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01.
arXiv (CS.CV) 2026-06-12

MPMWorlds: Material-Point-Method Simulations for Inferring and Extrapolating Physical Dynamics

作者:
\v{Z}iga Kova\v{c}i\v{c}↗Kevin Ellis↗

To study the ability to infer physical dynamics from videos and extrapolate them forward in time, we assemble a dataset of 2D Material Point Method (MPM) physical simulations covering rich physical phenomena such as deformable objects, fluids, kinetic objects, and emitters. We study code generation and video diffusion approaches on this dataset, identifying their strengths and weaknesses by varying the amount of physically relevant side information. The code generation model, beyond giving a working demonstration of automatic synthesis of MPM simulations, reveals that such an approach struggles with inferring physical parameters from visual input, but relative to video diffusion, produces physically and temporally stable extrapolations forward in time, while the video diffusion model more strongly identifies geometric properties from visual input but produces physically implausible extrapolations.

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02.
arXiv (quant-ph) 2026-06-16

Quantum Global Variational Learning for Quantum Error Correction

作者:
Shun Ryuzaki↗Hideo Mukai↗

arXiv:2606.08592v2 Announce Type: replace-cross Abstract: Efficient quantum error correction is essential for the advancement of quantum computing. We propose a quantum neural network with a global structure that reduces the number of unitary matrices required in quantum circuits. This approach resulted in a 97% reduction in training time and up to a 25% improvement in the training completion rate, ultimately achieving a 100% success rate in training while surpassing the error correction performance reported in previous studies. In addition, we demonstrated the enhanced robustness of quantum error correction against internal network noise. Moreover, the fidelity of quantum error correction under internal network noise increased by up to 15% due to the reduced computational load.

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

Interpolation between Convolution and Attention via K-Nearest Neighbors

作者:
Mingi Kang↗

The shift from Convolutional Neural Networks to Transformers has reshaped computer vision, yet these two architectural families are typically viewed as fundamentally distinct. Convolutional Neural Networks are defined by spatially local convolution operations, while Transformers rely on global self-attention. We argue that convolution and self-attention, despite their apparent differences, can be unified within a single k-nearest neighbor aggregation framework. The critical insight is that both operations are special cases of neighbor selection and weighted aggregation. Convolution selects neighbors by spatial proximity while self-attention selects by feature similarity, revealing that they lie on a continuous spectrum rather than representing categorically different computations. We introduce Convolutional Nearest Neighbors (ConvNN), a unified framework that formalizes this connection. ConvNN exactly recovers standard and depthwise convolution by restricting neighbor selection to normalized spatial coordinates, and exactly recovers self-attention and its sparse variants, including KVT-attention, by replacing spatial proximity with scaled dot-product similarity. Beyond these special cases, ConvNN serves as a drop-in replacement for both convolution and attention layers, enabling systematic exploration of the intermediate spectrum between local and global aggregation through configurable similarity functions, neighbor selection strategies, positional encodings, and aggregation kernels.

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04.
bioRxiv (Bioinfo) 2026-06-13

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

作者:
Sarkar↗

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.

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05.
arXiv (CS.CL) 2026-06-12

G-Long: Graph-Enhanced Memory Management for Efficient Long-Term Dialogue Agents

作者:
Minjun Choi↗Yoonjin Jang↗Sangwon Youn↗Youngjoong Ko↗

While Large Language Models (LLMs) have advanced open-domain dialogue systems, maintaining long-term consistency remains a challenge due to inherent limitations in long-context reasoning and the inefficiency of processing extensive raw text. Existing approaches typically rely on either unstructured memory storage, which is prone to information loss, or computationally expensive LLMs that incur high latency. To address these limitations, we propose G-Long, a graph-enhanced framework that utilizes a fine-tuned small Language Model (sLM) for structured triplet extraction and associative retrieval, significantly reducing operational costs. Furthermore, we introduce the novel attention-aware importance scoring mechanism that leverages the intrinsic cross-attention signals of a T5 summarizer to identify salient memories. Extensive experiments across diverse benchmarks demonstrate that G-Long achieves state-of-the-art performance in both response generation and memory retrieval, yielding performance gains of up to 9.8% in response quality on MSC and 40.8% in retrieval recall on LME, while significantly minimizing computational overhead.

