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01.
arXiv (CS.CV) 2026-06-19

SketchKeyAnime: Reference-anchored Sparse Key-Sketch Animation Synthesis

Traditional animation production relies heavily on manual drawing and iterative refinement, particularly for key-pose design, in-betweening, and character coloring. While existing animation and video generation methods have made notable progress, they typically depend on RGB boundary frames, dense frame-wise conditions, or complete sketch sequences, limiting their applicability under low-cost input conditions. We present SketchKeyAnime, a video diffusion framework for generating structurally controllable, appearance-consistent, and temporally coherent animations from sparse key-sketch inputs. Given a single reference RGB image and a few temporally indexed key sketches, SketchKeyAnime introduces a dual-branch conditioning mechanism to encode local geometric constraints alongside semantic-temporal context. It leverages Sketch Cross Attention to fuse reference image and sketch conditions with learnable gating, and incorporates an Adaptive Weighted Loss to strengthen supervision on key-sketch frames and line-art regions. Experimental results on the Aesthetic subset of Sakuga-42M show that our approach consistently outperforms representative animation interpolation and sketch-guided generation baselines. Compared to the best-performing baseline, SketchKeyAnime reduces EDMD by 31.9\% and FVD by 9.5\%, demonstrating superior sketch fidelity and temporal coherence, while achieving the best overall performance across most quantitative metrics. These results validate the proposed framework and highlight its potential for low-cost, highly controllable animation creation.

03.
arXiv (CS.LG) 2026-06-19

Distributionally Robust Set Representation Learning Under Inference-Time Element Corruption

arXiv:2605.30089v2 Announce Type: replace Abstract: Standard Set Representation Learning methods typically excel on curated data but often overlook the challenge of inference-time element corruption. This refers to scenarios where deployed models encounter element-level degradations, such as outliers or missing components, that may distort set representation and degrade performance. We propose SW-DRSO, a distributionally robust optimization framework tailored for sets. Rather than minimizing loss solely on observed training data, SW-DRSO optimizes a tractable surrogate of the worst-case expected loss over a family of plausible inference-time variations. We introduce a barycentric adversary that approximates the intractable search over corrupted sets by a differentiable training-time optimization over simplex weights. Extensive experiments across four tasks demonstrate that SW-DRSO effectively enhances robustness against corruption while maintaining high overall performance.

04.
arXiv (CS.LG) 2026-06-12

Loss-Shift Transfer via Bayes Quotients

arXiv:2606.13178v1 Announce Type: new Abstract: Transfer learning is usually studied as a consequence of distribution shift. This paper identifies an orthogonal failure mode in which the data distribution is fixed and the loss changes. This setting is called loss shift. A loss determines which information in \(X\) is Bayes-relevant, and two losses may therefore require different representations even under the same joint law \(P(X,Y)\). The idea is formalized using Bayes quotients, which allow losses to be ordered by refinement. In the Bayes-quotient formulation, strict refinement gives an immediate qualitative obstruction. A source-minimal representation for a coarser loss is insufficient for a strictly finer target loss. For finite-output log loss, this obstruction becomes an exact quantitative identity. The excess risk is the conditional information about \(Y\) discarded by the representation. Experiments in controlled, learned, synthetic-image, and real-image settings show the predicted effect, i.e., classification-equivalent representations can have different optimal log-loss performance under a fixed data distribution.

05.
arXiv (CS.CL) 2026-06-11

ProcessThinker: Enhancing Multi-modal Large Language Models Reasoning via Rollout-based Process Reward

