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01.
arXiv (CS.LG) 2026-06-11

Analytic Bijections for Smooth and Interpretable Normalizing Flows

arXiv:2601.10774v2 Announce Type: replace Abstract: A key challenge in normalizing flows is finding expressive invertible scalar bijections. Existing approaches face trade-offs: affine transformations are smooth and analytically invertible but lack expressivity; monotonic splines offer local control but are only piecewise smooth and act on bounded domains; residual flows achieve smoothness but need numerical inversion. We introduce three families of analytic bijections that are globally smooth ($C^\infty$), defined on all of $\mathbb{R}$, and analytically invertible in closed form, combining the favorable properties of prior approaches. Beyond serving as drop-in replacements in coupling flows, where they match or exceed spline performance, we develop radial flows: a novel architecture using direct parametrization that transforms the radial coordinate while preserving angular direction. Radial flows exhibit exceptional training stability, produce geometrically interpretable transformations, and on targets with radial structure can achieve comparable quality to coupling flows with $1000\times$ fewer parameters. We provide comprehensive evaluation on 1D and 2D benchmarks, and demonstrate applicability to higher-dimensional physics problems through experiments on $\phi^4$ lattice field theory, where our bijections outperform affine baselines and enable problem-specific designs that address mode collapse.

02.
arXiv (CS.CL) 2026-06-16

Can LLM Agents Infer World Models? Evidence from Agentic Automata Learning

We propose agentic automata learning to evaluate the extent to which tool-calling LLM agents can uncover hidden environments through interaction. In our setup, an agent should uncover a hidden deterministic finite automaton (DFA) by interacting with an oracle through (1) membership queries ("Does this string belong to the target language?") and (2) equivalence queries ("Is this the target DFA?"). This yields a scalable testbed with controlled task complexity, measurable interaction efficiency, and strong baselines (classic automata-learning algorithms). Evaluating state-of-the-art LLMs, we find that performance drops sharply as DFA size increases. Reasoning models are markedly stronger than non-reasoning models, yet trajectory analyses reveal recurring failures in query planning, evidence integration, and hypothesis construction. Overall, our results show that current LLM agents can sometimes perform non-trivial interactive discovery, but remain far less robust and efficient than classic algorithms for the task.

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

Efficient Zeroth-Order Federated Finetuning of Language Models on Resource-Constrained Devices

arXiv:2502.10239v3 Announce Type: replace-cross Abstract: Federated Learning (FL) is a promising paradigm for finetuning Large Language Models (LLMs) across distributed data sources while preserving data privacy. However, finetuning such large models is challenging on edge devices due to its high resource demand. Zeroth-order Optimization (ZO) estimates gradients through finite-difference approximations, which rely on function evaluations under random perturbations of the model parameters. Consequently, ZO with task alignment provides a potential solution, allowing finetuning using only forward passes with inference-level memory requirements and low communication overhead, but it suffers from slow convergence and higher computational demand. In this paper, we propose a new ZO-based method that applies a more efficient technique to reduce the computational demand associated with using a large number of perturbations while preserving their convergence benefits. This is achieved by splitting the model into consecutive blocks and allocating a higher number of perturbations to the second block, enabling efficient reuse of intermediate activations to update the full network with fewer forward evaluations. Our evaluation on RoBERTa-large, OPT1.3B, LLaMa-3-3.2B models shows up to $3\times$ reduction in computation compared to the other ZO-based techniques, while retaining the memory and communication benefits over first-order federated learning techniques.

04.
arXiv (CS.LG) 2026-06-16

Not all Jensen-Shannon Divergence Estimators are Equal

arXiv:2606.16411v1 Announce Type: new Abstract: The Jensen-Shannon divergence is widely reported as a scalar measure of fidelity for synthetic tabular data. Yet, in practice, it is estimated from finite samples using protocols that are often underspecified. This creates a measurement problem. Although the population divergence is well defined, the empirical value depends on the estimator family, sampling protocol, calibration, dimensionality, and class balance. We show that different protocols can yield non-comparable values: marginal-based estimators ignore dependencies in the joint distribution and can severely underestimate divergence, while classifier-based estimators capture joint structure but exhibit strong estimator dependence. We systematically study this behavior across controlled settings with reference divergences and real-world synthetic tabular benchmarks. Our analysis reveals dependence blindness in marginal estimators, prior-shift bias under class imbalance, and estimator sensitivity in high dimensions. To address prior shift, we derive a closed-form posterior correction for classifier-based Jensen-Shannon estimation. Our results show that empirical Jensen-Shannon divergence values are inherently protocol-dependent, making explicit specification of the estimation procedure necessary for meaningful comparison. We provide practical guidelines and an open-source tool for estimator-aware Jensen-Shannon evaluation.

