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

Reducing the Complexity of Deep Learning Models for EEG Analysis on Wearable Devices

arXiv:2606.12742v1 Announce Type: new Abstract: Wearable healthcare devices are the fastest-growing Internet of Things (IoT) sector. Many automated healthcare services rely on two crucial biological signals, namely ECG and EEG, which reflect the activity of the heart and brain, respectively. Although deep neural networks are considered the primary way to process and analyze these signals, the very tight energy and computational power constraints in wearable devices are far below the computational, energy, and memory bandwidth demands of DNN models, thereby impeding the deployment of deep learning in many practical wearable services. This paper investigates the feasibility of deploying state-of-the-art DNN models in resource-constrained wearable devices. Notably, we explore the trade-off between accuracy and computational complexity of DNNs when parameter quantization and electrode reduction methods are used. Our investigation centers on several state-of-the-art DNN models designed for EEG signal analysis, specifically for detecting epileptic seizures. Our findings demonstrate that, when applied judiciously, these techniques can significantly reduce the complexity of the DNNs under consideration with minimal adverse effects on accuracy. These results reveal the explicit trade-offs between accuracy and complexity reduction encountered when adapting DNN-based online EEG analysis for wearable devices.

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

LASA: A Weak Supervision Method for Open-Vocabulary Scene Sketch Semantic Segmentation

Open-vocabulary scene sketch semantic segmentation aims to assign dense semantic labels to sparse line drawings based on flexible category vocabularies specified at inference time, without relying on pixel-level annotations during training. Unlike natural images, sketches lack texture and color cues, making semantic understanding heavily dependent on stroke layout and spatial configuration, a challenge that renders single-layer vision-language features inherently unstable. Our key observation is that attention maps from different Vision Transformer layers encode complementary spatial cues: shallow layers capture global structural layouts, while deeper layers focus on local stroke intersections and object parts. This suggests that cross-layer aggregation provides a more robust structural prior than any individual layer alone. Leveraging this insight, we propose a structure-aware framework built upon Layer-wise Accumulated Structural Attention (LASA), which aggregates multi-layer attention to guide hierarchical semantic alignment under weak supervision and refine predictions during inference. Experiments on FS-COCO, SFSD, and FrISS show that LASA improves mIoU by $+3.43$, $+8.01$, and $+15.74$ over the prior weakly supervised baselines, demonstrating consistent gains in both segmentation accuracy and spatial coherence. Our source code will be made publicly available.

03.
arXiv (CS.CL) 2026-06-15

OdysSim: Building Foundation Models for Human Behavior Simulation

Large language models are increasingly deployed as human simulators for interactive evaluation and social simulation. Yet helpfulness-driven post-training pulls them toward a homogeneous, overly agreeable assistant register, creating a behavioral Sim2Real gap. We present OdysSim, the largest open systematic investigation of behavioral foundation models, i.e., models trained to simulate human behavior at scale. We propose SOUL, a taxonomy of five capability axes (CONV, SS, COG, ROLE, EVAL) that unifies 62 datasets and 23 benchmark tasks under one framework. Specifically, we curate the OdysSim corpus (21.4M interactions, 10B tokens, retrofitted with back-generated social contexts), construct the SOUL-Index benchmark, and develop an end-to-end training recipe combining midtraining, task-specific RL, and expert distillation. The resulting open 8B OSim model ranks first or tied-first on 8 of 23 tasks, outperforming any individual frontier model by this count, with the strongest gains on conversational and social tasks. Its outputs are also more human-like in length, formatting, and word choice, and it transfers zero-shot to out-of-distribution user simulation on $\tau$-bench, nearly matching real users on reaction alignment (93.2 vs. 93.5). We further show that LLM-as-judge RL induces reward-hacking patterns, and that our detectors can mitigate them during post-training. Together, our findings suggest that behavioral foundation models require rethinking the LLM training paradigm. We release all artifacts to support future research.

