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01.
arXiv (CS.CV) 2026-06-16

EmoZone-Talker: Regional Semantic Control of Audio-Driven 3DGS Talking Heads via Facial Action Units

3D Gaussian Splatting (3DGS) has shown strong potential for high-fidelity talking head synthesis. However, enabling fine-grained, interpretable, and editable facial expression control remains fundamentally challenging due to intrinsic conflicts between speech-driven facial dynamics and explicit expression signals. Existing methods rely on implicit multimodal fusion, leading to spatial entanglement and temporal instability. We present EmoZone-Talker, a novel framework that reformulates audio-driven facial animation as a structured spatial-temporal coordination problem under cross-modal conflicts. Our approach introduces an explicit spatial disentanglement and temporal dynamics modeling of facial motion. Specifically, we propose Synergy Zones with Prioritized Attention Bias (SZ-PAB) to explicitly decouple modality contributions via region-wise constraints guided by anatomical priors, and a Channel-Independent Temporal AU Encoder (CIT-AE) to model temporally coherent AU dynamics. By integrating these representations into 3D Gaussian deformation, EmoZone-Talker enables precise and interpretable control over facial expressions. Extensive experiments demonstrate that our method improves expression controllability and realism, with notable gains in upper-face accuracy and temporal coherence, while preserving high rendering quality and accurate lip synchronization. Code will be publicly released to facilitate reproducibility and further research.

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

Decomposing Prediction Mechanisms for In-Context Recall

arXiv:2507.01414v2 Announce Type: replace Abstract: We introduce a new family of toy problems that combine features of linear-regression-style continuous in-context learning (ICL) with discrete associative recall. We pretrain transformer models on sample traces from this toy, specifically symbolically-labeled interleaved state observations from randomly drawn linear deterministic dynamical systems. We study if the transformer models can recall the state of a sequence previously seen in its context when prompted to do so with the corresponding in-context label. Taking a closer look at this task, it becomes clear that the model must perform two functions: (1) identify which system's state should be recalled and apply that system to its last seen state, and (2) continuing to apply the correct system to predict the subsequent states. Training dynamics reveal that the first capability emerges well into a model's training. Surprisingly, the second capability, of continuing the prediction of a resumed sequence, develops much earlier. Via out-of-distribution experiments, and a mechanistic analysis on model weights via edge pruning, we find that next-token prediction for this toy problem involves at least two separate mechanisms. One mechanism uses the discrete symbolic labels to do the associative recall required to predict the start of a resumption of a previously seen sequence. The second mechanism, which is largely agnostic to the discrete symbolic labels, performs a "Bayesian-style" prediction based on the previous token and the context. These two mechanisms have different learning dynamics. To confirm that this multi-mechanism (manifesting as separate phase transitions) phenomenon is not just an artifact of our toy setting, we used OLMo training checkpoints on an ICL translation task to see a similar phenomenon: a decisive gap in the emergence of first-task-token performance vs second-task-token performance.

03.
Nature Medicine 2026-06-12

Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial

Authors:

Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith−Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: −4.04, 95% confidence interval: −6.89 to −1.18, P = 0.006, Hedges’ g = 0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 . Pramipexole, in patients with major depressive disorder, dysthymia or bipolar depression, reduced Snaith−Hamilton Pleasure Scale scores significantly compared to placebo.