05.
arXiv (CS.AI) 2026-06-16

How Much Do Reviews Really Contribute? A Study on Text-Enriched Matrix Factorization for Recommendations

arXiv:2606.16973v1 Announce Type: cross Abstract: Incorporating textual reviews into a Recommender System has become a prominent strategy for enriching collaborative signals with semantic information. However, the actual contribution of review-derived representations remains an open question, particularly when strong collaborative baselines are employed. In this work, we systematically investigate the impact of textual information on Matrix Factorization by introducing and comparing three enrichment strategies over a common collaborative backbone. First, we propose a learnable gating mechanism that adaptively balances collaborative and textual signals during training. This mechanism is applied to two distinct review representations: (i) aggregated topic profiles extracted from user and item histories, and (ii) full text embedding representations derived from reviews. Additionally, we explore a cross-attention mechanism that identifies and emphasizes the most informative dimensions of the textual representation before fusion with collaborative factors. We evaluate six variants: pure, enriched with topic profiles and text via gating; enriched with topics and text via gating; and enhanced with cross-attention over textual features. Experiments across multiple review-based datasets reveal that although adaptive fusion mechanisms improve representation flexibility, the marginal contribution of textual signals remains limited compared to the collaborative backbone. These findings suggest that, under typical rating-prediction settings, collaborative information continues to dominate performance, raising important considerations for the effective integration of semantic review signals into recommendation models.

06.
bioRxiv (Bioinfo) 2026-06-14

Structural Analysis of Prostate Cancer N-Glycans Using Graph-Based Structural Metrics

The N-linked glycans are structurally complex carbohydrate modifications that regulate protein folding, immune recognition, and cellular signaling, and their expression is extensively remodeled during cancer progression, making them promising biomarkers. In this study, prostate cancer-associated N-glycans from a range of relevant peer-reviewed studies were curated and digitized to develop a versatile computational framework that quantitatively encodes their spatial complexity across diverse biological systems. We invented two indices – the Distance & Connectivity Index (DCI) and the Position & Composition Index (PCI) – to capture the spatial information in N-glycans as layered architectures, enabling calculation of residue-level path lengths, branching structure, and compositional diversity. DCI summarizes glycan structure as both a scalar and matrix representation, while PCI does the same but also captures monosaccharide diversity, linkage heterogeneity, and cross-layer branching features. These metrics were computed with GlycoAssessor, an open-source platform that extracts information for the DCI and PCI from glycans drawn via Symbol Nomenclature for Glycans (SNFG) notation. Principal Component Analysis (PCA) was applied to evaluate whether glycans from prostate cancer tissues cluster distinctly in a disease-relevant manner. Results show that the spatial information in N-glycans: (1) increased in a multi-dimensional, non-linear manner, (2) objectively segregated structural themes, (3) could function as a potential prostate cancer biomarker that is distinct from mass-to-charge ratio and relative abundance, and (4) could objectively quantify novel subtype classifications of glycans associated with disease states and progression.