04.
arXiv (CS.AI) 2026-06-11

Robust Instruction Compliance in Cooperative Multi-Agent Reinforcement Learning

arXiv:2605.12655v3 Announce Type: replace Abstract: Multi-agent reinforcement learning (MARL) in real-world use cases may need to adapt to external natural language instructions that interrupt ongoing behavior and conflict with long-horizon objectives. However, conditioning rewards on instructions introduces a fundamental failure mode as Bellman updates couple value estimates across instruction contexts, leading to inconsistent values when instructions interrupt macro-actions. We propose Macro-Action Value Correction for Instruction Compliance (MAVIC), which corrects Bellman backups at instruction boundaries by correcting the incoming instruction objective and restoring the continuation value under the current objective. Unlike reward shaping, MAVIC modifies the bootstrapping target itself, enabling consistent value estimation under stochastic instruction switching within a unified policy. We provide theoretical analysis and an actor-critic implementation, and show that MAVIC achieves high instruction compliance while preserving base task performance in increasingly complex cooperative multi-agent environments.

05.
arXiv (quant-ph) 2026-06-16

Grid-state deformation in a no-jump non-Hermitian bosonic dimer

arXiv:2606.17036v1 Announce Type: new Abstract: We study the no-jump evolution of ideal grid states in a lossy bosonic dimer with differential decay. The effective non-Hermitian quadratic dynamics induces a complex symplectic flow in phase space that deforms both the primitive lattice vectors and the origin seed. The average decay rate controls common attenuation, while coherent hopping and differential decay control the reduced dimer deformation. The reduced sector contains elliptic, parabolic, and hyperbolic regimes with imaginary spectra, an exceptional point, and real spectra, producing oscillatory, linear, and exponential lattice deformations. Although projected lattice areas can change, the deformation comes from a determinant-one complex symplectic flow on the full four-dimensional phase space. For a Gaussian regularization of the origin seed, we derive the associated complex width matrix and identify the positivity conditions that preserve Gaussian form. For an initial two-mode qunaught product state, the lossless limit recovers the standard beam-splitter generation of a square GKP$+$ Bell pair, while the no-jump dynamics produces its non-Hermitian deformation with a postselection cost set by the no-jump probability.

06.
arXiv (math.PR) 2026-06-18

Multi-floor generalization of TASEP

arXiv:2603.13610v2 Announce Type: replace Abstract: We consider an interacting particle system, which generalizes the classical totally asymmetric simple exclusion process (TASEP), in that each site can contain up to a fixed finite number of particles, and the particle movement is governed by a back-pressure (BP) algorithm (also often called MaxWeight). There are $N$ sites (with $N$ finite or infinite), each may contain at most $c$ particles, $1 \le c < \infty$. New particles enter the system at the left-most site $1$ as a Poisson process of rate $\alpha\le 1$, unless site $1$ has $c$ particles. Particles (if any) are removed from the right-most site $N$ as a Poisson process of rate $\beta \le 1$. The left-to-right movement of particles between neighboring sites is governed by the BP rule: one particle moves from site $n$ to $n+1$ at epochs of a rate $1$ Poisson process, as long as the former site has strictly more particles than the latter. When $c=1$, this is the standard TASEP. Our main results address the asymptotics of the stationary distribution of a finite system, and especially the limit of the flux (current) as $N\to\infty$. In particular, we prove that interesting non-trivial phase transitions take place in a system with $c>1$. For example, if $c>1$ and $1/2 \le \beta \le 1$, the maximum limiting flux $1/4$ is achieved as long as $\alpha \ge \alpha_c^*$, where $\alpha_c^* < 1/2$ is some non-trivial threshold. (For the standard TASEP the threshold is $1/2$.) We also put forward a general conjecture about the stationary distribution asymptotics under an arbitrary parameter setting. We illustrate our formal results and the conjecture by simulations, and identify interesting directions for further research.

07.
arXiv (CS.LG) 2026-06-19

Kolmogorov-Arnold Reservoir Computing

arXiv:2606.19984v1 Announce Type: new Abstract: Reservoir computing offers a lightweight framework for forecasting dynamical systems but may struggle to capture long-range dependencies due to limited representational capacity. Conventional reservoir computing recurrently uses trainable reservoirs with hyperparameter sensitivity, while the next-generation reservoir computing removes recurrence at the cost of rapidly growing feature dimensions. Here, we develop Kolmogorov-Arnold Reservoir Computing (KARC), which replaces reservoirs with explicit basis-function expansions inspired by the Kolmogorov-Arnold representation theorem. We rigorously show that KARC is a lightweight design of Kolmogorov-Arnold networks (KANs), preserving the potential expressive capacity of KANs while admitting efficient closed-form training of reservoir computing. At comparable cost, KARC outperforms existing reservoir computing methods on challenging benchmarks including partial differential equations. It can also be integrated with generative diffusion models for text-to-image generation. This work thus establishes a principled bridge between reservoir computing and KANs, enabling efficient and high-fidelity dynamical system forecasting.

