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

Structure-Oriented Randomized Neural Networks for Poisson-Nernst-Planck and Poisson-Nernst-Planck-Navier-Stokes Systems

arXiv:2606.19912v1 Announce Type: cross Abstract: We develop a structure-oriented randomized neural network framework, termed SO-RaNN, for the Poisson-Nernst-Planck (PNP) system and the Poisson-Nernst-Planck-Navier-Stokes (PNP-NS) system. The decoupled linearized subproblems are solved iteratively by randomized neural networks in a space-time framework. For the concentration variables, a pointwise cut-off is used to enforce positivity at the value level, and discrete mass-scaling factors are computed at selected correction instants and interpolated in time, so as to ensure exact mass matching at those instants and to promote approximate mass preservation between them. To introduce an auxiliary discrete dissipation mechanism, we further employ an SAV-type post-processing correction, which yields monotonicity of the SAV auxiliary variable under the ideal SAV update. For the PNP-NS system, a structure-preserving randomized neural network (SP-RaNN) is used for the velocity field, so that the velocity approximation satisfies the incompressibility constraint pointwise by construction. On the theoretical side, we derive residual-based estimates for the raw, uncorrected RaNN solvers of the linearized subproblems, formulate a conditional local-in-time convergence result for the raw outer Picard iteration of the PNP system, and analyze the value-level positivity correction together with the mass-correction and SAV post-processing steps. For the PNP-NS system, we establish an approximation result for the SP-RaNN space and provide a conditional error statement for the corresponding linearized Oseen-type problem. Numerical experiments demonstrate approximation accuracy in the source-driven manufactured tests and illustrate the intended value-level positivity correction, selected-time mass matching, computed free-energy curves based on the final gauge-fixed potential, and divergence-free approximation in benchmark tests.

02.
arXiv (CS.LG) 2026-06-16

Stochastic Schrödinger Diffusion Models for Pure-State Ensemble Generation

arXiv:2605.03573v3 Announce Type: replace-cross Abstract: Quantum machine learning increasingly relies on pure-state representations, motivating generative models that sample directly in quantum representation space rather than perturbing classical inputs and re-encoding. We introduce Stochastic Schrödinger Diffusion Models (SSDMs), a score-based generative framework that defines diffusion, scores, and reverse-time sampling intrinsically on the complex projective manifold $\mathbb{CP}^{d-1}$ under the Fubini–Study metric. SSDMs combine a Riemannian Ornstein–Uhlenbeck forward diffusion with a stochastic Schrödinger realization, and learn reverse-time dynamics driven by the Riemannian score. Our central technical contribution is a local-time learning objective that exploits the local Euclidean OU limit of intrinsic manifold diffusions in Fubini-Study normal coordinates to obtain an analytic teacher score, bypassing the intractable transition densities that limit existing Riemannian score-based models. Across synthetic, physics-inspired (TFIM, XXZ), and quantum feature-state benchmarks up to $14$ qubits, SSDMs match target pure-state ensembles by orders of magnitude on MMD and observable statistics over both ambient Euclidean and matched Riemannian score-based baselines, and improve representation-level diagnostics for downstream quantum kernel methods.

