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01.
arXiv (CS.CL) 2026-06-17

Structural Role Injection in Handlebars-Templated LLM Prompts: Triple-Brace Interpolation, Delimiter Family, and the Limits of HTML Auto-Escaping

Large language model applications build prompts from templates, and Handlebars is a widely used templating engine and the default prompt-template format in Microsoft Semantic Kernel. Its double-brace {{x}} expression HTML-escapes the interpolated value and is documented as the safe default; its triple-brace {{{x}}} expression inserts the value raw. We show that this choice silently governs an application's exposure to structural role injection, where attacker-controlled data carries chat role delimiters that forge a higher-privilege turn. A model-free analysis establishes the mechanism: Handlebars escaping rewrites angle brackets but not square brackets, colons, or Markdown hashes, so it neutralises ChatML, Llama-3, and XML role delimiters (survival rate 0.00) while leaving Llama-2 [INST], legacy Human:/Assistant:, and Markdown ### delimiters intact (survival rate 1.00 for the last two). We then run 5760 trials across seven delimiter families, two attack objectives, and four models (GPT-3.5 Turbo, GPT-4o mini, GPT-4.1 mini, Claude Haiku 4.5) at a combined API cost of 1.63 USD. GPT-3.5 Turbo follows the task-hijack instruction in 97% of raw and 91% of escaped trials, with the escaping protection concentrated in the angle-bracket families and absent for the colon- and Markdown-based families; the harder secret-exfiltration objective, which does not saturate, exposes the same family interaction more cleanly. Claude Haiku 4.5 resists both objectives almost entirely. The escaped default protects only the delimiter schemes whose characters HTML escaping happens to cover, gives no protection for the rest, and cannot substitute for a structural separation of instruction and data.

02.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

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

Finite-Width Neural Tangent Kernels from Feynman Diagrams

arXiv:2508.11522v4 Announce Type: replace Abstract: Neural tangent kernels (NTKs) are a powerful tool for analyzing deep, non-linear neural networks. In the infinite-width limit, NTKs can easily be computed for most common architectures, yielding full analytic control over the training dynamics. However, at infinite width, important properties of training such as NTK evolution or feature learning are absent. Nevertheless, finite width effects can be included by computing corrections to the Gaussian statistics at infinite width. We introduce Feynman diagrams for computing finite-width corrections to NTK statistics. These dramatically simplify the necessary algebraic manipulations and enable the computation of layer-wise recursion relations for arbitrary statistics involving preactivations, NTKs and certain higher-derivative tensors (dNTK and ddNTK) required to predict the training dynamics at leading order. We demonstrate the feasibility of our framework by extending stability results for deep networks from preactivations to NTKs and proving the absence of finite-width corrections for scale-invariant nonlinearities such as ReLU on the diagonal of the Gram matrix of the NTK. We numerically implement the complete set of equations necessary to compute the first-order corrections for arbitrary inputs and demonstrate that the results follow the statistics of sampled neural networks for widths $n\gtrsim 20$.

04.
bioRxiv (Bioinfo) 2026-06-13

MoE-Bind: Guiding De Novo Protein Binder Generation with Sparse Experts

Authors:

De novo protein binder design has been dominated by structure-based pipelines that require known three-dimensional target conformations and consume substantial compute and generation time per design, limiting their throughput and accessibility for routine large-scale binder exploration. Sequence-only generative models promise a faster and lighter alternative, yet existing systems remain uniformly dense and frequently reintroduce structural computation at inference, undermining the core advantages they were intended to deliver. Across the broader language modelling community, transformers have meanwhile transitioned from fully dense designs to sparse Mixture-of-Experts architectures that decouple capacity from per-token compute, a shift that has yet to reach sequence-only protein binder generation. We present MoE-Bind, an autoregressive protein binder generator that, for the first time in this domain, combines Multi-head Latent Attention with a sparse Mixture-of-Experts feed-forward network and is evaluated under two independent structure predictors, Boltz-2 and AlphaFold2-Multimer. Despite activating less than half the per-token parameters of compute-matched dense baselines, MoE-Bind matches or exceeds them on full-length receptor-conditioned binder generation on a leakage-free Docking Benchmark 5.0 evaluation, transfers without peptide-specific training to short-peptide design, and reduces training and inference compute by a large margin. Routing analysis on generated binders reveals interpretable expert specialization at both the individual amino acid and biochemical group level, a structured expert-token alignment not previously reported for natural-language MoE models. These results show that sparse architectural design, rather than scale, can deliver fast, structure-free, and interpretable protein binder generation.

