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01.
arXiv (CS.AI) 2026-06-19

The Autonomy Tax: Defense Training Breaks LLM Agents

arXiv:2603.19423v2 Announce Type: replace-cross Abstract: Large language model (LLM) agents increasingly rely on external tools (file operations, API calls, database transactions) to autonomously complete complex multi-step tasks. Practitioners deploy defense-trained models to protect against prompt injection attacks that manipulate agent behavior through malicious observations or retrieved content. We reveal a fundamental capability-alignment paradox: defense training designed to improve safety systematically destroys agent competence while failing to prevent sophisticated attacks. Evaluating defended models against undefended baselines across 97 agent tasks and 1,000 adversarial prompts, we uncover three systematic biases unique to multi-step agents. Agent incompetence bias manifests as immediate tool execution breakdown, with models refusing or generating invalid actions on benign tasks before observing any external content. Cascade amplification bias causes early failures to propagate through retry loops, pushing defended models to timeout on 99\% of tasks compared to 13\% for baselines. Trigger bias leads to paradoxical security degradation where defended models perform worse than undefended baselines while straightforward attacks bypass defenses at high rates. Root cause analysis reveals these biases stem from shortcut learning: models overfit to surface attack patterns rather than semantic threat understanding, evidenced by extreme variance in defense effectiveness across attack categories. Our findings demonstrate that current defense paradigms optimize for single-turn refusal benchmarks while rendering multi-step agents fundamentally unreliable, necessitating new approaches that preserve tool execution competence under adversarial conditions.

02.
arXiv (CS.CL) 2026-06-18

Evaluating Prompting-Based Defenses Against Domain-Camouflaged Injection Attacks

作者:

Domain-camouflaged injection attacks embed malicious instructions in retrieved content using domain-appropriate vocabulary, evading standard detectors that rely on syntactic injection markers. When detection fails, practitioners need to know which defense architectures reduce attack success. We evaluate five prompting-based defenses (spotlighting, paraphrasing, prompt sandwiching, and two combinations) against domain-camouflaged injection across three model families (Claude Haiku, Llama 3.1 8B, Gemini 2.0 Flash) and three deployment domains (financial, legal, general) using 3,510 trials. Paraphrasing retrieved content before agent processing is the most consistently effective defense in this benchmark, reducing camouflage attack success rate by 55-84\% depending on model, and achieves lower attack success rates than our Llama Guard 4 configuration on every model tested. Defense effectiveness is strongly model-dependent: spotlighting halves attack success on Claude Haiku but provides no benefit on Llama 3.1 8B. Financial domain deployments face the highest residual risk at 26-33\% baseline attack success rate, with no prompting-based defense fully eliminating the threat on weaker models. These results provide the first systematic evaluation of prompting-based defenses specifically against camouflage-class injection attacks and establish benchmark-based recommendations for practitioners. All tasks use synthetically constructed professional documents; whether these benchmark rankings generalize to real enterprise documents remains an open question.

03.
arXiv (CS.CL) 2026-06-17

The Benchmark Illusion: Pruned LLMs Can Pass Multiple Choice but Fail to Answer

Compressing large language models reduces memory use and inference cost, but it can also create failures that standard benchmarks miss. A pruned model may still perform well on multiple-choice evaluations, yet fail to answer the same question in open generation. We ask what pruning changes: does it erase the correct answer, or does it make the answer harder to produce as the top output? We study this question with multilingual question answering, tracking the same questions before and after pruning. We find a benchmark illusion. Under high-sparsity pruning, especially Wanda, models often fail in greedy open generation while still selecting the correct answer under multiple-choice scoring. In these recognition-only errors, the answer is usually not gone, but demoted: it often reappears with beam search, sampling, or one in-context example. Overall, multiple-choice benchmarks can overstate the usability of compressed LLMs, creating an evaluation blind spot. Compressed models should be tested on what they can produce, not only on what they can recognize.

