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01.
arXiv (CS.CL) 2026-06-16

Modeling Sarcastic Speech: Semantic and Prosodic Cues in a Speech Synthesis Framework

Sarcasm is a pragmatic phenomenon in which speakers convey meanings that diverge from literal content, relying on an interaction between semantics and prosodic expression. However, how these cues jointly contribute to the recognition of sarcasm remains poorly understood. We propose a computational framework that models sarcasm as the integration of semantic interpretation and prosodic realization. Semantic cues are derived from an LLaMA 3 model fine-tuned to capture discourse-level markers of sarcastic intent, while prosodic cues are extracted through semantically aligned utterances drawn from a database of sarcastic speech, providing prosodic exemplars of sarcastic delivery. Using a speech synthesis testbed, perceptual evaluations show that semantic and prosodic cues enhance perceived sarcasm, with the combined system achieving the best downstream F1 while maintaining high subjective sarcasm ratings. These findings highlight the complementary roles of semantics and prosody in pragmatic interpretation and illustrate how modeling can shed light on the mechanisms underlying sarcastic communication.

02.
Nature Biotechnology 2026-06-05

Structural motif search across the protein universe with Folddisco

作者:

Detecting similar protein structural motifs in large structure collections is computationally expensive. We developed Folddisco, a fast structural motif search tool that uses an index of position-independent geometric features, including side-chain orientation, combined with a rarity-based scoring system. Folddisco is 20-fold faster in querying and fourfold more storage-efficient than existing methods while improving accuracy. Folddisco is freely available online ( https://folddisco.foldseek.com ), along with a webserver ( https://search.foldseek.com/folddisco ). Folddisco enables protein structural motif search in million scale databases.

03.
arXiv (CS.LG) 2026-06-16

Conditional Score-Based Modeling of Effective Langevin Dynamics

arXiv:2604.23952v2 Announce Type: replace-cross Abstract: Stochastic reduced-order models are widely used to represent the effective dynamics of complex systems, but estimating their drift and diffusion coefficients from data remains challenging. Standard approaches often rely on short-time trajectory increments, state-space partitioning, or repeated simulation of candidate models, which become unreliable or computationally expensive for high-dimensional systems, coarse temporal sampling, or unevenly sampled data. We introduce a data-driven calibration method based on a novel relationship between the coefficients of a stochastic reduced model and the conditional score of the finite-time transition density, defined as the gradient of the logarithm of the transition density with respect to the initial state. The resulting identity expresses derivatives of lagged correlation functions as stationary expectations over observed lagged pairs involving this conditional score and the unknown model coefficients. This formulation allows the drift and diffusion structure to be constrained directly from finite-lag statistics, without differentiating trajectories, partitioning state space, or repeatedly integrating candidate reduced models during calibration, yielding a least-squares fitting problem over stationary lagged pairs. We validate the approach on three systems of increasing complexity: an analytically tractable Cox–Ingersoll–Ross diffusion, a two-dimensional nonequilibrium diffusion with affine multiplicative noise, and a periodic soft-spin stochastic Landau–Lifshitz chain. Across these tests, the inferred models preserve the invariant statistics while reproducing finite-lag dynamical correlations. The framework provides a scalable route for learning stochastic reduced-order models from data that reproduce prescribed statistical and dynamical properties.

04.
bioRxiv (Bioinfo) 2026-06-19

Morpho-FM: spatial molecular reconstruction from routine H&E histology using transcriptomic foundation-model priors