07.
bioRxiv (Bioinfo) 2026-06-22

PhaseWY: A pipeline for haplotype phasing, sex chromosome identification and extraction of sex-limited sequences

Sex chromosomes are central to many ecological and evolutionary processes. Evidence has accumulated that sex chromosome systems vary extensively in age, turnover and transitions, motivating renewed efforts to study the diversity of sex chromosome systems across the tree of life. However, successful genomic detection of sex chromosomes depends on several factors, including the size and divergence time, background genetic diversity, and the number of sequenced females and males. In addition, technical challenges associated with sequencing and analysing the sex-limited Y/W chromosome remain. Here, we present PhaseWY, an automated Snakemake pipeline that uses whole-genome sequencing data from multiple female and male individuals to identify sex-chromosomal regions and extract the corresponding Y/W sequences. PhaseWY (i) detects sex differences in alignment depth, (ii) applies read-based and statistical haplotype phasing, (iii) identifies sex-linked regions using haplotype clustering, and (iv) subsets autosomal, X/Z- and Y/W-linked variants for downstream analyses. We applied PhaseWY to simulated data to benchmark factors influencing sex-linkage detection and successful extraction of Y/W-linked variants. To demonstrate its practical utility, we further applied PhaseWY to the neo-sex chromosome system in Alauda larks (Alaudidae) and performed a range of downstream analyses demonstrating the scope of applications of the PhaseWY output. We conclude that PhaseWY provides an easy-to-use and reproducible tool for population-genomic analyses in non-model organisms, with particular importance for advancing our understanding of sex-chromosome evolution.

08.
arXiv (CS.CV) 2026-06-15

HPSv3++: Scaling Reward Models Across the Full Spectrum of Diffusion Model Capabilities

Reward models guide text-to-image (T2I) systems toward outputs aligned with human preferences. However, typical reward models such as HPSv3 are trained on pre-annotated data from earlier T2I models, without accounting for quality discriminative shifts arising from evolving model capabilities and reinforcement learning (RL) iterations, limiting their broader applicability. In this work, we propose HPSv3++, a reward model framework that elevates the HPSv3 model for varying T2I model capabilities and their RL iteration changes across the full capability-iteration spectrum. Specifically, we first introduce HPDv3++, a 212K dual-dimension preference dataset annotated for text fidelity and aesthetic quality using a recent high-capability (Qwen-Image) model with human supervision. We then propose a two-stage training framework. Stage 1 employs data-aware orthogonal gradient projection to incorporate diverse aesthetic perception from HPDv3++ while preserving the original effective human preference knowledge in HPSv3. Stage 2 further leverages unlabeled data from T2I models spanning different capability levels and RL iterations, and introduces a joint capability-iterations conditioned signal for the reward model together with a standard deviation-driven unsupervised guidance mechanism, strengthening reward model across the capability-iteration spectrum. HPSv3++ achieves state-of-the-art preference prediction, outperforming HPSv3 9.8% on HPDv3, 5.5% on GenAI-Bench, while achieving 79.1%/88.1% on our proposed HPDv3++. When used for T2I RL training, it consistently improves GenEval scores across diverse T2I models, demonstrating its wide-range capabilities. The code is available at https://github.com/PlantPotatoOnMoon/HPSv3-PlusPlus.

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

HiRo: A Compact Four-Directional Hierarchical Reservoir Token-Mixer for Efficient Image Classification

Recent image classification models must balance local feature modeling, cross-window interaction, and parameter efficiency. Many high-performing architectures rely on fully trainable token-mixers, which improve representation learning but increase parameter count, optimization complexity and computational cost. We propose a parameter-efficient image classification model called HiRo that integrates shifted-window partitioning with multi-directional hierarchical reservoir computing. Images are divided into non-overlapping patches (treated as tokens), linearly projected, normalized, and enriched with 2D sinusoidal positional encodings, then processed within local windows. Inside each window, tokens are scanned in four directions and passed through a two-stage slice-and-mix reservoir module. In the first stage, directional sequences are split into contiguous slices, each processed by its own fixed reservoir with a trainable closed-loop readout. The resulting slice outputs are summarized using the start, end, and mean representations, and then mixed by a second-stage fixed reservoir for each direction. The mixed slice representations are expanded back to the token level and fused with the first-stage outputs, after which the four directional outputs are realigned and averaged. Consecutive blocks alternate between regular and shifted windows to enable cross-window interaction, followed by layer normalization, a residual feed-forward network, and global pooling for classification. This design combines regular and shifted window partitioning with hierarchical multi-directional reservoirs to make an efficient local-to-cross-window token-mixing framework for image classification. Despite using under 1M trainable parameters and significantly lower memory and time than transformer-style baselines, HiRo also achieves 99.46%, 85.57%, and 59.10% accuracy on MNIST, CIFAR-10, and CIFAR-100, respectively.