05.
arXiv (CS.CL) 2026-06-11

I Understand How You Feel: Enhancing Deeper Emotional Support Through Multilingual Emotional Validation in Dialogue System

Emotional validation - explicitly acknowledging that a user's feelings make sense - has proven therapeutic value but has received little computational attention. Emotional validation in dialogue systems can be decomposed into (i) validating response identification, (ii) validation timing detection, and (iii) validating response generation. To support research on all three subtasks, we release M-EDESConv, a 120k English-Japanese multilingual corpus created through hybrid manual and automatic annotation, and M-TESC, a multilingual spoken-dialogue test set. For timing detection, we propose MEGUMI, a Multilingual Emotion-aware Gated Unit for Mutual Integration, that fuses frozen XLM-RoBERTa semantics with language-specific emotion encoders via cross-modal attention and gated fusion. MEGUMI shows superior performance on both the M-EDESConv and M-TESC datasets, both objectively and subjectively. Finally, our EmoValidBench benchmarks of GPT-4.1 Nano and Llama-3.1 8B indicate that current LLMs generate contextually similar and diverse validating responses, but emotional understanding remains a major area for improvement. Project page: https://github.com/zihaurpang/Multilingual-Emotional-Validation

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

Text-Driven Fusion for Infrared and Visible Images: Achieving Image Scene Adaptation on Hyperbolic Space

Infrared and visible image fusion aims to integrate complementary modalities, while existing Euclidean methods impose rigid distance metrics that distort multi-modal interactions and parent-to-child semantic hierarchies. To overcome these limitations, we introduce a text-driven fusion framework empowered by hyperbolic manifold learning. During training, BLIP-extracted text prompts serve as topological anchors within the hyperbolic space, guiding vision-attribute alignment through hyperbolic embeddings that naturally accommodate varying semantic granularities. By exploiting the exponential volume growth dictated by the Poincaré ball's negative curvature, this approach seamlessly embeds hierarchical trees to encode coarse-to-fine semantics without metric saturation, while the vast peripheral space prevents texture distortion during cross-modal fusion. At inference, the fusion process autonomously adapts to input content using the learned text-attribute priors, completely eliminating the need for textual input. Experimental results show our method outperforms state-of-the-art approaches on benchmark datasets, with code available at https://github.com/Shaoyun2023/TEDFusion.

07.
arXiv (CS.LG) 2026-06-16

Contrastive Regularization for Accent-Robust ASR

arXiv:2605.03297v2 Announce Type: replace-cross Abstract: ASR systems based on self-supervised acoustic pretraining and CTC fine-tuning achieve strong performance on native speech but remain sensitive to accent variability. We investigate supervised contrastive learning (SupCon) as a lightweight, accent-invariant auxiliary objective for CTC fine-tuning. An utterance-level contrastive loss regularizes encoder representations without architectural modification or explicit accent supervision. Experiments on the L2-ARCTIC benchmark show consistent WER reductions across multiple pretrained encoders, with up to 25 – 29\% relative reduction under unseen-accent evaluation. Analysis using within-transcript cosine dispersion indicates that SupCon promotes more compact and stable representation geometry under accent variability. Overall, SupCon provides an effective and model-agnostic regularization strategy for improving accent robustness.

08.
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.

