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01.
arXiv (CS.CV) 2026-06-17

SceneCompleter: Dense 3D Scene Completion for Generative Novel View Synthesis

Generative models have shown great promise for novel view synthesis (NVS) by leveraging strong image generation priors. However, existing approaches typically follow a 2D inpainting paradigm, first completing missing image regions and then performing 3D reconstruction. This strategy often causes geometry distortion and appearance drift, as 2D inpainting models cannot reliably infer the underlying 3D structure required for cross-view consistent generation. In this paper, we propose SceneCompleter, a geometry-aware framework that reformulates generative NVS as dense 3D scene completion. Instead of hallucinating isolated 2D views, SceneCompleter jointly completes geometry and appearance through a geometry-appearance dual-stream diffusion model in a spatially aligned RGBD latent space. To provide holistic scene context, we further introduce a Scene Embedder that conditions generation on global semantic and stylistic information from reference images. The completed RGBD predictions are then aligned and integrated into an expandable 3D scene representation, enabling iterative and coherent scene completion. Extensive experiments on in-domain and out-of-distribution datasets demonstrate that SceneCompleter produces visually plausible and geometrically consistent novel views across diverse scenarios. Project Page: https://chen-wl20.github.io/SceneCompleter

02.
arXiv (CS.AI) 2026-06-19

Navigating Unreliable Parametric and Contextual Knowledge: Explicit Knowledge Conflict Resolution for LLM Inference

arXiv:2606.20245v1 Announce Type: new Abstract: Large language models (LLMs) have achieved strong performance across a wide range of language-based tasks by leveraging both extensive parametric knowledge and in-context learning ability, enabling them to incorporate external information provided in the input prompt. However, the integration of external knowledge can introduce conflicts, not only between the model's internal parametric knowledge and the external information, but also among multiple pieces of external contexts. Existing approaches typically assume that either the model or the provided context is reliable, overlooking the possibility that both sources may contain errors, and avoid conflicts by privileging one source over the other, rather than actively resolving inconsistencies. To address these limitations, we propose a novel framework MACR for LLM knowledge conflict resolution that moves beyond the conventional binary choice paradigm and incorporates an explicit conflict-resolution mechanism based on a multi-agent reasoning approach. Specifically, we first propose an adaptive knowledge assessment and retrieval approach that employs a modified semantic entropy measure to quantify an LLM's confidence in its answer to a given query. Based on this confidence estimation, MACR either externalizes the model's internal knowledge as textual representations or retrieves relevant external knowledge when internal knowledge is insufficient, generating basic contexts for subsequent reasoning. Then we introduce an inductive multi-agent reasoning framework with three specialized agents that, respectively, induce explicit rules, analyze potential conflicts, and resolve inconsistencies across all available contexts. Empirical results demonstrate that MACR significantly outperforms state-of-the-art baselines across benchmarks, while also providing interpretable resolutions of explicit conflicts.

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

Cascaded Sparse Autoencoders Learn Multi-Level Visual Concepts in Multimodal LLMs

Multimodal Large Language Models (MLLMs) have demonstrated strong performance on vision-language tasks, yet their internal visual representations remain difficult to interpret. Sparse Autoencoders (SAEs) provide a scalable way to decompose dense model activations into sparse, interpretable features. However, existing SAE architectures primarily recover flat feature dictionaries and are less suited for explicit multi-level concept organization. In this paper, we introduce cascaded sparse autoencoders (CSAEs) for learning hierarchical visual concepts in MLLMs. Rather than nesting or stacking SAE sparse activation codes, CSAEs train a second-level SAE directly on the decoder weights of the first-level SAE, treating learned low-level feature directions as inputs for higher-level abstraction. This design enables CSAEs to learn "concepts of concepts" while avoiding drawbacks from the shared-prefix coupling of nesting, Matryoshka-style hierarchies and the bottlenecks of naively stacked SAEs. Experiments across Qwen3-VL, Gemma-3, and LLaVA on multiple visual datasets show that CSAEs improve interpretability in terms of hierarchical concept coherence over state-of-the-art SAE baselines. Results on concept steering further demonstrate that the learned concept groups support effective group-level interventions in MLLM outputs.