Routine haematoxylin and eosin (H&E) histology captures tissue architecture at clinical scale, but lacks a direct molecular readout of the transcriptional programmes that organise tumour epithelium, stroma, vasculature and immune compartments. Spatial transcriptomics provides this context, yet cost, workflow complexity and sparse sampling limit routine use. Most existing histology-to-expression models are trained de novo on small paired cohorts and therefore remain weakly constrained when extrapolating from sparse measurements to dense, tissue-wide molecular maps. Here we introduce Morpho-FM, a weakly supervised framework that predicts spatial gene expression from routine H&E whole-slide images by conditioning a pretrained single-cell transcriptomic foundation-model prior on local histological neighbourhoods. A lightweight morphology-to-transcriptome adapter maps cached whole-slide histology features into a transcriptomic decoder, enabling prediction at measured locations, dense full-section reconstruction, and re-aggregation to the original measurement support. Across harmonized prostate cancer benchmarks, Morpho-FM achieved the strongest overall performance among five representative methods, reaching mean per-gene Pearson correlations of 0.286 in rotating single-slide evaluation and 0.298 in multi-slide held-out validation. The framework reproduced this advantage across kidney cancer sections, achieved a mean correlation of 0.210 across 56 directed single-slide evaluations and retained measurable predictive signal after external transfer to clear-cell renal cell carcinoma sections. Controlled ablation analyses identified pretrained transcriptomic initialization as a reproducible source of performance gain exceeding that attributable to changes in the histology feature backbone. Beyond predictive accuracy benchmarks, Morpho-FM recovered ERBB2-enriched tumour compartments, boundary-associated molecular gradients, and annotation-aligned tissue domains across Xenium and HER2ST breast cancer datasets. Together, these results support transcriptomic foundation-model priors as an effective constraint for morphology-conditioned molecular decoding and demonstrate the potential of Morpho-FM to extend spatial transcriptomic insight across routine pathology sections.

05.
arXiv (math.PR) 2026-06-11

Improved Amenability Bounds for Local Coordination Games

arXiv:2606.01963v2 Announce Type: replace-cross Abstract: We study local pure coordination games on finite social networks, continuing the framework of Hutchcroft, Rospuskova, and Tamuz. They showed that low inefficiency in local coordination forces the underlying graph to be amenable, with a square-root loss in the amenability parameter. We improve this loss in the binary unbiased setting. Using Shapley values of a mutual-information game associated with the players' local outputs, we prove that if the average disagreement is at most $\varepsilon$, then the graph is $(O(\varepsilon\log(1/\varepsilon)),r)$-amenable. This gives a sharper quantitative converse between local coordination and graph amenability.

06.
medRxiv (Medicine) 2026-06-22

A blinded, counterbalanced rater design for evaluating AI-assisted summarisation of tertiary clinical genomics reports: methodology of the QNOMX-VHIR-CPSP-001 Phase 1 study

Background. Tertiary clinical genomics reports condense layered molecular findings into documents that treating oncologists must read, translate, and act upon; manual summarisation of these reports is time-consuming and variable. Tools that assist summarisation and translation into local languages are emerging, yet the field lacks an agreed methodology for evaluating such tools before any downstream clinical use. The appropriate first endpoint is fidelity of the generated summary to its source report, assessed by qualified human raters under blinded scoring, not downstream variant classification. Methods. QNOMX-VHIR-CPSP-001 Phase 1 is a single-site, non-interventional clinical performance study conducted at Vall d'Hebron Institut de Recerca (VHIR) under ISO 20916:2019 as a Clinical Performance Study Protocol. De-identified tertiary cancer genomics reports from pediatric oncology cases are summarised by the AI-assisted summarisation system under evaluation and, in parallel, by the standard manual workflow. Qualified raters score both summary types against the source genomics report using the Quality Summary Index (QSI), a six-dimension, five-point rubric adapted from the Provider Documentation Summarization Quality Instrument, under a blinded, counterbalanced, two-period crossover with a minimum fourteen-day washout. Two co-primary composite endpoints, content and presentation, are analysed for non-inferiority under a Bayesian hierarchical model, with a frequentist linear mixed model as the convergence check. Inter-rater reliability is reported as Krippendorff's ; a Monte-Carlo power analysis of the fixed clustered design is pre-specified. Discussion. The design isolates summarisation quality from clinical decision-making by scoring both summary types against the same source report under blinding, counterbalancing, and a fourteen-day washout. Conclusion. The QSI rubric, the counterbalanced crossover, and the pre-specified Bayesian primary with frequentist convergence check define a replicable protocol for early-stage evaluation of AI-assisted summarisation in tertiary genomics reporting; observed variance components will inform sample-size determination for Phase 2.