08.
arXiv (CS.AI) 2026-06-17

Ternary Mamba: Grouped Quantization-Aware Training of W1.58A16 State Space Models

arXiv:2606.18114v1 Announce Type: cross Abstract: State Space Models (SSMs) such as Mamba-2 offer linear-time inference but their memory footprint limits edge deployment. Prior ternary SSM work (Slender-Mamba) trains from scratch on 150B tokens; we show a pretrained checkpoint suffices, reducing the marginal token budget by 1,000x. Using grouped quantization-aware training (QAT) with knowledge distillation from a frozen FP16 teacher, we compress Mamba-2 1.3B to 3.61x (2,687 to 744 MB) and achieve 48.1% zero-shot accuracy (7-task average) in just 102M tokens (4 GPU-hours, single H100) – approaching Bi-Mamba's 48.4% (within +/-0.9pp CI). This QAT-from-pretrained setting reveals zero-ratio collapse, a novel instability caused by learnable quantization scales that does not arise in from-scratch training. We further show that post-hoc correction strategies effective for Transformers fail for SSMs due to error accumulation through the recurrence. These results demonstrate that ternary SSMs do not require expensive from-scratch training: QAT from pretrained checkpoints with KD is a data-efficient alternative.

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

Rotational Symmetry based Object Pose Estimation from Point Clouds in the Absence of Known 3D Models

Object pose estimation is crucial to many industrial applications, with one example being automated spray painting using a robot. However, confidentiality concerns often limit access to high-quality 3D models, posing a significant challenge for point-cloud-based pose estimation. In such scenarios, rotational symmetry, a readily accessible characteristic of many industrial objects, can provide valuable prior information to facilitate pose estimation.In this paper, we propose a method that leverages the rotational symmetry commonly found in industrial objects to address the challenge caused by the absence of 3D models. The object pose is jointly estimated with point cloud refinement through an iterative optimization process. This optimization relies on a rotational symmetry constraint loss. To construct this loss, each 3D point is rotated according to the currently estimated pose, and multiple correspondences are identified using nearest-neighbor search by exploiting the rotational symmetry property. These correspondences are then used to compute the rotational symmetry constraint loss, which iteratively refines both the pose and the point cloud.By explicitly incorporating rotational symmetry into the optimization process, the proposed method achieves robust pose estimation and generalizes well across diverse object types. The proposed method is evaluated on a dataset specifically created for point clouds without known 3D models, consisting of four categories of synthetic objects and one real wheel hub collected from a production line. Experimental results demonstrate that the proposed method achieves performance comparable to methods that rely on known 3D models.

10.
arXiv (CS.LG) 2026-06-11

TaskFusion: Continual Anomaly Detection for Heterogeneous Tabular Data

arXiv:2606.11844v1 Announce Type: new Abstract: Continual anomaly detection in tabular data is challenging and remains largely underexplored, particularly in settings with heterogeneous feature schemas, distribution shifts, and severe class imbalance. In many real-world applications, data arrive sequentially from diverse domains, rendering conventional continual learning methods ineffective due to their reliance on a fixed input space. We propose a continual learning (CL) method, which can overcome these challenges and continually learn from different tasks. Our method consists of three main parts: our AGF model, Taskfusion augmentation, and outlier exposure. The AGF-model maps task-specific features into a shared space, then aligns distributions to reduce representation drift, and learns anomaly decision boundaries in the aligned space. To improve stability, we introduce Taskfusion augmentation, combining boundary-aware interpolation within tasks to refine the model anomaly boundaries and cross-task mixing to transfer anomaly structure across datasets. To handle class imbalance and memory constraints, we employ tabular dataset distillation to store compact synthetic replay samples, which are jointly used with augmented data in an outlier exposure objective for robust anomaly detection. We evaluate the approach on 21 heterogeneous datasets across multiple domains. Results show that our approach substantially improves continual anomaly detection performance over sequential fine-tuning and other CL baselines while reducing catastrophic forgetting and maintaining stable detection across heterogeneous datasets.