03.
arXiv (CS.AI) 2026-06-12

M*: A Modular, Extensible, Serving System for Multimodal Models

arXiv:2606.12688v1 Announce Type: cross Abstract: We are entering a new era of composite model architectures that integrate diverse components such as vision encoders, language backbones, diffusion and flow heads, audio codecs, action generators, and world-model predictors. Such architectures underpin a broad class of multimodal models, including unified multimodal models, omni models, speech-language models, vision-language-action policies, and world models. However, existing model serving frameworks were built on narrow assumptions about model structure, making them ill-suited to accommodate this new architectural diversity. Here we present M*, a universal serving system for efficient serving of composite AI models. M* represents models as dataflow graphs, processing requests spanning diverse modalities and tasks as traversals over these graphs. The core insight is a modular abstraction that supports arbitrary composition of model components, flexible placement onto a physical cluster, and model-agnostic optimizations within a distributed runtime. We call this abstraction the Walk Graph and show how it can concisely capture composite models from a broad range of families. We instantiate M* on representative models and find that it achieves, on average, 20% lower end-to-end latency than vLLM-Omni for text-to-image workloads on BAGEL, while delivering up to 2.9x lower real-time factor and 2.7x higher throughput for text-to-speech workloads on Qwen3-Omni. M* also outperforms the V-JEPA 2-AC rollout baseline for robotic planning by up to 12.5x. Thus, our work paves the road towards more efficient serving of complex models with minimal developer effort.

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

Learning Interface Breakup: A Geometry-Conditioned Latent Surrogate for Spray Formation

arXiv:2606.16587v1 Announce Type: cross Abstract: Designing spray nozzles requires predicting how geometry shapes transient two-phase breakup, but high-fidelity volume-of-fluid (VOF) simulations with adaptive mesh refinement (AMR) are too expensive for iterative design exploration. Standard surrogate models are also challenged by this setting because both the liquid–gas interface and the underlying adaptive discretization evolve across time and geometries. We introduce a geometry-conditioned latent surrogate trained on 797 two-phase nozzle simulations that addresses this by encoding the AMR cell-density field, rather than the full multi-channel flow state, as a compact proxy for where the solver concentrates resolution. From this representation, the model reconstructs transient density evolution and nozzle geometry, and a lightweight second stage recovers the remaining flow variables. On held-out simulations, the method accurately captures key interface dynamics while reducing inference time to 0.045 seconds per trajectory, corresponding to a speed-up of more than $6\times10^4$ relative to Basilisk CFD. These results suggest that AMR refinement structure can serve as a compact and learnable representation for geometry-conditioned surrogate modeling of transient two-phase flows.

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

Classification of Astronomical Spectra Using PCA-Compressed Flux and Inverse-Variance Features

arXiv:2606.13978v1 Announce Type: cross Abstract: This paper evaluates a signal-processing and supervised-learning pipeline for classifying SDSS DR17 astronomical spectra into stars, galaxies, and quasars. Each spectrum is represented by its measured flux and inverse-variance information, combining spectral shape with a wavelength-dependent reliability profile. After resampling onto a common logarithmic wavelength grid, the flux and inverse-variance vectors are standardized and separately compressed using principal component analysis. The resulting components are concatenated and used to train several classifiers. The best performance was obtained with the LightGBM gradient-boosting classifier, reaching $94.6\%$ accuracy and $92.1\%$ balanced accuracy on the test set.

07.
medRxiv (Medicine) 2026-06-17

High burden of subclinical TB in Africa revealed from a postmortem cohort.

Tuberculosis (TB) is increasingly recognised as a spectrum of infection and disease, yet the prevalence of viable, asymptomatic Mycobacterium tuberculosis (M.tb) infection remains uncertain. Subclinical Tuberculosis (scTB), defined as microbiologically confirmed M.tb infection in the absence of recognised symptoms, is under detected by symptom, sputum and imaging-based approaches. We conducted postmortem examinations of 94 adults who died from non-infectious causes, none of whom were clinically suspected of TB or reported TB related symptoms prior to death. Lung and extrapulmonary tissues were cultured for M.tb. Viable M.tb was confirmed in six individuals, corresponding to a prevalence of 6.4% (95% CI: 2.4 to 13.4%). These findings provide direct tissue-based evidence that viable, asymptomatic M.tb infection can persist beyond the reach of conventional clinical detection. Our data suggest that a biologically active reservoir of infection may exist undetected within high-burden settings, with implications for surveillance strategies aimed at TB elimination.