04.
arXiv (CS.CL) 2026-06-11

Beyond Fully Random Masking: Attention-Guided Denoising and Optimization for Diffusion Language Models

Diffusion large language models (dLLMs) offer an efficient alternative to autoregressive models through parallel decoding, yet existing post-training methods largely rely on random masking strategies that overlook intrinsic token dependencies. In this work, we present an empirical analysis of attention in dLLMs and show that tokens attending more strongly to unmasked context exhibit greater generation stability and play a critical role in reasoning. Motivated by these findings, we propose AGDO, an attention-guided denoising and optimization framework that aligns both training and optimization with attention-derived dependencies. AGDO determines the denoising order based on attention structure and emphasizes attention-critical tokens during supervised fine-tuning and reinforcement learning. Experiments on mathematical and coding benchmarks demonstrate that AGDO consistently improves reasoning performance, outperforming state-of-the-art post-training methods for dLLMs.

05.
medRxiv (Medicine) 2026-06-18

Guiding the development of climate counterfactuals for health impact attribution studies

Climate change detection and attribution (D&A) methods have become vital for quantifying the influence of anthropogenic forcing on the Earth's systems, including human health. Health impact attribution (HIA) studies seek to disentangle climate-driven health effects from natural variability yet are often constrained by the availability of accessible counterfactual climate scenarios. This tutorial paper presents a flexible, reproducible framework for developing counterfactual climates without reliance on computationally intensive global circulation models. We provide practical, R-based methodologies for constructing both trend-based (temperature and non-temperature) and event-based counterfactual, using a variety of techniques including model residual detrending, data-driven decomposition (e.g., Singular Spectrum Analysis and Empirical Mode Decomposition) and stochastic weather generators. The tutorial also explores the incorporation of greenhouse gas concentrations as forcing variables, rather than global mean temperature anomalies. By operationalising these methods through worked examples and an open code repository, this paper aims to build capacity within the HIA community, enhance methodological transparency, and foster interdisciplinary collaboration between climate and health researchers.

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

LiAuto-GeoX: Efficient Grounded Driving Transformer

Dense 3D reconstruction has demonstrated immense potential for spatial understanding, yet its viability as a real-time, onboard representation for autonomous driving remains an open challenge. Existing large-scale visual geometry models typically require substantial computational resources and lack the long-range geometric fidelity, surround-view consistency, and real-time efficiency demanded by dynamic driving environments. To bridge this gap, we present LiAuto-GeoX, an efficient grounded driving transformer designed for deployable, ego-centric 3D scene understanding. Our approach begins by learning a high-capacity driving geometry model from large-scale surround-view data, utilizing sparse LiDAR priors to provide robust geometric grounding in distant, ambiguous, or structure-sparse regions. We then instantiate this capability into a highly compact 155M-parameter onboard model through a novel geometry-preserving distillation framework. This framework employs mask-guided depth-aware distillation to retain fine-grained metric structures by emphasizing geometrically informative regions, and relative-pose relational distillation to enforce cross-view spatial consistency through pose-induced geometric relations. Extensive evaluations reveal that LiAuto-GeoX runs at 220 FPS on KITTI while maintaining high-fidelity dense reconstruction, enabling real-time deployment. The learned geometry transfers seamlessly to downstream autonomy tasks, achieving 90.6 PDMS in trajectory prediction, 24.63 mIoU in occupancy prediction, and 47.67 IoU in future-frame prediction. These all demonstrate that efficient dense 3D reconstruction can transcend its traditional role as a perception target to serve as a scalable, foundational geometric representation for next-generation autonomous driving.