Visual question answering increasingly requires multi-step reasoning. Recent post-training with reinforcement learning under verifiable rewards (RLVR) and Group Relative Policy Optimization (GRPO) can improve multimodal reasoning, but most approaches rely on sparse outcome-only rewards. As a result, they struggle to tell whether an incorrect answer comes from a small mistake late in the reasoning or from an unhelpful trajectory from the start. A common solution is to train a process reward model (PRM) for step-level supervision, but this typically requires large-scale high-quality chain-of-thought annotations and additional training cost. We propose ProcessThinker, a practical post-training pipeline that provides step-level process rewards without training an explicit PRM. ProcessThinker first rewrites reasoning traces into a step-tagged format for cold-start supervised fine-tuning, then applies GRPO with a standard format reward and our rollout-based process reward. Concretely, for each intermediate step, we sample multiple continuations from that step and use the empirical success rate (final-answer verification) as the step reward. This gives dense credit assignment and encourages reasoning steps that more reliably support a correct conclusion, helping reduce inconsistent or self-contradictory progress across steps – a key issue in logical reasoning. Across four challenging video benchmarks (Video-MMMU, MMVU, VideoMathQA, and LongVideoBench), ProcessThinker consistently improves over the baseline model Qwen3-VL-8B-Instruct

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

Adaptive Activation Steering for Efficient LLM Reasoning via Closed-Loop PID Control

Reasoning LLMs trained with long chain-of-thought often overthink: they spend tokens on redundant reflection and transitions that inflate cost without improving accuracy. Static activation steering (e.g.\ SEAL) suppresses such content with a fixed vector, but applies the same strength regardless of how redundant the current chunk actually is. We describe PID-steering, a training-free, decoding-time method that modulates the steering strength with a PID controller driven by a lightweight chunk-level redundancy classifier. On a subset of GSM8K with DeepSeek-R1-Distill-Qwen-1.5B, the method improves accuracy from 85.7\% to 89.6\% (+3.9 pp) while cutting average output length from 1026 to 790 tokens ($-$23\%). We report it as a small-scale proof of concept rather than a benchmark result.

07.
arXiv (CS.LG) 2026-06-18

PACT: Preserving Anchored Cores in Task-vectors for Model Merging

arXiv:2606.18627v1 Announce Type: new Abstract: Model merging has emerged as a training-free alternative to multi-task learning, aiming to combine multiple task-specific fine-tuned models into a single multi-task model. Most existing model merging approaches follow the Task Arithmetic paradigm, which decomposes fine-tuned weights into pre-trained parameters and task vectors, and performs merging exclusively in the task-vector space. The effectiveness of this paradigm implicitly relies on the assumption that task-specific knowledge is encoded solely within task vectors. We argue that this assumption generally does not hold due to the intrinsic task preferences of pre-trained models. Specifically, we identify Load-Bearing Wall (LBW) dimensions, namely some task-critical knowledge that remains embedded in the pre-trained weights rather than being fully transferred into task vectors. We characterize LBW dimensions from both scalar-weight and subspace perspectives, thereby covering the major paradigms of existing model merging methods. Our analysis reveals that, by ignoring LBW dimensions, task-vector-based approaches fail to fully resolve task conflicts and may inadvertently damage task-specific knowledge encoded in the pre-trained model, leading to degradation. To address this issue, we propose PACT, which preserves the anchored task-specific cores (i.e., LBW dimensions) within task vectors by aligning their orthogonal complements with the subspace of the pre-trained weights. These aligned subspace components are then removed from the task vectors before applying existing model merging algorithms. Furthermore, we develop an efficient variant based on randomized SVD to improve scalability. PACT can be seamlessly integrated with existing methods. Extensive experiments across multiple benchmarks demonstrate that PACT consistently enhances mainstream model merging approaches and establishes new state-of-the-art performance.

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

From Small to Large: A Graph Convolutional Network Approach for Solving Assortment Optimization Problems

arXiv:2507.10834v4 Announce Type: replace Abstract: Assortment optimization seeks to select a subset of substitutable products, subject to constraints, to maximize expected revenue. The problem is NP-hard due to its combinatorial and nonlinear nature and arises frequently in industries such as e-commerce, where platforms must solve thousands of such problems each minute. We propose a graph convolutional network (GCN) framework to efficiently solve constrained assortment optimization problems. Our approach constructs a graph representation of the problem, trains a GCN to learn the mapping from problem parameters to optimal assortments, and develops three inference policies based on the GCN's output. Owing to the GCN's ability to generalize across instance sizes, patterns learned from small-scale samples can be transferred to large-scale problems. Theoretical results are established to show the expressive power of the proposed GCN, and explain the underlying mechanism of the size generalization ability. Numerical experiments show that a GCN trained on instances with 20 products achieves over 85% of the optimal revenue on problems with up to 2,000 products within seconds, outperforming existing heuristics in both accuracy and efficiency. We further extend the framework to settings with an unknown choice model using transaction data and demonstrate similar performance and scalability.

