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

Your Mouse and Eyes Secretly Leak Your Preference: LLM Alignment using Implicit Feedback from Users

To align a Large Language Model (LLM), most existing methods collect explicit human feedback and train a reward model to predict the human preference based on the response text. These existing methods have two key limitations. First, the users rarely provide explicit feedback for LLM responses, which makes the high-quality preference annotation expensive to collect. Second, the methods do not leverage implicit human feedback, which has proven vital to the economic moats of Internet giants. To quantify the value of implicit feedback, we build a new dataset called IFLLM, which collects 1336 multi-turn questions from the 59 Mechanical Turk workers, their mouse trajectories, and eye gazing points to the LLMs' responses from their webcams. IFLLM shows that the users have very diverse types of gazing behavior and mouse trajectories. Our reward model based on the implicit user feedback boosts the accuracy of the text-based reward model from 55% to 64% and nearly triples the relative response quality improvements after applying the DPO to eight LLMs, demonstrating the value of implicit feedback in the wild. Our data collection website, dataset, and codes can be found at https://github.com/themehulpatwari/llm-implicit-feedback/.

02.
arXiv (CS.CV) 2026-06-11

Motion Reinforces Appearance: RGB-Skeleton Gated Residual Fusion for Micro-Gesture Online Recognition

Micro-gesture analysis attracts increasing attention for inferring spontaneous emotion from subtle body movements. Micro-gesture online recognition, which localizes and classifies each gesture instance in untrimmed videos, is a core task in the 4th EI-MiGA-IJCAI Challenge. Compared with typical temporal action detection, MGR emphasizes the localization and classification of actions, requiring the model to output the start time, end time, and category of each micro-gesture. Moreover, since micro-gestures are highly spontaneous, relying solely on a single modality makes it difficult to capture the complete and accurate multi-modal cues. In this work, we propose DyFADet+, which extends DyFADet into a dual-stream RGB-skeleton framework. In our model, both modalities are projected into shared multi-scale temporal embeddings and fused through a gated residual module, which adaptively injects skeleton motion into the RGB representation rather than using naive concatenation. Finally, these fused features are decoded by a Dynamic TAD head for online classification and boundary regression. On the SMG dataset, our method achieves an F1 score of 40.88, ranking 2nd in the Micro-gesture Online Recognition track.

03.
arXiv (CS.LG) 2026-06-18

Hierarchical Planning with Latent World Models

arXiv:2604.03208v2 Announce Type: replace Abstract: World models are a promising path to zero-shot embodied control through planning. However, existing world model planners struggle on long-horizon, multi-stage tasks: prediction errors compound and naive search is exponential in the planning horizon. Hierarchy mitigates both by decomposing tasks into shorter, tractable subproblems; yet prior hierarchical approaches either amortize control into task-specific policies (hierarchical RL) or assume low-dimensional states and known dynamics (classical hierarchical MPC). We present Hierarchical Planning with Latent World Models (HWM), an architecture and planning paradigm for hierarchical model predictive control (MPC) directly on visual world models trained solely via next-latent prediction. HWM learns world models at multiple temporal scales within a shared latent space, so predictions from the long-horizon model serve as subgoals for the short-horizon model via latent matching, without task-specific rewards, skill learning, or hierarchical policies. To keep long-horizon search tractable, HWM learns an action encoder that compresses primitive action chunks into latent macro-actions. On real-world Franka manipulation, HWM solves pick-and-place from a single goal image at 70% success vs. 0% for single-level planning. Across simulated push manipulation and maze navigation, HWM consistently improves performance on long-horizon tasks while requiring up to 3x less planning compute.