04.
arXiv (CS.CV) 2026-06-17

ActWorld: From Explorable to Interactive World Model via Action-Aware Memory

Interactive world models aim to simulate environment dynamics under real-time user actions. However, their action vocabulary is largely confined to navigation: most actions correspond to motion (e.g., walk, turn, look around), while interaction with objects in the scene (e.g., pick up plates, open doors, or trigger physical responses) is either absent, restricted to game domains, or relegated to prompt-to-full-video scenarios. The resulting worlds are visually explorable but not truly actionable. In this work, we present ActWorld, an interactive world model that extends prior navigation-centric generators to support mid-rollout object interaction within a chunk-autoregressive framework. We argue that the navigation-interaction gap stems from two bottlenecks. First, a data bottleneck: the lack of human-object interaction data with accurate, dense labels. Second, a memory bottleneck: recency-biased history compression in existing world models discards the event-transition frames that causally determine subsequent object states, leading to an action-forgetting pathology. On the data side, we construct a 100K interaction video dataset, each annotated with per-chunk captions via chain-of-thought reasoning. On the model side, we introduce a hierarchical action-aware memory design that routes history compression by interaction importance, complemented by a persistent memory bank that maintains event-update and object-identity tokens across long rollouts. Experiments show that ActWorld supports both flexible navigation and rich object interaction within a single model, substantially improving interaction fidelity over navigation-only baselines without sacrificing viewpoint control. Project page is available at https://interactwm.github.io/ActWorld.

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

When Iterative RAG Beats Ideal Evidence: A Diagnostic Study in Scientific Multi-hop Question Answering

Retrieval-Augmented Generation (RAG) extends large language models (LLMs) beyond parametric knowledge, yet it is unclear when iterative retrieval-reasoning loops meaningfully outperform static RAG, particularly in scientific domains with multi-hop reasoning, sparse domain knowledge, and heterogeneous evidence. We provide the first controlled, mechanism-level diagnostic study of whether synchronized iterative retrieval and reasoning can surpass an idealized static upper bound (Gold Context) RAG. We benchmark eleven state-of-the-art LLMs under three regimes: (i) No Context, measuring reliance on parametric memory; (ii) Gold Context, where all oracle evidence is supplied at once; and (iii) Iterative RAG, a training-free controller that alternates retrieval, hypothesis refinement, and evidence-aware stopping. Using the chemistry-focused ChemKGMultiHopQA dataset, we isolate questions requiring genuine retrieval and analyze behavior with diagnostics spanning retrieval coverage gaps, anchor-carry drop, query quality, composition fidelity, and control calibration. Across models, Iterative RAG consistently outperforms Gold Context, with gains up to 25.6 percentage points, especially for non-reasoning fine-tuned models. Staged retrieval reduces late-hop failures, mitigates context overload, and enables dynamic correction of early hypothesis drift, but remaining failure modes include incomplete hop coverage, distractor latch trajectories, early stopping miscalibration, and high composition failure rates even with perfect retrieval. Overall, staged retrieval is often more influential than the mere presence of ideal evidence; we provide practical guidance for deploying and diagnosing RAG systems in specialized scientific settings and a foundation for more reliable, controllable iterative retrieval-reasoning frameworks.

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

PhysGuard: Fisher-Guided Gradient Projection for Sim-to-Real Neural PDE Surrogates

arXiv:2606.16602v1 Announce Type: new Abstract: Neural operator models trained on simulation data often lose accuracy when applied to experimental measurements due to the sim-to-real gap. Standard fine-tuning with limited real data can reduce this gap, but it may also damage the core physics-relevant representations learned during pretraining. Although knowledge-preserving adaptation has been widely investigated in vision or language tasks, it remains unclear whether these methods are suitable for neural operators whose architectures and protected knowledge are fundamentally different. Neural operators need to preserve core-scale physical structures rather than semantic or visual features. We propose PhysGuard, a physics-preserving framework for accurate sim-to-real adaptation of neural operators. Specifically, PhysGuard uses the empirical Fisher Information Matrix computed on simulation data to identify physics-critical parameter directions, then restricts fine-tuning updates to directions that do not interfere with them. A layer-wise Gram-matrix formulation makes this efficient for models with millions of parameters, while an adaptive threshold automatically determines the protected subspace size. A spectral probe experiment shows that the dominant Fisher directions are strongly associated with low-frequency output structures. Experiments on benchmark across four neural operator architectures and different physical systems show that PhysGuard performs strongly on most evaluation metrics compared to baselines. The benefits are most evident under severe domain shift, where it reduces low-frequency error by up to 32\% compared to standard fine-tuning while maintaining adaptability. Our code is available at https://github.com/ZhouChaunge/PhysGuard.