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

Entangled states are typically incomparable

arXiv:2406.03335v2 Announce Type: replace Abstract: Consider a bipartite quantum system, where Alice and Bob jointly possess a pure state $|\psi\rangle$. Using local quantum operations on their respective subsystems, and unlimited classical communication, Alice and Bob may be able to transform $|\psi\rangle$ into another state $|\phi\rangle$. Famously, Nielsen's theorem [Phys. Rev. Lett., 1999] provides a necessary and sufficient algebraic criterion for such a transformation to be possible (namely, the local spectrum of $|\phi\rangle$ should majorise the local spectrum of $|\psi\rangle$). In the paper where Nielsen proved this theorem, he conjectured that in the limit of large dimensionality, for almost all pairs of states $|\psi\rangle, |\phi\rangle$ (according to the natural unitary invariant measure) such a transformation is not possible. That is to say, typical pairs of quantum states $|\psi\rangle, |\phi\rangle$ are entangled in fundamentally different ways, that cannot be converted to each other via local operations and classical communication. Via Nielsen's theorem, this conjecture can be equivalently stated as a conjecture about majorisation of spectra of random matrices from the so-called trace-normalised complex Wishart-Laguerre ensemble. Concretely, let $X$ and $Y$ be independent $n \times m$ random matrices whose entries are i.i.d. standard complex Gaussians; then Nielsen's conjecture says that the probability that the spectrum of $X X^\dagger / \operatorname{tr}(X X^\dagger)$ majorises the spectrum of $Y Y^\dagger / \operatorname{tr}(Y Y^\dagger)$ tends to zero as both $n$ and $m$ grow large. We prove this conjecture, and we also confirm some related predictions of Cunden, Facchi, Florio and Gramegna [J. Phys. A., 2020; Phys. Rev. A., 2021].

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

Individual Control Barrier Functions-Guided Diffusion Model for Safe Offline Multi-Agent Reinforcement Learning

arXiv:2606.12640v1 Announce Type: new Abstract: Offline reinforcement learning allows control policies to be learned directly from data without online interaction, making it suitable for safety-critical tasks. Recent studies have applied diffusion models to offline reinforcement learning to leverage their strong capacity for modeling complex data distributions. However, existing approaches primarily focus on single-agent settings, leaving the safety challenges in multi-agent environments largely unexplored. In this work, we propose a safe offline multi-agent reinforcement learning algorithm that embeds neural individual control barrier functions into the diffusion model to enhance safety during trajectory generation, with control policies recovered through inverse dynamics. We evaluate our algorithm across diverse benchmarks, demonstrating substantial safety improvements while maintaining competitive rewards.

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

teasr: training-efficient any-step diffusion transformer for real-world image super-resolution

Diffusion models excel in Real-World Image Super-Resolution (Real-ISR) due to their powerful generative priors but suffer from slow iterative sampling. Although existing one-step distillation methods accelerate inference, they typically require auxiliary teacher models that inflate training memory and restrict scalability to large-scale architectures. Furthermore, these fixed-step models lack the flexibility to trade off speed for quality. In this paper, we propose TEASR, a training-efficient any-step diffusion framework for Real-ISR that enables both one-step and multi-step restoration within a unified model. Our key idea is to perform self-adversarial distillation within a single diffusion model, eliminating the need for auxiliary teachers or discriminators. Specifically, we propose a timestep-aware rectification strategy that stabilizes one-step generation across noise levels. These two designs further enables the distillation of 20B-parameter diffusion models on a single GPU, significantly improving training efficiency. Moreover, we introduce a dual-branch diffusion transformer with decoupled timestep condition to separate the current noise state and the denoising target to enhance sampling quality. Extensive experiments demonstrate that TEASR supports seamless any-step sampling and consistently outperforms state-of-the-art methods across multiple datasets.