07.
arXiv (CS.AI) 2026-06-12

Benchmarking Counterfactual Prediction in Epidemic Time Series with Time-Varying Interventions

arXiv:2606.05692v2 Announce Type: replace-cross Abstract: Deep learning has enabled significant advances in time-series causal inference, yet progress remains constrained by the lack of realistic benchmarks with observable counterfactual outcomes. Existing datasets either rely on real-world observations without ground-truth counterfactuals or on simplified simulations that fail to capture complex causal dynamics. To address this gap, we develop a large-scale benchmark for counterfactual prediction in epidemic time series under dynamic interventions. Unlike existing benchmarks, it supports static and time-varying treatments, as well as both single-policy and multi-policy intervention settings, enabling evaluation of causal inference methods across a broad range of causal inference scenarios. Leveraging a calibrated agent-based model grounded in real-world demographic, mobility, epidemiological, and policy data, we generate realistic counterfactual trajectories across more than 150 U.S. counties. Using this benchmark, we evaluate widely used and state-of-the-art causal inference methods, revealing substantial performance differences and highlighting the challenges of realistic time-series causal reasoning.

08.
arXiv (CS.AI) 2026-06-16

CRC-Screen: Certified DNA-Synthesis Hazard Screening Under Taxonomic Shift

作者:

arXiv:2605.00074v2 Announce Type: replace-cross Abstract: DNA-synthesis providers screen incoming orders by searching the requested sequence against curated hazard lists. We show that this baseline collapses to a 100% false-flag rate when the hazardous sequence comes from a taxonomic family absent from the reference set: under Conformal Risk Control's certified miss-rate constraint, a low-discrimination signal forces the threshold below the entire test-benign mass. We compose three signals derived from a synthesis order's public annotation: $k$-mer Jaccard similarity to known toxins, the trimmed-mean score of a five-LLM judge panel, and cosine similarity to clustered embedding centroids. Fused under a monotone logistic aggregator and calibrated by Conformal Risk Control, the resulting screener certifies $\mathbb{E}[\mathrm{FNR}] \le \alpha + \mathrm{TV}$, where the additive term is the calibration-to-test distribution shift under family holdout (a certified ceiling of 24-49% across folds). Across ten leave-one-taxonomic-family-out folds at $\alpha=0.05$ on UniProt KW-0800 reviewed toxins, the calibrated screener achieves 0% empirical test miss rate on every fold and 0% test false-flag rate on nine of ten folds. The bound's finite-sample slack $1/(n_{\mathrm{cal}}+1)$ caps the certifiable miss rate at 1.77% on our 200-hazard subsample; reaching procurement-grade $\alpha=10^{-3}$ requires an $18\times$ larger calibration set, which the full reviewed UniProt KW-0800 corpus is large enough to deliver. The binding constraint on certifiable DNA-synthesis screening is calibration data, not algorithms. Code: https://github.com/najmulhasan-code/crc-screen

09.
arXiv (quant-ph) 2026-06-16

High-Order Hermite Optimization: Fast and Exact Gradient Computation in Open-Loop Quantum Optimal Control using a Discrete Adjoint Approach

arXiv:2505.09857v5 Announce Type: replace-cross Abstract: This work introduces the High-Order Hermite Optimization (HOHO) method, an open-loop discrete adjoint method for quantum optimal control. Our method is the first of its kind to efficiently compute exact (discrete) gradients when using continuous, parameterized control pulses while solving the forward equations (e.g. Schrodinger's equation or the Linblad master equation) with an arbitrarily high-order Hermite Runge-Kutta method. The HOHO method is implemented in QuantumGateDesign$.$jl (https://github.com/leespen1/QuantumGateDesign.jl), an open-source software package for the Julia programming language, which we use to perform numerical experiments comparing the method to Juqbox$.$jl (https://github.com/LLNL/Juqbox.jl). For realistic model problems we observe speedups up to 775x.

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

Pano3D: Unified 3D Reconstruction and Panoptic Segmentation

Recent advances in 3D feedforward reconstruction neural networks have achieved remarkable success in dense reconstruction from images without any camera parameters. Yet, equipping these models with robust semantic understanding remains an open problem. Here we introduce an approach that performs 3D reconstruction and 3D panoptic segmentation in a unified framework. We build on existing 3D reconstruction models and augment them with a set-based mask decoder. The approach is jointly trained with a geometric and semantic loss, which are shown to be mutually beneficial. More precisely, the features are initialized from the geometric information and then finetuned to capture jointly geometry and semantics. We demonstrate the generality of our approach by successfully applying our framework both to online and all-to-all attention reconstruction backbones. Our method achieves state-of-the-art performance in 3D panoptic segmentation across ScanNet, ScanNet200, and ScanNet++ datasets. Ablation studies show that such joint training of a unified model equips 3D feedforward reconstruction neural networks with panoptic segmentation and yields mutually beneficial improvements.