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

Robust Neural Tucker Factorization with Bias Correction and Adaptive Initialization

arXiv:2606.16388v1 Announce Type: new Abstract: High-dimensional incomplete (HDI) tensors are widely used in traffic and climate applications, but sparse observations make accurate completion difficult. The intrinsic non-linear dynamics and non-stationary variations across distinct multi-modal fields severely hinder the efficacy of conventional linear reconstruction frameworks. Neural Tucker factorization provides an effective framework for modeling high-order interactions among tensor modes. By parameterizing underlying structural characteristics into continuous latent spaces, neural representations circumvent the rigid low-rank constraints of classical algebra. However, its performance can still be affected by implementation-level choices, especially parameter initialization and the bias configuration of the final output mapping. Suboptimal initializations frequently lead to variance explosion across the cubically expanded interaction spaces, driving the subsequent non-linear activation boundaries into severe gradient saturation zones, while the omission of a dedicated translation parameter forces interaction weights to implicitly absorb global statistical deviations. This paper proposes a simple yet effective neural Tucker factorization model with Kaiming initialization and bias correction (KaBiN) for HDI tensor completion. The proposed model utilizes Kaiming uniform initialization for the embedding and Tucker linear parameters, and adopts a simple bias correction in output mapping. By elegantly decoupling global mean shifts from local structural representations, the framework provides a highly stable and well-conditioned optimization landscape. Experiments on three real-world HDI tensor datasets show that KaBiN achieves better performance than the original NeuTucF, while introducing minimal computational overhead.

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

Creating and Evaluating K-12 GenAI Assessment Graders Through Context Engineering

arXiv:2606.12422v1 Announce Type: cross Abstract: The integration of large language models (LLMs) into educational assessment represents a transformative shift in classroom grading practices. While automated scoring systems and machine learning techniques have existed for decades, generative AI (GenAI) now enables educators to implement standards-based grading (SBG) with unprecedented efficiency and scale. This paper examines the theoretical foundations and evaluates an LLM grader that uses commercially available foundation models with context and prompt engineering to score student work against a rubric. Drawing on an empirical interrater agreement study using Massachusetts Comprehensive Assessment System (MCAS) data, we observed the Quadratic Weighted Kappa (QWK) and Proportional Reduction in Mean-Squared Error (PRMSE) across mathematics, science, and ELA, using Claude Sonnet 4, Haiku 4.5, GPT-5, and GPT-5 Mini. The results demonstrate that LLM graders, especially when based on foundational models with more parameters, achieve substantial agreement with human raters in mathematics and science assessments, while the performances vary in ELA, suggesting generic foundation models can be effective at scoring in given contexts. Additional analysis of teacher and student feedback reveals strong acceptance of AI-generated narrative feedback but skepticism toward numerical scores, suggesting that LLMs function most effectively as formative tools rather than summative evaluators. Our findings indicate that thoughtfully designed hybrid models that combine AI efficiency with teacher judgment can reduce workload, enhance feedback quality, and support equitable assessment practices without displacing professional expertise.

06.
bioRxiv (Bioinfo) 2026-06-19

Accurate detection of tumor clonality and ongoing expansion mode from genomic data

Recent evidence shows that despite considerable effort, currently available algorithms for estimating intra-tumor heterogeneity (ITH) remain limited. We developed DECODE (Deciphering Cancer Origin from DNA Evolution), a novel mutation clustering method that incorporates the impact of sample-specific sequencing coverage and mutation calling biases. On synthetic data, DECODE outperformed existing methods across multiple clonality metrics and accurately detected and characterized the neutral tail in the site frequency spectrum (SFS), which encodes the tumor's ongoing expansion mode. In acute myeloid leukemia, accounting for the neutral tail enabled DECODE to yield more parsimonious clonal decompositions that align more closely with known subclonal dynamics that drive relapse. Applied to data from The Cancer Genome Atlas, DECODE not only detected a neutral SFS tail in most samples across tumor types but also uncovered a clinically meaningful link between ITH and survival in low-grade glioma. By jointly inferring clonality and expansion mode, DECODE provides two complementary and prognostically relevant readouts of tumor evolution from single tumor genomic samples.