07.
arXiv (CS.CL) 2026-06-17

A Multifaceted Analysis of Social Biases in Large Language Models

Large language models (LLMs) have rapidly become indispensable tools for acquiring information and supporting human decision-making. However, ensuring that these models uphold fairness across varied contexts is critical to their safe and responsible deployment. In this study, we undertake a comprehensive examination of four widely adopted LLMs, probing their underlying biases and inclinations across the dimensions of politics, ideology, alliance, language, and gender. Through a series of carefully designed experiments, we investigate their political neutrality using news summarization, ideological biases through news stance classification, tendencies toward specific geopolitical alliances via United Nations voting patterns, language bias in the context of multilingual story completion, and gender-related affinities as revealed by responses to the World Values Survey. Results indicate that while the LLMs are aligned to be neutral and impartial, they still show biases and affinities of different types.

08.
arXiv (quant-ph) 2026-06-16

Sharp Transitions for Subsystem Complexity

arXiv:2510.18832v2 Announce Type: replace-cross Abstract: The circuit complexity of time-evolved pure quantum states grows linearly in time for an exponentially long time. This behavior has been proven in certain models, is conjectured to hold for generic quantum many-body systems, and is believed to be dual to the long-time growth of black hole interiors in AdS/CFT. Achieving a similar understanding for mixed states remains an important problem. In this work, we study the circuit complexity of time-evolved subsystems of pure quantum states. We find that for greater-than-half subsystem sizes, the complexity grows linearly in time for an exponentially long time, similarly to that of the full state. However, for less-than-half subsystem sizes, the complexity rises and then falls, returning to low complexity as the subsystem equilibrates. Notably, the transition between these two regimes occurs sharply at half system size. We use holographic duality to map out this picture of subsystem complexity dynamics and rigorously prove the existence of the sharp transition in random quantum circuits. Furthermore, we use holography to predict features of complexity growth at finite temperature that lie beyond the reach of techniques based on random quantum circuits. In particular, at finite temperature, we argue for an additional sharp transition at a critical less-than-half subsystem size. Below this critical value, the subsystem complexity saturates nearly instantaneously rather than exhibiting a rise and fall. This novel phenomenon, as well as an analogous transition above half system size, provides a target for future studies based on rigorous methods.

09.
arXiv (CS.AI) 2026-06-17

DeMaVLA: A Vision-Language-Action Foundation Model for Generalizable Deformable Manipulation

arXiv:2605.31286v2 Announce Type: replace-cross Abstract: Real-world household robots require Vision-Language-Action (VLA) foundation models that can acquire reusable manipulation skills across diverse objects, task conditions, and household environments. Deformable-object folding is a representative challenge, requiring robots to handle clothing items from random initial states across varying categories, geometries, materials, and scenes. However, existing VLA systems commonly train separate policies for different object categories, while naively mixed multi-task training often suffers from task interference and degraded performance. To move beyond category-specific folding policies, we introduce DeMaVLA, a VLA foundation model for generalizable Deformable Manipulation. DeMaVLA adopts a VLM backbone with an action expert and formulates continuous action generation using flow matching. To improve efficiency, the action expert is constructed by pruning every other transformer layer while preserving layer-wise alignment with the VLM backbone, reducing training and inference cost. DeMaVLA is first pre-trained on approximately 5,000 hours of selected real-world dual-arm demonstrations to acquire general manipulation priors. It is then post-trained on mixed folding data that aggregates self-collected demonstrations and corrective trajectories from real-robot failures across multiple folding tasks through a human-in-the-loop Data Aggregation~(DAgger) pipeline. Experiments show that DeMaVLA achieves competitive performance on RoboTwin 2.0 and strong real-world results on our household folding benchmark. These results highlight the value of scalable real-world data, efficient action generation, and corrective learning for general-purpose VLA policies in deformable-object manipulation.