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

TopoHR: Hierarchical Centerline Representation for Cyclic Topology Reasoning in Driving Scenes with Point-to-Instance Relations

Topology reasoning is crucial for autonomous driving. Current methods primarily focus on instance-level learning for centerline detection, followed by a sequential module for topology reasoning that relies on simplified MLP layers. Moreover, they often neglect the importance of point-to-instance (P2I) relationships in topology reasoning. To address these limitations, we present TopoHR (Topological Hierarchical Representation), a novel end-to-end framework that establishes cyclic interaction between centerline detection and topology reasoning, allowing them to iteratively enhance each other. Specifically, we introduce a hierarchical centerline representation including point queries, instance queries, and semantic representations. These multi-level features are seamlessly integrated and fused within a hierarchical centerline decoder. Furthermore, we design a hierarchical topology reasoning module that captures both fine-grained P2I relationships and global instance-to-instance (I2I) connections within a unified architecture. With these novel components, TopoHR ensures accurate and robust topology reasoning. On the OpenLane-V2 benchmark, TopoHR refreshes state-of-the-art performance with significant improvements. Notably, compared with previous best results, TopoHR achieves +3.8 in $\mathrm{DET}_{l}$, +5.4 in $\mathrm{TOP}_{ll}$ on $subset_A$ and +11.0 in $\mathrm{DET}_{l}$, +7.9 in $\mathrm{TOP}_{ll}$ on $subset_B$, validating the effectiveness of the proposed components. The code will be shared publicly at https://github.com/Yifeng-Bai/TopoHR.git.

12.
arXiv (CS.CL) 2026-06-15

Learning to Hear Hesitation: Continual Learning for Disfluency-Aware ASR

Despite advances in large-scale Automatic Speech Recognition (ASR), disfluent speech remains challenging, as state-of-the-art systems are often optimized to omit disfluencies, leading to information loss and hallucinations. Prior work has focused on verbatim transcription and the integration of disfluency markers, but adapting models on limited datasets can lead to catastrophic forgetting of general-domain knowledge. We address this gap by leveraging continual learning (CL) with explicit disfluency tokens. We first introduce these tokens into a pretrained ASR model to establish stable token mechanisms, and then continue training on additional datasets with varying disfluency distributions. Through a detailed analysis of model dynamics during training, we identify a trade-off between marker learning and ASR performance, and a consistent cross-attention head mechanism shared across CL methods.

13.
arXiv (CS.CL) 2026-06-15

Chronological Thinking in Full-Duplex Spoken Dialogue Language Models

Recent advances in spoken dialogue language models (SDLMs) reflect growing interest in shifting from turn-based to full-duplex systems, where the models continuously perceive user speech streams while generating responses. This simultaneous listening and speaking design enables real-time interaction and the agent can handle dynamic conversational behaviors like user barge-in. However, during the listening phase, existing systems keep the agent idle by repeatedly predicting the silence token, which departs from human behavior: we usually engage in lightweight thinking during conversation rather than remaining absent-minded. Inspired by this, we propose Chronological Thinking, an on-the-fly conversational thinking mechanism that aims to improve response quality in full-duplex SDLMs. Specifically, chronological thinking presents a paradigm shift from conventional LLM thinking approaches, such as Chain-of-Thought, purpose-built for streaming acoustic input. (1) Strictly causal: the agent reasons incrementally while listening, updating internal hypotheses only from past audio with no lookahead. (2) No additional latency: reasoning is amortized during the listening window; once the user stops speaking, the agent halts thinking and begins speaking without further delay. Experiments demonstrate the effectiveness of chronological thinking through both objective metrics and human evaluations show consistent improvements in response quality. Furthermore, chronological thinking robustly handles conversational dynamics and attains competitive performance on full-duplex interaction metrics.