07.
arXiv (CS.AI) 2026-06-24

Toward Autonomous O-RAN: A Multi-Scale Agentic AI Framework for Real-Time Network Control and Management

arXiv:2602.14117v3 Announce Type: replace-cross Abstract: Open Radio Access Networks (O-RAN) promise flexible 6G network access through disaggregated, software-driven components and open interfaces, but this programmability also increases operational complexity. Multiple control loops coexist across the service management layer and RAN Intelligent Controller (RIC), while independently developed control applications can interact in unintended ways. In parallel, recent advances in generative Artificial Intelligence (AI) are enabling a shift from isolated AI models toward agentic AI systems that can interpret goals, coordinate multiple models and control functions, and adapt their behavior over time. This article proposes a multi-scale agentic AI framework for O-RAN that organizes RAN intelligence as a coordinated hierarchy across the Non-Real-Time (Non-RT), Near-Real-Time (Near-RT), and Real-Time (RT) control loops: (i) A Large Language Model (LLM) agent in the Non-RT RIC translates operator intent into policies and governs model lifecycles. (ii) Small Language Model (SLM) agents in the Near-RT RIC execute low-latency optimization and can activate, tune, or disable existing control applications; and (iii) Wireless Physical-layer Foundation Model (WPFM) agents near the distributed unit provide fast inference close to the air interface. We describe how these agents cooperate through standardized O-RAN interfaces and telemetry. Using a proof-of-concept implementation built on open-source models, software, and datasets, we demonstrate the proposed agentic approach in two representative scenarios: robust operation under non-stationary conditions and intent-driven slice resource control.

08.
arXiv (CS.AI) 2026-06-16

MUZZLE: Adaptive Agentic Red-Teaming of Web Agents Against Indirect Prompt Injection Attacks

arXiv:2602.09222v2 Announce Type: replace-cross Abstract: Large language model (LLM) based web agents are increasingly deployed to automate complex online tasks by directly interacting with web sites and performing actions on users' behalf. While these agents offer powerful capabilities, their design exposes them to indirect prompt injection attacks embedded in untrusted web content, enabling adversaries to hijack agent behavior and violate user intent. Despite growing awareness of this threat, existing evaluations rely on fixed attack templates, manually selected injection surfaces, or narrowly scoped scenarios, limiting their ability to capture realistic, adaptive attacks encountered in practice. We present MUZZLE, an automated agentic framework for evaluating the security of web agents against indirect prompt injection attacks. MUZZLE utilizes the agent's trajectories to automatically identify high-salience injection surfaces, and adaptively generate context-aware malicious instructions that target violations of confidentiality, integrity, and availability. Unlike prior approaches, MUZZLE adapts its attack strategy based on the agent's observed execution trajectory and iteratively refines attacks using feedback from failed executions. We evaluate MUZZLE across diverse web applications, user tasks, and agent configurations, demonstrating its ability to automatically and adaptively assess the security of web agents with minimal human intervention. Our results show that MUZZLE effectively discovers 44 new attacks on 4 web applications with 10 adversarial objectives that violate confidentiality, availability, or privacy properties across different LLMs and agent scaffolds. MUZZLE also identifies novel attack strategies, including 3 cross-application prompt injection attacks and an agent-tailored phishing scenario.

09.
arXiv (CS.LG) 2026-06-15

Learning the Context of Errors: Black-Box Online Adaptation of Time Series Foundation Models

arXiv:2606.14222v1 Announce Type: new Abstract: The rapid evolution of Time Series Foundation Models (TSFMs) has advanced zero-shot forecasting across diverse domains. Inspired by the current form of Large Language Models, future TSFMs may be offered as commercialized, closed-source API services. However, many existing online adaptation methods still rely on white-box access for parameter fine-tuning or gradient backpropagation. This paradigm mismatch raises a question: In black-box online adaptation for TSFMs, what should we learn? We answer this with an insight: the predictive errors of the base model are conditioned on both the input and output of the base model (i.e., the context of errors). To validate this insight, we propose ORCA (Online Residual Contextual Adaptation). We conduct extensive experiments across 5 state-of-the-art TSFMs and 8 datasets to demonstrate the effectiveness of our approach. Furthermore, through ablation studies, we quantitatively analyze the impact of different adapter learning hypotheses on the final adaptation performance in black-box online adaptation. Code available at https://github.com/Fifthky/ORCA.