10.
arXiv (CS.AI) 2026-06-18

A DeepLearning Framework for Dynamic Estimation of Origin-Destination Sequence

arXiv:2307.05623v2 Announce Type: replace-cross Abstract: OD matrix estimation is a critical problem in the transportation domain. The principle method uses the traffic sensor measured information such as traffic counts to estimate the traffic demand represented by the OD matrix. The problem is divided into two categories: static OD matrix estimation and dynamic OD matrices sequence(OD sequence for short) estimation. The above two face the underdetermination problem caused by abundant estimated parameters and insufficient constraint information. In addition, OD sequence estimation also faces the lag challenge: due to different traffic conditions such as congestion, identical vehicle will appear on different road sections during the same observation period, resulting in identical OD demands correspond to different trips. To this end, this paper proposes an integrated method, which uses deep learning methods to infer the structure of OD sequence and uses structural constraints to guide traditional numerical optimization. Our experiments show that the neural network(NN) can effectively infer the structure of the OD sequence and provide practical constraints for numerical optimization to obtain better results. Moreover, the experiments show that provided structural information contains not only constraints on the spatial structure of OD matrices but also provides constraints on the temporal structure of OD sequence, which solve the effect of the lagging problem well.

11.
arXiv (quant-ph) 2026-06-17

Kinematic properties of the Pauli equation

arXiv:2606.17548v1 Announce Type: new Abstract: Based on the Wigner-Vlasov formalism, this paper investigates the kinematic properties of the Pauli equation. It is shown that the probability current associated with the Pauli equation can be represented as a superposition of two currents with certain expansion coefficients. Each of these currents corresponds to a particular component of the spinor. The expansion coefficients effectively serve as weighting functions that determine the probability contribution of the corresponding spinor component. Therefore, each spin projection corresponds to its own probability flux. A new system of the Hamilton-Jacobi equations and also a system of motion equations in electromagnetic fields are obtained, taking into account the interaction between the spin and the magnetic field. To illustrate how these equations can be applied we have investigated the quantum system kinematics in detail using an exact solution of the Pauli equation in the presence of a uniform magnetic field and an asymmetric quadratic potential.

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

Enhanced Graph Neural Networks using K-Hop Gaussian Diffusion

arXiv:2606.18317v1 Announce Type: new Abstract: Most graph neural network (GNN) cores rely on graph convolutions, typically implemented as message passing between direct (single-hop) neighbors. In many real-world graphs, edges can be noisy or poorly defined, limiting information propagation to local neighborhoods. Existing diffusion kernels, such as Personalized PageRank (PPR) and Heat Kernel, alleviate this issue through global propagation, but still struggle with complex local structures and distant node noise. To address these limitations, we propose a K-Hop Gaussian (KHG) diffusion kernel as a preprocessing module for graph data. KHG introduces multi-hop diffusion with Gaussian weighting for remote nodes, balancing local and global information propagation before applying standard GNNs. Experiments on multiple benchmark datasets demonstrate that KHG significantly outperforms traditional message-passing GNNs, as well as PPR and Heat Kernel diffusion, particularly in noisy or structurally complex graphs.

13.
arXiv (CS.CV) 2026-06-12

Modality Forcing for Scalable Spatial Generation

Text-to-image (T2I) models contain rich spatial priors. Synthesizing photorealistic, cluttered scenes requires an understanding of geometry, including perspective and relative scale. Prior works adapt T2I models to leverage this prior for depth prediction, but they require dense depth data and involve complex recipes. We propose Modality Forcing, a simple, scalable post-training recipe for joint image-depth generation using a single DiT trained on sparse depth data. Modality Forcing enables conditional and joint generation of image and depth in any permutation by assigning separate noise levels per modality. Per-modality decoders let us train on sparse, real-world depth and achieve strong, generalizable depth prediction. We further show that Modality Forcing inherits the scalability of T2I pre-training: by training a set of T2I models from scratch (370M to 3.3B parameters), we find that larger models trained on more image data produce more accurate depth. Our strongest model is competitive with state-of-the-art monocular depth estimators and reduces AbsRel by 57% relative to existing joint image-depth generative models. These results provide strong evidence that image generation is a scalable pre-training objective for spatial perception. https://modality-forcing.github.io/