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

Quantum ergodicity and semiclassical measures: mathematical results

作者:
St\'ephane Nonnenmacher↗

arXiv:2606.12098v1 Announce Type: new Abstract: In this chapter we review some results describing the high-frequency eigenmodes of the Laplacian on compact manifolds, or Euclidean domains, for which the geodesic flow is chaotic. We focus on the macroscopic distribution of these eigenmodes, which is described by the concept of semiclassical measure. The main result on the question is the Quantum Ergodicity theorem, originally due to Schnirelman. We provide the detailed proof of this theorem, including the adjustments necessary to treat the case of manifolds with boundary. We also discuss the Quantum Unique Ergodicity conjecture, and some progress towards this conjecture for strongly chaotic (Anosov) systems. In particular, we describe the constraints on admissible semiclassical measures, in terms of their Kolmogorov-Sinai entropy, as well as more recent delocalization results.

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

Afrispeech Semantics: Evaluating Audio Semantic Reasoning in Spoken Language Models Across Domains and Accents

作者:
Chibuzor Okocha↗Christan Grant↗

Audio language models (ALMs) are increasingly used for speech-based understanding, yet their ability to perform semantic reasoning beyond transcription, Text-to-Audio Retrieval, Captioning, and Question-Answering accuracy remains insufficiently benchmarked. In particular, the effects of accent variation, domain shift, and semantic over-inference on audio reasoning are poorly understood. We evaluate audio language models across five semantic and paralinguistic reasoning tasks: entailment, consistency, plausibility, accent drift, and accent restraint. Collectively, these tasks assess a model's ability to reason over spoken audio as the primary evidence source, including whether a textual hypothesis can be inferred, contradicted, or left undetermined by the audio, whether statements align or conflict with spoken content, whether claims are plausible given the discourse, and whether model predictions remain stable or appropriately constrained across accent variation. These findings highlight critical limitations in current audio reasoning evaluations and hope to provide guidance for more robust and equitable ALM design and assessment

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08.
arXiv (CS.AI) 2026-06-18

ARIADNE: Agnostic Routing for Inference-time Adapter DyNamic sElection

作者:
Enrico Cassano↗Micha{\l} Brzozowski↗Zuzanna Dubanowska↗Paolo Mandica↗Neo Christopher Chung↗

arXiv:2606.19079v1 Announce Type: new Abstract: The increasing deployment of parameter-efficient fine-tuning (PEFT) has led to model ecosystems in which a single backbone is paired with many task-specialized adapters. In this setting, inference-time queries often arrive without task labels, requiring the system to automatically select the most appropriate adapter from a growing and heterogeneous adapter pool. Existing routing methods either depend on access to adapter internals, such as weight decompositions or gradient-based statistics, or require additional router training, which limits scalability and portability as new adapters are added. We introduce ARIADNE, a training-free, adapter-agnostic routing framework for dynamic adapter selection at inference time. ARIADNE represents each adapter through a set of centroids computed from embeddings of its training set, capturing the data distribution associated with that adapter. Given an unlabeled input, it selects an adapter by measuring proximity to these centroids in latent space. Because routing is performed entirely in the input embedding space, ARIADNE is compatible with arbitrary PEFT methods and requires no modification to the adapters or training procedures. Primarily evaluated with Llama 3.2 1B Instruct on 23 diverse NLP tasks, ARIADNE recovers 97.44% of the upper bound performance. Scaling to 44 tasks, it achieves 89.7% average selection accuracy, without additional training or access to adapter internals.

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

Non-Gaussian Phase Transition and Cascade of Instabilities in the Dissipative Quantum Rabi Model

作者:
Mingyu Kang↗Yikang Zhang↗Kenneth R. Brown↗Thomas Barthel↗

arXiv:2507.07092v3 Announce Type: replace Abstract: The open quantum Rabi model describes a two-level system coupled to a harmonic oscillator. A Gaussian phase transition for the nonequilibrium steady states has been predicted when the bosonic mode is soft and subject to damping. We show that oscillator dephasing is a relevant perturbation, which leads to a non-Gaussian phase transition and an intriguing cascade of instabilities for $k$-th order bosonic operators, as well as a jump in the steady-state qubit polarization. For the soft-mode limit, the equations of motion form a closed hierarchy and spectral properties can be efficiently studied. To this purpose, we establish a fruitful connection to non-Hermitian Hamiltonians. The results for the phase diagram, stability boundaries, and relevant observables are based on mean-field analysis, exact diagonalization, perturbation theory, and Keldysh field theory.