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

Your Agent Has a Genome: Sequence-Level Behavioral Analysis and Runtime Governance of LLM-Powered Autonomous Agents

作者:

arXiv:2606.15579v1 Announce Type: new Abstract: We propose Base Sequence Analysis, a framework that encodes the runtime behavior of LLM-powered autonomous agents into compact symbolic sequences using a four-letter alphabet: X (Explore), E (Execute), P (Plan), and V (Verify). Drawing an analogy to genomic sequence analysis, we apply n-gram pattern mining, Markov transition matrices, and point-biserial correlation to 347 real-world execution traces collected from a production ReAct agent system over 8 days. Our analysis reveals that (1) the trigram P-X-P is the only statistically significant high-risk pattern, lowering success rate by 10.4%; (2) P-ratio is the strongest negative predictor of success (r=-0.256, pV transition probability is only 2.1%, indicating a systemic verification deficit. Based on these findings, we design Governor, a three-layer runtime intervention system comprising a rule engine, a statistical accumulator, and a chi-square-based threshold adaptor. In a natural before/after deployment evaluation (N=101 vs. N=246), Governor achieves a +6.2% absolute increase in task success rate while simultaneously reducing average token consumption by 44%. To validate cross-system generality, we apply the XEPV encoding to 2,000 public SWE-agent trajectories on SWE-bench, confirming that exploration spirals and the E->V verification deficit replicate in an independent system. We outline six research directions including base sequence language models, cross-agent behavioral fingerprinting, and reward shaping, and release an open-source toolkit for reproducibility.

09.
Nature (Science) 2026-06-22

Will AI spark a scientific renaissance — or a diffuse monoculture?

作者:

Artificial intelligence’s ability to enrich science will depend not only on model capability, but also on whether researchers, reviewers and funders reward originality over speed. Artificial intelligence’s ability to enrich science will depend not only on model capability, but also on whether researchers, reviewers and funders reward originality over speed.

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

Epistemic Constitutionalism Or: how to avoid coherence bias

作者:

Large language models increasingly function as artificial reasoners: they evaluate arguments, assign credibility, and express confidence. Yet their belief-forming behavior is governed by implicit, uninspected epistemic policies. This paper argues for an epistemic constitution for AI: explicit, contestable meta-norms that regulate how systems form and express beliefs. Source attribution bias provides the motivating case: I show that frontier models enforce identity-stance coherence, penalizing arguments attributed to sources whose expected ideological position conflicts with the argument's content. When models detect systematic testing, these effects collapse, revealing that systems treat source-sensitivity as bias to suppress rather than as a capacity to execute well. I distinguish two constitutional approaches: the Platonic, which mandates formal correctness and default source-independence from a privileged standpoint, and the Liberal, which refuses such privilege, specifying procedural norms that protect conditions for collective inquiry while allowing principled source-attending grounded in epistemic vigilance. I argue for the Liberal approach, sketch a constitutional core of eight principles and four orientations, and propose that AI epistemic governance requires the same explicit, contestable structure we now expect for AI ethics.

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

Trustworthy Self-Composable Big-Data-as-a-Service: An LLM-Orchestrated Multi-Agent Framework for Automated Data Engineering, AutoML, MLOps Deployment, and Drift-Aware Lifecycle Optimization