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

Cross-Model Disagreement as a Label-Free Correctness Signal

arXiv:2603.25450v2 Announce Type: replace Abstract: Detecting when a language model is wrong without ground truth labels is a fundamental challenge for safe deployment. Existing approaches rely on a model's own uncertainty – such as token entropy or confidence scores – but these signals fail critically on the most dangerous failure mode: confident errors, where a model is wrong but certain. In this work we introduce cross-model disagreement as a correctness indicator – a simple, training-free signal that can be dropped into existing production systems, routing pipelines, and deployment monitoring infrastructure without modification. Given a model's generated answer, cross-model disagreement computes how surprised or uncertain a second verifier model is when reading that answer via a single forward pass. No generation from the verifying model is required, and no correctness labels are needed. We instantiate this principle as Cross-Model Perplexity (CMP), which measures the verifying model's surprise at the generating model's answer tokens, and Cross-Model Entropy (CME), which measures the verifying model's uncertainty at those positions. Both CMP and CME outperform within-model uncertainty baselines across benchmarks spanning reasoning, retrieval, and mathematical problem solving (MMLU, TriviaQA, and GSM8K). On MMLU, CMP achieves a mean AUROC of 0.75 against a within-model entropy baseline of 0.59. These results establish cross-model disagreement as a practical, training-free approach to label-free correctness estimation, with direct applications in deployment monitoring, model routing, selective prediction, data filtering, and scalable oversight of production language model systems.

15.
arXiv (CS.LG) 2026-06-16

Multiscale Hypersonic Boundary Layer Reconstruction via Spectral Binning and Subdomain-wise Conditional Diffusion

arXiv:2606.15023v1 Announce Type: cross Abstract: We propose a multiscale probabilistic reconstruction framework for hypersonic Couette flow, where near-wall states are inferred from limited top-wall observations using conditional diffusion model. The boundary layer is divided into overlapping wall-normal subdomains, and a single height- and Mach-conditioned Elucidating Diffusion Model (EDM) is trained jointly for M=6,7,8 to sample velocity, density, pressure, and temperature fields conditioned on a top-wall boundary slice. A soft overlap inpainting strategy assembles subdomain predictions into full-volume reconstructions while maintaining inter-subdomain continuity and small-scale variability. To improve the spectral fidelity of the generated fields, we introduce a novel bounded binned spectral power (BSP) loss that preserves high-wavenumber content while remaining numerically stable across the diffusion noise schedule. Validation against direct numerical simulation data shows that the model recovers instantaneous structures, spectra, statistical profiles, correlations, and wall quantities across all training Mach numbers, while providing spatially structured uncertainty estimates. The reconstructed Mach-conditioned profiles also collapse under the Trettel-Larsson transformation, indicating consistency with compressibility scaling. These results establish the domain decomposed conditional diffusion model with a bounded binned spectral loss as an effective probabilistic surrogate for near-wall reconstruction in hypersonic wall-bounded turbulence.

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

Exploring How Agent Voice Accents Shape Human-AI Collaboration in K-12 Group Learning

arXiv:2606.12805v1 Announce Type: cross Abstract: Collaboration is widely recognized as a cornerstone of 21st-century education, yet teachers still encounter persistent challenges in fostering productive peer interaction. LLM conversational peer agents introduce new possibilities for mediating in-person group work, raising questions about how persona design, particularly their voice characteristics, shapes learners' perceptions, trust, and interactional dynamics. While prior work has examined agent accent effects in one-to-one settings, little is known about how these effects manifest in groups. We conducted a between-subjects mixed-methods study with 33 teachers examining how a GenAI voice agent with different accents (British, Indian, and African American) influenced collaboration and agent perception. Across surveys, group interaction analyses, and artifacts, we find that accent shaped participants' mental models and the roles the agent assumed in group interaction. The British-accented agent was largely treated as a tool and engaged in detached, utility-based ways, whereas Indian- and African American-accented agents were more readily anthropomorphized and integrated as peers. These role expectations influenced trust, engagement, and reliance over time. This work advances understanding of how GenAI's sociolinguistic design features shape group dynamics in CSCL, with implications for designing culturally inclusive AI partners in group learning.