04.
medRxiv (Medicine) 2026-06-15

Entity-Aware Generation of Synthetic Clinical Progress Notes for Prostate Cancer using Large Language Model

Objectives: This study investigates large language models (LLMs) for clinical entity projection across substantial textual transformation. Specifically, we evaluate whether entities annotated in Spanish prostate cancer case reports can be preserved and explicitly projected when the source narratives are transformed into hospital-style clinical progress notes. Entity projection is treated as a generation-driven task, allowing paraphrase, condensation and narrative reorganisation, providing that clinically relevant entities remain recoverable as structured annotations. Methods: A corpus of 109 Spanish prostate cancer case reports was annotated using a silver-standard pipeline combining Spanish biomedical named-entity recognition with rule-based prostate-specific antigen (PSA) and Gleason extractors. The resulting silver-standard annotations were validated on a subset of generated notes against a gold-standard consensus produced by medical experts in prostate cancer. Four LLMs were evaluated for note generation and entity projection: GPT-5.4 Nano, Qwen 3.5:35B-A3B, GLM5 and Claude Sonnet 4.6. Entity-to-Entity (E2E) generation used XML-annotated cases as RAG-supported input, whereas Text-to-Entity (T2E) generation required models to generate and annotate notes directly from plain text cases. Zero-shot and few-shot prompting were tested. Projection quality was measured using precision, recall and F1-score, and complemented by LLM-as-a-judge evaluation using Kimi K2.6. Results: E2E consistently outperformed T2E, indicating that explicit entity-enriched in- put substantially facilitates entity preservation and localisation. GLM5 achieved the best E2E zero-shot result (F1 = 0.915), followed by Claude Sonnet 4.6 (F1 = 0.896). In T2E, few-shot prompting improved performance, with Claude Sonnet 4.6 reaching the highest score (F1 =0.718). Age, Gleason, Disease, Procedure, Duration and negation-related entities were robustly projected, whereas PSA and Dose showed less stable behaviour. Conclusion: LLMs can generate clinically plausible synthetic prostate cancer evolution notes while preserving a substantial proportion of source entities, particularly when explicit semantic annotations are provided as input. However, the lower and more variable performance observed in T2E highlights the difficulty of jointly generating clinical narratives and projecting entities without source-side information, especially for numerical and measure-related entities.

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

Shape of Thought: Progressive Object Assembly via Visual Chain-of-Thought

Multimodal models for text-to-image generation have achieved strong visual fidelity, yet they remain brittle under compositional structural constraints, notably generative numeracy, attribute binding, and part-level relations. To address these challenges, we propose Shape-of-Thought (SoT), a visual CoT framework for process-supervised progressive shape assembly in the rendered 2D domain, without external engines at inference time. SoT trains a unified multimodal autoregressive model to generate interleaved textual plans and rendered intermediate states, helping the model capture shape-assembly logic without producing explicit geometric representations. Unlike text-only CoT, each decision is grounded in a rendered state, making counts, attachments, topology, and intermediate part-addition errors inspectable across the trajectory. To support this paradigm, we introduce SoT-26K, a large-scale dataset of grounded assembly traces derived from part-based CAD hierarchies, and T2S-CompBench, a benchmark for evaluating structural integrity and trace faithfulness. Fine-tuning on SoT-26K achieves 88.4% on component numeracy and 84.8% on structural topology, outperforming direct generation by +24.2 points on component numeracy and +19.3 points on structural topology. SoT establishes a transparent testbed for rendered-domain structure-aware generation. The code is available at https://github.com/yuhuo03/Shape-of-Thought.

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

Runtime Enforcement of Hybrid System Properties

arXiv:2606.12022v1 Announce Type: cross Abstract: Runtime enforcement has emerged as a promising approach for ensuring the safety of autonomous and cyber-physical systems operating in uncertain and dynamic environments. Unlike traditional runtime verification, runtime enforcement actively intervenes during execution to prevent property violations by modifying unsafe system behaviors. Existing enforcement frameworks primarily focus on untimed or discrete-time specifications and are often limited to delaying or suppressing events, making them inadequate for reactive systems exhibiting complex continuous dynamics. In this paper, we propose a runtime enforcement framework where safety requirements are modeled using Hybrid Automata (HA). The framework combines discrete-event editing with continuous-time monitoring to support enforcement actions such as suppression, delay, and insertion of events at arbitrary time instants. Upon observing environmental inputs, the automaton is initialized, and runtime reachability analysis is used to synthesize safe corrective actions. We formally define the enforcement problem for safety hybrid automata, establish enforceability conditions, and present an online enforcement algorithm for reactive systems. A detailed case study on an Adaptive Cruise Control (ACC) system demonstrates the effectiveness of the proposed approach in maintaining safety properties under unsafe controller behaviors. Experimental results show that the framework introduces minimal computational overhead while ensuring continuous compliance with safety requirements in real time.