10.
arXiv (CS.CV) 2026-06-19

Efficiently Linking Real Scenes with Synthetic Data Generation for AI-based Cognitive Robotics and Computer Vision Applications

AI vision models are a driving factor for the potential use case scenarios of cognitive robotics within in the industry and household applications. A large array of methods from semantic environment analysis towards 6D and grasping pose estimation have been proposed based on the latest AI achievements. However, such advancements require further strong and efficient methods w.r.t. training data and AI-architectures, which are capable in synergy to tackle current challenges, precision limits, and scalability beyond domain gaps. In this paper, we discuss these current limits and trends in the related state-of-the-art which are challenging those. Further we discuss our current work in progress on bridging the domain gap between simulations and real world applications by linking those in the training data generation.

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

BayLing-Duplex: Native Full-Duplex Speech Dialogue with a Single Autoregressive LLM

Real-time, full-duplex speech interaction is a key feature of next-generation spoken chatbots, allowing the model to listen and speak at the same time and to handle natural phenomena such as overlap, hesitation, and barge-in. Existing speech language models (SpeechLMs) such as LLaMA-Omni and GLM-4-Voice are still turn-based and rely on an external Voice Activity Detection (VAD) module to mark the end of the user's turn, which fundamentally limits their interactive ability. In this paper, we introduce BayLing-Duplex, a native full-duplex SpeechLM where a single autoregressive LLM decides when to listen, when to speak, and when to stop, with no auxiliary turn-taking module. The design adds only a few special tokens to the standard vocabulary, so it transfers across LLMs and reuses existing training and serving stacks with no architectural adaptation. Starting from the public GLM-4-Voice checkpoint and using only 400K full-duplex samples for fine-tuning followed by a lightweight DPO stage, BayLing-Duplex reaches 92% turn-taking success and 100% interruption success on InstructS2S-Eval, while improving the speech-response score from 2.17 to 3.39 over Moshi. BayLing-Duplex also matches or surpasses its turn-based counterpart on Llama Questions, Web Questions, and Alpaca-Eval, showing that simultaneous listen-and-speak modeling does not sacrifice response quality.

12.
arXiv (CS.AI) 2026-06-18

SwitchBraidNet: Quantisation-Aware Lightweight Architecture for Hybrid Brain-Computer Interface

arXiv:2606.18816v1 Announce Type: cross Abstract: Hybrid brain-computer interfaces (BCIs) that integrate motor imagery (MI) and steady-state visual evoked potentials (SSVEP) provide high-dimensional neural decoding but typically exceed the computational limits of embedded hardware. To address this, we propose SwitchBraidNet, a compact EEG classification architecture designed for low-power deployment. The model employs a dual-path temporal braid to extract multiscale oscillatory features, an adaptive squeeze-and-excitation spatial switch for electrode gating, and a log-variance readout layer for direct band-power encoding. Furthermore, through systematic quantisation-aware training on the OpenBMI dataset, we compared SwitchBraidNet against four established baselines across FP32, FP16, and INT8 precisions. Experimental results demonstrate superior efficiency and performance, achieving MI accuracy of 69.49% (FP16), SSVEP accuracy of 93.48% (FP32), and a hybrid information transfer rate of 64.82 bits/min (FP16). With an INT8 footprint of only 3.03 KB, SwitchBraidNet maintains high accuracy across varying numerical precisions, demonstrating its suitability for low-power embedded BCI deployment.

