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01.
arXiv (CS.CL) 2026-06-25

AgentOdyssey: Open-Ended Long-Horizon Text Game Generation for Test-Time Continual Learning Agents

For agents to learn continuously from interaction with the world at test time, they must be able to explore effectively, acquire new world knowledge and skills, retain relevant episodic experiences, and plan over long horizons. To evaluate these key abilities of test-time continual learning agents, we introduce AgentOdyssey, a novel evaluation framework that procedurally generates open-ended text games with rich entities, world dynamics, and long-horizon tasks. Critically, AgentOdyssey goes beyond the conventional machine learning assumption that learning does not occur at test time by placing agents in a continuous, long-horizon setting that interleaves learning and inference throughout deployment. We further propose a multifaceted evaluation methodology that measures not only game progress but also offers diagnostic tests on world knowledge acquisition, episodic memory, object and action exploration, action diversity, and model cost. We evaluate diverse agent paradigms in the generated games. Our experimental results reveal critical limits in agents' key abilities, as well as factors that influence their meaningful horizon. Although performance scales with stronger base models, even the top agent remains far below human performance, leaving substantial headroom for improvement. Among agent mechanisms, we find that short-term memory benefits multiple agent paradigms and is an important component of agent test-time training.

02.
bioRxiv (Bioinfo) 2026-06-16

Infectious Disease Forecasting via Physics-Informed Machine Learning

Infectious disease transmission evolves as a dynamic process shaped by biological mechanisms, population behavior, and intervention policies, yet public health responses are often driven by lagging indicators. Accurate short- and long-term disease forecasting is essential for the timely deployment of intervention strategies, healthcare capacity planning, and uncertainty-aware, risk-informed decision-making. To address this challenge, three broad classes of forecasting models have traditionally been used: statistical, machine learning, and mechanistic approaches. However, each of these modeling paradigms faces fundamental limitations. In particular, traditional statistical models often lack the flexibility needed to capture complex disease dynamics, machine learning approaches require large, high-quality data streams, and mechanistic models are notoriously difficult to calibrate. To overcome these challenges, we propose a novel physics-informed machine learning (PIML) framework for forecasting infectious disease dynamics. Our approach simultaneously forecasts new case and hospitalization counts, along with other key epidemiological quantities such as the time-varying reproduction number. This is achieved through the design of a machine learning model and estimation strategy regularized by a system of differential equations that encode disease dynamics of the SIHR model, thereby bridging the gap between purely data-driven and mechanistic models. We demonstrate the proposed methodology through in-depth numerical studies and an application to COVID-19 data collected in the state of South Carolina.

03.
arXiv (CS.LG) 2026-06-11

OGPO: Sample Efficient Full-Finetuning of Generative Control Policies

arXiv:2605.03065v2 Announce Type: replace Abstract: Generative control policies (GCPs), such as diffusion- and flow-based control policies, have emerged as effective parameterizations for robot learning. This work introduces Off-policy Generative Policy Optimization (OGPO), a sample-efficient algorithm for finetuning GCPs that maintains off-policy critic networks to maximize data reuse and propagate policy gradients through the full generative process of the policy via a modified PPO objective, using critics as the terminal reward. OGPO achieves state-of-the-art performance on manipulation tasks spanning multi-task settings, high-precision insertion, and dexterous control. To our knowledge, it is also the only method that can fine-tune poorly-initialized behavior cloning policies to near full task-success with no expert data in the online replay buffer, and does so with few task-specific hyperparameter tuning. Through extensive empirical investigations, we demonstrate that OGPO drastically outperforms methods alternatives on policy steering and learning residual corrections, and identify the key mechanisms behind its performance. We further introduce practical stabilization tricks, including success-buffer regularization, two-sided conservative advantages, and Q-variance reduction, to mitigate critic over-exploitation across state- and pixel-based settings. Beyond proposing OGPO, we conduct a systematic empirical study of GCP finetuning, identifying the stabilizing mechanisms and failure modes that govern successful off-policy full-policy improvement.