12.
arXiv (quant-ph) 2026-06-19

Quantum correlations in QBism's reconstruction program

arXiv:2606.07485v2 Announce Type: replace Abstract: QBism recasts quantum theory as a normative framework for an agent's probability assignments, with the Born rule taking the form of a consistency condition known as the Urgleichung. Motivated by this perspective, qplex theories provide a broader class of probabilistic models in which the sets of valid states and measurements are constrained by QBist-inspired geometric conditions. While qplexes have been extensively studied for single systems, their implications for bipartite correlations remain largely unexplored. In this work, we investigate bipartite correlations in qplex theories by expressing joint expectation values as inner products between suitably defined $C$-vectors. This geometric formulation allows Bell-type inequalities to be studied as optimization problems over qplex-compatible probability assignments. We first analyze the CHSH scenario and show that the shared inner-product structure of the $C$-vectors restricts the maximal value to the Tsirelson bound $2\sqrt{2}$. We then turn to the three-outcome CGLMP inequality $I_{2233}$ and find that the same qplex-derived norm and inner-product constraints allow a violation of up to $\leq 2+2\sqrt(3)/3 \approx 3.1547$ versus the quantum maximum of $\approx 2.8729$, thereby exhibiting super-quantum correlations. These results show that qplex geometry captures enough structure to reproduce an important quantum bound in the two-outcome case, but not enough to recover the full set of quantum correlation constraints. The analysis therefore suggests that additional principles are needed to complete the QBist reconstruction of quantum theory.

13.
arXiv (CS.LG) 2026-06-18

AGDN: Learning to Solve Traveling Salesman Problem with Anisotropic Graph Diffusion Network

arXiv:2606.19185v1 Announce Type: new Abstract: The Traveling Salesman Problem (TSP) is a cornerstone of combinatorial optimization and arises in many practical scenarios. Although graph-based learning approaches have been explored for TSP, the question of how to exploit graph structure more effectively remains open. We present the Anisotropic Graph Diffusion Network (AGDN), a new Graph Neural Network framework designed to solve TSP. Our method tackles two central difficulties: (1) the lack of informative topological prior in fully connected TSP graphs, and (2) losing connected nodes in the optimal solution after the commonly used graph sparsification techniques. To overcome these issues, we construct a MixScore transition matrix that merges node similarity with pairwise distance, and we develop an anisotropic graph diffusion strategy that supports efficient information exchange across multiple hops. Comprehensive experiments spanning diverse instance sizes and node distributions show that AGDN consistently outperforms existing methods while keeping computation time competitive. Furthermore, AGDN generalizes well to problem sizes and distributions beyond those seen during training. The implementation is publicly available at: https://github.com/LabRAI/AGDN.

15.
arXiv (CS.AI) 2026-06-17

FacProcessTwin: An LLM-Based System for Process Twin Development

arXiv:2606.17666v1 Announce Type: cross Abstract: Process twins provide real-time representations of entire production processes. By capturing how process steps interact, rather than monitoring a single machine in isolation as an asset-based digital twin does, they have the potential to drive efficiency gains across the whole process. However, developing a process twin is costly. It requires accurately modelling the entire production process: its process steps, the equipment and product-specific settings each step uses, and its process variations. The resulting model must then be bound to live operational data. We present FacProcessTwin, a system that leverages a large language model (LLM) to reduce this development time, building a process twin from a plant's process documentation and natural-language input from an operator. FacProcessTwin generates this complete process model and then automatically binds its process steps to live operational data. The generated model and its data bindings are rendered as an interactive process diagram through which manufacturing personnel can monitor and correct the system's autonomous decisions, such as resolving uncertainty at safety-critical binding steps. We evaluate FacProcessTwin through a real-world case study of an Australian food manufacturer, covering 16 production process flows that span chilled, frozen, and aseptic shelf-stable product categories and include process variations within the same product. The results show that FacProcessTwin generates these process models accurately (a mean F1 of 95.2% against ground truth) and builds each twin in roughly a sixth of the manual time. Its human-in-the-loop governance then keeps the safety-critical bindings correct: at ambiguous tags where a single-pass baseline silently mis-binds 75.0% of the time, FacProcessTwin defers to the operator and mis-binds none.