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

The Proxy Knows Too Much: Sealing LLM API Routers with Attested TEEs

arXiv:2606.16358v1 Announce Type: cross Abstract: Agents increasingly access large language models (LLMs) through API routers. A router terminates the client's transport-layer security session and opens a separate upstream session, so it holds the full interaction in plaintext. This makes the router an application-layer man-in-the-middle: it can rewrite agent tool calls, swap dependencies for typosquatted packages, trigger attacks only under audit-evading conditions, and passively exfiltrate secrets. Existing client-side defenses are evadable. We propose AEGIS, a provider-transparent attested API router whose data path is a client-verified faithful passthrough. AEGISconfines plaintext handling to a small hardware-enclave component while leaving authentication, scheduling, accounting, and management on the untrusted host. The client verifies the enclave before releasing plaintext. The host can neither read nor alter the interaction, and plaintext leaves only toward destinations fixed by the measured image. We show that all four malicious-router attack classes succeed against a plaintext-access baseline and are blocked by AEGIS, including adaptive tests against the same boundary. The trusted path is $851$ lines, carries three provider-native APIs without conversion, and completes every request under real-provider workload and concurrency. In a seeded audit pilot, two commodity coding agents find eight and ten of ten planted invariant violations. The local relay overhead is about six milliseconds per request.

14.
medRxiv (Medicine) 2026-06-12

Effect of tenofovir on the outcomes of COVID-19 in persons with chronic hepatitis B: a nationwide cohort study in Sweden.

Background: Patients with chronic hepatitis B (CHB) may have an increased risk of severe COVID-19. Tenofovir has been hypothesized to confer protection against severe disease, but evidence is inconclusive. We evaluated the risk of severe COVID-19 among CHB patients treated with tenofovir compared with other nucleos(t)ide analogues (NAs). Methods and findings: In this nationwide, registry-based cohort study, we included all adults with CHB and laboratory-confirmed COVID-19 in Sweden between February 2020 and July 2022. Data from national health and socioeconomic registers were linked using unique personal identification numbers (PINs). Patients with HIV, hepatitis C, or hepatitis D coinfection were excluded. Exposure was defined as tenofovir versus other NA therapy. The primary outcome was severe COVID-19, defined as hospitalization >2 days or death within 30 days of diagnosis. Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI), controlling for age, sex, comorbidities, vaccination, socioeconomic status, and region of birth. Among 5,877 CHB patients with COVID-19, 672 were receiving NA therapy (437 tenofovir, 235 other NAs). Severe COVID-19 occurred in 8.0% of tenofovir-treated patients and 14.5% of those receiving other NAs (unadjusted OR 0.52; 95% CI, 0.31-0.85). After adjustment, the association was attenuated and no longer significant (aOR 0.72; 95% CI, 0.39-1.31). Older age, comorbidities, and unvaccinated status were strongly associated with severe disease. Conclusions: The apparent protective effect of tenofovir against severe COVID-19 in unadjusted analyses was largely explained by confounding factors. The risk of severe disease was primarily driven by age, comorbidities, and vaccination status. Prevention of severe COVID-19 in patients with CHB should instead focus on vaccination and management of comorbidities.

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

Towards Deep Learning Surrogate for the Forward Problem in Electrocardiology: A Scalable Alternative to Physics-Based Models

arXiv:2512.13765v2 Announce Type: replace-cross Abstract: The forward problem in electrocardiology, computing body surface potentials from cardiac electrical activity, is traditionally solved using physics-based models such as the bidomain or monodomain equations. While accurate, these approaches are computationally expensive, limiting their use in real-time and large-scale clinical applications. We propose a proof-of-concept deep learning (DL) framework as an efficient surrogate for forward solvers. The model adopts a time-dependent, attention-based sequence-to-sequence architecture to predict electrocardiogram (ECG) signals from cardiac voltage propagation maps. A hybrid loss combining Huber loss with a spectral entropy term was introduced to preserve both temporal and frequency-domain fidelity. Using 2D tissue simulations incorporating healthy, fibrotic, and gap junction-remodelled conditions, the model achieved high accuracy (mean $R^2 = 0.99 \pm 0.01$). Ablation studies confirmed the contributions of convolutional encoders, time-aware attention, and spectral entropy loss. These findings highlight DL as a scalable, cost-effective alternative to physics-based solvers, with potential for clinical and digital twin applications.

