PIS: A Physics-Informed System for Accurate State Partitioning of $Aβ_{42}$ Protein Trajectories

Understanding the conformational evolution of $β$-amyloid ($Aβ$), particularly the $Aβ_{42}$ isoform, is fundamental to elucidating the pathogenic mechanisms underlying Alzheimer's disease. However, existing end-to-end deep learning models often struggle to capture subtle state transitions in protein trajectories due to a lack of explicit physical constraints. In this work, we introduce PIS, a Physics-Informed System designed for robust metastable state partitioning. By integrating pre-computed physical priors, such as the radius of gyration and solvent-accessible surface area, into the extraction of topological features, our model achieves superior performance on the $Aβ_{42}$ dataset. Furthermore, PIS provides an interactive platform that features dynamic monitoring of physical characteristics and multi-dimensional result validation. This system offers biological researchers a powerful set of analytical tools with physically grounded interpretability. A demonstration video of PIS is available on https://youtu.be/AJHGzUtRCg0.

Don't Break the Boundary: Continual Unlearning for OOD Detection Based on Free Energy Repulsion

Deploying trustworthy AI in open-world environments faces a dual challenge: the necessity for robust Out-of-Distribution (OOD) detection to ensure system safety, and the demand for flexible machine unlearning to satisfy privacy compliance and model rectification. However, this objective encounters a fundamental geometric contradiction: current OOD detectors rely on a static and compact data manifold, whereas traditional classification-oriented unlearning methods disrupt this delicate structure, leading to a catastrophic loss of the model's capability to discriminate anomalies while erasing target classes. To resolve this dilemma, we first define the problem of boundary-preserving class unlearning and propose a pivotal conceptual shift: in the context of OOD detection, effective unlearning is mathematically equivalent to transforming the target class into OOD samples. Based on this, we propose the TFER (Total Free Energy Repulsion) framework. Inspired by the free energy principle, TFER constructs a novel Push-Pull game mechanism: it anchors retained classes within a low-energy ID manifold through a pull mechanism, while actively expelling forgotten classes to high-energy OOD regions using a free energy repulsion force. This approach is implemented via parameter-efficient fine-tuning, circumventing the prohibitive cost of full retraining. Extensive experiments demonstrate that TFER achieves precise unlearning while maximally preserving the model's discriminative performance on remaining classes and external OOD data. More importantly, our study reveals that the unique Push-Pull equilibrium of TFER endows the model with inherent structural stability, allowing it to effectively resist catastrophic forgetting without complex additional constraints, thereby demonstrating exceptional potential in continual unlearning tasks.

Halt the Hallucination: Decoupling Signal and Semantic OOD Detection Based on Cascaded Early Rejection

Efficient and robust Out-of-Distribution (OOD) detection is paramount for safety-critical applications.However, existing methods still execute full-scale inference on low-level statistical noise. This computational mismatch not only incurs resource waste but also induces semantic hallucination, where deep networks forcefully interpret physical anomalies as high-confidence semantic features.To address this, we propose the Cascaded Early Rejection (CER) framework, which realizes hierarchical filtering for anomaly detection via a coarse-to-fine logic.CER comprises two core modules: 1)Structural Energy Sieve (SES), which establishes a non-parametric barrier at the network entry using the Laplacian operator to efficiently intercept physical signal anomalies; and 2) the Semantically-aware Hyperspherical Energy (SHE) detector, which decouples feature magnitude from direction in intermediate layers to identify fine-grained semantic deviations. Experimental results demonstrate that CER not only reduces computational overhead by 32% but also achieves a significant performance leap on the CIFAR-100 benchmark:the average FPR95 drastically decreases from 33.58% to 22.84%, and AUROC improves to 93.97%. Crucially, in real-world scenarios simulating sensor failures, CER exhibits performance far exceeding state-of-the-art methods. As a universal plugin, CER can be seamlessly integrated into various SOTA models to provide performance gains.