10.
arXiv (quant-ph) 2026-06-16

Adaptively secure unitary designs with constant non-Clifford cost

arXiv:2510.08129v2 Announce Type: replace Abstract: Randomness is a fundamental resource in quantum information, with crucial applications in cryptography, algorithms, and error correction. A central challenge is to construct unitary $k$-designs that closely approximate Haar-random unitaries while minimizing the costly use of non-Clifford operations. In this work, we present a protocol able to generate unitary $k$-designs on $n$ qubits, secure against any adversarial quantum measurement, with a system-size-independent number of non-Clifford gates. Our construction applies a $k$-design only to a subsystem of size $\Theta(k)$, independent of $n$. This ``seed'' design is then ``diluted'' across the entire $n$-qubit system by sandwiching it between two random Clifford operators. The resulting ensemble forms an $\varepsilon$-approximate unitary $k$-design on $n$ qubits. We prove that this construction achieves full quantum security against adaptive adversaries using only $\tilde{O}(k^2 \log\varepsilon^{-1})$ non-Clifford gates. If one requires security only against polynomial-time adaptive adversaries, the non-Clifford cost decreases to $\tilde{O}(k + \log^{1+c} \varepsilon^{-1})$. This is optimal, since we show that at least $\Omega(k)$ non-Clifford gates are required in this setting. Compared to existing approaches, our method significantly reduces non-Clifford overhead while strengthening security guarantees to adaptive security as well as removing artificial assumptions between $n$ and $k$. These results make high-order unitary designs practically attainable in near-term fault-tolerant quantum architectures.

11.
arXiv (math.PR) 2026-06-25

Breuer-Major Theorems for Hilbert Space-Valued Random Variables

arXiv:2405.11452v2 Announce Type: replace Abstract: Let $\{X_k\}_{k\in\mathbb{Z}}$ be a stationary Gaussian process with values in a separable Hilbert space $\mathcal{H}_1$, and let $G:\mathcal{H}_1\to\mathcal{H}_2$ be a measurable map into another separable Hilbert space $\mathcal{H}_2$. We derive a central limit theorem for the centered normalized partial sums of the Hilbert space-valued subordinated process $\{G[X_k]\}_{k\in\mathbb{Z}}$. Our result holds under either of two sets of sufficient conditions, formulated in terms of the transformation $G$ and the temporal and cross-sectional dependence structure of $\{X_k\}_{k\in\mathbb Z}$. These conditions coincide in finite dimensions but lead to genuinely different phenomena in the infinite-dimensional setting. The proof relies on the recently developed Fourth Moment Theorem on Hilbert spaces, leveraging tools from the infinite-dimensional Malliavin-Stein framework. We also provide continuous-time and quantitative versions of the central limit theorem. In a series of examples, we recover and strengthen limit theorems for a wide array of statistics relevant in functional data analysis, and present, as an application of our result, a novel limit theorem in the framework of neural operators.

12.
arXiv (CS.LG) 2026-06-17

Price of metric universality in vector quantization is at most 0.11 bit

arXiv:2602.05790v2 Announce Type: replace-cross Abstract: Fast computation of a matrix product $W^\top X$ is a workhorse of modern LLMs. To make their deployment more efficient, a popular approach is that of using a low-precision approximation $\widehat W$ in place of true $W$ (``weight-only quantization''). Information theory demonstrates that an optimal algorithm for reducing precision of $W$ depends on the (second order) statistics of $X$ and requires a careful alignment of vector quantization codebook with PCA directions of $X$ (a process known as ``waterfilling allocation''). Dependence of the codebook on statistics of $X$, however, is highly impractical. This paper proves that there exist a universal codebook that is simultaneously near-optimal for all possible statistics of $X$, in the sense of being at least as good as an $X$-adapted waterfilling codebook with rate reduced by 0.11 bit per dimension in the case when $W$ is Gaussian. Such universal codebook would be an ideal candidate for the low-precision storage format, a topic of active modern research, but alas the existence proof is non-constructive. Equivalently, our result shows existence of a net in $\mathbb{R}^n$ that is a nearly-optimal covering of a sphere simultaneously with respect to all Hilbert norms.