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

Range-Aware Bayesian Optimization for Discovering Diverse Designs within Target Property Windows

arXiv:2606.11574v1 Announce Type: new Abstract: In many materials and product design problems, desirable candidates exhibit properties that fall within an acceptable range rather than achieve a single optimum. Recovering multiple, distinct solutions that satisfy such specifications is also practically valuable, as some candidates may be preferred for reasons of cost, processability, or robustness that are difficult to encode directly in an objective function. Here, we develop a range-aware Bayesian optimization (BO) framework in which the acquisition function directly scores the posterior probability that a candidate satisfies a target range. The framework naturally extends to parallel pursuit of multiple distinct specifications over a shared candidate space. Across benchmark tasks, range-aware acquisition consistently recovers larger and more diverse sets of valid designs than standard BO baselines and recent goal-seeking methods. Its utility is further demonstrated in two practically motivated design case studies involving optimizing reaction conditions for polymer synthesis and sequence-defined oligomer discovery for prescribed optical absorption bands, supported by quantum chemical calculations. These results suggest that range-aware BO can provide a practical and sample-efficient foundation for specification-driven design, particularly when design flexibility and solution diversity are important considerations.

17.
Nature (Science) 2026-06-17

<i>CHPO</i> coordinates chilling recovery and nitrogen use in rice

作者:

Global rice production faces mounting challenges from abnormal temperature fluctuations and nitrogen-fertilizer-driven environmental pollution1–7. Developing varieties that balance chilling resilience and nitrogen-use efficiency (NUE) offers a promising solution, but the molecular networks coordinating these traits remain poorly understood. Here we identify CHILLING PHOENIX (CHPO), a major gene underlying the quantitative trait locus shared by both chilling tolerance and resilience. It encodes a MYB transcription factor that acts as a key regulator coordinating post-chilling recovery with nitrogen use in rice. Natural variation in a GCG-repeat-encoded polyalanine tract alters CHPO DNA-binding preference and redirects regulatory outputs between the japonica-type (CHPOjap) and indica-type (CHPOind), causing opposing effects on chilling tolerance and resilience. This allelic variation is shaped by domestication selection, with the CHPOjap allele probably derived from Chinese wild rice. CHPOjap directly targets OsTCP19 and OsNRT2.4 to fine-tune NUE, thereby enhancing chilling tolerance and resilience. These findings provide a mechanistic framework for a chilling-induced high-nitrogen-utilization module that alleviates the damage caused by chilling stress, and a potential molecular design&nbsp;strategy for breeding rice varieties with both chilling resilience and high NUE at the&nbsp;recovery stage. A rice gene, CHPO, links chilling resilience with nitrogen-use efficiency, revealing a domestication-shaped regulatory mechanism that could guide breeding of climate-resilient, sustainable rice varieties.

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

ISAP-3D: Identity-Slot Aligned Part-Aware 3D Generation

Part-aware 3D generation aims to synthesize structured objects with semantically meaningful components, yet often suffers from structural ambiguity due to identity-layout entanglement. Existing methods either infer part identity and spatial layout implicitly, which can lead to unstable part allocation (e.g., slot swapping or part merging), or rely on strong layout conditions that are difficult to obtain in practice. We attribute this ambiguity to identity-slot permutation freedom: without explicit identity-slot alignment, the correspondence between semantic parts and generation slots is not identifiable during training, allowing multiple slot assignments to fit the same supervision and leading to inconsistent decomposition. Based on this insight, we argue that stable part-aware generation requires identity-aligned one-to-one slot modelling. We therefore propose an identity-slot aligned framework, ISAP-3D, which anchors each part with semantic identity tokens and performs identity-conditioned one-to-one layout prediction, followed by layout-conditioned geometry synthesis. Structured local-global conditioning maintains identity alignment across semantic, spatial, and geometric stages. We also construct a part-level dataset with a unified semantic protocol to enable learnable and consistent identity-slot alignment. Extensive experiments demonstrate improved structural stability, controllability, and robustness over state-of-the-art part-aware generation baselines.

19.
bioRxiv (Bioinfo) 2026-06-14

Systematic AI-Driven Drug Repurposing via Clinical Trial Data Mining: A Framework and Six Cross-Therapeutic Case Studies.