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

Lyapunov-Based Sample Complexity Analysis for Weakly-Coupled MDPs

arXiv:2606.14095v1 Announce Type: new Abstract: We study the sample complexity of learning in average-reward weakly-coupled Markov decision processes (WCMDPs) and Restless Bandits (RBs) under a generative model. Naive reduction to a tabular MDP leads to high complexity bounds as the state-action space is exponentially large in the number of arms $N$. By exploiting the weakly coupled structure, we show that near-optimal policies can be learned with sample and computational complexities that are polynomial in $N$. Specifically, we analyze the plug-in approach, which applies an efficient planning algorithm to an empirical model estimated from data. For fully heterogeneous WCMDPs, we establish the first finite-sample PAC guarantee with polynomial complexity and an $O(1/\sqrt{N})$ optimality gap. For homogeneous RBs, we further prove that a smaller optimality gap is achievable under mild structural assumptions. A primary technical contribution of our work is a novel Lyapunov-based analysis framework. Unlike classical approaches that rely on the difficult-to-control bias function, our framework uses an explicitly constructed Lyapunov function along with a drift transfer technique between the true and empirical models. A key step of independent interest in our framework is a fine-grained perturbation analysis for the underlying linear programming (LP) relaxation, which provides a general tool for analyzing LP-based policies and weakly-coupled systems.

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

Surprise-Guided MergeSort: Budget-Efficient Human-in-the-Loop Ranking via Adaptive Comparison Scheduling

arXiv:2606.15623v1 Announce Type: cross Abstract: Pairwise comparison is the gold standard for subjective ranking tasks; however, exhaustive annotation requires a massive number of human comparisons ($O(n^2)$). While sorting-based methods have reduced this burden to $O(n\log n)$, they still require expensive human judgment for every single comparison. To further improve annotation efficiency, we propose leveraging a Vision-Language Model (VLM) not as an annotator replacement, but as a question prioritizer to identify which comparisons genuinely require human judgment. The proposed Surprise-Guided MergeSort (SGS) framework achieves this through three integrated components: (1) a bottom-up MergeSort scheduler that structures comparisons and exploits transitivity, (2) a composite Surprise Scorer – combining position-bias-cancelled VLM confidence, Elo gap, and vote entropy – to quantify comparison ambiguity, and (3) an adaptive budget allocator that routes high-surprise pairs to humans while automating low-surprise pairs via transitivity inference. Validation was conducted on six diverse benchmarks spanning text similarity (STS-B, BIOSSES, SICKR-STS) and image quality assessment (KonIQ-10k, TID2013, LIVE Challenge). SGS effectively identified and skipped up to 535 non-informative comparisons per session. Consequently, it achieved Kendall's $\tau{\times}100$ improvements of $+6$ to $+12$ over Active Elo under the same total budget. These results demonstrate that combining VLM-guided surprise metrics with algorithmic sorting provides a generally consistent accuracy-efficiency trade-off across diverse domains.

12.
arXiv (CS.CV) 2026-06-16

The Importance of Phase in Neural Representations: An Internal Oppenheim-Lim Test of Image Classifiers

Oppenheim and Lim (1981) showed that natural images stay recognizable when reconstructed from their Fourier phase alone, while the magnitude carries little of their identity. We ask whether trained image classifiers reproduce this asymmetry inside their hidden layers, and we test it causally: given two images, we transplant the phase of one onto the magnitude of the other at a chosen layer and record which image the prediction follows. In PRISM2D, GFNet, and ViT-B/16 the prediction follows the phase or sign donor, and deleting all image-specific magnitude barely moves accuracy, so identity rides on phase while image-specific magnitude is largely dispensable to the readout. ResNet-50 at first seems to break the pattern, because transplanting sign after its ReLUs does nothing; a fair intervention before the ReLU reveals a strong latent sign code in the late blocks, and a DC-only control shows the readout consumes a channel-wise spatial average. Controls rule out the trivial case in which magnitude simply stops depending on the image. The architectures therefore share a phase/sign identity code but expose it in different bases, set by rectification and readout geometry, which gives a mechanistic account of the texture–shape gap between CNNs and attention models.