07.
arXiv (CS.LG) 2026-06-11

From inverse problems to neural operators: prediction, mechanism, and generalization of data-driven models

作者:

arXiv:2606.08956v2 Announce Type: replace Abstract: Scientists have historically relied on mathematical models based on differential equations to relate system inputs – forces, fluxes, or heat sources – to outputs, such as displacement, velocity, concentration, and temperature. These models rely on deep domain knowledge to determine the form of the governing differential equation, which is then calibrated with data by solving an inverse problem. In recent years, the field of Scientific Machine Learning has introduced a variety of alternative modeling strategies for physical systems. A method called Sparse Identification of Nonlinear Dynamics learns the governing equation as a sparse linear combination of terms in a user-defined library. Neural Ordinary Differential Equations construct the governing equation by taking in the state and its derivatives at the input layer of a neural network. Entirely foregoing the modeling framework of differential equations, neural operators directly learn a non-linear mapping between the system inputs and outputs. From inverse problems to neural operators, all of these modeling strategies can be conceptualized as data-driven machinery to predict a system's response over a range of inputs. It is then natural to wonder how exactly these various strategies relate to each other, and whether they can be neatly taxonomized. Drawing from the philosophical literature on scientific models, we argue that many model types have a common structure, differing only in the assumed model class of the input-output relation they define. Connecting to philosophical ideas on mechanism, and arguing that data from physical systems arises from solutions to parsimonious differential equations, we propose that only certain models are capable of mechanism discovery, and thus generalization. Our analysis is intended to unite apparently disparate modeling strategies and provide insight into their appropriate use cases.

08.
arXiv (CS.CL) 2026-06-18

Dual Dimensionality for Local and Global Attention

Decoder-only Transformers compute attention over the KV cache of preceding tokens. Keys (and Values) are typically represented with the same dimensionality, regardless of its distance from the prediction target. In natural language, however, the next word is most strongly influenced by the immediately preceding tokens. We hypothesize that local and distant tokens impose asymmetric demands on representational capacity: local tokens are more critical for predicting immediate outputs and thus require richer representations, whereas distant tokens primarily serve as long-range memory, for which lower-dimensional representations may suffice. We formalize this idea as Distance-Adaptive Representation (DAR), implemented in a controlled setting that preserves full-dimensional representations within a local context window while assigning reduced-dimensional representations (e.g. 1/4 of the original dimensionality) to tokens beyond that window. Across multiple pretraining scales (70M to 410M parameters), as well as continued supervised fine-tuning on a 1B-scale model, this approach closely matches the performance of full-dimensional baselines. In contrast, uniformly reducing dimensionality across all token positions leads to worse performance. These results challenge the common assumption that key and value dimensionality should be uniform across token positions. Our findings suggest a new direction for designing attention architectures that adaptively allocate representational capacity across sequences, enabling further reductions in KV cache during inference.

09.
arXiv (CS.CV) 2026-06-15

Gaze Heads: How VLMs Look at What They Describe

How a vision-language model internally solves the task of describing an image is far from obvious. We find that the model develops a specific mechanism for this: a small set of attention heads in its language-model backbone, which we call gaze heads, whose attention tracks the image region the model is currently describing. We find them with a simple correlation score from a few forward passes, using comic strips as a controlled testbed where narrative order is laid out spatially. These gaze heads do not just track the image tokens being described: redirecting their attention to a chosen region forces the VLM to describe that region instead. A single attention-mask intervention on the top-100 gaze heads, fewer than 9% of all heads, steers the model's answer to any chosen comic panel at 83.1% accuracy, while the same intervention on random heads fails to redirect the answer, and intervening on all heads destroys generation. The same lever also extends to continuous control: switching the gaze target mid-generation makes the model wrap up its current panel description and move to the new one within a few tokens. Beyond comics, the same intervention redirects answers to chosen regions in natural COCO images. The mechanism further recurs across model sizes from 2B to 32B parameters and across other VLM architectures, although some frozen-encoder families show no comparable head set. More broadly, this shows that targeted edits identified through mechanistic analysis can serve as practical inference-time levers for steering multimodal model behavior, without any retraining. Our code, interactive demo, and datasets are available at https://gaze.baulab.info/