14.
arXiv (quant-ph) 2026-06-11

Collective neutrino oscillations: Many-body non-forward effects and non-classicality

arXiv:2606.12404v1 Announce Type: cross Abstract: Neutrino evolution in dense astrophysical environments is typically described either within a quantum kinetic framework, which neglects the build-up of multi-body correlations, or through simplified many-body calculations that allow significant entanglement to develop. In this work, we compare these two approaches in a simple neutrino-gas configuration, with particular emphasis on the role of non-forward scattering processes. These effects are incorporated either through a collision term in the kinetic description, or by considering the full neutrino-neutrino many-body Hamiltonian. We highlight differences between the two descriptions in both their characteristic timescales and asymptotic behavior. Motivated by the natural suitability of quantum computing for many-body calculations, we further investigate the non-classicality of neutrino evolution, discussing Trotter error scaling, along with the associated costs of constructing quantum circuits in terms of entangling gates and non-Clifford gates. We find that the resources needed for neutrino many-body evolution are on the low end of typical high-energy physics problems and on the mid to high end with respect to quantum chemistry problems. For the full Hamiltonian, resource requirements increase relative to the truncated version. We emphasize the importance of efficient fermion-to-qubit encodings, which are essential for reducing the substantial computational resources required for such simulations.

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

Redirecting the Flow: Image Customization through Attention Distribution Shift

Subject-driven image customization aims to generate images that not only follow textual instructions but also preserve the identity of a given reference subject. Existing approaches, including test-time fine-tuning, encoder-based methods, and token competition in shared attention spaces, suffer from limited efficiency, misalignment between extracted reference features and the generative process, and interference from irrelevant information. To address these limitations, we formulate the customization task as a distribution shift induced by incorporating reference images into text-to-image generation, and derive a Conditional Attention Distribution Shift formulation grounded in maximum entropy theory. Building on this formulation, we propose CustomShift, a dual-branch architecture based on Stable Diffusion 3. The Reference-Alignment Branch leverages self-attention between reference images and subject names to achieve layer-wise alignment with latent representations, while the Cross-Guidance Branch integrates textual and reference cues to guide generation. Experiments on the DreamBooth and Custom101 benchmarks demonstrate that our method consistently outperforms state-of-the-art approaches, achieving a better balance between semantic fidelity and subject consistency.

16.
arXiv (CS.LG) 2026-06-18

ToolChain-CRC: Conformal Risk Control for Agentic AI Under Retrieval and Tool-Use Drift

arXiv:2606.18467v1 Announce Type: cross Abstract: Modern AI agents retrieve documents, call tools, check intermediate information, and then produce a final answer or action. This creates a risk-control problem that is not visible from the final answer alone. A final response may look acceptable even when the retrieval was weak, a tool output was wrong, or an earlier step was unsupported. We propose ToolChain-CRC, a conformal risk-control method for retrieval-augmented and tool-using agents under drift. The method treats each agent run as a full trajectory of actions, observations, and final output. It builds step-level risk scores, combines them into a trajectory risk score, calibrates an accept-or-intervene rule, and adds an anytime alarm that can stop risky runs before the final answer. We prove trajectory-level risk control under exchangeable calibration runs, give a drift-aware extension with auditable constants, and prove an anytime escalation rule through a supermartingale construction. Experiments cover synthetic tool-chain drift, RAG/tool-use stress tests, public SQuAD-derived retrieval tasks, an API-free agentic QA case study, ablations, target-risk sensitivity checks, 20-seed robustness checks, a drift-margin audit, and a live RAG/tool-use agent benchmark. Across these settings, final-answer-only calibration can miss retrieval and tool failures, while trajectory-level calibration keeps accepted-trajectory risk below the target.

17.
Nature (Science) 2026-06-10

Human migration has surged since 2000 — these maps reveal where people are going

Modelling with artificial-intelligence tools has filled gaps in migration data, revealing detailed global population movements from 1990 to 2023. Modelling with artificial-intelligence tools has filled gaps in migration data, revealing detailed global population movements from 1990 to 2023.