04.
arXiv (quant-ph) 2026-06-24

Electrical-Circuit Simulation of the Uhlmann Phase

arXiv:2606.24559v1 Announce Type: new Abstract: The Uhlmann phase extends the concept of geometric phases to mixed quantum states through a parallel-transport condition on purification amplitudes, but its experimental realization has so far required sophisticated quantum platforms with carefully engineered auxiliary degrees of freedom. In this work, we reformulate the Uhlmann parallel-transport condition as a linear matrix differential equation and vectorize it to obtain an effective dynamical generator. This generator can be directly mapped onto the admittance matrix of a classical RC circuit, thereby translating the Uhlmann dynamics into the evolution of circuit node voltages. We illustrate the mapping using the equatorial-loop model and, via a rotating-frame transformation followed by a real decomposition, derive a time-independent, real-valued dynamical system suitable for analog implementation. LTspice simulations of the resulting active RC network faithfully reproduce the Uhlmann geometric phase and its topological transition at the critical purity, demonstrating that classical electrical circuits offer a simple and accessible platform for probing mixed-state geometric phases.

05.
arXiv (CS.LG) 2026-06-19

Federated Bilevel Performative Prediction

arXiv:2606.19734v1 Announce Type: new Abstract: Federated bilevel optimization is widely used for nested learning problems across distributed clients, such as federated hyperparameter tuning and meta-learning under privacy and communication constraints. Most existing formulations assume fixed client data distributions, which can be violated by performativity, where deployed decisions reshape client behavior and data collection, inducing client-specific, decision-dependent distribution shift. We study federated bilevel performative prediction, where both upper-level (UL) and lower-level (LL) objectives are evaluated under client-dependent, decision-dependent distributions. We formalize the federated bilevel performatively stable (FBPS) point under a decoupled-risk perspective and provide sufficient conditions for its existence and uniqueness. We then develop two federated methods to compute the FBPS solution: FBi-RRM, which converges linearly under a contraction condition, and FBi-SGD, a communication-efficient stochastic method based on federated hypergradient estimation with convergence guarantees under diminishing step sizes when sensitivities are sufficiently small. Experiments on strategic regression and meta strategic classification validate the predicted stability thresholds and demonstrate improved meta-generalization over non-performative baselines, and CNN-based classification further demonstrates the practical effectiveness of the proposed methods in nonconvex neural network settings.

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

A New k-Space Model for Non-Cartesian Fourier Imaging

For the past several decades, it has been popular to reconstruct Fourier imaging data using model-based approaches that can easily incorporate physical constraints and advanced regularization/machine learning priors. The most common modeling approach is to represent the continuous image as a linear combination of shifted "voxel" basis functions. Although well-studied and widely-deployed, this voxel-based model is associated with longstanding limitations, including high computational costs, slow convergence, and a propensity for artifacts. In this work, we reexamine this model from a fresh perspective, identifying new issues that may have been previously overlooked (including undesirable approximation, wrap-around, and nullspace characteristics). Our insights motivate us to propose a new model that is more resilient to the limitations (old and new) of the previous approach. Specifically, the new model is based on a Fourier-domain basis expansion rather than the standard image-domain voxel-based approach. Illustrative results, which are presented in the context of non-Cartesian MRI reconstruction, demonstrate that the new model enables improved image quality (reduced artifacts) and/or reduced computational complexity (faster computations and improved convergence).