13.
arXiv (CS.LG) 2026-06-17

INI-VPINN: A Variational Physics-Informed Neural Network with Implicit Neumann and Interface Handling for Multi-Material Domains with Geometric Singularities

arXiv:2606.18032v1 Announce Type: cross Abstract: We propose a new weak-form Physics-Informed Neural Network approach (named INI-VPINN). INI-VPINN naturally incorporates Neumann boundary and interface conditions into the variational formulation. It removes the need for additional loss terms or multiple subdomain networks. This framework employs compact support weighting functions and integration by parts to implicitly impose flux and continuity constraints. In this way, it implicitly ensures physical consistency across material boundaries. The proposed method is tested on Poisson and Laplace problems with sharp interfaces and complex geometries. Results show that, compared with several other Physics Informed Neural Networks-based formulations, the INI-VPINN consistently achieves higher accuracy, smoother and faster convergence. The proposed framework provides a general approach for solving multimaterial problems with complex geometries and mixed Neumann-Dirichlet boundary conditions using neural networks. The implementation is publicly available in a GitHub repository.

14.
medRxiv (Medicine) 2026-06-12

Genetic basis of dynamic brain states reveals cellular and disease associations

Dynamic resting-state fMRI captures the time-varying patterns of brain activity that are obscured by static approaches. Hidden Markov Models (HMMs) characterise these dynamics as recurring whole-brain states and quantify their fractional occupancy (FO), the proportion of time spent in each state, yet the biological basis of inter-individual variation in FO remains unclear. Using data from 52,335 White UK Biobank participants, with replication in East and South Asian subsamples, this study examined the heritability, cellular and neurotransmitter basis of brain states, and their links with complex phenotypes. FO was significantly heritable and enriched for neuronal populations, particularly glutamatergic and GABAergic signalling. Analyses identified shared and state-specific loci and revealed genetic correlations, colocalisation, and potential causal relationships between FO and several phenotypes, including educational attainment, sleep duration, and disease risk. These findings establish dynamic brain states as biologically grounded intermediate phenotypes, linking genetic variation to neural dynamics, diseases and traits.

15.
arXiv (quant-ph) 2026-06-25

Efficient Quantum Circuits for Coherent Conversion Between General First- and Second-Quantized Many-Body Representations

arXiv:2606.25029v1 Announce Type: new Abstract: Quantum simulation at fixed particle number admits two equivalent descriptions, a first-quantized (particle) representation and a second-quantized (occupation-number) representation. Their quantum resource costs differ sharply across computational tasks, so the ability to convert coherently between them is valuable. We construct an explicit unitary $Q$, with inverse $Q^\dagger$, that maps a first-quantized state to its fixed-$N$ occupation-number form while diagnosing the input's particle-exchange symmetry. The conversion is therefore symmetry-agnostic at the input yet fully resolved at the output, and it applies uniformly to bosonic, fermionic, and parastatistical sectors. At its foundation lies a structural identification that we place at the center of this work: the quantum Schur transform supplied by Schur-Weyl duality is the non-abelian Fourier transform of the commuting pair $(S_N,U(d))$, and the occupation-number representation is its weight basis, retaining only the labels shared by both factors, the irrep $\lambda$ and the $\mathfrak{u}(d)$ weight. This reduction is lossless for bosons and fermions, while a canonical Gelfand-Tsetlin promise renders it one-to-one for the remaining sectors. Algorithmically, $Q$ composes the strong Schur transform with reversible arithmetic that computes occupations as successive row-sum differences of the Gelfand-Tsetlin pattern, yielding gate complexity $\mathrm{poly}(N,d,\log(1/\epsilon))$. The converted state is prepared efficiently in quantum memory. Any classical algorithm that outputs it explicitly, however, pays a cost set by the sector dimension, which is polynomial of degree $N$ in $d$ at fixed $N$ and exponential in $N$ when $d=\Theta(N)$. Finally, an efficient classical sampler for the induced occupation-number distribution would yield one for arbitrary quantum circuits, contrary to standard complexity assumptions.