10.
arXiv (quant-ph) 2026-06-16

Black Hole–Entropy Container or Creator

arXiv:2603.18374v3 Announce Type: replace-cross Abstract: Do black holes possess entropy or do they create it? The dominant assumption is that they possess entropy, and a they evaporate that entropy is emitted and decreases. In this paper I use a model of a linear amplifier, in which I argue that the amplifier has not entropy and yet it emits entropy in the process of it operation. This model is closely related to behaviour of black holes, resulting in answer the question of that title that black holes do not have entropy, but nevertheless them create and emit entropy with the total entropy emitted being the same as the usual expression proportional to the square of the mass of the black hole.

11.
arXiv (quant-ph) 2026-06-16

Long-range nonstabilizerness of topologically encoded states from mutual information

arXiv:2605.22424v2 Announce Type: replace Abstract: We study long-range nonstabilizerness (LRN), namely the obstruction to remove nonstabilizerness with shallow-depth local quantum circuits. In one-dimensional settings, the mutual information between disconnected spatial regions has proven to be a powerful tool to diagnose LRN. In this work, we focus on encoded states of two-dimensional topologically-ordered systems, and explore the ability of the mutual information to serve as a diagnostic of LRN. Focusing on the concrete setting of lattice models defined on a torus, we show that information about LRN can be gained from the analysis of the mutual information between non-overlapping regions containing non-contractible loops, and of the change of such mutual information under modular real-space transformations. We exemplify this idea in the toric code and the non-abelian string-net model with doubled Fibonacci topological order. In the former case, we show that the mutual information provides a full classification, certifying LRN for all encoded non-stabilizer states. In the latter case, instead, our approach does not lead to a full classification, as it detects LRN for all states except from a finite subset with special transformation properties under the modular group. Finally, we discuss how our results on LRN constrain the logical gates that can be implemented fault-tolerantly on the torus.

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

Where, What, Why, and Importance: Structured Defect Grounding for Text-to-Image Feedback

Despite generating increasingly photorealistic images, text-to-image (T2I) models still exhibit localized, subtle, and structurally complex failures. Diagnosing these failures requires instance-level feedback that answers where a defect occurs, what type it is, why it is defective, and its importance to overall image quality. While recent dense-feedback methods move beyond scalar supervision, their heatmap-centric representations still formulate diagnosis as pixel-field regression, making it difficult to localize variable-cardinality defects and bind semantic reasons to individual failures. To address this representation bottleneck, we propose Structured Defect Grounding (SDG), which casts T2I diagnosis as structured set prediction by modeling each defect as a (location, type, reason, importance) tuple. To make this formulation trainable and measurable, we introduce SDG-30K, a 30K-image dataset with box-grounded annotations across four modern T2I generators, together with a dedicated evaluation protocol, SDG-Eval. Building on this structured representation, we further present a diagnosis-to-alignment framework in which a Vision-Language Model (VLM) serves as the SDG detector, and BoxFlow-GRPO converts predicted defect sets into box-derived, importance-weighted spatial rewards for diffusion model alignment. Extensive experiments show that our SDG detector outperforms leading proprietary VLMs on structured defect grounding, while SDG-guided rewards consistently improve T2I alignment and support localized image refinement. These results establish SDG as a unified, instance-level interface for diagnosing, evaluating, and enhancing modern generative models.

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

Cross-modal Identity Mapping: Minimizing Information Loss in Modality Conversion via Reinforcement Learning

Large Vision-Language Models (LVLMs) often omit or misrepresent critical visual content in generated image captions. Minimizing such information loss will force LVLMs to focus on image details to generate precise descriptions. However, measuring information loss during modality conversion is inherently challenging due to the modal gap between visual content and text output. In this paper, we argue that the quality of an image caption is positively correlated with the similarity between images retrieved via text search using that caption. Based on this insight, we further propose Cross-modal Identity Mapping (CIM), a reinforcement learning framework that enhances image captioning without requiring additional annotations. Specifically, the method quantitatively evaluates the information loss from two perspectives: Gallery Representation Consistency and Query-gallery Image Relevance. Supervised under these metrics, LVLM minimizes information loss and aims to achieve identity mapping from images to captions. The experimental results demonstrate the superior performance of our method in image captioning, even when compared with Supervised Fine-Tuning. Particularly, on the COCO-LN500 benchmark, CIM achieves a 20% improvement in relation reasoning on Qwen2.5-VL-7B.