18.
arXiv (CS.CV) 2026-06-16

Reasoning in Computer Vision: Taxonomy, Models, Tasks, and Methodologies

Visual reasoning matters for many computer vision tasks that go beyond surface-level object detection and classification. Despite progress in relational, symbolic, temporal, causal, and commonsense reasoning, existing surveys typically cover only one part of the problem, such as visual question answering, scene-graph generation, neuro-symbolic AI, or multimodal chain-of-thought, and rarely analyze reasoning types, methodologies, and evaluation protocols together. This survey addresses that gap. Following a structured literature review, we group visual reasoning into five major types (relational, symbolic, temporal, causal, and commonsense) and examine how each is implemented across methods that range from graph-based models, memory networks, attention mechanisms, and neuro-symbolic systems to reasoning with vision-language models (VLMs) and multimodal large language models (MLLMs), including visual chain-of-thought, visual programming, and tool-augmented and test-time reasoning. We then review evaluation protocols for functional correctness, structural consistency, and causal validity, and we analyze their limits in generalizability, reproducibility, faithfulness, and explanatory power. We also identify open challenges: scaling to complex scenes, integrating symbolic and neural paradigms more deeply, the shortage of comprehensive benchmarks, language-prior shortcuts and hallucination in foundation models, and reasoning under weak supervision. Finally, we set out a research agenda for vision systems and argue that connecting perception and reasoning is necessary for transparent, trustworthy, and cross-domain models, especially in high-stakes settings such as autonomous driving and medical diagnostics.

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

Effective Gaussian Management for High-fidelity Object Reconstruction

This paper proposes an effective Gaussian management framework for high-fidelity scene reconstruction of both appearance and geometry. Unlike recent Gaussian Splatting (GS) pipelines that treat all primitives uniformly during optimization, our framework explicitly manages the attribute activation, representation and pruning of Gaussian. Specifically, our framework first introduces GauSep, a novel densification strategy that selectively activates Gaussian color or normal attributes to alleviate destructive gradient conflicts arising from dual supervision. We further propose GauRep, an adaptive Gaussian representation that dynamically adjusts spherical harmonics (SHs) orders and performs task-decoupled pruning to reduce redundancy at both the individual and global levels. To provide reliable geometric supervision for above mangement process, we additionally introduce CoRe, an regularized surface reconstruction module that distills robust normal fields from an SDF branch to the Gaussian representation through a confidence mechanism. Notably, the proposed Gaussian management is compatible with various reconstruction architectures and can be seamlessly integrated to improve performance while reducing size of the model. Extensive experiments demonstrate that our approach achieves superior or comparable performance in appearance and geometry reconstruction compared with state-of-the-art methods, while using significantly fewer parameters.

20.
arXiv (quant-ph) 2026-06-12

Instabilities in a Non-KAM System via Information Scrambling: A Note

arXiv:2606.12761v1 Announce Type: new Abstract: We study operator growth in quantized non-KAM systems using out-of-time-ordered correlators (OTOCs), focusing on the kicked harmonic oscillator as a representative example. Since the classical harmonic oscillator is degenerate, the dynamics fall outside the usual Kolmogorov-Arnold-Moser (KAM) framework, and resonances play a central role in shaping the phase space. We examine the system near resonances, where the ratio between the oscillator and driving frequencies takes integer values. Even though the classical Lyapunov exponent remains small at these points, and hence no conventional chaos, the phase space still undergoes strong structural changes. The OTOCs are particularly sensitive to these resonances, with a quadratic-in-time growth at resonance compared to linear growth away from it. Within a perturbative treatment, we derive closed-form expressions for the OTOCs and uncover a number-theoretic structure emerging in the behavior of OTOCs, governed by the Euler totient function of the frequency ratio. Overall, the results we present in this short note imply that resonant structures can play an important role in controlling information spreading.

21.
arXiv (quant-ph) 2026-06-16

Fast and high-fidelity transfer of edge states via dynamical control of topological phases and effects of dissipation

arXiv:2505.16606v2 Announce Type: replace-cross Abstract: Topological edge states are robust against symmetry-preserving perturbations and noise, making them promising for quantum information and computation, particularly in topological quantum computation through the braiding operations of Majorana quasiparticles. Realizing these applications requires fast and high-fidelity dynamic control of edge states. In this work, we theoretically propose a high-fidelity protocol for transferring topological edge states by dynamically moving a domain wall between two regions with different topological numbers in one dimension. This protocol fundamentally relies on Lorentz invariance and relativistic effects, because moving the domain wall at a constant speed is described by a mass term with the uniform linear motion in the Dirac equation. We demonstrate the effectiveness of our protocol in transferring edge states with high fidelity using a one-dimensional quantum walk with two internal states, which is feasible with current experimental technology. We also investigate how bit-flip and dephasing dissipation to the environment affect transfer efficiency. Remarkably, bit (dephasing) dissipation does not affect the fidelity at the slow (fast) transfer limit, which can be explained by the relativistic effects on the edge states.