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10.
arXiv (CS.CL) 2026-06-12

BOUTEF: A Multilingual Corpus for FakeNews in North Africa – Language as a Weapon

作者:
Kamel Smaili↗Yassine Toughrai↗Amina Laggoun↗David Langlois↗

The rapid spread of fake news on social media has become a major challenge, particularly in multilingual and under-resourced contexts such as North Africa. In this paper, we introduce BOUTEF, a large-scale multilingual corpus designed to study the propagation, characteristics, and impact of fake news in Algeria and Tunisia. The corpus integrates three complementary components: fake narratives, genuine narratives, and associated user-generated comments, along with verified debunking information. It covers a wide range of languages and linguistic varieties, including MSA, Algerian and Tunisian dialects, Arabizi, French, English, and code-switched language. Building on this resource, we conduct a comprehensive empirical analysis combining quantitative and qualitative approaches. We examine thematic distributions, linguistic and rhetorical strategies, sentiment patterns, and social engagement dynamics. Statistical analyses reveal significant associations between thematic categories and message veracity, as well as strong correlations between user engagement and the visibility of fake content. Our findings show that fake news relies heavily on emotionally charged narratives, sensational framing, and hybrid linguistic practices that enhance virality and audience engagement. In contrast, debunking content adopts a more factual and verification-oriented style. Furthermore, a comparative analysis between Algeria and Tunisia highlights both shared dynamics and country-specific characteristics shaped by sociopolitical contexts. The results emphasize the role of informal language practices in the diffusion and reception of misinformation. By providing a rich, annotated, and publicly available dataset, this work contributes to advancing research on fake news detection, low-resource language processing, and the understanding of information disorders in complex linguistic environments.

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11.
arXiv (quant-ph) 2026-06-16

Chiral Lattice Gauge Theories from Symmetry Disentanglers

作者:
Ryan Thorngren↗John Preskill↗Lukasz Fidkowski↗

arXiv:2601.04304v2 Announce Type: replace-cross Abstract: We propose a Hamiltonian framework for constructing chiral gauge theories on the lattice based on symmetry disentanglers: constant-depth circuits of local unitaries that transform not-on-site symmetries into on-site ones. When chiral symmetry can be realized not-on-site and such a disentangler exists, the symmetry can be implemented in a strictly local Hamiltonian and gauged by standard lattice methods. Using lattice rotor models, we realize this idea in 1+1 and 3+1 spacetime dimensions for $U(1)$ symmetries with mixed 't Hooft anomalies, and show that symmetry disentanglers can be constructed when anomalies cancel. As an example, we present an exactly solvable Hamiltonian lattice model of the (1+1)-dimensional "3450" chiral gauge theory, and we argue that a related construction applies to the $U(1)$ hypercharge symmetry of the Standard Model fermions in 3+1 dimensions. Our results open a new route toward fully local, nonperturbative formulations of chiral gauge theories.

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12.
arXiv (math.PR) 2026-06-16

Interplay of insurance and financial risks in a non Levy-Renewal environment

作者:
Dimitrios G. Konstantinides↗Charalampos D. Passalidis↗

arXiv:2606.15596v1 Announce Type: new Abstract: In this paper we consider a multivariate risk model, with common counting process and common process of logarithmic returns for the investment portfolio. We assume that the claim-vectors, the counting process and the logarithmic returns of the investment portfolio satisfy a weak dependence structure. Further, we consider that the counting process represents an inhomogeneous renewal process, and the logarithmic returns represent a cadlag process with independent but not necessarily stationary increments. Under these conditions we provide an asymptotic expression for the infinite-time entrance probability of the discounted aggregate claims into some rare set xA, where A denotes a set from a general set family, crucial for the actuarial practice, when the common distribution of the claim vectors belong to a multivariate heavy-tailed distribution class. This result, is derived under a moment condition for the financial risks, and underlines the multivariate linear single big jump principle. When we restrict the distribution class of the claim-vectors to multivariate regular variation, we find more explicit asymptotic expressions, weakening the moment conditions on the financial risks. The asymptotic formulas, derived through double dependence solution, become more direct and practical in applications. With respect to the technical part, due to non Levy-Renewal framework, the classical Kesten-Goldie theorems are not applicable, nor their extensions. The way we make the discretization of the process of the discounted aggregate claims permits to derive uniform asymptotics with respect to the number of summands, that facilitate the approximation of the infinite sums of the main results.