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

Robustness Verification of Recurrent Neural Networks with Abstraction Refinement

arXiv:2606.12490v1 Announce Type: new Abstract: Certified local robustness verification for recurrent neural networks (RNNs) is challenging because approximation errors introduced by nonlinear relaxations can propagate through recurrent connections and accumulate over time. As a result, scalable linear bound propagation methods often become overly conservative and fail to certify inputs that are in fact robust, especially when many pre-activation intervals cross zero. We propose an abstraction-refinement framework for RNN verification that partitions such intervals to remove the dominant relaxation error: on each refined branch, ReLU becomes exact, and smooth activations such as tanh and sigmoid admit substantially tighter linear envelopes. To control the combinatorial cost of splitting in long sequences, we introduce a SHAP-guided timestep selection strategy that ranks hidden states by their contribution to the verification objective and refines only the most critical timesteps in temporal order. Experiments on CIFAR10 and MNIST stroke benchmarks demonstrate consistent improvements in verification success and robustness-margin tightness over abstraction-only baselines, while exposing clear runtime trade-offs between ReLU and tanh models.

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

PCR-CA: Parallel Codebook Representations with Contrastive Alignment for Multiple-Category App Recommendation

arXiv:2508.18166v5 Announce Type: replace-cross Abstract: Modern app store recommender systems struggle with multiple-category apps, as traditional taxonomies fail to capture overlapping semantics, leading to suboptimal personalization. We propose PCR-CA (Parallel Codebook Representations with Contrastive Alignment), an end-to-end framework for improved CTR prediction. PCR-CA first extracts compact multimodal embeddings from app text, then introduces a Parallel Codebook VQ-AE module that learns discrete semantic representations across multiple codebooks in parallel – unlike hierarchical residual quantization (RQ-VAE). This design enables independent encoding of diverse aspects (e.g., gameplay, art style), better modeling multiple-category semantics. To bridge semantic and collaborative signals, we employ a contrastive alignment loss at both the user and item levels, enhancing representation learning for long-tail items. Additionally, a dual-attention fusion mechanism combines ID-based and semantic features to capture user interests, especially for long-tail apps. Experiments on a large-scale dataset show PCR-CA achieves a +0.76% AUC improvement over strong baselines, with +2.15% AUC gains for long-tail apps. Online A/B testing further validates our approach, showing a +10.52% lift in CTR and a +16.30% improvement in CVR, demonstrating PCR-CA's effectiveness in real-world deployment. The new framework has now been fully deployed on the Microsoft Store.

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

Your Agent Has a Genome: Sequence-Level Behavioral Analysis and Runtime Governance of LLM-Powered Autonomous Agents

作者:

arXiv:2606.15579v1 Announce Type: new Abstract: We propose Base Sequence Analysis, a framework that encodes the runtime behavior of LLM-powered autonomous agents into compact symbolic sequences using a four-letter alphabet: X (Explore), E (Execute), P (Plan), and V (Verify). Drawing an analogy to genomic sequence analysis, we apply n-gram pattern mining, Markov transition matrices, and point-biserial correlation to 347 real-world execution traces collected from a production ReAct agent system over 8 days. Our analysis reveals that (1) the trigram P-X-P is the only statistically significant high-risk pattern, lowering success rate by 10.4%; (2) P-ratio is the strongest negative predictor of success (r=-0.256, pV transition probability is only 2.1%, indicating a systemic verification deficit. Based on these findings, we design Governor, a three-layer runtime intervention system comprising a rule engine, a statistical accumulator, and a chi-square-based threshold adaptor. In a natural before/after deployment evaluation (N=101 vs. N=246), Governor achieves a +6.2% absolute increase in task success rate while simultaneously reducing average token consumption by 44%. To validate cross-system generality, we apply the XEPV encoding to 2,000 public SWE-agent trajectories on SWE-bench, confirming that exploration spirals and the E->V verification deficit replicate in an independent system. We outline six research directions including base sequence language models, cross-agent behavioral fingerprinting, and reward shaping, and release an open-source toolkit for reproducibility.