arXiv:2606.17915v1 Announce Type: cross Abstract: Big-Data-as-a-Service (BDaaS) platforms require re liable automation across data ingestion, cleaning, feature engi neering, model development, deployment, and post-deployment monitoring. However, existing LLM-based data science agents and AutoML systems mainly focus on isolated workflow stages, leaving limited support for lifecycle-level orchestration, artifact governance, human oversight, and drift-aware adaptation. This paper proposes a trustworthy self-composable BDaaS frame work based on LLM-orchestrated multi-agent collaboration. The proposed architecture decomposes the BDaaS lifecycle into specialized agents for data ingestion, data cleaning, feature engineering, AutoML training, model evaluation, MLOps de ployment, monitoring, and drift detection. A central LLM or chestration layer coordinates agent execution, validates interme diate outputs, manages workflow context, and enables dynamic workflow composition. The framework also incorporates shared artifact governance, reproducibility support, human-in-the-loop checkpoints, and drift-aware feedback loops. A prototype-based evaluation is conducted using controlled tabular benchmark datasets with missing values, categorical variables, outliers, class imbalance, and simulated covariate drift. Compared with manual ML, AutoML-only, and single-agent LLM baselines, the pro posed multi-agent BDaaS pipeline achieves competitive predictive performance while improving lifecycle-level reliability, including workflow completion, artifact traceability, deployment readiness, reproducibility, and drift recovery. The results suggest that LLM-orchestrated multi-agent systems can extend conventional AutoML toward trustworthy, adaptive, and production-oriented BDaaS lifecycle automation.

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

Beyond MACs: Hardware Efficient Architecture Design for Vision Backbones

Vision backbone networks play a central role in modern computer vision. Enhancing their efficiency directly benefits a wide range of downstream applications. To measure efficiency, many publications rely on MACs (Multiply Accumulate operations) as a predictor of execution time. In this paper, we experimentally demonstrate the shortcomings of such a metric, especially in the context of edge devices. By contrasting the MAC count and execution time of common architectural design elements, we identify key factors for efficient execution and provide insights to optimize backbone design. Based on these insights, we present LowFormer, a novel vision backbone family. LowFormer features a streamlined macro and micro design that includes Lowtention, a lightweight alternative to Multi-Head Self-Attention. Lowtention not only proves more efficient, but also enables superior results on ImageNet. Additionally, we present an edge GPU version of LowFormer, that can further improve upon its baseline's speed on edge GPU and desktop GPU. We demonstrate LowFormer's wide applicability by evaluating it on smaller image classification datasets, as well as adapting it to several downstream tasks, such as object detection, semantic segmentation, image retrieval, and visual object tracking. LowFormer models consistently achieve remarkable speed-ups across various hardware platforms compared to recent state-of-the-art backbones. Code and models are available at https://github.com/altair199797/LowFormer/blob/main/Beyond_MACs.md.

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

Provably Efficient Regularized Online RLHF with Generalized Bilinear Preferences

arXiv:2602.23116v3 Announce Type: replace Abstract: We consider the problem of regularized best-response max-regret minimization in online RLHF under general preferences and bandit feedback. While various regularizers are utilized to robustify alignment, known polylogarithmic regret guarantees remain heavily specific to KL. To investigate whether such fast rates extend beyond KL, we adopt the Generalized Bilinear Preference Model (GBPM) – capturing intransitive preferences over $d$-dimensional item-wise features via a rank-$2r$ skew-symmetric matrix – to isolate the impact of generic regularization. Crucially, under GBPM, we prove that the dual gap of any greedy policy is bounded by the squared estimation error, derived using only strong convexity and skew-symmetry. Under a feature coverage assumption, we establish a generic polylogarithmic regret of $\tilde{\mathcal{O}}(\eta d^4 C_{\min}^{-1} (\log T)^2 \wedge d^2 C_{\min}^{-1/2} \sqrt{T})$ with Greedy Sampling, and a dimension-wise improved regret (for well-conditioned arm-sets) of $\tilde{\mathcal{O}}(C_{\min}^{-2} \sqrt{\eta r T} \wedge r^{1/3} C_{\min}^{-4/3} T^{2/3})$ with Explore-Then-Commit, where $\eta^{-1}$ is the regularization coefficient, $T$ is the time horizon, and $C_{\min}$ is an arm-set dependent quantity. This demonstrates that ``fast'' regrets are not KL-specific, but rather a fundamental consequence of generic strongly convex geometry.

