains, where catalytic, substrate-proximal, and conserved structural regions must remain protected. In this paper, we present EditorForge, a modular constraint-and-audit suite for editor-domain protein redesign that wraps fixed-backbone inverse folding with explicit design masks, fixed-position enforcement, active-site-proximity auditing, active-site-shielded regeneration, and downstream structural quality control. Using full-length Moloney murine leukemia virus reverse transcriptase structure 4MH8 (MMLV RT 4MH8) as a demonstration target, EditorForge first restricted redesign to a bounded 25-position envelope while fixing 428 residues. An initial audit detected active-site-proximal failure modes despite fixed-position integrity. Later, the Active Site Shield module then removed five unsafe design positions, replaced them with lower-contact alternatives, and regenerated candidates under stricter constraints. Post Shield Audit evaluated 24 regenerated candidates, all of which satisfied the hard sequence/mask and active-site-shield constraints. For the eight candidates that were selected or returned for structure-prediction/refolding quality control. Enhanced RefoldQC found that all 8 evaluated predicted structures passed the computational structure-QC screen. That said, the selected 8 candidates passed the computational structure-QC screen, with global C RMSD values of 1.2061–1.5555~[A], active-site C RMSD values of 0.4098–1.8397~[A], mutation-neighborhood C RMSD values of 1.3155-1.6848~[A], and average pLDDT-like confidence values of 94.87-95.11. In short, EditorForge provides a reproducible triage layer that converts general inverse-folding output into constrained and editor-specific candidate sets for downstream structural and biological review on top of existing structural prediction tools.

24.
arXiv (CS.AI) 2026-06-24

Neural Network-Based Parametric Model Reduction for Predicting Turbulent Flow for Different Vehicle Geometries

arXiv:2606.24265v1 Announce Type: cross Abstract: Numerical simulations in industrial applications often require performing numerous high-precision computations parameterized by specific experimental conditions. For instance, in vehicle body design, aerodynamic simulations are essential for evaluating the aerodynamic characteristics of various proposed body geometries. However, computational resource constraints often become a bottleneck. Therefore, achieving the desired accuracy while minimizing computational cost is crucial. To address this challenge, model reduction methods have been developed to decrease the degrees of freedom by constraining the possible states of a physical system to a lower-dimensional subspace. In particular, reduction techniques that project the system onto a nonlinear subspace using neural networks have been actively studied. Our previous research developed a reduced-order model that integrates neural-network-based model reduction with a time-evolution method, implemented as a distributed parallel training framework to process high-resolution flow field data efficiently. In this study, we extend this reduction approach by incorporating a variational autoencoder to assess its robustness in high-Reynolds-number flows around multiple vehicle bodies with varying geometries. Specifically, we evaluate the reconstruction accuracy of vortex generation across different spatial and temporal scales using a compact latent representation, with a particular focus on the flow behavior near the rear end of the vehicle body.

25.
medRxiv (Medicine) 2026-06-22

COVID-19 containment policies and hyperglycemia in pregnancy: correlation with the Stringency Index in a nationwide Belgian cohort

Background During the COVID-19 pandemic, gestational diabetes (GD) prevalence showed variable changes across regions, with most reporting increases and others decreases; however, its association with perinatal outcomes in Belgium remains unknown. We aimed to compare the prevalence of hyperglycemia in pregnancy (HIP) in 2020 versus 2019 and examined the correlation between HIP prevalence and pandemic-related restrictions measured by the Stringency Index (SI) and evaluate neonatal weight percentiles changes. Methods: We included all singleton live births in Belgium in 2019 and 2020 from Belgian birth registry data. We compared monthly proportions of HIP prevalence and Small for gestational age (SGA) and Large for gestional age (LGA) newborns in 2019 and 2020. Crude and adjusted odds ratios (ORs, aORs) were estimated with logistic and multinomial regression. The Spearman correlation coefficient was used to assess the correlation between the monthly average SI and the monthly aORs of HIP. Results: For deliveries from January to June 2020, no significant differences in HIP prevalence were observed compared with 2019. From July to December 2020, there was a significant increase in HIP, with peaks in July (GD screening in April) (aOR 1.41, 1.26-1.58) and November (GD screening in August) (aOR 1.33, 95% CI 1.18-1.49). There was no significant change in neonatal weight percentiles. The Spearman correlation coefficient between the SI and HIP aORs was 0.86 (p = 0.02). Conclusion During the pandemic, we observed an increase in the prevalence of HIP, compared to 2019, without a measurable impact on LGA or SGA newborns. The aOR of HIP in a given month was strongly correlated with the corresponding SI.