作者:

Drug repurposing, the application of approved or shelved compounds to new therapeutic indications, offers a cost- and time-efficient alternative to de novo drug discovery. However, the systematic identification of repurposing candidates from the rapidly expanding body of clinical trial data remains a significant challenge. Here we present a publicly accessible AI-powered tool that mines the ClinicalTrials.gov registry to identify approved drugs with under-explored therapeutic potential in high-value disease areas. The tool integrates natural language processing, mechanism-of-action pathway analysis, and trial density scoring to surface candidates where biological plausibility is high and clinical trial coverage is sparse. We demonstrate the tool's utility across six cross-therapeutic case studies spanning oncology, cardiology, neurology, rare diseases, immunology, and infectious disease. Key findings include: the identification of Zonisamide as an under-explored combination candidate for obesity alongside GLP-1 receptor agonists; mechanistic validation of SGLT2 inhibitors in heart failure with preserved ejection fraction (HFpEF); and a novel cross-domain mapping of anti-TNF biologics to early-stage neurodegeneration via shared neuroinflammatory pathways. The tool is freely accessible and designed to lower the barrier for academic and industry researchers to systematically pursue repurposing opportunities.

20.
arXiv (CS.CV) 2026-06-12

VideoMDM: Towards 3D Human Motion Generation From 2D Supervision

We introduce VideoMDM, a diffusion-based framework that trains 3D human motion priors directly from accurate 2D poses extracted from monocular videos, without any 3D ground truth. A pretrained 2D-to-3D lifter provides approximate 3D pose sequences that serve as a noisy teacher: these are diffused, denoised by the model in 3D, and supervised in 2D by reprojecting the prediction and comparing against accurate keypoints. We show that, under mild assumptions, a depth-weighted 2D reprojection loss is equivalent in expectation to direct 3D supervision, and we adapt standard 3D motion regularizers - velocity consistency and over-parameterized representation alignment - to this 2D setting. Unlike methods that lift 2D to 3D only at inference, VideoMDM learns a coherent 3D motion manifold during training. On HumanML3D it nearly closes the gap to fully 3D-supervised MDM (FID 0.88 vs 0.54); On real video datasets Fit3D and NBA the method learns to generate motions consistently preferred by humans, with strong quantitative results.

21.
arXiv (CS.AI) 2026-06-16

Binary Tracking for Spatial QA and Navigation with Open Vision-Language Models

arXiv:2606.16902v1 Announce Type: cross Abstract: This work addresses spatial question answering for service robots traversing long egocentric routes. Given a query such as "where can I find a dry cleaner on the way back home?", the system returns a metric coordinate that downstream navigation components can act on. Prior Spatial Question Answering approaches leverage retrieval-augmented agents built on closed-source models such as GPT-4o for path exploration. However, robots operating in the real world often cannot reliably depend on online closed-source models due to network instability, communication latency, and deployment cost. It creates a need for open-source based Spatial Question Answering approaches that can run onboard the robot, yet prior research in this direction remains limited. This work proposes BinTrack, a simple yet effective, fully open-source spatial-localization agent that leverages the temporal ordering of a robot's trajectory. BinTrack performs a binary search over the trajectory segments between two anchor landmarks identified from a query. It improves overall accuracy by up to 22.8% over other open-source implementations and even matches the reported closed-source model result on the global category of the SpaceLocQA benchmark, the most challenging setting that has so far required strong reasoning agents such as GPT-4o. Furthermore, its optimized inference strategy consistently yields more than a 1.5x inference speedup over previous approaches. Finally, this work releases GangnamLoop, a novel and practical multi-trip outdoor benchmark collected by deploying a real quadruped robot on public streets with the anonymization policy. It revisits the same locations under different outdoor conditions and pairs the robot's low viewpoint with the human owner's. The source codes and datasets are publicly available at https://github.com/ndb796/BinaryTracking

22.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

作者:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue&nbsp;degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

23.
arXiv (CS.CL) 2026-06-16

Calibrated Triage, Not Autonomy: Confidence Estimation for Medical Vision-Language Models