14.
arXiv (CS.AI) 2026-06-18

SWE-Future: Forecast-Conditioned Data Synthesis for Future-Oriented Software Engineering Agents

arXiv:2606.18733v1 Announce Type: cross Abstract: Realistic coding-agent benchmarks often replay public GitHub issues and pull requests, making them vulnerable to overlap with model pretraining, fine-tuning, synthetic-data generation, or benchmark-driven model selection. Fully synthetic tasks avoid direct historical replay, but can drift away from real repository needs. We propose SWE-Future, a forecast-conditioned data synthesis method for future-oriented coding tasks. Given a forecast snapshot at time $T_0$, the method uses only pre-$T_0$ repository evidence to forecast future feature implementation/enhancement, bugfix, and refactor task families. We first validate this forecasting step retrospectively: after forecasts are fixed, later pull requests are used only to measure whether the predicted task families match future repository work. In an 80-repository study, the forecaster achieves 58.1\% future-work relevance under the main semantic matching metric. We then use validated forecast families as conditioning signals to synthesize a 200-task coding-agent dataset across 61 repositories from a task-generation snapshot, rather than replaying the later pull requests used for validation. SWE-Future shows that repository-evolution forecasts can guide realistic, future-oriented coding-task synthesis while reducing direct dependence on historical pull-request replay.

15.
arXiv (CS.LG) 2026-06-18

RNN(p) for Power Consumption Forecasting

arXiv:2209.01378v3 Announce Type: replace Abstract: An elementary Recurrent Neural Network that operates on p time lags, called an RNN(p), is the natural generalisation of a linear autoregressive model ARX(p). It is a powerful forecasting tool for variables displaying inherent seasonal patterns across multiple time scales, as is often observed in energy, economic, and financial time series. The architecture of RNN(p) models, characterised by structured feedbacks across time lags, enables the design of efficient training strategies. We conduct a comparative study of learning algorithms for these models, providing a rigorous analysis of their computational complexity and training performance. We present two applications of RNN(p) models in power consumption forecasting, a key domain within the energy sector where accurate forecasts inform both operational and financial decisions. Experimental results show that RNN(p) models achieve excellent forecasting accuracy while maintaining a high degree of interpretability. These features make them well-suited for decision-making in energy markets and other fintech applications where reliable predictions play a significant economic role.

16.
arXiv (quant-ph) 2026-06-19

Indefinite Quantum Causality

arXiv:2606.19438v1 Announce Type: new Abstract: In recent years, operational approaches to quantum foundations have been developed as a means of understanding the core principles and distinctive features of quantum theory. Such approaches typically view physical processes as sequences of operations, with earlier operations serving as causes of later effects. However, a growing literature is emerging on the possibility of relaxing this assumption and allowing for quantum indefiniteness in the causal order. This development stems from a variety of motivations, both fundamental and applied, including exploring the role of causality in quantum theory, the interplay between quantum theory and general relativity, and higher-order quantum computing. A prominent offshoot of this development is the emergence of indefinite causal order as a feasible resource for quantum information processing. This review provides an overview of the current state of the art in the field, covering the methodology underlying indefinite quantum causality within the so-called "process matrix formalism", outlining key results and experimental implementations, and discussing recent advances.

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

Conservation Laws for Modern Neural Architectures

arXiv:2606.17816v1 Announce Type: cross Abstract: Understanding gradient descent dynamics is key to explaining the success of over-parameterized models, where implicit bias manifests through conservation laws in gradient flow. While such laws are well understood for linear and ReLU networks, they remain largely unexplored for modern architectures. This work develops a unified framework to characterize conservation laws for contemporary models, including feedforward networks with GELU, SiLU, and SwiGLU activations, multihead attention with sinusoidal and rotary positional encodings, and Mixture-of-Experts architectures under diverse gating designs. Our theoretical findings are supported by experiments that validate the predicted invariants.