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13.
medRxiv (Medicine) 2026-06-23

Acute Ischemic Stroke Detection on Non-Contrast CT: A Deep Learning Approach

作者:
Goyal↗Stevens↗R. D↗

Acute ischemic stroke (AIS) is a leading cause of disability and death while effective treatment requires quick and accurate diagnosis. Non-contrast CT (NCCT) is widely used in the initial screening of AIS, but stroke detection is challenging because early changes on NCCT are subtle or indistinguishable. Using hyperacute NCCTs as inputs and diffusion-weighted MRI as ground truth, we trained a deep learning algorithm to classify patients with AIS and segment the stroke lesions. We hypothesized that this approach would accurately detect hyperacute tissue density changes on NCCT. For the classification task, our ResNet50 model delivered the best performance (with 98.5% accuracy, 97.4% precision, and 100% recall on an evaluation set). Classification performance remained strong when restricted to lesions smaller than 5 mL, which constituted the majority of our evaluation cases. For the segmentation task accomplished using a range of U-Net architectures, performance was acceptable for large lesions and declined sharply for smaller lesions. Together, these findings demonstrate the feasibility of deep learning for AIS detection and represent a step towards faster triage and treatment for stroke patients.

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

SeamEdit: A Black-Box VLM-Agnostic Pipeline for Large-Image Semantic Editing

作者:
Xiangyu Lyu↗Dan Lei↗

Semantic region editing for large images must satisfy two requirements at the same time: high generative quality and natural integration with surrounding content. Some related methods rely on white-box models and leave the strong generation capability of closed-source models underexplored. Directly applying closed-source models to tiled editing, however, introduces several failure modes: semantic deformation, canvas-level alignment drift, and visible seam artifacts. This paper presents SeamEdit, a training-free and model-agnostic pipeline that treats any VLM with inpainting capability as a black-box oracle. SeamEdit mitigates these issues through a five-stage post-hoc pipeline: overlay-based tile decomposition, black-box VLM inpainting, geometric and color-consistency correction, seam-risk-based multi-candidate ranking, and dynamic-programming curved seam fusion. The pipeline reduces seam visibility and supports semantic modification of arbitrary tile regions.

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15.
arXiv (math.PR) 2026-06-16

Universality in the target arrival statistics of non-conservative search processes

作者:
Jos\'e Giral-Barajas↗Samantha Linn↗Paul C. Bressloff↗

arXiv:2606.16025v1 Announce Type: cross Abstract: Stochastic search processes in which searchers are continuously introduced to and removed from a target search domain are fundamental to a wide class of physical and artificial systems. The theory of such non-conservative search processes is, however, much less developed than for search processes with a fixed number of particles. Here we exploit a natural mapping between non-conservative stochastic search and queueing theory to derive the full time-dependent distribution of target arrivals under minimal assumptions on the underlying search process. Remarkably, we find that the steady-state inter-arrival time distribution is exactly exponential, regardless of the details of the search process, showing a robust universality that emerges directly from the queueing framework. Thus, counterintuitively, the arrival statistics of a non-conservative search process are much simpler than sequential search-and-capture processes involving a fixed number of searchers. This has major implications for target resource accumulation, where the delivery of resources is counter-balanced by their downstream consumption.

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

CMI-RewardBench: Evaluating Music Reward Models with Compositional Multimodal Instruction

作者:
Yinghao Ma↗Haiwen Xia↗Hewei Gao↗Weixiong Chen↗Yuxin Ye↗Yuchen Yang↗Sungkyun Chang↗Mingshuo Ding↗Yizhi Li↗Ruibin Yuan↗Simon Dixon↗Emmanouil Benetos↗…