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

Estimating Mutual Information between Time Series and Temporal Event Sequences Across Diverse Analysis Tasks

arXiv:2606.01602v2 Announce Type: replace-cross Abstract: Pairwise dependence measures such as correlation and causality are fundamental to temporal data mining, yet there is still no principled and robust way to quantify dependence between heterogeneous data types, especially between continuous time series and discrete temporal event sequences. Existing approaches rely on ad hoc transformations or mutual-information estimators that are highly sensitive to quantization, repeated values, and event redundancy, leading to biased or unstable results in practice. We propose a nonparametric mutual information estimator that directly measures the dependence between time series and event sequences without data transformation, learning, or ad hoc discretization. Our method models the continuous-discrete duality of real-world time series to handle quantization and repeated-value artifacts and introduces a latent event clustering strategy to mitigate bias from event co-occurrence and redundancy. Together, these yield a robust and unified framework that bridges discrete and continuous mutual information. We evaluate the proposed estimator on four representative tasks: discrete-continuous time-delayed mutual information for causality analysis, global and local temporal repetition discovery, discrete covariate selection for time series forecasting, and continuous feature selection for classification. Experiments on synthetic and real-world datasets show consistent improvements over existing methods in accuracy, robustness, and interpretability, positioning our approach as a general-purpose dependence operator for heterogeneous temporal data, similar to Pearson correlation for homogeneous time series. Code available at: https://github.com/HaojiHu/Multimodal-Temporal-Data-Quantification

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

ChronoID: Infusing Explicit Temporal Signals into Semantic IDs for Generative Recommendation

arXiv:2606.14260v1 Announce Type: cross Abstract: Semantic IDs are crucial in generative recommendation, but with a fundamental limitation: temporal information is not well incorporated into semantic IDs. Instead, time influences recommendation only implicitly (e.g., through session construction heuristics, preference alignment, or sequence order), while existing semantic ID learning remains entirely time-agnostic. This design conflates interactions occurring under distinct temporal contexts into identical semantic representations, implicitly assuming that item semantics and user intent are temporally stationary. Such an assumption is misaligned with real-world recommendation scenarios, where evolving interaction rhythms play a central role. In this work, we investigate where and how the explicit time should be incorporated into semantic ID for generative recommendation. First, we systematically characterize the design space along three orthogonal dimensions of temporal signals and present a unified framework, ChronoID, for time-aware semantic ID learning. Then, by contributing a new time-explicit generation recommendation benchmark, ChronoID answers the questions: what is the effective way of infusing time, how to design the architecture, and where does the gain come from.

19.
arXiv (CS.AI) 2026-06-11

Power Term Polynomial Algebra for Boolean Logic

arXiv:2603.13854v2 Announce Type: replace-cross Abstract: We introduce power term polynomial algebra, a representation language for Boolean formulae designed to bridge conjunctive normal form (CNF) and algebraic normal form (ANF). The language is motivated by the tiling mismatch between these representations: direct CNFANF conversion may cause exponential blowup unless formulas are decomposed into smaller fragments, typically through auxiliary variables and side constraints. In contrast, our framework addresses this mismatch within the representation itself, compactly encoding structured families of monomials while representing CNF clauses directly, thereby avoiding auxiliary variables and constraints at the abstraction level. We formalize the language through power terms and power term polynomials, define their semantics, and show that they admit algebraic operations corresponding to Boolean polynomial addition and multiplication. We prove several key properties of the language: disjunctive clauses admit compact canonical representations; power terms support local shortening and expansion rewrite rules; and products of atomic terms can be systematically rewritten within the language. Together, these results yield a symbolic calculus that enables direct manipulation of formulas without expanding them into ordinary ANF. The resulting framework provides a new intermediate representation and rewriting calculus that bridges clause-based and algebraic reasoning and suggests new directions for structure-aware CNFANF conversion and hybrid reasoning methods.