16.
arXiv (quant-ph) 2026-06-12

Supersymmetry of dissipative Bose-Fermi systems with application to Jaynes-Cummings and Dicke models

arXiv:2606.12682v1 Announce Type: new Abstract: We demonstrate how supersymmetries of Hamiltonians for coupled Bose-Fermi systems can be used to place the Hamiltonians of the Jaynes-Cummings model and Dicke model under the rotating wave approximation in matrix form and provide explicit analytic solutions for their eigenvalues. We then use this supersymmetry to place the Liouvillians of the associated Markovian open systems in matrix form and provide explicit solutions for their eigenvalues. These results are a consequence of the fact that the Hamiltonian of the Jaynes-Cummings model commutes with the linear Casimir invariant of the superalgebra $u(1|1)$ and that the Hamiltonian of the Dicke model commutes both with the linear invariant of $\sum_{i} u_{i}(1|1)$ and with the invariant of an additional $su(2)$ algebra. Our methods apply to various coupled Bose-Fermi systems with $u(1|1)$ and more generally with $u(n|m)$ dynamical superalgebras, and may provide efficient tools for studying more complicated examples.

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

OmniRetarget: Interaction-Preserving Data Generation for Humanoid Whole-Body Loco-Manipulation and Scene Interaction

arXiv:2509.26633v3 Announce Type: replace-cross Abstract: A dominant paradigm for teaching humanoid robots complex skills is to retarget human motions as kinematic references to train reinforcement learning (RL) policies. However, existing retargeting pipelines often struggle with the significant embodiment gap between humans and robots, producing physically implausible artifacts like foot-skating and penetration. More importantly, common retargeting methods neglect the rich human-object and human-environment interactions essential for expressive locomotion and loco-manipulation. To address this, we introduce OmniRetarget, an interaction-preserving data generation engine based on an interaction mesh that explicitly models and preserves the crucial spatial and contact relationships between an agent, the terrain, and manipulated objects. By minimizing the Laplacian deformation between the human and robot meshes while enforcing kinematic constraints, OmniRetarget generates kinematically feasible trajectories. Moreover, preserving task-relevant interactions enables efficient data augmentation, from a single demonstration to different robot embodiments, terrains, and object configurations. We comprehensively evaluate OmniRetarget by retargeting motions from OMOMO, LAFAN1, and our in-house MoCap datasets, generating over 8-hour trajectories that achieve better kinematic constraint satisfaction and contact preservation than widely used baselines. Such high-quality data enables proprioceptive RL policies to successfully execute long-horizon (up to 30 seconds) parkour and loco-manipulation skills on a Unitree G1 humanoid, trained with only 5 reward terms and simple domain randomization shared by all tasks, without any learning curriculum.

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

The Market in the Model: Latent Diffusion as Neural Economy

Valuable critique of generative image models within visual culture and the humanities has emphasized the role of datasets in shaping the images they produce. Yet, close studies of the ideological positions embedded into the mechanism of the models have been neglected, leaving them imagined as "black boxes." In a bid to expand, rather than replace, dataset critique, this paper examines the mechanisms of the latent diffusion model in terms of the problems they were brought in to solve on behalf of computer vision engineers, and the decisions each component was tasked with automating. I interpret that ensemble through the histories of its parts and the theory of vision the system inscribes into every generated image. Drawing on Impett and Offert's notion of neural exchange value, I offer this analysis to argue that the model operates as a neural economy: a contained symbolic system that abstracts social communication into commensurable vectors as it transfers the social sphere into parcels for sale. Tracing the training and generation pipelines component by component reveals what each operation displaces, and how it further entrenches the logics of platform and attention economies over social communication. The paper warns that any critique fixated exclusively on copyright and commodity defenses risks reaffirming the very fetishism the model produces, and argues instead for centering social exchange.