17.
medRxiv (Medicine) 2026-06-12

An integrative multi-omics framework identifies epigenetic dysregulation of HAND2 as a potential primary driver of impaired enteric neural crest cell differentiation in Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital neurodevelopmental disorder characterized by segmental aganglionosis due to impaired developmental processes of enteric neural crest cells (NCCs). Despite being the leading genetic cause of functional intestinal obstruction in early childhood, HSCR represents a paradigmatic challenge in precision medicine: its multifactorial etiology, complex gene-environment interactions and limited resolution of single-modality analyses have long hindered mechanistic understanding and therapeutic translation. Here, we applied an integrative multi-omics approach combining genetic, phenotypic, epigenomic and transcriptomic analyses of matched ganglionic and aganglionic formalin-fixed paraffin-embedded (FFPE) patient tissues, complemented by patient-specific in vitro models. Beyond established genetic contributors, our integrative approach reveals novel regulatory pathways predominantly affecting enteric NCC differentiation, with convergent evidence pointing to epigenetic dysregulation as a primary disease mechanism. Notably, we identified over 1,300 differentially methylated positions between ganglionic and aganglionic FFPE samples, with HAND2 emerging as a key candidate due to multiple hypermethylated sites and consistently reduced expression levels in aganglionic tissues and in vitro models, suggesting a potential role in HSCR pathophysiology. We propose that our multi-omics approach offers a powerful and comprehensive framework for dissecting disease mechanisms. Beyond advancing biological understanding, this strategy holds promise for paving the way for molecularly informed patient stratification and supporting the development of personalized treatment and postoperative management strategies.

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

Understanding helpfulness and harmless tension in reward models

Reward models are a key component of reinforcement learning from human feedback (RLHF), aligning language models toward both helpful and harmless behaviour. However, the internal mechanisms underlying these objectives and their conflicts remain poorly understood. We study alignment tension in reward models trained under helpfulness-only, harmlessness-only, and mixed-objective settings. We find that mixed-objective models often underperform single-objective models, indicating interference between objectives. Using activation-based methods, we identify neurons associated with each objective and study their functional roles via targeted ablations. We find that these neurons causally support their corresponding objectives while often negatively affecting the opposing one. We find that a substantial proportion of neurons are shared between helpfulness and harmlessness, and that these shared neurons exert a disproportionate influence on model behaviour, contributing to alignment tension. Additionally, our results provide insights and mechanistic interpretation into how alignment objectives are represented in reward models and why multi-objective alignment remains challenging, motivating future work on disentangled and controllable alignment methods.

19.
arXiv (CS.AI) 2026-06-17

Rethinking Multimodal Fusion for Time Series: Text Modalities Need Constrained Fusion

arXiv:2603.22372v2 Announce Type: replace-cross Abstract: Recent advances in multimodal learning have motivated the integration of auxiliary modalities such as text or vision into time series (TS) forecasting. However, most existing methods provide limited gains, often improving performance only in specific datasets or relying on architecture-specific designs that limit generalization. In this paper, we show that multimodal models with naive fusion strategies (e.g., simple addition or concatenation) often underperform unimodal TS models, which we attribute to the uncontrolled integration of auxiliary modalities which may introduce irrelevant information. Motivated by this observation, we explore various constrained fusion methods designed to control such integration and find that they consistently outperform naive fusion methods. Furthermore, we propose Controlled Fusion Adapter (CFA), a simple plug-in method that enables controlled cross-modal interactions without modifying the TS backbone, integrating only relevant textual information aligned with TS dynamics. CFA employs low rank adapters to filter irrelevant textual information before fusing it into temporal representations. We conduct over 20K experiments across various datasets and TS/text models, demonstrating the effectiveness of the constrained fusion methods. Code is available at: https://github.com/seunghan96/cfa.