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

LLM-as-an-Investigator: Evidence-First Reasoning for Robust Interactive Problem Diagnosis

arXiv:2606.13220v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly used as interactive assistants for technical problem solving. However, when users provide incomplete descriptions or plausible but unverified explanations, LLMs may prematurely align with these assumptions and propose solutions before collecting sufficient evidence. We refer to this behavior as user-driven sycophancy: the tendency of an LLM to reinforce a user-provided hypothesis instead of testing alternative explanations. This paper introduces LLM-as-an-Investigator, an evidence-first agentic AI methodology for robust problem diagnosis. The approach is implemented through a Solution Investigator Agent, which estimates the ambiguity of an initial problem description, generates candidate hypotheses, asks targeted clarification questions, and updates hypothesis probabilities after each answer. Rather than producing an immediate response, the agent continues the investigation until the evidence makes one candidate explanation stronger than the alternatives. To evaluate the approach, we build a benchmark from solved technical forum threads in mechanical, electrical, and hydraulic domains. We use a three-agent evaluation pipeline in which a Problem-Solution Extractor Agent converts solved threads into structured cases, a Ground-Truth Evaluator Agent simulates the user while hiding the known solution, and the tested assistant attempts to recover the solution through dialogue. The experiments compare standard assistants, reasoning-oriented LLMs, and the proposed investigator-based model across LLM backbones. In addition to diagnostic accuracy, we analyze how standard assistants follow misleading user hypotheses in diagnostic cases. The results show that the proposed approach identifies the problem more accurately than direct prompting and reasoning-only baselines, while its evidence-first protocol helps reduce user-induced conversational bias.

09.
medRxiv (Medicine) 2026-06-16

Re-evaluating the Cross-Sectional Prevalence of Severe Age-Related Hearing Loss Using Extreme Value Statistics

作者:

Standard demographic models of age-related hearing loss (presbycusis) predominantly utilize symmetric functions, such as log-normal distributions for age-binned thresholds and 4-parameter logistic curves for prevalence estimates. While these models capture early-to-moderate degradation effectively, they structurally struggle to characterize the heavy tails associated with severe clinical impairment. In this study, we present a statistical critique using a secondary analysis of the historical Medical Research Council (MRC) National Study of Hearing (1980-1986) dataset. By applying Generalized Extreme Value (GEV) distribution theory, we demonstrate that as severity increases, the underlying statistical geometry of hearing loss shifts. The asymmetric, heavy-tailed GEV distribution provides a parsimonious description of severe impairment, requiring fewer parameters than standard symmetric models. However, we explicitly acknowledge that utilizing static population data to infer progression introduces an ecological fallacy. Furthermore, the dataset's historical nature embeds unquantified generational cohort effects. We conclude that while extreme value statistics offer a compelling mathematical framework for modeling the variance of severe presbycusis, true longitudinal datasets are required to isolate physiological degradation from historical cohort variance.

10.
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.

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

Graph2Idea:Retrieval-Augmented Scientific Idea Generation with Graph-Structured Contexts

arXiv:2606.09105v3 Announce Type: replace Abstract: Generating novel, feasible, and high-quality research ideas is an important yet challenging task in scientific discovery. Recent Large Language Model (LLM)-based methods often ground idea generation with retrieved literature, but the retrieved evidence is usually provided as flat text, such as titles, abstracts, or summaries. Such flat contexts may contain redundant or weakly relevant information, while making cross-paper relations among problems, methods, mechanisms, and findings difficult to identify and trace. To address this challenge, we propose Graph2Idea, a knowledge graph-guided framework for retrieval-augmented scientific idea generation.Graph2Idea first retrieves papers according to the input topic, transforms them into structured knowledge triples, and dynamically constructs a target-centered knowledge graph to make literature relations explicit. It then extracts compact graph-derived contexts that retain target-relevant relational evidence while reducing noisy textual input. Based on these contexts, a two-stage generation process first identifies promising research directions and then guides the LLM to synthesize candidate ideas from graph-grounded evidence. Experiments on a scientific idea generation benchmark show that Graph2Idea outperforms representative baselines under the automatic evaluation protocol. Compared with the strongest baseline scores, it improves Novelty from 0.45 to 0.52, Quality from 0.24 to 0.29, and Feasibility from 0.22 to 0.28. These results suggest that graph-structured evidence helps LLMs generate research ideas through more explicit, compact, and traceable recombination of prior scientific knowledge.