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

MAGE-RAG: Multigranular Adaptive Graph Evidence for Agentic Multimodal RAG in Long-Document QA

Long-document multimodal question answering requires a system to locate sparse evidence in long PDFs and integrate clues from text, tables, images, charts, and complex layouts. Existing RAG methods mostly rely on fixed Top-k retrieval over text chunks or pages. Text retrieval can compress the context but often loses visual and layout information; page-level visual retrieval preserves the original page, yet it also sends large irrelevant regions to the reader, leading to a static trade-off among evidence coverage, noise, and inference cost. This paper proposes MAGE-RAG, a multigranular adaptive graph evidence framework for long-document multimodal QA. MAGE-RAG uses page retrieval as the entry point for query-time evidence construction. Offline, it builds an evidence graph with page nodes and element nodes, encoding containment, reading order, layout adjacency, section hierarchy, and semantic-neighbor relations. At query time, an online evidence controller iteratively activates, opens, searches, and prunes evidence under explicit budgets. The resulting evidence subgraph is then rendered into structured multimodal reader input, allowing the LVLM to consume compact and relevant evidence within a limited context. On LongDocURL and MMLongBench-Doc, we establish a unified comparison and analysis protocol covering Direct MLLM, Text RAG, Page-level Visual RAG, and Graph/Agentic RAG. Experiments show that MAGE-RAG achieves 52.75 overall accuracy on LongDocURL, and 53.26 accuracy with 51.19 F1 on MMLongBench-Doc. Fine-grained breakdowns, budget-performance curves, ablations, and trace-based analysis further show that query-time evidence subgraph construction can balance dispersed evidence coverage with context-noise control. Our code is available at https://github.com/laonuo2004/MAGE-RAG.git.

14.
arXiv (CS.LG) 2026-06-18

How Does the ReLU Activation Affect the Implicit Bias of Gradient Descent on High-dimensional Neural Network Regression?

arXiv:2603.04895v2 Announce Type: replace-cross Abstract: Overparameterized ML models, including neural networks, typically induce underdetermined training objectives with multiple global minima. The implicit bias refers to the limiting global minimum that is attained by a common optimization algorithm, such as gradient descent (GD). In this paper, we characterize the implicit bias of GD for training a shallow ReLU model with the squared loss on high-dimensional random features. Prior work (Vardi and Shamir, 2021) showed that the implicit bias does not exist in the worst-case, or corresponds exactly to the minimum-$\ell_2$-norm interpolating solution under exactly orthogonal data (Boursier et al., 2022). Our work interpolates between these two extremes and shows that, for sufficiently high-dimensional random data, the implicit bias approximates the minimum-$\ell_2$-norm solution with high probability with a gap on the order $\Theta(\sqrt{n/||\lambda||_1})$, where $n$ is the number of training examples and $\lambda$ denotes the spectrum of the data covariance matrix. Our results are obtained through a novel primal-dual analysis that carefully tracks the evolution of predictions, data-span coefficients, as well as their interactions, and show that the ReLU activation pattern quickly stabilizes with high probability over random data.

15.
arXiv (CS.CL) 2026-06-17

Environment-Grounded Automated Prompt Optimization for LLM Game Agents

LLM agents in interactive environments are highly sensitive to their prompts, yet prompt engineering remains a manual, task-specific process. We introduce an automated prompt optimization framework for LLM agents that decomposes the observation-to-action pipeline into a goal-conditioned descriptor agent and an action selection agent, and iteratively refines each module's prompt through an LLM-driven evolutionary loop guided by environment returns. We propose a behavior analyzer to attribute episode outcomes to specific prompt components, and a mutator to propose targeted revisions to the prompt, before validating them through environment rollouts. We evaluate on all five BabyAI tasks in the BALROG benchmark, comparing our pipeline against BALROG's RobustCoTAgent under both plain and guided prompt initializations. Optimization improves performance consistently across tasks and conditions, without requiring updates to the model weights. On PutNext, a multi-step coordination task where the RobustCoTAgent achieves 0% success, our framework reaches up to 72.5% success rate using the same underlying LLM with optimized prompts. These results suggest that a multi-agent framework, combined with automatic prompt optimization, enhances LLMs without the need for fine-tuning or extensive human supervision.