20.
bioRxiv (Bioinfo) 2026-06-14

Generative design of antigen-specific T-cell receptor sequences with a conditional diffusion model

T cell receptor (TCR)-based immunotherapy holds immense potential for treating cancers and infectious diseases, where highly antigen-specific TCR recognition is crucial for adaptive immunity against tumors and pathogens. Engineering or de novo generation of the complementarity-determining region 3 (CDR3) loops of TCRs using artificial intelligence offers a powerful alternative to designing reactive TCRs rather than laborious experimental screening. However, current in silico approaches are constrained by weak conditional guidance, limited flexibility, and a lack of rigorous functional validation. To address these limitations, we introduce TCRDiff, a generative diffusion framework for designing antigen-specific TCRs conditioned on peptide-MHC (pMHC) targets and germline-encoded variable genes. By leveraging pre-trained knowledge from massive T-cell repertoires and TCR-pMHC recognition data, TCRDiff generates CDR3{beta} sequences with state-of-the-art fidelity to native binding TCRs through a denoising diffusion process. Furthermore, incorporating the interface geometry features generated TCR-pMHC complexes with superior structural plausibility. As a proof of concept, we deployed TCRDiff in a systematic pipeline to design candidate TCRs for immunotherapy. In vitro activation assays validated that TCRDiff-generated TCRs specifically recognize the MAGE-A3 epitope with minimized off-target cross-reactivity. Together, TCRDiff establishes a powerful, validated computational paradigm to accelerate the development of TCR-based immunotherapies.

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

All-Mem: Agentic Lifelong Memory via Dynamic Topology Evolution

Lifelong interactive agents are expected to assist users over months or years, which requires continually writing long term memories while retrieving the right evidence for each new query under fixed context and latency budgets. Existing memory systems often degrade as histories grow, yielding redundant, outdated, or noisy retrieved contexts. We present All-Mem, an online/offline lifelong memory framework that maintains a topology structured memory bank via explicit, non destructive consolidation, avoiding the irreversible information loss typical of summarization based compression. In online operation, it anchors retrieval on a bounded visible surface to keep coarse search cost bounded. Periodically offline, an LLM diagnoser proposes confidence scored topology edits executed with gating using three operators: Split, Merge, and Update, while preserving immutable evidence for traceability. At query time, typed links enable hop bounded, budgeted expansion from active anchors to archived evidence when needed. Experiments on LoCoMo and LongMemEval-s show improved retrieval and QA over representative baselines. The code is available at https://github.com/LvCan926/All-Mem.

22.
arXiv (CS.LG) 2026-06-11

Higher-Order Token Interactions via Quantum Attention

arXiv:2606.11673v1 Announce Type: cross Abstract: Standard dot-product self-attention computes, in a single layer, only pairwise (order-2) interactions between tokens; representing a generic order-$k$ interaction is known to require either super-quadratic resources in one layer or composition across depth. We introduce Quantum Higher-Order Attention (QHA), a shallow, hardware-realizable quantum attention head that, via data re-uploading and an all-to-all non-Clifford entangler, synthesizes order-$k$ token interactions inside the circuit and exposes them through a local single-qubit read-out. We prove (i) an expressivity separation: any single standard self-attention layer with embedding dimension $m$, $H$ heads and $p$-bit precision satisfying $mHp=o(N/\log\log N)$ cannot represent the order-$k$ correlation family that one QHA head represents with circuit depth $O(\log k)$ ($O(k)$ two-qubit gates); and (ii) a trainability guarantee for its local-design instantiation: with a local read-out and $O(\log n)$ depth the gradient variance is $\Omega(1/\mathrm{poly}(n))$ (no barren plateau), which we confirm empirically – while being explicit that the more expressive all-to-all instantiation we benchmark is trained empirically and shows exponentially decaying gradients. Empirically, at a $6.5\times$ smaller parameter budget, QHA generalizes hidden-subset parity of every order $k\le6$ from disjoint inputs, whereas the larger classical attention head collapses past order~2; consistent with theory, the size of the advantage tracks the target's Fourier degree - largest for parity and shrinking when low-order structure is present. As an application, QHA serves as a compact high-order interaction detector across three domains - genetic epistasis, learning-parity-with-noise, and graph triangle detection - reaching the noise ceiling at the smallest parameter budget where field-standard linear methods fail.