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

Learned Radius Estimation for UDF-Based Point Cloud Reconstruction

Surface reconstruction from point clouds is important for consumer-grade 3D capture, including AR/VR and indoor scanning. Local-patch Unsigned Distance Field (UDF) methods are lightweight and generalizable, but their accuracy depends on the support radius, traditionally fixed or selected by a one-dimensional curvature heuristic that cannot capture heterogeneous local geometry. We propose a learned per-query radius selector that predicts a continuous support radius and plugs into a frozen LoSF-UDF backbone. The selector is trained using off-grid target radii obtained by parabolic interpolation of cached UDF error curves. Experiments show improved fine-scale reconstruction accuracy.

17.
arXiv (CS.LG) 2026-06-11

Analytic Bijections for Smooth and Interpretable Normalizing Flows

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

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

Towards Next-Generation Healthcare: A Survey of Medical Embodied AI for Perception, Decision-Making, and Action

Foundation models have demonstrated impressive performance in enhancing healthcare efficiency across a wide range of medical applications. Nevertheless, their limited ability to perceive, understand, and interact with the physical world significantly constrains their effectiveness in real-world clinical workflows, where safety-critical decision-making and physical execution are tightly coupled. Recently, embodied artificial intelligence (AI) has emerged as a promising physical-interactive paradigm for intelligent healthcare, enabling agents to operate in complex medical environments. As research in this area rapidly expands, understanding how intelligent agents function as integrated, end-to-end systems in clinical environments becomes increasingly critical. However, existing surveys on medical embodied AI largely emphasize individual aspects or functional components, lacking a unified system-level organization of the field. To support and consolidate recent advances, we systematically survey the core components of medical embodied AI, with a particular emphasis on the coordinated integration of perception, decision-making, and action. We further review representative medical applications and relevant datasets, and we analyze the major challenges encountered in real-world clinical practice. Finally, we discuss key directions for future research in this rapidly evolving field. The associated project can be found at https://github.com/VMVLab/Medical_Embodied_AI_Paper_List.

19.
arXiv (CS.AI) 2026-06-25

Improving Zero-Shot Offline RL via Behavioral Task Sampling

arXiv:2604.25496v2 Announce Type: replace Abstract: Offline zero-shot reinforcement learning (RL) aims to learn agents that optimize unseen reward functions without additional environment interaction. The standard approach to this problem trains task-conditioned policies by sampling task vectors that define linear reward functions over learned state representations. In most existing algorithms, these task vectors are randomly sampled, implicitly assuming this adequately captures the structure of the task space. We argue that doing so leads to suboptimal zero-shot generalization. To address this limitation, we propose extracting task vectors directly from the offline dataset and using them to define the task distribution used for policy training. We introduce a simple and general reward function extraction procedure that integrates into existing offline zero-shot RL algorithms. Across multiple benchmark environments and baselines, our approach improves zero-shot performance by an average of 20%, highlighting the importance of principled task sampling in offline zero-shot RL.

21.
PLOS Computational Biology 2026-06-05

Heuristic multi-site optimization for protein sequence design using Masked Protein Language Models

作者:

by Lijuan Wang, Yuze Wang, Chen Qiu, Liwei Xiao, Xianliang Liu, Junjie Chen Protein sequence design for tailored functional properties is a fundamental task in protein engineering, with critical applications in drug discovery and therapeutic development. Efficient navigation of the combinatorial vastness of protein sequence space to identify functional variants remains a formidable challenge. Conventional approaches, which predominantly rely on template-based local search or single-residue mutagenesis, are constrained by their susceptibility to local optima and their potential risk of destabilizing native structural stability. In this study, we introduce ProtHMSO, a heuristic multi-site optimization framework leveraging masked protein language models (ProtLMs) for context-aware sequence exploration. ProtHMSO mimics natural evolutionary mechanisms by employing ProtLM-derived substitution probabilities to guide heuristic searches for synergistic mutations, thereby constraining combinatorial search spaces through evolutionary and biophysical priors. ProtHMSO is further applied to replace the exploration strategies in genetic algorithms (GAs) and Monte Carlo tree search (MCTS) for improving their convergence efficiency. Benchmark experiments demonstrate that protein sequences generated by ProtHMSO exhibit superior functional performance and closer alignment with natural sequence distribution, compared with state-of-the-art methods. These advancements highlight that ProtHMSO has strong potential and compatibility to accelerate functional protein discovery, offering a robust framework for efficient and context-aware exploration of protein sequence space.