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

FlowBender: Feedback-Aware Training for Self-Correcting Conditional Flows

Conditional diffusion and flow models routinely fail to satisfy the very constraints that define their task. For instance, a depth-conditioned model often produces images whose re-extracted depth disagrees with the input, even though the forward operator–the depth predictor defining the constraint–is available during both training and inference. Existing approaches generally fall into two categories: supervised models that treat the conditioning signal as a static cue and ignore alignment information at inference, and guidance-based methods that consult it through hand-tuned linear updates, typically trading fidelity to the condition against the plausibility of the generated sample. We argue that the fundamental gap in both paradigms is that the model is never trained to utilize its own alignment error. We introduce FlowBender, a closed-loop framework that treats this error as a first-class input, training the network to learn a correction policy conditioned on inference-time feedback. At each step, an unguided look-ahead pass estimates the clean signal, a task-specific deviation is computed via the forward operator, and a refinement pass consumes this signal to produce a corrected velocity. We propose several variants of FlowBender, including a gradient-based formulation for differentiable operators and a zero-order variant for non-differentiable settings such as JPEG compression. For efficient sampling, we introduce a prior-step shortcut that enables closed-loop correction at a minimal additional computational cost. Across image-to-image translation, restoration, and 3D mesh texturing, FlowBender consistently outperforms standard supervised baselines, alignment-loss-augmented training, and state-of-the-art inference-time guidance, improving fidelity and plausibility simultaneously rather than trading them against each other. Project page: https://flow-bender.github.io/

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

Attribution-Guided and Coverage-Maximized Pruning for Structural MoE Compression

arXiv:2606.18304v1 Announce Type: cross Abstract: Mixture-of-Experts (MoE) models scale compute efficiently, yet remain expensive to deploy due to their substantial memory footprint and inference overhead. Prior compression methods mainly operate at the expert level, either removing entire experts or ranking experts by coarse-grained importance scores. However, such expert-wise decisions are often too coarse to capture fine-grained redundancy, leading to misallocated pruning budgets and limited compression. To address this problem, we observe that information within MoE experts is highly concentrated in a small subset of channels, leaving substantial redundancy even in experts deemed important. Based on this observation, we propose a structural pruning framework tailored for MoE models. Our method reformulates prune-ratio allocation as a channel-score coverage maximization problem and solves it efficiently using an attribution-based approximation. Experiments on DeepSeek and Qwen MoE models show that our method preserves model accuracy under 50% or 25% structured pruning when combined with 4-bit quantization. On Qwen3-30B-A3B, our approach reduces memory footprint by 5.27$\times$ and consistently outperforms state-of-the-art baselines across diverse benchmarks.

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

Budget-Aware Adaptive Adversarial Patches for Black-Box Object Detection

Adversarial patches pose a practical threat to modern object detectors. Prior work shows vulnerability, but three gaps limit actionable insight: (i) few score-based black-box attacks jointly optimize patch location, texture, and size under tight query budgets; (ii) success is rarely tied to the patch's visual footprint; and (iii) evaluations often conflate EOT robustness with plain-view suppression. We present \method{}, a query-efficient, budget-adaptive black-box attack that couples a lightweight Contextual Thompson-Sampling placer with NES-style pixel updates, growing the patch only when progress stalls. Reporting is anchored by a strict plain-image suppression test; EOT is audited but never used as a substitute for success, and optional appearance/printability weights expose strength–visibility trade-offs. Across YOLOv5, Faster R-CNN, and YOLOS, \method{} achieves strong suppression on CNN-based detectors and substantial suppression on the transformer-based detector, using compact patches and exposing clear query–footprint trade-offs relative to fixed-size and heuristic baselines. A print–capture pilot further shows transfer across unseen physical objects and viewpoints.