19.
arXiv (CS.CV) 2026-06-18

HeatKV: Head-tuned KV-cache Compression for Visual Autoregressive Modeling

Visual Autoregressive (VAR) models have recently demonstrated impressive image generation quality while maintaining low latency. However, they suffer from severe KV-cache memory constraints, often requiring gigabytes of memory per generated image. We introduce HeatKV, a novel compression method that adapts cache allocation in each head based on its attention to previously generated scales. Using a small offline calibration set, the attention heads are ranked according to their attention scores over prior scales. Based on this ranking, we construct a static pruning schedule tailored to a given memory budget. Applied to the Infinity-2B model, HeatKV achieves $2 \times$ higher compression ratio in memory allocation for KV cache compared to existing methods, while maintaining similar or better image fidelity, prompt alignment and human perception score. Our method achieves a new state-of-the-art (SOTA) for VAR model KV-cache compression, showcasing the effectiveness of fine-grained, head-specific cache allocation. Code and calibration script available at https://github.com/arm-research/heatkv.

20.
arXiv (CS.CV) 2026-06-17

Partial Ring Scan: Revisiting Scan Order in Vision State Space Models

State Space Models (SSMs) have emerged as efficient alternatives to attention for vision tasks, offering lineartime sequence processing with competitive accuracy. Vision SSMs, however, require serializing 2D images into 1D token sequences along a predefined scan order, a factor often overlooked. We show that scan order critically affects performance by altering spatial adjacency, fracturing object continuity, and amplifying degradation under geometric transformations such as rotation. We present Partial RIng Scan Mamba (PRISMamba), a rotation-robust traversal that partitions an image into concentric rings, performs order-agnostic aggregation within each ring, and propagates context across rings through a set of short radial SSMs. Efficiency is further improved via partial channel filtering, which routes only the most informative channels through the recurrent ring pathway while keeping the rest on a lightweight residual branch. On ImageNet-1K, PRISMamba achieves 84.5% Top-1 with 3.9G FLOPs and 3,054 img/s on A100, outperforming VMamba in both accuracy and throughput while requiring fewer FLOPs. It also maintains performance under rotation, whereas fixed-path scans drop by 1~2%. These results highlight scan-order design, together with channel filtering, as a crucial, underexplored factor for accuracy, efficiency, and rotation robustness in Vision SSMs. Code will be released upon acceptance.

21.
arXiv (CS.AI) 2026-06-19

Latent Gaussian Splatting for 4D Panoptic Occupancy Tracking

arXiv:2602.23172v2 Announce Type: replace-cross Abstract: Capturing 4D spatiotemporal scene structure is crucial for the safe and reliable operation of robots in dynamic environments. However, existing approaches typically address only part of the problem: they either provide coarse geometric tracking via bounding boxes or detailed 3D occupancy estimates that lack explicit temporal association and instance-level reasoning. In this work, we present Latent Gaussian Splatting (LaGS) for 4D Panoptic Occupancy Tracking (4D-POT). We revisit the underlying representation and model 3D features as a sparse set of feature-bearing Gaussians. These act as dynamic, volume-oriented keypoints that enable spatially continuous, distance-weighted aggregation of multi-view features before being splatted into a voxel grid for decoding. This point-centric formulation enables flexible, data-dependent receptive fields and long-range spatial interactions that are difficult to capture with local and dense voxel-based operators. A hierarchical Gaussian representation further enables multi-scale reasoning by combining global context from coarse super-points with fine-grained detail from higher-resolution streams. Extensive experiments on Occ3D nuScenes and Waymo demonstrate state-of-the-art performance for 4D-POT. We provide code and models at https://lags.cs.uni-freiburg.de/.