11.
arXiv (CS.AI) 2026-06-18

Optimizing Lithium Production Decisions under Geological, Demand, and Pricing Uncertainties: A POMDP Framework for Multi-Objective Decision Making

arXiv:2606.18598v1 Announce Type: new Abstract: Decision making in lithium production is challenging, whether from an investor's perspective or a strategic production standpoint. Determining which mines to open and when to open them involves not only geological and price uncertainties, but also complexities around the choice of extraction method, from direct lithium extraction to hard rock mining. Prior work explored models of this problem and different methods to optimize mining decisions; these models did not account for uncertainty in pricing, uncertainty in demand, or different mining technologies to extract lithium. Incorporating different pricing models and extraction technology into these models enables more robust strategies for determining not only when and where to open a mine, but also which method of production to pursue. We frame the problem as a partially observable Markov decision process (POMDP) and solve using belief state planning methods to get optimal decision making. In our study, we show that POMDP solvers outperform human inspired heuristics by dynamically adapting to shifting lithium price regimes (static, linear, exponential, and stochastic) through belief state planning and explicit uncertainty management. By optimally sequencing exploration, production, and technology choice, the framework achieves higher demand fulfillment and more balanced economic environmental outcomes over the projects lifetime in all different pricing and deposit scenarios.

12.
arXiv (quant-ph) 2026-06-19

Computing noise-canceling observables via Pauli propagation

arXiv:2606.20441v1 Announce Type: new Abstract: The pursuit of quantum advantage is driving the co-evolution of quantum processors and classical simulation methods. Despite advances in scale and quality, the accuracy of quantum simulation is ultimately limited by error rates and sampling overheads. Similarly, while classical simulation methods such as Pauli propagation have made remarkable progress, their accuracy is ultimately limited by the exponential growth of operator paths and the truncations needed to control memory and runtime. Here we show that these complementary limitations can be mitigated by embedding Pauli propagation within a hybrid error-mitigation framework that reduces quantum sampling overhead while achieving lower truncation errors with fewer classical resources than traditional Pauli propagation alone. In this framework, a target observable is classically propagated through noise-canceling inverse channels, producing a modified observable that is measured directly on a quantum processor. We prototype two implementations and benchmark their performance numerically on canonical models that challenge traditional Pauli propagation. We also perform experiments on a quantum processor using 56 superconducting qubits, revealing the tradeoffs of their respective truncation strategies. These results illustrate how classical and quantum resources can be orchestrated to extend observable estimation beyond the limits of either approach alone, providing a foundation for quantum-centric supercomputing and future demonstrations of quantum advantage.

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

ChLogic: Evaluating Robustness of Logical Reasoning in Chinese Expressions

Large language models perform increasingly well on standardized logical reasoning benchmarks, but whether this ability remains robust beyond English is unclear. We introduce ChLogic, an English–Chinese aligned benchmark that tests whether models preserve logical reasoning performance when the same latent logical structure is expressed in English and diverse Chinese surface realizations. Built from formal logical templates, the benchmark contains three data sets: (i) the General aligned set, derived from 60 General Propositions across nine template families; (ii) the Difficult aligned set, derived from 40 Difficult Problems; and (iii) the Chinese-only set, covering 15 language-specific phenomenon types. Each aligned item pairs one English reference expression with five Chinese realizations. Experiments on Qwen3, Ministral, and GLM models reveal a persistent English–Chinese performance gap. Back-translation from standard Chinese into English often improves performance on the General aligned set, but produces mixed effects on the Difficult aligned set, where Qwen3-32B and GLM-5.1 perform worse after translation. These results indicate that Chinese surface realization, translation artifacts, and model-specific behavior jointly affect multilingual logical reasoning. Overall, ChLogic provides a useful stress test for the robustness of multilingual reasoning.