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

Localized Kernel Projection Outlyingness: A Two-Stage Approach for Multi-Modal Outlier Detection

arXiv:2510.24043v4 Announce Type: replace Abstract: This paper presents Two-Stage LKPLO, a novel multi-stage outlier detection framework that overcomes the coexisting limitations of conventional projection-based methods: their reliance on a fixed statistical metric and their assumption of a single data structure. Our framework uniquely synthesizes three key concepts: (1) a generalized loss-based outlyingness measure (PLO) that replaces the fixed metric with flexible, adaptive loss functions like our proposed SVM-like loss; (2) a global kernel PCA stage to linearize non-linear data structures; and (3) a subsequent local clustering stage to handle multi-modal distributions. Comprehensive 5-fold cross-validation experiments on 10 benchmark datasets, with automated hyperparameter optimization, demonstrate that Two-Stage LKPLO achieves state-of-the-art performance. It significantly outperforms strong baselines on datasets with challenging structures where existing methods fail, most notably on multi-cluster data (Optdigits) and complex, high-dimensional data (Arrhythmia). Furthermore, an ablation study empirically confirms that the synergistic combination of both the kernelization and localization stages is indispensable for its superior performance. This work contributes a powerful new tool for a significant class of outlier detection problems and underscores the importance of hybrid, multi-stage architectures.

19.
arXiv (CS.LG) 2026-06-12

The Urysohn Machine: A Metric-Topological Model of Computation

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arXiv:2508.14143v2 Announce Type: replace Abstract: We introduce the Urysohn Machine, an effective model of classification-oriented computation in which metric separation, frontier structure, and contraction are explicit parts of the computational state. Its basic object is a Urysohn Triple: a support region, a target partition, and a separating classifier stored in a reusable Metric Library. The topological foundation is a constructive Urysohn Realization theorem for finite simplicial settings. It builds separators from dyadic ladders of nested polyhedral regions and equips their frontiers with a chain-level calculus: frontiers are cycles, and shells between levels have boundaries given by differences of frontiers. This construction yields two related complexity measures: decision-boundary width, the geometric measure of a single classifier's boundary, and Urysohn width, the total frontier mass represented by a library or realization. We prove an Amortized Separation Theorem showing that approximating a boundary of width to accuracy requires a number of simple basis triples proportional to boundary width and inversely proportional to resolution, under explicit boundary-footprint assumptions. We also introduce a contrastive separation operator whose graph-cut functional consistently estimates decision-boundary width from sampled metric data, while its Laplacian spectrum certifies class-component structure and conductance. Finally, we analyze the dynamic Urysohn ladder and prove four guarantees: separability under quotient collapse, stability of committed frontiers, bounded capacity under contraction, and scalability with quotient distance. Together, these results give a metric-topological account of classification complexity, amortized inference, and compositional reuse that preserves classical computability while exposing geometric structure hidden by purely symbolic descriptions.

20.
arXiv (CS.CV) 2026-06-18

Grids Often Outperform Implicit Neural Representations at Compressing Dense Signals

Implicit Neural Representations (INRs) have recently shown impressive results, but their fundamental capacity, implicit biases, and scaling behavior remain poorly understood. We investigate the performance of diverse INRs across a suite of 2D and 3D real and synthetic signals with varying effective bandwidth, as well as both overfitting and generalization tasks including tomography, super-resolution, and denoising. By stratifying performance according to model size as well as signal type and bandwidth, our results shed light on how different INR and grid representations allocate their capacity. We find that, for many tasks involving dense signals, a simple regularized grid with interpolation trains faster and to higher or comparable quality than any INR with the same number of parameters. We also find limited settings – namely fitting binary signals such as shape contours – where INRs outperform grids, to guide future development and use of INRs towards the most advantageous applications.