arXiv:2603.00610v3 Announce Type: replace-cross Abstract: While music generation models have evolved to handle complex multimodal inputs mixing text, lyrics, and reference audio, evaluation mechanisms have lagged behind. In this paper, we bridge this critical gap by establishing a comprehensive ecosystem for music reward modeling under Compositional Multimodal Instruction (CMI), where the generated music may be conditioned on text descriptions, lyrics, and audio prompts. We first introduce CMI-Pref-Pseudo, a large-scale preference dataset comprising 110k pseudo-labeled samples, and CMI-Pref, a high-quality, human-annotated corpus tailored for fine-grained alignment tasks. To unify the evaluation landscape, we propose CMI-RewardBench, a unified benchmark that evaluates music reward models on heterogeneous samples across musicality, text-music alignment, and compositional instruction alignment. Leveraging these resources, we develop CMI reward models (CMI-RMs), a parameter-efficient reward model family capable of processing heterogeneous inputs. We evaluate their correlation with human judgment scores on musicality and alignment on CMI-Pref along with previous datasets. Further experiments demonstrate that CMI-RM not only correlates strongly with human judgments, but also enables effective inference-time scaling via top-k filtering. Code is available at GitHub (https://github.com/Haiwen-Xia/CMI-RewardBench). Model weights: CMI-RM (https://huggingface.co/HaiwenXia/CMI-RM). Datasets: CMI-Pref-Pseudo (https://huggingface.co/datasets/HaiwenXia/cmi-pref-pseudo) and CMI-Pref (https://huggingface.co/datasets/HaiwenXia/cmi-pref)

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

UMA-Split: unimodal aggregation for both English and Mandarin non-autoregressive speech recognition

作者:
Ying Fang↗Xiaofei Li↗

This paper proposes a unimodal aggregation (UMA) based nonautoregressive model for both English and Mandarin speech recognition. The original UMA explicitly segments and aggregates acoustic frames (with unimodal weights that first monotonically increase and then decrease) of the same text token to learn better representations than regular connectionist temporal classification (CTC). However, it only works well in Mandarin. It struggles with other languages, such as English, for which a single syllable may be tokenized into multiple fine-grained tokens, or a token spans fewer than 3 acoustic frames and fails to form unimodal weights. To address this problem, we propose allowing each UMA-aggregated frame map to multiple tokens, via a simple split module that generates two tokens from each aggregated frame before computing the CTC loss.

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

On the Generalization Bounds of Symbolic Regression with Genetic Programming

作者:
Masahiro Nomura↗Ryoki Hamano↗Isao Ono↗

arXiv:2604.17402v2 Announce Type: replace Abstract: Symbolic regression (SR) with genetic programming (GP) aims to discover interpretable mathematical expressions directly from data. Despite its strong empirical success, the theoretical understanding of why GP-based SR generalizes beyond the training data remains limited. In this work, we provide a learning-theoretic analysis of SR models represented as expression trees. We derive a generalization bound for GP-style SR under constraints on tree size, depth, and learnable constants. Our result decomposes the generalization gap into two interpretable components: a structure-selection term, reflecting the combinatorial complexity of choosing an expression-tree structure, and a constant-fitting term, capturing the complexity of optimizing numerical constants within a fixed structure. This decomposition provides a theoretical perspective on several widely used practices in GP, including parsimony pressure, depth limits, numerically stable operators, and interval arithmetic. In particular, our analysis shows how structural restrictions reduce hypothesis-class growth while stability mechanisms control the sensitivity of predictions to parameter perturbations. By linking these practical design choices to explicit complexity terms in the generalization bound, our work offers a principled explanation for commonly observed empirical behaviors in GP-based SR and contributes towards a more rigorous understanding of its generalization properties.

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

Understanding Scam Trends and Rail Paths from Reddit Self-Disclosure Narratives

作者:
Yangjun Zhang↗Mirko Bottarelli↗Mark Hooper↗Carsten Maple↗

Online scam behavior is inherently multi-stage, and the lifecycle includes temporally ordered rails and events rather than isolated signals. Existing works analyze characteristics of scam types and rails, but they do not track scam trends across years. Moreover, the work on the relations between rails is hampered due to the lack of open-source datasets with annotations and coverage of different scam types. To address these gaps, we build a dataset to analyze the yearly trend of scam characteristics and rail paths using Reddit self-disclosure narratives from 2023 to 2025. We collect 21,304 posts from scam-related subreddits with at least one rail among identity, communication, platform, and payment for trend analysis by heuristic annotation. Then, we label 1,800 posts containing explicit or recoverable scam chains by an LLM-assisted method for scam path analysis. The method is evaluated with human annotation. Lastly, we run a topic model on the comments of the posts to analyze the community support behavior. The results reveal that scam processes are predominantly multi-rail. Across years, different scam types and rail components dominate. Different scam types vary systematically in path complexity. Reddit support behaviors have become more detailed over time. This work supports synthetic scam chain data simulation and AI-related scam risk assessment, though findings may not generalise to other platforms.