12.
arXiv (CS.AI) 2026-06-19

Hard or Just Unreached? Diagnosing the Sampling Blind Spot in Math-Reasoning Difficulty Estimation

arXiv:2606.19636v1 Announce Type: cross Abstract: Math and science reasoning benchmarks rely on pass@k, the fraction of sampled chains that reach gold, as the canonical per-example difficulty signal. The same signal drives RL with verifiable rewards, math data curation, synthetic curricula, and verifier training. We show this proxy has a persistent blind spot on its hardest stratum: on the eight free-form math cells we test (GSM8K and MATH across four open-weight models), 10.3-22.9% of the examples that no sampling seed solves in six tries are instead solved at matched compute by a six-chain deterministic regime. These are greedy decoding plus five cheap residual-stream perturbations applied via activation grafting, while greedy alone solves at most 6% on these math cells. Recovery scales with the additional budget, across perturbations whose mechanistic distinctness we verify across all twelve cells (cross-kind fix-set Jaccard

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

Contrastive Learning for Seismic Horizon Tracking with Domain-Specific Priors

Unsupervised 3D seismic horizon tracking faces a key limitation: signal-based propagators provide accurate trace-level alignment but often fail near faults, whereas texture-driven deep models are more robust to discontinuities, typically at the cost of labeled data requirements and reduced trace-level precision. We propose a self-supervised fusion of both paradigms in which signal-derived local horizon correspondences act as domain-specific priors to train a texture-based deep learning model. Specifically, we estimate reliable trace-to-trace flows from reflector slopes and use them to form positive pairs in a contrastive objective, while restricting training to high-confidence neighborhoods, optionally augmented with a fault mask. The objective is not to infer ambiguous correspondences close to discontinuities, but to preserve horizon identity across them. As a result, the network learns voxel-wise embeddings that preserve local signal continuity while enabling horizon propagation beyond discontinuities through similarity search. Experiments on the public F3 dataset and a faulted synthetic dataset achieve lower mean absolute error (MAE) than unsupervised baselines and competitive performance against a semi-supervised method using a single labeled slice.

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

Rethinking Reward Supervision: Rubric-Conditioned Self-Distillation

Post-training of reasoning language models is commonly driven by supervised distillation and reinforcement learning with verifiable rewards. Distillation often relies on chain-of-thought annotations that are expensive to obtain and may themselves be noisy, incomplete, or partially incorrect; even when the final solution is correct, an imperfect rationale can interfere with learning. Reinforcement learning with verified rewards, on the other hand, typically compresses evaluative feedback into a scalar signal, obscuring which aspects of a response should be improved. We propose Rubric-Conditioned Self-Distillation, a framework that incorporates rubrics as structured, fine-grained feedback for on-policy self-distillation. Our method conditions the teacher model on criterion-level rubrics and uses it to provide token-level guidance on the student's own sampled trajectories. This design avoids treating a single reference rationale as the sole supervision target. Instead, rubrics specify what a strong response should satisfy, enabling more fine-grained credit assignment over the reasoning process than scalar reward optimization. We instantiate this framework with a two-stage pipeline that first learns to generate task-specific rubrics and then trains a rubric-guided reasoner. We evaluate on a diverse suite of science reasoning benchmarks and results show that rubric-conditioned self-distillation effectively converts rubric-level criteria into token-level guidance over the reasoning process, surpassing GRPO by 1.0 points and OPSD by 0.9 points on average.