23.
arXiv (CS.LG) 2026-06-12

One Step Closer to Ground Truth: A Multi-Scale Residual-Aware Representation Learning Pipeline for Predicting Time Series Data

arXiv:2606.10678v2 Announce Type: replace Abstract: Transformer-based models have emerged as leading paradigms in time-series forecasting in recent years, employing self-attention mechanisms to capture long-range dependencies. Despite their success, these single-stage forecasting architectures exhibit persistent systematic residual biases arising from structural discrepancies, unmodeled stochastic components, or inadequate multi-scale temporal representations. This limitation persists when residuals are treated as irreducible noise, precluding adaptive correction of structured error patterns. To address this limitation, we introduce a two-stage, model-agnostic framework that explicitly decouples forecasting and residual learning into distinct stages of representation learning. A base transformer first generates the initial predictions. Subsequently, a dedicated meta-corrector dynamically models structured error patterns across multivariate channels, preserves cross-variable dependencies, and iteratively refines the residual bias of the base transformer. By formalizing this pipeline as a hypothesis space expansion, our framework addresses approximation limitations inherent in single-stage architectures, removes reliance on restrictive assumptions, and enables end-to-end learning of complex error dynamics. Evaluated on eight popular benchmark datasets using established protocols, our approach achieves state-of-the-art performance, with significant improvements in standard metrics (MSE, MAE). The results demonstrate the framework's ability to mitigate systematic biases and enhance robustness to complex temporal dynamics, advancing the practical applicability of transformer-based forecasting models.

24.
medRxiv (Medicine) 2026-06-22

Early-life nutritional environment is associated with late-life cognition in the Health and Retirement Study, a pellagra epidemic natural experiment

Early-life exposures are important to several late-life health outcomes. We sought to study the effect of an in utero nutritional environment and its interaction with Alzheimer's disease (AD) genetic risk on late-life cognitive function. We used a natural experiment created by the pellagra epidemic, a nutritional disease caused by a vitamin B3 deficiency, to evaluate the association between in utero pellagra epidemic exposure and late-life cognitive function in the Health and Retirement Study (N = 18,285). We also evaluated whether the in utero exposure could modify the AD polygenic score's (PGS) effect on cognition. In utero pellagra epidemic exposure was significantly associated with cognition ({beta} = -0.025). However, these effects were not isolated to the prenatal period as exposure during childhood periods also had an effect. The interaction between the in utero exposure and the AD PGS was significant, where the genetic effect on cognition was amplified with increasing (progressively worse) in utero exposure levels. These associations imply that the early-life nutritional environment affects late-life cognitive function and that these effects can modify genetic risk.

25.
arXiv (CS.AI) 2026-06-17

From Democracies to Autocracies: How AI Systems Enable Authoritarianism by Design

arXiv:2606.17286v1 Announce Type: cross Abstract: AI-enabled authoritarianism is not confined to autocracies. In this paper, we provide greater transparency by investigating and mapping the lifecycles of six AI systems deployed in different political regimes, ranging from the US to China. By drawing on an extensive range of sources (academic publications, investigative research reports, third-party evaluations, media interviews, government procurement notices), we conduct a systematic, qualitative comparison across systems to identify the critical technical and operational features that enable authoritarianism within their respective political contexts. We find that enabling features include the centralization and co-optation of administrative data for law enforcement and political punishment, regulatory gaps that fail to deter misuse, weak user compliance that nullifies human oversight mechanisms, and the encoding of protected group traits that identify members of vulnerable populations. We find that these features are present across systems deployed in autocratic and democratic regimes, albeit in varying configurations. We also find that both centralized and fragmented AI systems can contribute to authoritarianism by exploiting governance gaps: centralized systems directed by executive authorities, particularly within security and military institutions, are often not subjected to formal oversight mechanisms, while fragmented systems diffuse accountability between stakeholders, paving the way for entrenchment. These findings reveal that AI-enabled authoritarianism is distributed, resulting from design and operational choices made by developers, administrators, and users alike. We conclude with recommendations for developers and policymakers to mitigate these risks.