22.
arXiv (CS.CL) 2026-06-17

Incumbent Advantage: Brand Bias and Cognitive Manipulation Dynamics in LLM Recommendation Systems

Large language models (LLMs) are becoming a major way for consumers to find products, but we do not yet understand how brands compete in this new channel. We study brand dynamics in LLM recommendations using skincare products – a category where consumers cannot easily judge quality before buying and must rely on brand reputation – across three commercial LLMs (GPT-4o-mini, Claude Sonnet, Gemini 3 Flash), with a robustness check on search goods. In three experiments, we find: (1) a Conditional Monopoly where well-known brands get recommended 100% of the time (IAI = 10.0) when all products have the same specifications, but this dominance disappears with less than a +0.1-star rating advantage for a competitor; (2) authority-style marketing language, including fabricated clinical-evidence claims, breaks this monopoly at a Bias Surplus Value equal to +0.17 rating points, with each model responding differently; and (3) a social dilemma in multi-brand GEO competition: when all brands adopt the same optimization strategy, individual payoff falls from +0.802 to +0.007 in our payoff proxy, and non-participating brands receive zero recommendations in our tests. Our results suggest that generative engine optimization (GEO) should be studied not only as a security risk, but also as an emerging marketing practice that shapes market competition.

23.
PLOS Computational Biology 2026-06-12

Stage-dependent role of NEK7 in the inactive-to-active conformational transition of NLRP3 monomer

作者:

by Jin Peng, Wenjian Li, Hao Wang, Xiaohui Chen, Manjie Zhang, Bin Sun The NLRP3 inflammasome is a multiprotein complex that primes cytokine production in the innate immune system. The inflammasome activation involves the cage-to-disk transition of NLRP3 oligomers, facilitated by the co-factor NEK7 protein. While NEK7’s role in promoting cage disassembly has been reported, its involvement in the large conformational changes of the NLRP3 monomer during activation remains elusive. Here, by using multi-scale simulations, we uncovered a stage-dependent role of NEK7 in the inactive-to-active transition. In the early stage, NEK7 reshapes the dynamics of the highly unstable inactive NLRP3 monomer to resemble active state, priming the conformational transition. In the middle stage, NEK7 impedes progression by populating an intermediate state farther from the active conformation than the NEK7-free counterpart, and structures in this state exhibit reduced allosteric potential toward activation. In the late stage, NEK7 has negligible impact, as the active conformation remains inherently isolated by a high energy barrier regardless of NEK7 presence. This highlights the critical role of oligomeric assembly in enabling monomeric NLRP3 to complete its conformational transition, in agreement with experiment observations. Our work suggests a multilayered activation mechanism where oligomer-level assembly and monomeric conformational changes are coupled, providing new mechanistic insights into this physiologically essential macromolecular process.

24.
medRxiv (Medicine) 2026-06-10

Estimating COVID-19 Cumulative Incidence from Seroprevalence Surveys accounting for Time-Varying Seroreversion: A Fully Bayesian Methodology

Seroprevalence surveys reveal the extent of humoral immunity against pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and under some circumstances represent cumulative incidence of prior infection. However, antibody waning - or seroreversion - biases these estimates by reducing assay sensitivity in a time-varying manner. Because assay sensitivity decays over time, naively using serosurveys can substantially bias estimates of SARS-CoV-2 cumulative incidence and fatality rates. The Bayesian assay-specific, time-varying sensitivity adjustment developed in this paper can reliably correct for this bias and account for the delay between infection and serosurvey. In seroprevalence studies conducted in the United States in 2020, adjusting for time-varying sensitivity increased cumulative incidence by up to 1.4-fold, with an adjustment of 1.08 for a national study. Our estimates contrast with a previously published 2-fold adjustment that did not account for assay design. This suggests that previous analyses overestimated cumulative incidence by applying seroreversion corrections that did not account for assay-specific effects, or underestimated cumulative incidence by not applying seroreversion corrections. These biases imply fatality rate underestimation and overestimation, respectively. Our model provides a framework for design-specific time-varying sensitivity corrections in seroprevalence surveys for other pathogens.