20.
bioRxiv (Bioinfo) 2026-06-18

A data-driven rediscovery of the specificity-conferring code of adenylation domains in nonribosomal peptide synthetases

Nonribosomal peptide synthetases (NRPSs) are large modular enzymes that assemble structurally diverse peptides, many of pharmacological importance, including antibiotics and immunosuppressants. Within each NRPS module, the adenylation (A) domain selects the substrate to be incorporated, a choice governed by a small set of residues lining the binding pocket. For two decades, computational prediction of A-domain substrate specificity has relied on residue sets - most prominently the Stachelhaus code and the 34-residue "8 Angstrom code" - that were defined by spatial proximity to the substrate rather than by demonstrated predictive value. Here we revisit which residues govern substrate specificity from a purely data-driven perspective. We assembled a non-redundant dataset of 5,366 A-domain sequences (4,693 bacterial and 673 fungal) and used information-theoretic measures to rank alignment positions by their statistical association with substrate identity, without restricting candidate positions to any predefined structural shell. This procedure yielded two compact, kingdom-specific codes: IG15B (15 positions) for bacterial and IG13F (13 positions) for fungal A-domains. Both match or exceed the predictive accuracy of the 34-residue 8 Angstrom code while using fewer than half its positions, and both independently recover the majority of the classical Stachelhaus positions. Notably, our analysis identifies four positions (242, 280, 281, and 284) that lie outside all conventional codes yet carry non-redundant specificity information and co-localize with classical determinants on two helices flanking the binding pocket. These positions provide new candidate sites for the rational engineering of A-domain specificity.

21.
arXiv (CS.AI) 2026-06-19

Can In-Context Learning Support Intrinsic Curiosity?

arXiv:2606.19476v1 Announce Type: cross Abstract: Effective machine learning depends not only on how we model data, but also on what data we choose to collect. While large sequence models have revolutionized data modeling, the problem of automated data selection, or "intrinsic curiosity", remains a significant challenge. Classic approaches incentivize exploration by rewarding an agent based on its "learning progress", which measures how much a newly acquired observation improves a world model's predictive ability. However, evaluating these rewards traditionally requires expensive inner loops of gradient descent updates within each trajectory, rendering them computationally impractical at scale. In this work, we investigate whether the emergent in-context learning (ICL) capabilities of sequence models can eliminate this bottleneck by serving as immediate, update-free world models. Specifically, we evaluate whether an exploration policy can be trained to maximize learning progress, using solely the prediction errors and counterfactual context manipulations of an in-context learner. We first prove that in general Markov decision processes, this is in fact impossible in an unbiased way: the resulting intrinsic rewards either suffer from nuisance terms that bias their estimation of true learning progress, or they cannot be implemented using an in-context learner's prediction errors. Conversely, we prove a positive result for a broad subclass of non-temporal settings, encompassing active learning and Bayesian Experimental Design: here, ICL-derived rewards successfully bound and asymptotically converge to the true learning progress. We corroborate our theory with controlled experiments across continuous and symbolic environments, demonstrating that our ICL-driven framework successfully trains curious data-collection policies that explore optimally.

22.
bioRxiv (Bioinfo) 2026-06-22

From hotspot dependence to distributed robustness in resistance-aware lead optimization

Drug resistance remains a recurrent failure mode in targeted anticancer and antiviral therapy, and resistance evidence often enters only after compound selection. ResistAgent is an evidence-constrained framework that converts mutational liabilities into design-time objectives through site- and combo-aware resistance mapping, deterministic mechanism diagnosis and robust counter-design. In EGFR-Erlotinib and HIV-RT-Rilpivirine, the framework separated residue-level liabilities from observed HIV combination liabilities and linked prioritized mutations to anchor loss, pocket rearrangement, electrostatic shifts and contact redistribution. Same-budget paired searches showed that robust objectives changed lower-tail mutant-panel behavior and interaction-dependence profiles while prioritizing robustness over average-affinity behavior. Under predefined liability panels, selected robust-best trajectories shifted support away from mutable hotspot contacts toward more distributed interaction networks. Supplementary physical summaries and ranking-first benchmarks support the scope of this resistance-aware design strategy while preserving clear boundaries for prospective validation.