15.
arXiv (quant-ph) 2026-06-12

Simple analytical flux-tuned iSWAP pulses for leakage suppression

arXiv:2606.13052v1 Announce Type: new Abstract: Fast, high-fidelity two-qubit gates are a key requirement for fault-tolerant quantum computation. Tunable coupler architectures provide a flexible approach for implementing entangling gates through flux control with large on-off ratios, but fast flux modulation can induce diabatic transitions and population leakage to non-computational states, limiting gate performance. Here we present an analytical flux control method enabling derivative removal by adiabatic gate ($\Phi$-DRAG) for suppressing leakage in flux tunable two-qubit gates. We show that $\Phi$-DRAG differs fundamentally from conventional microwave implementations and derive modified flux modulation protocols that suppress leakage below $10^{-4}$ for fast entangling gates. The method remains effective across a range of asymmetry between qubit anharmonicities and different circuit parameters, enabling high-fidelity two-qubit gates within the fifteen nanosecond range.

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

A non-asymptotic bound on the TV distance between a Wishart matrix and an appropriately scaled GOE matrix

arXiv:2606.16018v1 Announce Type: new Abstract: In this note, we prove a non-asymptotic version of a theorem by Bubeck, Ding, Eldan, and Rácz, showing that a Wishart matrix is close in total variation to an affine transformation of a GOE matrix. The proof mirrors the proof given by Bubeck et al., with some changes made to make it non-asymptotic.

17.
medRxiv (Medicine) 2026-06-17

Method comparisons for differentiation of Schizophrenia and Bipolar based on rs-fMRI Intrinsic and Functional Networks

Psychosis as a symptom manifests in schizophenia and bipolar disorder, two highly heterogeneous psychiatric illnesses with overlapping clinical manifestations. Resting-state functional Magnetic Resonance Imaging (rsfMRI), represents a promising tool for identifying objective biomarkers of functional brain alterations to aid differential diagnosis. In this work, we comparatively evaluate multiple rs-fMRI representations for differentiating schizophrenia and bipolar disorder using intrinsic connectivity network (ICN) temporal profiles and several functional network connectivity (FNC) approaches, including static, dynamic, and high-order connectivity analyses. The study was conducted on a cohort of 371 subjects with psychosis, while evaluation was performed using a separate held-out cohort of 315 subjects. We investigated convolutional neural network architectures applied to ICN temporal profiles, spectrograms, and scalograms, alongside classical machine learning models trained on connectivity-derived features. Across the evaluated approaches, ICN temporal profiles provided the most consistent discriminative performance, with a 1D convolutional neural network achieving the strongest overall results under the benchmark protocol. Among connectivity-based methods, static functional connectivity generally outperformed dynamic and high-order representations, suggesting that increased representational complexity did not necessarily translate into improved generalization. Although the obtained classification performance remained modest, the results highlight the challenges of robust psychosis differentiation using rs-fMRI while emphasizing the relative stability of low-order connectivity representations and temporal ICN features. These findings contribute to ongoing efforts toward reproducible and interpretable neuroimaging biomarkers for psychiatric disorders.

18.
medRxiv (Medicine) 2026-06-15

Quality Improvement Based Implementation and Evaluation of a Decision Aid for Patients with Nephrolithiasis

Introduction Patients with nephrolithiasis face challenges in making a high-quality, preference sensitive decision. Our prior work established feasibility and patient acceptance of a software-based decision aid (DA). The objectives for this study were to identify implementation strategies for the DA in routine care and determine whether DA implementation enhances decisional quality for patients. Methods New nephrolithiasis patients were recruited from the institution Medical Center from June 2018 to April 2024 to receive a software-based pre-visit DA that measured care preferences and used decision analysis to rank treatments. The RE-AIM framework and Plan-Do-Study-Act (PDSA) cycles were used to improve implementation outcomes. Patients completed survey instruments evaluating decisional conflict, shared decision-making, care satisfaction, and treatment choice following their provider visit. These metrics were compared in the DA cohort (n=81) to those in a usual care cohort (n=78) with Wilcoxon rank-sum and Chi-square (or Fishers exact) tests. Results Implementation data revealed sustained reach and progressive improvement in fidelity. The DA cohort reported higher decisional quality relative to controls (p=0.003) and reported greater support/advice to make a choice (p=0.005). The DA cohort more often discussed options with their doctor (87.5% vs 69.2%, p=0.005) and were more likely to be promoters of their provider (p