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

UNIEGO: Proxies as Mediators for Unified Egocentric Video Representation Learning

作者:
Wenhao Chi↗Arkaprava Sinha↗Dominick Reilly↗Hieu Le↗Srijan Das↗

arXiv:2606.20559v1 Announce Type: cross Abstract: Egocentric video understanding is inherently limited by the narrow perspective of wearable cameras: a single viewpoint, a single modality, a single model cannot capture the full richness of human action. We argue that a truly expressive egocentric representation must subsume complementary knowledge across viewpoints, modalities, and foundation model representations, yet remain deployable from egocentric video alone. To this end, we introduce a hierarchical multi-teacher distillation framework that produces UNIEGO, a unified egocentric encoder trained with nine teachers spanning ego-exo viewpoints, RGB, depth, and skeleton modalities, and four foundation models. Rather than distilling directly from heterogeneous teachers whose incompatible architectures and feature geometries induce conflicting gradients, our framework interposes a layer of representation-specific Proxy models that translate diverse teacher knowledge into a homogeneous egocentric space. A second distillation stage, Selective Proxy Distillation (SPD), then adaptively selects, for each training sample, the subset of proxies that are both correct and confident, distilling exclusively from reliable supervision and suppressing erroneous signals. SPD is further stabilized by initializing UNIEGO as a learned convex combination of proxy parameters, placing the unified model in a well-conditioned region of the loss landscape before distillation begins. UNIEGO achieves state-of-the-art performance across three egocentric video understanding tasks - action recognition, video retrieval, and action segmentation on three challenging ego-exo benchmarks, outperforming naive multi-teacher distillation baselines and demonstrating that structured, proxy-mediated knowledge transfer yields richer and more discriminative egocentric representations.

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21.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

作者:
Yi Zang↗

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

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22.
arXiv (CS.LG) 2026-06-18

Contextualizing Biological Language Models across Modalities via Logit-Space Contrastive Alignment

作者:
Yanjun Shao↗Yundi Chen↗Yashvi Patel↗Aurelien Pelissier↗Mar\'ia Rodr\'iguez Mart\'inez↗

arXiv:2606.18703v1 Announce Type: new Abstract: Pretrained biological language models expose per-token probability distributions through masked-token prediction, providing the likelihood interface central to sequence design, variant scoring, and mechanistic interpretation. Yet these distributions are learned from broad unlabeled corpora and are not naturally conditioned on task-specific biological contexts such as interaction partners, cellular environments, or therapeutic interventions. Existing contextual matching methods often distort this interface through pooled embeddings, contrastive latent spaces, or task-specific prediction heads. We introduce LOGICA (Logit-space Contrastive Alignment), a framework for context-conditioned prediction that performs contrastive learning directly in output-logit space. Using gated cross-modal adapters compatible with each model's native token head, LOGICA preserves the pretrained likelihood interface and converts contextualized token log-likelihoods into matching scores. Alignment is defined through context-sensitive token probabilities rather than proximity in a shared embedding space, enabling learning from sparse paired data across models with distinct vocabularies, without a shared tokenizer or decoder. LOGICA is particularly effective for mutation-local variant ranking, where comparisons reduce to context-conditioned likelihoods of mutant tokens at perturbed sites. Across protein–ligand binding, TCR–peptide activity, and drug-conditioned resistance prediction, LOGICA improves over prior state-of-the-art methods, including matched latent-contrastive and conditional MLM baselines, while retaining a token-level interface for interpretation and generation. On held-out-gene single-mutation drug-resistance prediction, LOGICA improves AUC from near-random latent-space baselines of $\sim$0.55 to $\sim$0.65.

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23.
arXiv (CS.LG) 2026-06-18

Structural MRI Synthesis for Alzheimer's Disease via Conditional Diffusion on Anatomical Masks