14.
arXiv (CS.AI) 2026-06-24

SemChunk-C: Semantic Segmentation for C Code

arXiv:2606.23697v1 Announce Type: cross Abstract: Semantic segmentation of code written in a C-family language remains a challenging problem, due to the language's complex syntax, macro expansion, and irregular structural patterns. Existing chunking methods, such as fixed-sized windows, heuristic splitting, and syntax-based tools, often fail to capture meaningful functional units, limiting the efficacy of retrieval and other downstream LLM driven tasks. In this paper, we address the problem of chunking in C-related languages. First, we define a set of code chunk categories. Second, we train an LLM-based classifier to a) identify chunk boundaries, and b) assign each chunk a descriptive functional attribute (a category), which can be useful for downstream tasks. By leveraging the LLM's ability to capture semantic context within the code, we assume flexible chunk boundaries, allowing to adapt to the specific structure and context of each instance. Third, we introduce SemChunk-C, a family of lightweight language models for semantic chunking of C-related files (.c, .cpp, .h, .cs, etc.). These models are based on the first four Ettin encoders [1] with 17M, 32M, 68M, and 150M parameters. Despite their relatively small size, they are capable of identifying cohesive code units, such as data structures, interface blocks, and other components. Furthermore, we demonstrate the robustness of our approach on real-world code, including challenging constructs such as nested definitions and macros. We test our approach on various datasets, and show that it achieves high boundary accuracy and semantic coherence, matching or outperforming chunkers that are based on much larger code-oriented LLMs. We also validate the improved performance of the downstream tasks on a few curated benchmarks.

15.
arXiv (CS.CL) 2026-06-12

sebis at CRF Filling 2026: A Two-Stage Local LLM Pipeline for Medical CRF Filling

The extraction of structured clinical information from unstructured EHR notes is a persistent bottleneck in healthcare informatics. While large language models (LLMs) offer high performance, their deployment in clinical settings is hindered by privacy risks, inference costs, and the tendency to hallucinate beyond textual evidence. We address these challenges for the CL4Health 2026 Case Report Form (CRF) filling task by proposing a fully local, domain-adapted pipeline using the MedGemma-27B model. Our two-stage architecture, which separates binary presence classification from value extraction, enforces strict adherence to textual evidence and ensures deterministic outputs for negated, uncertain, or unknown states. By leveraging item-specific, few-shot in-context learning without external API calls or fine-tuning, our approach achieves a macro-F1 score of 0.55 on the official English test track. This result secures second place among all locally-hosted, open-source submissions. Our work demonstrates that privacy-preserving, on-premise LLM pipelines can achieve near-competitive performance with proprietary frontier models, providing a practical, data-sovereign framework for clinical NLP.

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

Grouped Query Experts: Mixture-of-Experts on GQA Self-Attention

arXiv:2606.20945v2 Announce Type: replace Abstract: Self-attention is central to Transformer performance and is often the most expensive part of the Transformer at long context lengths because its pairwise token interactions scale quadratically with sequence length. Standard dense attention also applies the same set of attention heads to every token regardless of token difficulty or information content. This uniform activation can waste compute, especially as sequences grow longer and attention cost increases rapidly. We propose Grouped Query Experts (GQE), a mixture-of-experts layer on top of grouped-query attention (GQA). Within each GQA group, a router selects k query-head experts per token while all key-value (KV) heads remain dense and unchanged. Thus, GQE keeps the KV cache benefits of GQA and reduces only the active query-head computation. On a fixed 30B token budget at the 250M parameter scale, GQE matches the all-active GQA baseline in downstream accuracy while activating half the query heads per token.