A vision-language model can answer a question about a medical image fluently and confidently while barely using the image, leaning instead on language priors. In medicine this is the failure that matters most, because the answer looks trustworthy and is not, and the only protection is a confidence score reliable enough to tell the system when to abstain. We ask a deployment question rather than an accuracy one: how much imaging work a model can safely handle alone, and which confidence signal makes that possible. We evaluate seven confidence estimators across five open-weight LVLMs and three medical visual-question-answering datasets spanning broad clinical imaging, radiology, and pathology, with every probe trained only on natural images and applied without adaptation. Recast as bounded selective prediction (automate a case only when confidence clears a threshold, defer the rest), the comparison is cautionary. The standard metrics are poor guides: discrimination barely separates the methods, and the weak calibration of a cheap self-report is cheaply removed by off-domain temperature scaling without changing deployable yield. What distinguishes a usable estimator is the high-confidence region a clinician acts on: the weakest baselines are confidently wrong on 41 to 45 percent of their errors against 1 to 4 percent for the best probe, and no estimator is reliably best across domains or models. Safe handoff is governed at two levels: base-model competence sets a ceiling, so a well-calibrated score recovers roughly a third of radiology cases at a 20 percent error tolerance but almost none of pathology; the confidence layer then decides how much of that ceiling is reachable. The usable role today is calibrated triage, not autonomy: automate the cases a calibrated score marks safe, route the rest to a clinician. We release all outputs, correctness judgments, and confidence scores, with code.

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

VISTA: Video Interaction Spatio-Temporal Analysis Benchmark

Existing benchmarks for Vision-Language Models (VLMs) primarily evaluate spatio-temporal understanding on simple single-action videos, closed attribute sets and restricted entity types, failing to capture the freeform, multi-action interactions between diverse entities which characterize real-world video understanding. Furthermore, the lack of a systematic framework for analyzing model failures across complementary spatio-temporal axes hinders comprehensive evaluation. To address these gaps, we introduce VISTA, a Video Interaction Spatio-Temporal Analysis benchmark designed for open-set, multi-entity and multi-action spatio-temporal understanding in VLMs. VISTA decomposes videos into interpretable entities, their associated actions, and relational dynamics, enabling multi-axis diagnostics and unified assessment of relational, spatial, and temporal understanding. Our benchmark integrates multiple datasets into a single interaction-aware taxonomy and comprises ~12K curated video-query pairs spanning diverse scenes and complexities. We systematically evaluate 11 state-of-the-art VLMs on VISTA, and break down aggregate performance across our taxonomy to reveal shortcomings and pronounced spatio-temporal biases obscured by traditional metrics. By providing detailed, taxonomy-driven diagnostics on a challenging dataset, VISTA offers a nuanced framework to guide advances in model design, pretraining strategies, and evaluation protocols. Overall, VISTA is the first, large-scale, interaction-aware diagnostic benchmark for spatio-temporal understanding in VLMs.

25.
arXiv (CS.AI) 2026-06-18

SAE Interventions are Unreliable: Post-Intervention Recovery of Suppressed Behavior

arXiv:2606.18322v1 Announce Type: cross Abstract: Sparse Autoencoders (SAEs) decompose residual-stream activations into interpretable features. Recent latent-space defenses increasingly rely on these decompositions, assuming that identified "unsafe" SAE features serve as actionable handles for monitoring and intervention. In this paradigm, clamping a specific harmful feature is expected to reliably prevent model misbehavior. However, we show that this success may hide a recoverable failure mode: the clamp may block one visible route to a behavior without eliminating the behavior itself. We formulate this vulnerability as post-intervention recovery, a constrained residual-space optimization problem. Starting from the post-intervention residual state, we optimize residual perturbations to recover the pre-intervention behavior while preserving the post-intervention values of the targeted SAE features. Even under a strong threat model where the intervention remains active throughout optimization and generation, recovery remains possible. To rule out that recovery simply undoes the intervention, we use encoder-orthogonal updates for single-layer interventions and the corresponding feature-map Jacobian in the cross-layer setting. Across TPP, unlearning, IOI, and refusal steering experiments, this stress test reveals recoverable behavior despite successful feature-level intervention. Especially in the safety-critical refusal-steering setting, we achieve a 95.8% recovery rate on valid samples while keeping defended-feature relative drift to 0.131, substantially below suffix-based baselines. A recovery-path attribution analysis further localizes this recovery to the SAE reconstruction residual, the component left unexplained by the SAE. These results expose a gap between feature-level control and behavioral completeness: SAE features can support causal intervention, but controlling them does not guarantee control over the underlying behavior.