作者:
Muge Zhang↗Muhammad Ali Khaliq↗Jamal Alsakran↗Byeong Kil Lee↗Jeeho Ryoo↗

arXiv:2606.18354v1 Announce Type: cross Abstract: Recent advances in generative machine learning models have significantly improved medical imaging, offering promising solutions for data augmentation, privacy preservation, and improved model generalization. However, synthesizing high-quality structural MRI data for Alzheimer's Disease (AD) remains challenging due to the subtle, region-specific, and progressive anatomical changes associated with neurodegeneration. In this paper, we extend the Med-DDPM conditional diffusion model – originally designed for brain tumor synthesis – to generate 3D structural MRIs specifically tailored to AD. We adopted Med-DDPM due to its established stability and structural fidelity compared to other generative models, which makes it particularly suitable for capturing the subtle anatomical changes characteristic of AD. Our approach conditions the diffusion process on anatomical segmentation masks derived from the ADNI dataset, incorporating key AD-relevant brain structures into the generation process. We systematically evaluate the quality and utility of the synthetic images by training segmentation models on real, synthetic, and hybrid (mixed) datasets. Experimental results demonstrate that segmentation models trained exclusively on synthetic data achieve comparable Dice scores (0.6532) to those trained on real data (0.6513), while exhibiting significantly enhanced recall. Notably, models trained on hybrid datasets (mixing real and synthetic images) outperform both real and synthetic-only baselines, achieving a Dice score of 0.7244. These findings underscore the successful use of conditional diffusion models for generating anatomically accurate, AD-specific synthetic MRIs, and highlight their potential for enhancing training data availability, improving diagnostic accuracy, and promoting research reproducibility in neuroimaging studies.

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

Intrinsic Computational Functionalism and Simulated Consciousness

作者:
Ryota Kanai↗Shuqin Ma↗

arXiv:2606.15348v1 Announce Type: cross Abstract: A common objection to artificial or simulated consciousness is that a simulated brain is no more conscious than simulated water is wet. We address this from the perspective of Intrinsic Computational Functionalism (ICF): if consciousness is computationally constituted, it depends not on externally imposed descriptions but on the computational structures a system physically realizes in virtue of its own causal-dynamical organization. In previous work we developed Canonical Functionalism as a mathematically precise special case of this anti-interpretivist program, identifying functional states by their complete future input-output roles under a fixed interface. Here we argue that this input-output construction, though important, is incomplete: as a behavioral boundary case of ICF, it makes lookup tables and unfolded systems that preserve the same boundary behavior canonically equivalent. A consciousness-relevant canonical representation must instead include internal mechanisms, interventions, and joint readouts belonging to the relevant intrinsic organization. We therefore define a mechanism-enriched canonical structure and use it to formulate Intrinsic Causal-Computational Realization (ICCR), a realization relation preserving physical implementation, intrinsic state individuation, transition structure, intervention profiles, and the relevant agent-body-world boundary. The central result is conditional: if conscious properties are invariants of intrinsic causal-computational organization, then any system satisfying ICCR realizes the same consciousness-relevant properties, whether biological, artificial, or simulated. We discuss objections including biological naturalism and integrated information theory. We conclude that to deny consciousness to a simulation, one must identify a consciousness-relevant intrinsic causal-computational structure that the simulation fails to realize.

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25.
medRxiv (Medicine) 2026-06-17

Identifying anaphylaxis using weakly-supervised prediction models and natural language processing

作者:
Williamson↗B. D↗Cronkite↗D. J↗Yu↗Ramaprasan↗Fuller↗Covey↗Kiniry↗Park↗Winter↗Whitaker↗…

Objectives Scalable computable phenotyping algorithms are critical for conducting high-throughput disease-outcome research in large, distributed-data electronic health record (EHR) and claims data settings. We developed and evaluated a claims- and EHR-based computable phenotyping algorithm for anaphylaxis, a rare acute condition that is challenging to accurately identify using claims data alone. Materials and Methods Potential anaphylaxis events came from two healthcare systems (Kaiser Permanente Washington [KPWA] and Vanderbilt University Medical Center [VUMC]). We engineered features from clinical text using automated natural language processing (NLP) methods. We then developed a phenotyping algorithm using four NLP- and diagnosis code-based silver labels (proxies for the gold-standard labels). Gold-standard abstracted outcomes were used to evaluate algorithm performance. Results The largest area under the receiver operating characteristic curve (AUC) was 0.931 for an NLP-based silver-label model at KPWA. Depending on the model and healthcare system site, positive predictive value (PPV) and sensitivity at the threshold of predicted probability that maximized F1 score ranged from 0.52 to 0.77 (PPV) and 0.78 to 1 (sensitivity). Discussion NLP-based silver-label models had large AUC at KPWA but not at VUMC. This may be because clinical text at KPWA is only available for outpatient encounters and secure messaging. High sensitivity for identifying anaphylaxis can be obtained using our best-performing models. Conclusion The best-performing models had better PPV and sensitivity tradeoffs than prior bespoke anaphylaxis models with costly, manually curated features. The simplicity of the approach compared to traditional phenotyping methods allows it to be deployed easily at multiple health care systems.

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