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

Learning from Own Solutions: Self-Conditioned Credit Assignment for Reinforcement Learning with Verifiable Rewards

arXiv:2606.18810v1 Announce Type: cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has driven substantial progress in training LLMs for reasoning tasks, but representative methods such as GRPO assign uniform credit across all tokens, wasting gradient on routine tokens while under-crediting pivotal reasoning steps. Existing token-level credit assignment methods require resources beyond the model's own rollouts. GRPO variants rely on process reward models or ground-truth answers. Knowledge distillation assigns credit through per-token divergence but requires external teachers (On-Policy Distillation) or privileged information (On-Policy Self Distillation). However, these dependencies limit applicability in the pure RLVR setting. We observe that conditioning the model on its own verified trajectories induces a measurable per-token KL divergence between the original and conditioned distributions, and prove that distilling from a self-teacher constructed by verified trajectories leads to infeasible weighted-average solutions when multiple verified trajectories exist. We propose SC-GRPO (Self-Conditioned GRPO), which uses KL divergence mentioned before as a multiplicative weight on GRPO gradients. Across five benchmarks spanning math, code, and agentic tasks, SC-GRPO consistently outperforms 8.1% over GRPO and 5.9% over DAPO with stronger OOD performance. Moreover, SC-GRPO achieves higher performance than OPD.

18.
arXiv (CS.LG) 2026-06-16

An Integrable Token Mixing Layer from the Generalized Yang Baxter Equation

arXiv:2606.15085v1 Announce Type: new Abstract: The YB Mixer is a sequence token mixing layer derived from free fermion and generalized Yang Baxter structures. It applies a core principle from integrable systems where a local algebraic constraint guarantees global computational stability. By using the Ising exchange algebra the mixer creates a free fermionic structure that acts as an exactly norm preserving orthogonal map. This algebra also produces commuting transfer matrices which allow inference to be order free and adaptable to any variable budget. To ensure the model can generalize to longer sequence lengths it uses a spectral circulant generator. This generator maintains the crucial orthogonal and commuting properties of the system. The result is a highly stable and mathematically grounded architecture for sequence processing.

19.
medRxiv (Medicine) 2026-06-22

Level of Physical Activity and ApoE Status - Effects on Alzheimer's Disease and on Mortality

Background: Alzheimer's disease and related dementias (ADRD) affect over 7.2 million Americans aged 65 and older, with the APOE-4 allele representing the strongest known genetic risk factor. Physical activity (PA) has been associated with reduced dementia risk, but its interaction with APOE genotype remains poorly characterized in large, genomically informed cohorts. Methods: We conducted a retrospective cohort analysis using linked genomic, survey, and longitudinal electronic health record data from the VA Million Veteran Program (MVP). Veterans aged

20.
arXiv (CS.CV) 2026-06-16

Beer-Lambert Guided Representation Learning for Unsupervised Anomaly Detection in Sub-THz Food Inspection Images

Food manufacturing requires reliable inspection systems to detect foreign material contamination and maintain product safety. Sub-THz transmission imaging provides material-dependent attenuation characteristics that are useful for detecting low-density contaminants in food products. However, existing unsupervised anomaly detection methods mainly rely on RGB-pretrained visual representations, which may not adequately capture the transmission behavior of Sub-THz images. This paper proposes a Beer-Lambert guided representation learning framework for unsupervised anomaly detection in Sub-THz food inspection images. The proposed method introduces an attenuation decomposition module as an auxiliary regularization module that constrains student representations through attenuation reconstruction during training. In addition to the conventional one-class setting, we introduce a Leave-One-Food-Out protocol to evaluate generalization capability under unseen food categories. Experimental results on the Inline-Food-Inspection-THz dataset show that the proposed method improves overall anomaly detection performance over the baseline method.