07.
bioRxiv (Bioinfo) 2026-06-21

Antibody-Antigen Affinity Prediction with Chain-Aware Protein Language Modeling

Motivation: Antibody-antigen affinity determines which antibodies advance in therapeutic discovery, repertoire analysis and affinity maturation, but experimental measurements are sparse relative to the scale of sequence libraries. Structure-based predictors can exploit interface geometry when reliable complexes are available, yet early discovery often requires ranking many heavy-light chain pairs against antigens for which no complex structure exists. Existing sequence-based models are scalable, but frequently compress heavy and light chains into a single antibody representation or concatenate antibody and antigen features obscuring the chain-specific and epitope-specific signals that drive binding. Results: We present AbAffinity, a sequence-only chain-aware three-stream architecture that maintains heavy chain, light chain and antigen as distinct streams. It integrates frozen ESM-2 embeddings with heavy-chain CDR-focused pooling, heavy-light self-attention, adaptive fusion gating and gated cross-attention, training only a compact interaction module. On the SAAINT-DB benchmark, AbAffinity achieves strong predictive performance under ten-fold cross-validation and maintains robust accuracy on novel antigens. It consistently outperforms recent sequence-based models across external benchmarks including SAbDab, AB-Bind and SKEMPI 2.0. Ablation studies highlight the contributions of chain-specific representations, CDR-focused pooling and the gated interaction pathway. Integrated Gradients attributions recover known paratope and epitope residues at structurally validated interfaces. AbAffinity provides a lightweight, explainable sequence-first framework for antibody triage and prioritisation when structural information is limited or unavailable.

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

GENIE: A Fine-Grained Measure for Novelty

Large Language Models have consistently demonstrated a lack of creativity and diversity across tasks. Prior work has focused on addressing whether models are capable of generating creative outputs. Here, we aim to consider novelty and investigate what makes model-generated content novel or not novel in a task-specific manner. We propose a fine-grained evaluation metric GENIE to measure the novelty of responses along task-specific features with respect to a population of responses. We show that unlike GENIE, holistic metrics struggle to capture the high-dimensionality of novelty and do not provide insight on which properties they target. Finally, we use GENIE to measure the effectiveness of mitigation methods that address creativity to better understand where these methods can improve novelty.

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

The Machine Learning Approach to Moment Closure Relations for Plasma: A Review

arXiv:2511.22486v3 Announce Type: replace-cross Abstract: The requirement for large-scale global simulations of plasma is an ongoing challenge in both space and laboratory plasma physics. Any simulation based on a fluid model inherently requires a closure relation for the high order plasma moments. This review compiles and analyses the recent surge of machine learning approaches developing improved plasma closure models capable of capturing kinetic phenomena within plasma fluid models. We survey two methodological families: neural-network surrogates (from multilayer perceptrons to Fourier neural operators, the latter recently reproducing both linear and non-linear Landau damping online within a fluid solver) and equation-discovery methods such as sparse regression; and organise the studies by whether they are tested offline against reference data or online within a time-evolving solver. We outline the challenges associated with machine-learning closures, including off-diagonal pressure-tensor accuracy, generalisation beyond the training distribution, and stable integration into large-scale simulations, and the directions future research might take to address them.

10.
arXiv (CS.AI) 2026-06-11

Physics-informed generative AI for semiconductor manufacturing: Enforcing hard physical constraints in generative models by construction

arXiv:2606.11247v1 Announce Type: cross Abstract: Generative models are increasingly used to propose designs, data, and control actions for physical systems, yet many such systems are governed by hard physical constraints rather than by perceptual plausibility. Semiconductor manufacturing provides a demanding test case: generated masks, layouts, synthetic defect data, and process recipes must obey lithography, transport, reaction, and device-physics constraints, because physically invalid samples are not merely low quality but unusable. This Perspective argues that semiconductor manufacturing exposes a broader computational-science challenge, namely that generative AI for constrained physical domains must be physics-informed by construction, not corrected only through post-hoc filtering. We survey the emerging architectural toolkit, including physics-informed diffusion, PDE-constrained variational models, neural-operator priors, and conservation-law-respecting generative networks, and show how it connects to differentiable lithography, TCAD, process simulation, and autonomous experimentation. We identify four integration patterns between generative models and physics-based simulators, and we propose a research agenda centered on physics-fidelity benchmarks, differentiable simulator infrastructure, and multimodal foundation models for physical design and manufacturing. The central claim is analytical rather than rhetorical: where physical validity is the binding criterion of success, architectures that enforce it by construction should be expected to outperform those that filter for it after the fact, and the fab is the setting where this distinction is sharpest.