23.
arXiv (CS.AI) 2026-06-17

Adaptive Domain Models: Bayesian Evolution, Warm Rotation, and Principled Training for Geometric and Neuromorphic AI

arXiv:2603.18104v5 Announce Type: replace Abstract: Prevailing AI training assumes reverse-mode automatic differentiation over IEEE-754 arithmetic. The memory overhead of training relative to inference, optimizer complexity, and structural degradation of geometric properties through training are consequences of this arithmetic substrate. This paper develops an alternative training architecture grounded in three prior results: the Dimensional Type System and Deterministic Memory Management framework (Haynes 2026), which establishes stack-eligible gradient allocation and exact quire accumulation as design-time verifiable properties; the Program Hypergraph (Haynes 2026), which establishes grade preservation through geometric algebra computations as a type-level invariant; and the b-posit bounded-regime design (Jonnalagadda et al. 2025), which makes posit arithmetic tractable across hardware targets conventionally considered inference-only. Their composition enables depth-independent training memory bounded to approximately twice the inference footprint, grade-preserving weight updates, and exact gradient accumulation, applicable uniformly to loss-function-optimized and spike-timing-dependent neuromorphic models. We introduce *Bayesian distillation*, a mechanism by which the latent prior structure of a general-purpose model is extracted through the ADM training regime, resolving the data-scarcity bootstrapping problem for domain-specific training. For deployment, we introduce *warm rotation*, an operational pattern in which an updated model transitions into an active inference pathway without service interruption, with correctness formalized through PHG certificates and signed version records. The result is a class of domain-specific AI systems that are smaller and more precise than general-purpose models, continuously adaptive, verifiably correct with respect to the physical structure of their domains, and initializable from existing models.

24.
arXiv (CS.CV) 2026-06-16

Attention-Based Prototype Calibration for Multi-Rater Few-Shot Medical Image Segmentation

Few-shot medical image segmentation methods typically assume a single ground-truth annotation, overlooking systematic variability across expert raters commonly observed in clinical datasets. We propose an attention-based prototype calibration framework for few-shot multi-rater segmentation that models rater-specific deviations from a consensus representation in prototype space. A lightweight yet principled attention operator directly refines rater prototypes without modifying the backbone feature extractor, making the approach fully compatible with existing prototype-based few-shot segmentation methods. This design preserves semantic consistency while enabling personalized segmentation outputs with minimal computational overhead. Experiments on multi-rater medical imaging datasets demonstrate consistent improvements over baseline prototype approaches, highlighting the effectiveness of structured prototype calibration for modeling annotation variability. Our code is available at https://github.com/truong2710-cyber/JAPC.

25.
arXiv (CS.CV) 2026-06-11

A Turbo-Inference Strategy for Object Detection and Instance Segmentation

Object detection and instance segmentation tasks are closely related. Existing top-down instance segmentation methods usually follow a detect-then-segment paradigm, where an initial detector is used to recognize and localize objects with bounding boxes, followed by the segmentation of an instance mask within each bounding box. In such methods, the detection accuracy directly influences the subsequent segmentation performance. However, previous research has seldom explored the impact of the instance segmentation task on object detection. In this paper, we present a turbo-inference strategy for the top-down methods that leverages the complementary information between detection and segmentation tasks iteratively. Specifically we design two modules: turbo-detection head and turbo-segmentation head, which facilitate communication between the tasks. The two modules form a closed loop that interlaces the detection and segmentation results without retraining the model. Comprehensive experiments on the COCO, iFLYTEK, and Cityscapes datasets demonstrate that our method substantially enhances both detection and segmentation accuracies with a certain increase in computational cost. The proposed method represents a tradeoff between prediction accuracy and inference speed. Codes are available at https://github.com/zhaozhen2333/Turbo-Learning.git.