21.
arXiv (CS.CV) 2026-06-17

Vision-language models for chest radiography do not always need the image

Medical vision-language models report strong chest radiograph accuracy, and this is increasingly read as evidence that they use the image. That inference is unsafe: a model exploiting finding-name priors scores like one that reads the scan, and no standard benchmark separates them. We introduce a causal audit that intervenes on the image, occluding the relevant region, occluding an irrelevant one, and swapping in another patient's same-label scan, and combines three behavioral metrics to test whether a correct answer depends on the image. Across nine systems, a text-only model with no image access reaches within 5.7 accuracy points of the best multimodal one, and a 119-billion-parameter multimodal model is statistically indistinguishable from a 7-billion text-only baseline. The audit splits the cohort into three models that ignore the image, one that is unstable, and five that use it selectively, for a subset of findings; the categories hold across a second dataset, resolution, and prompt phrasing. Against board-certified radiologists, a text-only model is statistically indistinguishable from a radiologist's accuracy while grounding at zero, whereas the image-using models ground at radiologist-comparable rates. Reported confidence flags ungrounded answers only when a model uses the image. Grounding audits, not accuracy, should gate clinical deployment.

22.
arXiv (CS.LG) 2026-06-24

A Physics-Informed Fourier-Wavelet Transformer for Multiscale Computational Fluid Dynamics Surrogate Modeling

arXiv:2606.24696v1 Announce Type: cross Abstract: Physics-informed surrogate models can accelerate computational fluid dynamics simulations. However, many existing methods reproduce global flow patterns more reliably than localized multiscale structures. This study presents a physics-informed Fourier-wavelet transformer for next-step velocity-field reconstruction in real-world flow benchmarks. The proposed formulation combines hybrid Fourier-wavelet spectral encoding with physics-biased self-attention based on partial differential equation residual diagnostics. It also uses self-supervised pretraining through Masked Physics Prediction and Equation Consistency Prediction. The experiments are conducted on two real benchmark cases: cylinder-wake flow and fluid-structure interaction. All approaches are evaluated under a shared local protocol and compared with spectral, transformer-based, operator-learning, and physics-informed neural-network baselines. On the cylinder-wake benchmark, the proposed model achieves the best aggregate accuracy, with an all-channel normalized mean-squared error of 0.05875 and an all-channel Pearson correlation coefficient of 0.97019. On the fluid-structure-interaction benchmark, it gives the lowest all-channel normalized mean-squared error of $2.70 \times 10^{-4}$, compared with $4.02 \times 10^{-4}$ for the strongest baseline. Component-wise field comparisons and scale-separated diagnostics further show stronger recovery of localized wake structures, including near-body, wake-core, and far-wake features. The results demonstrate improved real-world flow reconstruction while maintaining a practical accuracy-cost tradeoff.

23.
bioRxiv (Bioinfo) 2026-06-14

FENNEC: Fine-Tuned Ensemble Neural Networks Accelerate Chemically Modified siRNA Design and Screening

Small interfering RNAs (siRNAs) are a clinically validated therapeutic modality, yet designing potent chemically modified siRNAs remains a costly and iterative process, limited by scarce public data. Computational prediction of siRNA efficacy is therefore essential for rational design and accelerated preclinical development. However, despite the critical role of chemical modifications in therapeutic performance, current state-of-the-art machine learning methods either are not designed to model the chemical diversity of therapeutic siRNAs, or exhibit poor generalization performance. Here, we present FENNEC (Fine-Tuned Ensemble of Neural Networks for siRNA Efficiency Characterization), a machine-learning framework for predicting siRNA activity across chemically diverse design spaces. To support this effort, we curated the largest patent-derived dataset to date of chemically modified siRNAs from 42 patents using OCR-based table extraction and stringent filtering. FENNEC combines temporal convolutional networks with thermodynamic descriptors, experimental covariates, and embeddings from RNA foundation models to capture both local chemical determinants and broader target-context information. Importantly, we show that language-model-derived embeddings provide meaningful higher-order representations of target transcripts, particularly in data-scarce settings. FENNEC achieved robust predictive performance across both gene-level and scaffold-level validation settings, with additional experimental validation on a novel AHSA1-targeting dataset further supporting its generalizability across chemically modified siRNAs. In benchmarking, FENNEC outperformed classical machine-learning and state-of-the-art deep learning models, demonstrating generalization to unseen chemistry. Model interpretation recovered established design principles, including position-specific effects of glycol nucleic acid, 2'-fluoro modifications, and phosphorothioate backbones. Furthermore, in silico perturbation analyses suggest that FENNEC can serve not only as a predictive model, but also as an oracle for the design and optimization of chemically modified siRNAs. Together, our work addresses a key gap in the field by enabling chemically aware deep learning for siRNA design, supported by a large and diverse collection of chemically modified siRNA measurements.