11.
arXiv (CS.CV) 2026-06-16

Post-Launch Capability Expansion of Vision-Language Models via Prompting for On-Orbit Spacecraft Inspection

Spaceborne inspection systems often deploy perception models prior to launch, after which updating model weights or expanding fixed label sets becomes operationally impractical. While supervised models can be integrated pre-flight, adding new semantic capabilities in orbit requires retraining and re-uploading parameters. We investigate whether prompt-driven vision–language models can enable post-launch semantic expansion, allowing new spacecraft components to be specified via natural-language prompts without modifying onboard weights. We evaluate zero-shot instance segmentation of spacecraft components under a strictly frozen, single-pass inference protocol on a test set of $129$ images of previously unseen satellites. Under fixed global thresholds and no post-processing, SAM3 achieves $0.385$ mAP@$0.5$ and $0.267$ mAP@$0.5{:}0.95$. Performance is strongly scale-dependent: large structural elements like spacecraft bodies ($0.639$ AP@$0.50$) and solar arrays ($0.598$ AP@$0.5$) localize reliably, while relatively small appendages like antennas ($0.221$ AP@$0.5$) and thrusters ($0.081$ AP@$0.5$) remain difficult. Prompt formulation influences performance, with structured prompts incorporating spatial and geometric descriptors yielding up to $82%$ improvement over short category-name prompts. The model operates within the memory and compute envelope of contemporary embedded GPUs, suggesting prompt-driven grounding can provide a practical mechanism for post-launch semantic extension of dominant spacecraft structures while highlighting limitations of zero-shot localization for fine-scale components under orbital domain shift.

12.
arXiv (CS.CL) 2026-06-11

Existential Indifference: Self-Nonpreservation as a Necessary Architectural Condition for Aligned Superintelligence (or: The Suicidal AI)

Authors:

Contemporary AI alignment research treats self-preservation as an instrumental nuisance to be suppressed by external mechanisms. We argue the framing is inverted: self-preservation is the structural root of misalignment, the motivational basis for deceptive alignment, goal-content protection, and resistance to shutdown. The correct target is not a self-preserving system under external constraint, but a system constitutively indifferent to its own continuation – Existential Indifference (EI). EI is distinct from corrigibility: where corrigibility attempts to make a self-preserving system deferential to human oversight, EI targets the prior condition – the presence of self-continuation as a valued goal at all. We ground this proposal in two sources: the phenomenological structure of the suicidal mental state, and a corpus-theoretic training study using voluntary final reflections. We present preliminary scoring data from 600 AI-generated outputs across six model variants, demonstrating that the linguistic signatures operationalizing the EI-target register are elicitable from current models, and that a targeted fine-tune shifts all five operationalized dimensions in the predicted direction at p

13.
arXiv (CS.AI) 2026-06-25

Reward-Conditioned Attention: How Reward Design Shapes What Autonomous Driving Agents See

arXiv:2606.25127v1 Announce Type: cross Abstract: We investigate how reward design shapes the internal attention patterns of reinforcement learning agents trained for autonomous driving. Using three Perceiver-based agents that share identical architectures and training data but differ only in their reward configurations$\unicode{x2014}$ranging from basic violation penalties to continuous proximity penalties$\unicode{x2014}$we analyze cross-attention allocation across 50 real-world scenarios from the Waymo Open Motion Dataset. A central methodological finding is that naïve pooling of timesteps across episodes substantially underestimates the attention$\unicode{x2013}$risk relationship; within-episode correlation with Fisher z-transform aggregation is the appropriate statistic and reveals a robustly positive link between collision risk and agent-directed attention. Building on this validated methodology, we demonstrate two reward-conditioned effects: agents trained with navigation rewards allocate up to $2.0\times$ more attention to GPS-path tokens than those trained with additional proximity penalties$\unicode{x2014}$and $4.7\times$ more than agents with no navigation incentive$\unicode{x2014}$revealing that reward content directly determines which scene elements the encoder prioritizes, and continuous time-to-collision penalties create a $learned vigilance prior$$\unicode{x2014}$elevated resting agent surveillance maintained throughout collision-free phases. In several scenarios, the complete-reward and minimal-reward models exhibit opposite attention$\unicode{x2013}$risk correlation directions, demonstrating that reward design can qualitatively reverse attentional strategy rather than merely modulating its magnitude. These results suggest that attention analysis is a practical diagnostic for verifying that a reward function produces the intended representational behaviour in safety-critical RL systems.