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

NeuronFabric: A Software Reference Architecture for On-Chip Transformer Training with Local Adam

arXiv:2606.16440v1 Announce Type: cross Abstract: Publicly documented accelerator architectures generally separate training computation from optimizer-state updates or rely on external memory and host orchestration. This paper presents NeuronFabric, a software reference architecture intended for future FPGA and ASIC implementations of transformer training with local Adam updates. A complete C# prototype implements forward pass, backpropagation, and Adam optimization without external machine-learning frameworks. The goal is to validate numerical correctness and memory requirements before hardware implementation. The evaluated model is a 334K-parameter autoregressive transformer (d=88, H=4, f=264, L=4, vocab=256) trained on the Shakespeare corpus. The BF16W configuration achieves evaluation loss 1.5426 after 80K samples, compared with 1.5224 for an FP32 GPU reference, while producing coherent character-level text. The paper introduces BF16W, which stores weights in BF16 while retaining Adam optimizer moments in FP32. This reduces memory requirements for on-chip training. A 334K-parameter FP32 model with Adam moments requires approximately 4.0 MB, matching the BRAM capacity of a Xilinx ZCU102 device. The BF16W variant requires approximately 3.34 MB, leaving memory available for activation storage. We describe the vocabulary-budget constraint observed during earlier experiments, quantify BF16W memory savings, and outline FPGA training as the next stage of development. No FPGA measurements are included in this paper. This publication serves as a public architectural disclosure and software reference implementation for future FPGA and ASIC exploration of the NeuronFabric architecture.

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

Spatial-Aware Reduction Framework: Towards Efficient and Faithful Visual State Space Models

arXiv:2606.19932v1 Announce Type: cross Abstract: Mamba demonstrates strong efficiency in modeling long visual sequences. However, when token reduction is applied to structurally enhanced Mamba variants, these models exhibit a severe performance collapse. We attribute this degradation to the spatially agnostic nature of existing reduction methods, which violate the two-dimensional structural premise required by the selective scanning mechanism. In this work, we propose STORM, a spatial-aware token reduction framework designed to maintain structural integrity throughout the compression process. STORM reformulates reduction into a structured operation on spatial units, enforcing localized constraints to maintain both grid topology and neighborhood coherence. As a plug-and-play module, STORM equips existing reduction pipelines with explicit spatial awareness without any training. Empirical results demonstrate that STORM achieves state-of-the-art pruning accuracy across diverse vision Mamba backbones under training-free settings. Notably, STORM delivers a substantial accuracy recovery on VMamba, outperforming prior methods by up to 63.3\% in top-1 accuracy. Meanwhile, STORM incurs only a 1.0\% accuracy drop on PlainMamba, achieving performance comparable to ViT.

21.
Nature Biotechnology 2026-06-08

Single-cell spatial pharmacobiology for imaging antibody-based therapies in solid tumors

作者: 未知作者

We have developed single-cell spatial pharmacobiology (SSP), which combines in situ imaging of a systemically infused fluorescent therapeutic antibody with high-plex spatial proteomics. Applied to head and neck and pancreatic tumors from patients treated in phase 1 trials, SSP revealed marked spatial heterogeneity in antibody delivery and target engagement, which was shaped by conserved stromal barriers.

22.
arXiv (CS.LG) 2026-06-16

Latent space mapping of interpretable structural coordinates from stochastic single-molecule signals

arXiv:2606.16950v1 Announce Type: cross Abstract: Nanopores are versatile single-molecular sensors, but their utility is fundamentally constrained by stochastic translocation dynamics warping any encoded information. We resolve it by shifting from time-domain analysis to a learned latent-space mapping via a contrastive encoder trained exclusively on simulated signals from a physics-informed model. This encoder maps solid-state nanopore signals of engineered DNA barcodes into an interpretable molecular coordinate system. The learned representation is responsive to structural barcode parameters while remaining invariant to acquisition conditions and translocation conformation, allowing data pooling across devices. Molecule identification requires a single pass through the encoder, reducing computational cost by three orders of magnitude relative to alignment-based methods. We experimentally validate through mixture quantification, rare-variant detection, consensus barcode reconstruction, and real-time signal acquisition. This shift from temporal analysis to mapping structural coordinates into a latent space changes the paradigm behind analyzing stochastic sensor signals by linking classification to interpretable encoded molecular information.