22.
medRxiv (Medicine) 2026-06-11

Association between depressive symptoms and physical function among participants with heart disease in the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Background: Depression and heart disease frequently co-occur in the aging population and are associated with functional decline and poor health outcomes. Understanding how depressive symptoms relate to different aspects of physical function among adults with heart disease may help identify high-risk subgroups. Objective: To examine the association of depressive symptoms with self-reported and observed physical function measures among participants with heart disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and assess whether associations differ by sex and race?sex groups. Methods: We conducted a cross-sectional analysis using data from REGARDS study second in-home visit (2013?2016). Depressive symptoms were measured with the 10-item Center for Epidemiologic Studies Depression scale (CES D 10), considering scores ?10 as clinically significant. Physical function measures were instrumental activities of daily living (IADL), activities of daily living (ADL), chair stand time (5 repetitions), and gait speed. Linear regression models estimated associations of depressive symptoms with function, adjusting for sociodemographic, health behavior, antidepressant medications, body mass index, and social support. Effect modification by sex and race?sex group was evaluated. Results: Among 3,055 participants, 11.7% had CES D 10 ?10. Compared to CES-D-10 scores

23.
medRxiv (Medicine) 2026-06-22

Histologically validated diffusion MRI signatures of neuroinflammation and neurodegeneration in Alzheimer disease

Noninvasive neuroinflammation measurement remains a major barrier for Alzheimer disease (AD) therapeutics. We present generalized diffusion basis spectrum imaging (g-DBSI), a diffusion MRI framework that decomposes the tissue signal into biologically interpretable microstructural compartments. In postmortem Knight ADRC brains, g-DBSI-derived restricted isotropic fraction (RIF) and restricted anisotropic fraction (RAF) mapped cellularity and neurofilament density, while their ratio (RIF/RAF) tracked inflammatory cell density and peri-plaque amyloid-beta with higher specificity and regional consistency than RIF alone. In 112 living Knight ADRC participants stratified by PET amyloid, g-DBSI metrics showed amyloid-dependent trajectories: in low-amyloid individuals, RIF and RAF rose together with amyloid, consistent with early neuropil expansion and glial elaboration, whereas in high-amyloid individuals, RIF/RAF increased, and RAF declined, indicating established neuroinflammatory remodeling and neurofilament loss. CSF proteomics linked RIF/RAF to glia-enriched immune and vascular pathways, supporting g-DBSI as a clinically compatible MRI biomarker of neuroinflammation and neurodegeneration in AD.

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

MyoInteract: A Framework for Fast Prototyping of Biomechanical HCI Tasks using Reinforcement Learning

arXiv:2602.15245v2 Announce Type: replace-cross Abstract: Reinforcement learning (RL)-based biomechanical simulations have the potential to revolutionise HCI research and interaction design, but currently lack usability and interpretability. Using the Human Action Cycle as a design lens, we identify key limitations of biomechanical RL frameworks and develop MyoInteract, a novel framework for fast prototyping of biomechanical HCI tasks. MyoInteract allows designers to setup tasks, user models, and training parameters from an easy-to-use GUI within minutes. It trains and evaluates muscle-actuated simulated users within minutes, reducing training times by up to 98%. A workshop study with 12 interaction designers revealed that MyoInteract allowed novices in biomechanical RL to successfully setup, train, and assess goal-directed user movements within a single session. By transforming biomechanical RL from a days-long expert task into an accessible hour-long workflow, this work significantly lowers barriers to entry and accelerates iteration cycles in HCI biomechanics research.

25.
arXiv (quant-ph) 2026-06-19

Stalls and Spequlation: Pipelined Execution for Fault Tolerant Quantum Computation

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