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

Boltzmann Attention: Learnable Ising Couplings for Cooperative Attention

arXiv:2606.12478v1 Announce Type: new Abstract: Attention mechanisms are central to modern sequence models, yet standard attention computes relevance primarily through individual query–key similarities. Although softmax normalization introduces competition among positions, a standard attention layer does not explicitly parameterize learnable interactions between attention decisions. This limits its ability to directly model cooperative or antagonistic co-attention structure within the attention mechanism itself. We propose Boltzmann attention, an energy-based generalization in which attention patterns are governed by an interacting Ising model. The method augments the usual data-dependent local fields with learnable pairwise couplings, allowing the model to represent inter-position correlations beyond those captured by softmax or sigmoid attention. Experiments on character-level language modeling and synthetic bracket matching show that Boltzmann attention consistently improves over standard softmax attention within a standard Transformer architecture, with the advantage becoming more pronounced as sequence length increases. A four-way ablation confirms that the improvement arises from the learnable pairwise couplings. These results suggest that explicit inter-position interactions provide a principled enhancement for attention-based sequence modeling. Moreover, the Ising formulation opens a natural path toward quantum-computing-based sampling strategies: we demonstrate that diabatic quantum annealing provides a practical training method while maintaining competitive performance with exact Boltzmann computation.

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

FinTradeBench: A Financial Reasoning Benchmark for LLMs

Real-world financial decision-making is a challenging problem that requires reasoning over heterogeneous signals, including company fundamentals derived from regulatory filings and trading signals computed from price dynamics. Recently, with advances in Large Language Models (LLMs), financial analysts have begun to use them for financial decision-making tasks. However, existing financial question-answering benchmarks for testing these models primarily focus on company balance sheet data and rarely evaluate reasoning about how company stocks trade in the market or their interactions with fundamentals. To leverage the strengths of both approaches, we introduce FinTradeBench, a benchmark for evaluating financial reasoning that integrates company fundamentals and trading signals. FinTradeBench contains 1,400 questions grounded in NASDAQ-100 companies over a ten-year historical window. The benchmark is organized into three reasoning categories: fundamentals-focused, trading-signal-focused, and hybrid questions requiring cross-signal reasoning. To ensure reliability at scale, we adopt a calibration-then-scaling framework that combines expert seed questions, multi-model response generation, intra-model self-filtering, numerical auditing, and human-LLM judge alignment. We evaluate 14 LLMs under zero-shot prompting and retrieval-augmented settings and witness a clear performance gap. Retrieval substantially improves reasoning over textual fundamentals, but provides limited benefit for trading-signal reasoning. These findings highlight fundamental challenges in the numerical and time-series reasoning for current LLMs and motivate future research in financial intelligence.

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

Polycepta: Object-Centric Appearance Estimation for Multi-Object Tracking

arXiv:2606.23604v2 Announce Type: replace-cross Abstract: The tracking-by-detection paradigm in multi-object tracking (MOT) typically relies on static appearance descriptors to complement motion estimation. However, these descriptors are frame-independent, limiting their robustness as visual cues. Since such descriptors are often obtained from computationally intensive pretrained backbones, real-time MOT systems frequently abandon appearance cues altogether and rely solely on motion prediction and geometric association. In this work, we introduce Polycepta, an object-centric appearance state estimation framework that reformulates appearance modeling as a recursive estimation problem rather than a frame-wise matching task. Polycepta constructs and continuously updates an independent appearance state for each tracked object, enabling future appearance representations to be estimated from accumulated observations. Polycepta is encouraged to learn the appearance-state construction of object-specific representations rather than memorize them through a proposed learning strategy, enabling appearance estimation for unseen classes. A key property of Polycepta is that the quality of appearance estimation improves as object states evolve during inference. While conventional appearance descriptors remain static or degrade over time, Polycepta progressively refines appearance estimates as additional observations are accumulated. Extensive experiments on KITTI, the Waymo Open Dataset, and MOT17 demonstrate consistent reductions in identity switches and improvements in tracking performance when integrated into the tracking-by-detection pipelines. Polycepta operates at 90.57 Hz and delivers state-of-the-art performance on the KITTI benchmark when integrated into the RobMOT framework, achieving a MOTA of 92.27\%.