22.
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.

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

APCyc: Property-Informed Design of Cyclic Peptides via Automated Cyclization

arXiv:2606.12991v1 Announce Type: new Abstract: Cyclic peptides represent a promising class of therapeutic compounds in modern drug discovery, often offering improved stability and binding affinity. However, the de novo design of cyclic peptides remains challenging because methods must identify pocket-adaptive cyclization patterns and linkage sites while simultaneously controlling drug-relevant properties. This challenge is particularly pronounced for recent generative models trained predominantly on linear peptide data, which may fail to capture cyclization-specific constraints. To address the limitation, we introduce APCyc, a target-aware de novo cyclic peptide generation framework that explicitly models cyclization and jointly optimizes multiple essential physicochemical properties. By using an expanded residue vocabulary and explicitly encoding cyclization-site and linkage-type information, APCyc learns cyclization-aware representations and leverages Bayesian posterior guidance to steer sampling toward cyclic peptides satisfying multiple property objectives. Experimental results demonstrate that our model learns target-dependent cyclization preferences, and enables effective and controllable multi-property optimization for cyclic peptide design. The source code of this paper is available at https://github.com/HKUSTGZ-ML4Health-Lab/APCyc.

24.
bioRxiv (Bioinfo) 2026-06-20

A network approach to DNA methylation clocks

Biological age predicts health and lifespan better than chronological age, but remains difficult to measure. One leading molecular proxy for biological age is DNA methylation, which underlies age predictors known as "clocks". These clocks use penalized linear regression to predict chronological age from methylation levels using selected cytosine–guanine pairs (CpGs) along DNA. Although they predict chronological age within a few years and track mortality risk, there are several issues. Different clocks share a vanishingly small number of CpG sites, many of which show weak associations with age. Also, the clocks often do not transfer across methylation array platforms. This paper takes a network approach to better understand these issues. By using 12 public datasets from human blood, we build a co-methylation network of the sites that show the strongest age correlation. After pruning weak links, we find that it has a small number of large modules of covarying CpGs surrounded by many small modules and singleton sites. These modules are biologically interpretable, as they are associated with CpG island contexts and enriched for distinct Gene Ontology functions. We also map five established clocks onto this network (Horvath, Hannum, AltumAge, Skin & Blood, and Han) and find that they select some CpGs from the same module. This suggests that they are more similar than they appear. The network structure also suggests new ways to build clocks. A simple clock that retains one CpG per module matches the performance of established clocks. A second one, built from module-level principal components, outperforms all five established clocks in three validation cohorts and is transferable across array platforms (Illumina Infinium Methylation 450K or EPIC arrays). Overall, the network perspective shifts attention from individual CpG sites to modules of covarying sites. This perspective helps explain why DNA methylation clocks perform so well despite their differences and provides a more systematic approach for developing the next generation of aging biomarkers.

25.
arXiv (CS.CL) 2026-06-16

The Art of Mixology: Mixup-based Obfuscation for Privacy-Preserving Split Learning in Large Language Models

Split learning provides a practical paradigm for resource-constrained users to train Large Language Models (LLMs) by offloading computation-intensive layers to a server while keeping raw data local. However, existing privacy-preserving split learning methods still face a difficult trade-off among utility, privacy, efficiency, and stability. Specifically, these methods often suffer from substantial utility degradation, remain vulnerable to advanced data reconstruction attacks, incur prohibitive computational and communication overhead, or exhibit unstable performance across different tasks. In this paper, we propose MIXGUARD, a novel mixup-based privacy-preserving split learning framework for LLMs. MIXGUARD introduces token-level obfuscation, representation-level obfuscation, and adaptive gradient perturbation mechanisms, which operate jointly to preserve useful learning signals while preventing privacy leakage to the server. Technically, MIXGUARD first constructs a lightweight calibration model on a public dataset to refine the approximated target representation, and then applies this model during privacy-preserving fine-tuning on private data. We conduct extensive experiments on four classification tasks and four text generation tasks across multiple LLM families, model sizes, architectures, and fine-tuning strategies. The results show that MIXGUARD preserves model utility comparable to non-split training baselines, consistently achieves stronger privacy protection than existing split learning defense methods against state-of-the-art data reconstruction attacks, and remains robust under adaptive attack settings.