Learning with Adaptive Prototype Manifolds for Out-of-Distribution Detection

Out-of-distribution (OOD) detection is a critical task for the safe deployment of machine learning models in the real world. Existing prototype-based representation learning methods have demonstrated exceptional performance. Specifically, we identify two fundamental flaws that universally constrain these methods: the Static Homogeneity Assumption (fixed representational resources for all classes) and the Learning-Inference Disconnect (discarding rich prototype quality knowledge at inference). These flaws fundamentally limit the model's capacity and performance. To address these issues, we propose APEX (Adaptive Prototype for eXtensive OOD Detection), a novel OOD detection framework designed via a Two-Stage Repair process to optimize the learned feature manifold. APEX introduces two key innovations to address these respective flaws: (1) an Adaptive Prototype Manifold (APM), which leverages the Minimum Description Length (MDL) principle to automatically determine the optimal prototype complexity $K_c^*$ for each class, thereby fundamentally resolving prototype collision; and (2) a Posterior-Aware OOD Scoring (PAOS) mechanism, which quantifies prototype quality (cohesion and separation) to bridge the learning-inference disconnect. Comprehensive experiments on benchmarks such as CIFAR-100 validate the superiority of our method, where APEX achieves new state-of-the-art performance.

VMF-GOS: Geometry-guided virtual Outlier Synthesis for Long-Tailed OOD Detection

Out-of-Distribution (OOD) detection under long-tailed distributions is a highly challenging task because the scarcity of samples in tail classes leads to blurred decision boundaries in the feature space. Current state-of-the-art (sota) methods typically employ Outlier Exposure (OE) strategies, relying on large-scale real external datasets (such as 80 Million Tiny Images) to regularize the feature space. However, this dependence on external data often becomes infeasible in practical deployment due to high data acquisition costs and privacy sensitivity. To this end, we propose a novel data-free framework aimed at completely eliminating reliance on external datasets while maintaining superior detection performance. We introduce a Geometry-guided virtual Outlier Synthesis (GOS) strategy that models statistical properties using the von Mises-Fisher (vMF) distribution on a hypersphere. Specifically, we locate a low-likelihood annulus in the feature space and perform directional sampling of virtual outliers in this region. Simultaneously, we introduce a new Dual-Granularity Semantic Loss (DGS) that utilizes contrastive learning to maximize the distinction between in-distribution (ID) features and these synthesized boundary outliers. Extensive experiments on benchmarks such as CIFAR-LT demonstrate that our method outperforms sota approaches that utilize external real images.

Breaking Semantic Hegemony: Decoupling Principal and Residual Subspaces for Generalized OOD Detection

While feature-based post-hoc methods have made significant strides in Out-of-Distribution (OOD) detection, we uncover a counter-intuitive Simplicity Paradox in existing state-of-the-art (SOTA) models: these models exhibit keen sensitivity in distinguishing semantically subtle OOD samples but suffer from severe Geometric Blindness when confronting structurally distinct yet semantically simple samples or high-frequency sensor noise. We attribute this phenomenon to Semantic Hegemony within the deep feature space and reveal its mathematical essence through the lens of Neural Collapse. Theoretical analysis demonstrates that the spectral concentration bias, induced by the high variance of the principal subspace, numerically masks the structural distribution shift signals that should be significant in the residual subspace. To address this issue, we propose D-KNN, a training-free, plug-and-play geometric decoupling framework. This method utilizes orthogonal decomposition to explicitly separate semantic components from structural residuals and introduces a dual-space calibration mechanism to reactivate the model's sensitivity to weak residual signals. Extensive experiments demonstrate that D-KNN effectively breaks Semantic Hegemony, establishing new SOTA performance on both CIFAR and ImageNet benchmarks. Notably, in resolving the Simplicity Paradox, it reduces the FPR95 from 31.3% to 2.3%; when addressing sensor failures such as Gaussian noise, it boosts the detection performance (AUROC) from a baseline of 79.7% to 94.9%.