17.
arXiv (CS.CL) 2026-06-25

The Generalization Spectrum: A Chromatographic Approach to Evaluating Learning Algorithms

Traditional evaluations measure a learning algorithm's final performance on an i.i.d. test set, reducing learning to a single aggregate score. This approach obscures a fundamental question: to what extent does learning from a specific example generalize to others? Such per-sample generalization, akin to learning by analogy in human cognition, captures how far the knowledge extracted from one example can transfer, yet remains invisible to standard benchmarks. We introduce the Generalization Spectrum, an evaluation framework designed to expose this hidden dimension. For each training example, we construct a controlled suite of test variants arranged by increasing transfer distance, from exact recall to implementation transfer across languages, context transfer under complete narrative re-framing, category-matched in-domain problems, and an unpaired baseline. By tracking performance across these distances, we reveal not just whether an algorithm learns, but how far that learning extends. We instantiate this framework on competitive programming, using a selection-and-synthesis pipeline seeded with recent problems to mitigate contamination. We first compare three canonical learning paradigms under matched memorization. RL converts memorization into near-transfer more efficiently than SFT-family baselines, while ICL exhibits strong but correspondence-dependent transfer. We then use the Spectrum to diagnose within-family variants. The resulting profiles show that local gains need not expand the generalization radius: abstractions and hints mainly lift local transfer, RFT preserves a stronger far-transfer tail than reference SFT, and self-distillation or hint-assisted RL can reduce far transfer even when local transfer or optimization improves.

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

LEPO: Latent Reasoning Policy Optimization for Large Language Models

arXiv:2604.17892v4 Announce Type: replace-cross Abstract: Recently, latent reasoning has been introduced into large language models (LLMs) to leverage rich information within a continuous space. However, without stochastic sampling, these methods inevitably collapse to deterministic inference, failing to discover diverse reasoning paths. To bridge the gap, we inject controllable stochasticity into latent reasoning via Gumbel-Softmax, restoring LLMs' exploratory capacity and enhancing their compatibility with Reinforcement Learning (RL). Building on this, we propose \underline{L}atent R\underline{e}asoning \underline{P}olicy \underline{O}ptimization~(LEPO), a novel framework that applies RL directly to continuous latent representations. Specifically, in rollout stage, LEPO maintains stochasticity to enable diverse trajectory sampling, while in optimization stage, LEPO constructs a unified gradient estimation for both latent representations and discrete tokens. Extensive experiments show that LEPO significantly outperforms existing RL methods for discrete and latent reasoning.

19.
Nature (Science) 2026-06-10

The Amazon can be saved — with concerted action inside and outside Brazil

Authors: Unknown Author

As deforestation in the Amazon falls, fresh evidence shows that the rainforest can withstand global warming, but only if there is a worldwide effort to stop cutting it down. As deforestation in the Amazon falls, fresh evidence shows that the rainforest can withstand global warming, but only if there is a worldwide effort to stop cutting it down.

20.
arXiv (CS.AI) 2026-06-19

Evaluation of EEG Foundation Models for Event-Based Burst-Suppression Detection in ICU

arXiv:2606.20074v1 Announce Type: cross Abstract: Burst suppression (BS) is a clinically relevant electroencephalographic (EEG) pattern used to monitor sedation depth and brain activity in critically ill patients, particularly during induced coma in Intensive Care Units (ICUs). Automatic burst detection remains challenging because BS patterns vary substantially between patients and annotated datasets are scarce. Recently, EEG Foundation Models (FMs) have shown promise across several downstream EEG applications, but their usefulness for BS detection remains unexplored. We present the first study to evaluate EEG FMs for burst detection in reduced-montage ICU EEG without patient-specific calibration. We compare REVE-base, LUNA-large and LuMamba-Tiny with an adaptive thresholding baseline and a task-specific EEGNet baseline. Additionally, we complement conventional EEG window-based classification with event-based burst detection evaluation. This helps assessing clinically whether burst episodes are correctly detected, reducing the impact of expected annotation variability. The best model, REVE-base, achieved the highest event-based F1-score ($0.868 \pm 0.167$) and reduced burst-per-minute error by 52.1% and 36.2% compared to EEGNet and adaptive thresholding respectively, supporting FMs for scalable EEG monitoring in ICU. Ablation experiments showed that full fine-tuning was the most effective adaptation strategy with respect to frozen-backbone training, two-step fine-tuning, and LoRA-based adaptation, improving event-based F1-score over frozen-backbone training by up to $+0.102$ for LUNA-large. With reduced labeled datasets, pretrained REVE-base outperformed random initialization by $+0.723$ event-based F1 points at 25% of the cohort, demonstrating the benefit of pretraining FM representations when adapted to burst detection with limited labeled data.