24.
arXiv (CS.CL) 2026-06-12

The Illusion of Multi-Agent Advantage

Prevailing wisdom posits that Multi-Agent Systems (MAS) are superior to Single-Agent Systems (SAS), citing advantages like context protection, parallel processing and distributed decision-making. However, empirical support for this claim relies primarily on comparisons with SAS baselines using benchmarks that prioritize isolated reasoning tasks, which do not adequately assess these advantages. Focusing on automatically generated MAS that are designed for enhanced generalizability over manually-designed counterparts, we perform a rigorous, systematic evaluation against SAS, specifically Chain-of-Thought with Self-Consistency (CoT-SC). Across traditional reasoning datasets and tasks with interactive multi-step workflows (e.g., BrowseComp-Plus), we demonstrate that automatic MAS consistently underperform CoT-SC despite being up to 10x more expensive. To isolate these failures from limitations inherent to task structure, we introduce a diagnostic synthetic dataset tailored for MAS featuring explicit task decomposition, context separation and parallelization potential. We show that expert-architected MAS consistently outperforms automatically generated architectures in both raw performance and cost-efficiency on this dataset, demonstrating that existing evaluation frameworks mask critical architectural gaps and inefficiencies of complex MAS by failing to account for the marginal utility of increased computational cost. Critically, systematic deconstruction of the generated MAS architectures reveals that current automated design paradigms produce architectural bloat that prioritizes superficial complexity which does not translate into functional utility, exposing a fundamental misalignment with multi-agent principles.

25.
bioRxiv (Bioinfo) 2026-06-18

Benchmarking gene expression reconstruction from single-cell latent representations

Single-cell transcriptomics is typically modeled in low-dimensional latent representations that improve the signal-to-noise ratio of the data. Such representations underpin data integration, cell state discovery, and perturbation prediction, with applications ranging from large-scale organ atlases to latent trajectory modeling. Recent virtual cell approaches further leverage these representations to predict cellular responses as distributional shifts in latent space. Each of these applications ultimately requires faithful gene expression reconstruction from latent spaces for biological interpretation, enabling gene-level analysis of predicted perturbed or batch-corrected cells. Yet representation choice is typically treated as an implementation detail rather than a primary modeling decision, with no systematic evaluation of how well latent representations support gene expression reconstruction. Here, we introduce ReconEval, a benchmark for evaluating gene expression reconstruction from single-cell latent spaces. We benchmark two classes of latent representations: end-to-end trained models such as PCA, autoencoders, and variational autoencoders, and pretrained single-cell foundation model embeddings coupled to newly trained decoders. Reconstruction is evaluated both directly and after latent-space perturbation prediction. Across perturbational and observational datasets totaling over 100 million cells, our metric suite quantifies statistical fidelity; biological signal preservation, including differential expression, coexpression, cell-cycle structure, cytokine response and pathway activity; and perturbation-specific effects. We find that autoencoders achieve the strongest stand-alone reconstruction at low dimensionality, while variational regularization does not improve generalization in reconstruction. Frozen foundation model embeddings retain recoverable gene-level information, with reconstruction quality depending strongly on decoder architecture and pretraining objective. In latent perturbation modeling, high-dimensional PCA matches foundation model embeddings, while low-dimensional AE embeddings are optimal for flow-based generative models. Overall, reconstruction depends critically on the interplay between representation and downstream model, and simpler representations can outperform complex alternatives given appropriate capacity. Our benchmark establishes reconstruction as a critical evaluation axis for single-cell foundation models. We envision it improving the biological interpretability of latent-space modeling, a prerequisite for future virtual cell models to be validated by domain experts and grounded in biology.