19.
arXiv (CS.CL) 2026-06-15

TVIR: Building Deep Research Agents Towards Text-Visual Interleaved Report Generation

Deep Research Agents have shown strong capability in multi-step information retrieval, reasoning, and long-form report generation, but existing benchmarks and systems remain predominantly text-centric, with limited evaluation of whether visual elements are factually reliable and well aligned with the surrounding analysis. To address this gap, we introduce TVIR (Text-Visual Interleaved Report Generation), which includes TVIR-Bench, a benchmark of 100 expert-curated multimodal deep research tasks that require visual elements to serve specific analytical sub-goals, and TVIR-Agent, a hierarchical multi-agent framework that serves as a strong baseline for constructing outlines, retrieving images, generating charts with traceable sources, and composing reports through context-aware sequential writing. We further develop a dual-path evaluation framework that combines Textual Assessment and Visual Assessment. Experiments across nine deep research systems show that TVIR-Agent achieves strong overall performance, underscoring the importance of explicit multimodal design and evaluation for evidence-driven report generation.

20.
arXiv (CS.LG) 2026-06-18

Predicting the Neutrino Mass Ordering Using Neural Networks

arXiv:2606.03745v1 Announce Type: cross Abstract: Determining the neutrino mass ordering remains a central open problem in particle physics. While next-generation long-baseline experiments are expected to resolve this question, current data provide limited sensitivity because the spectral differences between normal and inverted ordering are subtle and entangled with parameter degeneracies. We investigate a machine-learning strategy for mass-ordering determination using a feed-forward neural-network classifier trained on synthetic long-baseline datasets generated with three-flavour oscillation probabilities, matter effects, and statistical fluctuations. We evaluate the classifier against standard $\chi^2$ and $\log\mathcal{L}$ approaches using common discrimination metrics, including receiver-operating-characteristic curves, to quantify sensitivity and to illustrate how operating points can be selected to prioritise purity or efficiency. We find that the neural network achieves performance comparable to conventional fits for the scenarios studied, providing a flexible, independent cross-check of established analyses. The framework can be extended to incorporate systematic uncertainties and to explore joint inference of oscillation parameters, and it may also serve as a pedagogical tool for introducing machine-learning methods in neutrino physics.

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

Rethinking Dataset Distillation for Classification: Do Distilled Sets Outperform Coresets?

arXiv:2606.18209v1 Announce Type: new Abstract: Dataset distillation (DD) has emerged as a prominent approach in data centric machine learning, aiming to synthesize compact training sets for efficient training by compressing the information in large datasets into a small number of synthetic samples. However, DD methods are often evaluated under inconsistent evaluation protocols, ranging from standard ERM to single/multi-teacher supervision, making it difficult to isolate the effectiveness of distilled data from evaluation. Moreover, many prior methods claim that DD outperforms data pruning approaches such as coreset selection (CS), based on the assumption that restricting condensed datasets to subsets of real samples fundamentally limits their expressiveness. In this work, we critically evaluate DD methods through large-scale experiments using standardized datasets and evaluation protocols to assess their intrinsic effectiveness. We benchmark seven state-of-the-art (SOTA) DD methods on ImageNet-1K, ImageNet100, and ImageNette, using three widely adopted training protocols against three CS strategies. Our results show that while some DD methods fail to outperform even simple random subsets, the SOTA DD approaches are comparable to or worse than coresets on large-scale datasets and incur a substantially higher cost for construction. Beyond accuracy, we also evaluate the representativeness, diversity, and quality of condensed sets, and find that coresets consistently achieve better coverage of the original data distribution. These findings highlight the limited practical advantages of current DD methods and show that coresets remain competitive and are often a more computationally efficient alternative for data-centric learning.