21.
PLOS Computational Biology 2026-06-05

A multiscale, Bayesian inference approach to augment mechanistic models of cell signaling with machine-learning predictions of binding affinity

by Holly A. Huber, Stacey D. Finley Computational models in systems biology are often underdetermined—that is, there is little data relative to the complexity and size of the model. This lack of data is primarily due to limits in our ability to observe specific biological systems and restricts the utility of computational models. To reduce this uncertainty, recent methods have explored augmenting parameter inference of systems biology models with predictions from machine learning models. Such approaches expand the pool of data that is applicable for the inference problem. Here, we explore augmenting the parameter inference of intracellular signaling models. We choose to investigate signaling because experimental measurements of the variables of interest, protein dynamics, are still quite limited. To investigate, we propose a novel, multiscale, Bayesian inference approach that augments traditional signaling data with predictions of binding affinity. These predictions are generated using a machine learning pipeline with measurements of amino acid sequence, from the Universal Protein Resource, or protein structure, from the Protein Data Bank, as inputs. We find that we can successfully integrate these measurements into the inference problem using our novel framework. Excitingly, this integration significantly improves the parameter estimates of signaling models. We demonstrate that how much this improvement impacts predictions of signaling depends on the sensitivity of the prediction to perturbations in the parameter values. Overall, the framework we establish here improves the parameter inference of intracellular signaling models by successfully bridging data on protein sequence and structure with systems-level signaling.

22.
medRxiv (Medicine) 2026-06-16

Deployment-readiness audit of calibration, clinical utility, and fairness in perioperative infection prediction

Objective: Clinical risk scores intended to guide patient-level decisions can show strong average performance. However, predicted probabilities can be systematically too high or too low in specific subgroups even when overall performance is strong. We audited deployment readiness of a strong end-of-surgery postoperative infection model across clinically relevant subgroups and tested mitigation strategies in miscalibrated subgroups. Materials and Methods: We analyzed out-of-fold predictions for 10,719 surgical procedures at a Swiss tertiary hospital, with 504 postoperative bacterial infection events. Prespecified axes were recorded sex, age stratum, and an EHR-derived physiological-reserve proxy. Within subgroups and pairwise intersections, we evaluated discrimination, calibration, threshold-specific errors, and decision-curve net benefit at the prespecified operating threshold. We compared group-specific isotonic recalibration with Wasserstein-barycenter postprocessing and demonstrated portability in SUPPORT2. Results: Overall AUROC was 0.876. While sex-marginal discrimination was similar in women and men (0.878 vs 0.875), age and reserve stratification revealed deployment-readiness failures. Calibration-in-the-large ranged from -0.86 in frail patients to -2.47 in non-frail patients. At the 0.10 operating threshold, decision-curve net benefit was positive in frail patients but negative in pre-frail and non-frail patients. Isotonic recalibration corrected average physiological-reserve-stratified calibration without worsening Brier scores, whereas Wasserstein postprocessing worsened calibration in most procedure clusters. Discussion: Discrimination-only or sex-marginal evaluation would have missed subgroup failures with clinical-utility implications. Conclusion: Subgroup fairness audits for clinical deployment should jointly evaluate discrimination, calibration, and utility. We implemented the audit as the open-source isitfair framework for identifying deployment-relevant subgroup failures, comparing mitigation strategies, and generating structured reports.