23.
arXiv (quant-ph) 2026-06-19

Stalls and Spequlation: Pipelined Execution for Fault Tolerant Quantum Computation

arXiv:2606.19593v1 Announce Type: new Abstract: Fault-tolerant quantum computation requires the coordinated action of three distinct systems: classical control logic, quantum hardware, and classical error decoders. Current scheduling models treat logical operations as atomic, hiding the fact that these subsystems operate sequentially and spend significant time idle. We present a pipelined execution framework that decomposes each logical operation into its component stages i.e. Control, Execute, and Decode. Building on this, we discuss some speculation strategies that allow successor operations to begin processing before their predecessors have completed decoding. We evaluate our framework on several common benchmarks and show that pipelining with speculation reduces total pipeline steps by 20-40% compared to a no-speculation baseline. The most aggressive strategy consistently outperforms conservative alternatives, even though partial rollback is needed at times, because the per-rollback penalty is small relative to the parallelism gained. We further show that speculation facilitates load balancing by distributing work more evenly across the heterogeneous subsystems of a fault-tolerant quantum computer, converting idle time into useful computation while also saving on execution time.

24.
arXiv (CS.AI) 2026-06-15

Metabolic cost of information processing in Poisson variational autoencoders

arXiv:2602.13421v2 Announce Type: replace-cross Abstract: Computation in biological systems is fundamentally energy-constrained, yet standard theories of computation treat energy as freely available. Here, we argue that variational free energy minimization under a Poisson assumption offers a principled path toward an energy-aware theory of computation. Our key observation is that the Kullback-Leibler (KL) divergence term in the Poisson free energy objective becomes proportional to the prior firing rates of model neurons, yielding an emergent metabolic cost term that penalizes high baseline activity. This structure couples an abstract information-theoretic quantity – the *coding rate* – to a concrete biophysical variable – the *firing rate* – which enables a trade-off between coding fidelity and energy expenditure. Such a coupling arises naturally in the Poisson variational autoencoder (P-VAE) – a brain-inspired generative model that encodes inputs as discrete spike counts and recovers a spiking form of *sparse coding* as a special case – but is absent from standard Gaussian VAEs. To demonstrate that this metabolic cost structure is unique to the Poisson formulation, we compare the P-VAE against Grelu-VAE, a Gaussian VAE with ReLU rectification applied to latent samples, which controls for the non-negativity constraint. Across a systematic sweep of the KL term weighting coefficient $\beta$ and latent dimensionality, we find that increasing $\beta$ monotonically increases sparsity and reduces average spiking activity in the P-VAE. In contrast, Grelu-VAE representations remain unchanged, confirming that the effect is specific to Poisson statistics rather than a byproduct of non-negative representations. These results establish Poisson variational inference as a promising foundation for a resource-constrained theory of computation.

25.
arXiv (CS.CL) 2026-06-12

SupraBench: A Benchmark for Supramolecular Chemistry

Supramolecular chemistry, which includes the study of non-covalent host-guest assemblies, has advanced various applications. However, designing host-guest systems remains time-consuming, requiring days of dry-lab verification per candidate pair. Although LLMs have emerged as a fast alternative with strong performance on molecular binding tasks, no benchmark currently systematically evaluates LLMs for host-guest reasoning across fundamental supramolecular chemistry tasks, e.g., binding affinity prediction. To this end, we collaborate with domain experts to release the first Supramolecular Benchmark, called SupraBench, to evaluate LLMs in chemistry reasoning. Specifically, we design four fundamental tasks, i.e., binding affinity prediction, top-binder selection, solvent identification, and host-guest description, plus an auxiliary vision-based task for molecular identification. We also release SupraPMC, a curated 16M-token corpus of Supramolecular chemistry articles distilled from Europe PMC, to support the adaptation to the supramolecular domain. We benchmark a broad range of open and proprietary LLMs and find that LLMs leave substantial headroom across all tasks. Domain adaptation pretraining over SupraPMC transfers cleanly to in-distribution regression but trades off against strict letter-format output. Moreover, the difficulty profile differs sharply across task families, revealing distinct failure modes that indicate specific gaps in current supramolecular chemistry reasoning. Our source codes and benchmark datasets are available at https://github.com/Tianyi-Billy-Ma/SupraBench.