22.
bioRxiv (Bioinfo) 2026-06-11

Integrating Spatially Adjusted Protein Summaries for Survival Prediction in Spatial Proteomics

Recent advances in spatial proteomics, particularly imaging mass cytometry, enable the measurement of protein expression at the single-cell level while preserving a spatial context. Conventional survival analyses, however, typically rely on patient-level averages of protein intensities and therefore overlook spatial heterogeneity and tissue architecture. To address this limitation, we introduce a framework that incorporates spatial information into survival modeling by generating spatially adjusted protein summaries (SAPS). In this approach, cell-level protein intensities within each patient are modeled using spatial spline regression to capture spatial trends. From these models, we extract two complementary features: a spatially adjusted mean expression and a residual variance that reflects cell-to-cell variability unexplained by spatial effects. These summaries are then incorporated into Cox proportional hazards models in combination with clinical covariates. In simulation studies, our proposed framework achieved improved predictive performance compared to other alternative methods. The application of the method to breast cancer imaging mass cytometry data indicate that spatially adjusted summaries may enhance survival prediction and reveal biologically interpretable spatial protein patterns, suggesting high translational potential. This methodology offers an efficient means of translating complex spatial proteomics data into patient-level features, providing both improved survival prediction and new insights into the role of spatial heterogeneity in cancer outcomes.

23.
medRxiv (Medicine) 2026-06-15

The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease

Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts.

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

SPATIA: Multimodal Generation and Prediction of Spatial Cell Phenotypes

Understanding how cellular morphology, gene expression, and spatial context jointly shape tissue function is a central challenge in biology. Image-based spatial transcriptomics technologies now provide high-resolution measurements of cell images and gene expression profiles, but existing methods typically analyze these modalities in isolation or at limited resolution. We address the problem by introducing SPATIA, a multi-level generative and predictive model that learns unified, spatially aware representations by fusing morphology, gene expression, and spatial context from the cell to the tissue level. SPATIA also incorporates a spatially conditioned generative framework with confidence-aware OT reweighting and morphology-profile alignment for modeling target-state morphology distributions. Specifically, we propose a confidence-aware flow matching objective that reweights weak optimal-transport pairs based on uncertainty. We further apply morphology-profile alignment to encourage biologically meaningful image generation, enabling the modeling of microenvironment-dependent phenotypic transitions. We assembled a multi-scale dataset consisting of 25.9 million cell-gene pairs across 17 tissues. We benchmark SPATIA against 18 models across 12 tasks, spanning categories such as phenotype generation, annotation, clustering, gene imputation, and cross-modal prediction. SPATIA achieves improved performance over state-of-the-art models, improving generative fidelity by 8% and predictive accuracy by up to 3%.

25.
arXiv (quant-ph) 2026-06-11

A Pfaffian quantum Hall state of ultracold bosons

arXiv:2606.12409v1 Announce Type: cross Abstract: Fractional quantum Hall states are a cornerstone of topological physics, hosting fractionally charged quasiparticles with exotic statistics that promise to enable topologically protected quantum information processing. Among these, the Pfaffian state introduced by Moore and Read implements a p-wave pairing structure that supports excitations with non-Abelian exchange statistics. Despite extensive study in electronic systems, direct access to its pairing structure has remained limited. Here we realize a three-particle bosonic Pfaffian state of ultracold $^{87}\mathrm{Rb}$ atoms in an optical lattice subject to a Floquet-engineered synthetic magnetic field. Using a Bayesian-optimized adiabatic protocol, we prepare a state exhibiting Pfaffian pairing correlations. Site-resolved measurements of multi-point density correlations reveal a pronounced suppression of short-range three-body coincidences, reflecting the underlying pairing structure. We further probe the state's transport response through Hall drift measurements. Our results establish a bottom-up approach to engineering non-Abelian topological order and lay the groundwork for future explorations of anyonic braiding in synthetic matter.