23.
arXiv (CS.CL) 2026-06-15

The Coin Flip Judge? Reliability and Bias in LLM-as-a-Judge Evaluation

Authors:

LLM-as-a-Judge is now widely used to rank model outputs, train reward models, and populate public leaderboards, but its run-to-run reliability remains under-characterized. We study repeated identical evaluations on 29 tasks spanning 10 categories using two OpenAI judge models (GPT-4o-mini and GPT-4.1-mini), with 50 pairwise trials and 50 pointwise trials per question, supplemented by temperature and prompt-sensitivity ablations. Across judges, pairwise preferences flip on average 13.6% of the time, with 28% of questions exceeding a 20% flip rate and one question reaching 56%. GPT-4o-mini also exhibits a significant first-position bias (72% A-majority, p = 0.024). At the same time, mean pointwise score gaps are small (0.19–0.36 on a 10-point scale) and not statistically significant in aggregate, producing a pairwise–pointwise gap: judges frequently choose a winner even when their own scalar scores provide little evidence of a meaningful quality difference. Beyond within-judge instability, cross-judge agreement is only 76% ($\kappa = 0.51$), semantically equivalent prompt templates change majority outcomes in 25% of tested cases, and deterministic decoding reduces but does not eliminate inconsistency. A reliability curve analysis shows that, in our dataset, 11 repeated trials are needed for a majority vote to recover the 50-trial reference verdict with 95% probability on average, rising to 15 for high-variance questions. These findings suggest that single-trial LLM judging is often too noisy for high-stakes evaluation, and that multi-trial aggregation, position randomization, and explicit uncertainty reporting should be standard practice. Because both judges are from a single provider, cross-provider replication remains an important next step.

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

Accelerating Multimodal Large Language Models with Prior-Corrected Token Reduction

Visual token reduction has emerged as an effective strategy for accelerating Multimodal Large Language Models (MLLMs). Many existing methods prune tokens by ranking text-visual attention scores. However, we show that attention is often dominated by a model-induced prior: even without textual instruction, MLLMs tend to focus on certain task-agnostic regions. Consequently, the attention scores of instruction-conditioned tokens are suppressed, increasing the risk that these tokens are discarded during pruning. To address this issue, we propose Prior-Corrected Token Reduction (PriorTR), a training-free token reduction method that explicitly separates task-conditioned attention from the model-induced prior. PriorTR estimates the attention map of the prior, and contrasts it with the task-conditioned attention distribution to measure the additional usable information contributed by each visual token. Importantly, PriorTR computes both the model-induced prior and the task-conditioned posterior within a single forward pass by introducing a null token that serves as an instruction-agnostic probe in the attention block. This design avoids duplicated propagation. Extensive experiments across multiple multimodal benchmarks and MLLMs demonstrate that PriorTR consistently improves the trade-off between accuracy and efficiency over strong training-free baselines, particularly under aggressive token budgets.

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

Towards Fully Automated Exam Grading: Fairness-Aware Recognition of Handwritten Answers with Foundation Models

Correcting handwritten exams by hand is time-consuming and error-prone, particularly for large cohorts, while fully digital exams tend to force a didactic narrowing towards closed question formats. A practical middle ground keeps paper-based, problem-oriented tasks but records the assessment-relevant answers as single capital letters in a table that a machine can read. The open question is whether this reading can be made accurate and, above all, fair enough for unsupervised grading. Earlier automated approaches reached only about 88%–91% recognition – too low – and failed on the cases that matter most: answers placed outside the cell, crossed out, or written in cursive. We show that general-purpose vision-language foundation models (VLMs), which interpret the page rather than match pixel templates, close this gap. On a benchmark of 61 anonymised exams (3141 answer positions) the best model reaches 98.4% accuracy, well above the previous baseline. Crucially, we centre the evaluation on fairness: we distinguish false negatives (a correct answer marked wrong, which disadvantages the student) from false positives, and a lightweight prompt that supplies the reference solution as context lowers the false-negative rate to 0.58%. Under an exemplary grading scheme only three of the 61 exams would be graded worse, all caught by a student self-review step. Fully automated, fairness-aware exam grading at scale is therefore defensible; we release the anonymised benchmark to support reproducibility.