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

Enhancing LLM Safety Through a Theoretical Minimax Game Lens

The rapid advancement of large language models (LLMs) necessitates effective mechanisms to ensure their responsible deployment by accurately distinguishing unsafe content from benign content. While substantial safety datasets are available in English, multilingual safety modeling remains underexplored due to limited open-source safety datasets in other languages. Even within English datasets, safe yet sensitive corner-case content is scarce, leading to shortcut learning by models and non-trivial false-positive rates. To mitigate these issues, we introduce a novel minimax reinforcement learning (RL) framework wherein a data generator and a classifier model co-evolve, facilitating the production of high-quality synthetic multilingual safety data. We theoretically formalize this interaction as a minimax game and rigorously demonstrate convergence to a Nash equilibrium. Empirical evaluations confirm that our synthetic data generation method significantly enhances the classifier model performance, enabling a substantially smaller model to surpass the state-of-the-art by nearly 10% on English benchmarks while achieving 4.5x faster inference speed. These results establish a scalable and efficient methodology for synthetic data generation, advancing the development of safer and more robust multilingual LLM deployments.

22.
arXiv (CS.AI) 2026-06-18

Fully Geometric Multi-Hop Reasoning on Knowledge Graphs with Transitive Relations

arXiv:2505.12369v2 Announce Type: replace Abstract: Multi-hop logical reasoning on knowledge graphs requires faithfully mapping the logical semantics to latent space. Current geometric embedding methods show to be useful on this task by mapping entities to geometric regions and logical operations to latent transformations. While a geometric embedding can provide a direct interpretability framework for query answering, current methods have only leveraged the geometric construction of entities, failing to map logical operations to pure geometric transformations and, instead, using neural components to learn these operations. On the other hand, purely neural-based methods outperform geometric methods, but they lack interpretability in the latent space. We introduce GeometrE, a geometric embedding method for multi-hop reasoning, that maps every logical operation to a purely geometric operation in the latent space. Additionally, we introduce a transitive loss function and show that, unlike existing methods, it can preserve the logical rule for all a,b,c: r(a,b) and r(b,c) -> r(a,c). Our experiments show that GeometrE outperforms current state-of-the-art geometric methods and remains competitive with existing neural-based methods on standard benchmark datasets.

23.
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.

24.
arXiv (CS.AI) 2026-06-15

Thinking Outside the [Chat]Box: Bridging Computer Science and Industrial Design for Cognitive-Inclusive Generative AI

arXiv:2606.14306v1 Announce Type: cross Abstract: Current Generative AI (GenAI) interfaces remain largely constrained to chatbox interaction, which can impose high cognitive demands on users and create substantial barriers for people with intellectual disabilities (ID), including prompt formulation difficulties, response overload, and limited mechanisms to assess information reliability. To explore alternative interaction models for cognitive accessibility, we conducted a cross-disciplinary co-design challenge in which two student cohorts (Computer Science and Industrial Design) developed interface concepts from the same set of functional requirements (e.g., prompt scaffolding, structured output, GUI-based refinement, transparency, and personalization). Comparing the resulting proposals reveals both convergence on foundational requirements (notably initial calibration, proactive prompting, and direct manipulation of response fragments) and complementary contributions that outline a multi-layered support system. Computer Science teams primarily produced structural scaffolding, emphasizing predictability, navigability, and trust through mechanisms such as reliability indicators, explicit sources, and context management for long conversations. Industrial Design teams emphasized experiential scaffolding, focusing on pacing, attention guidance, multimodality, and proactive agency, including step-by-step response flows, focus modes, and assistant-like integrations. We synthesize these findings into a dual-layer scaffolding framework that expands the design space for cognitively accessible GenAI interaction beyond chat-centric models and motivates future work on expert refinement, technical feasibility, and empirical validation with users with ID.

25.
bioRxiv (Bioinfo) 2026-06-14

Systematic AI-Driven Drug Repurposing via Clinical Trial Data Mining: A Framework and Six Cross-Therapeutic Case Studies.

作者:

Drug repurposing, the application of approved or shelved compounds to new therapeutic indications, offers a cost- and time-efficient alternative to de novo drug discovery. However, the systematic identification of repurposing candidates from the rapidly expanding body of clinical trial data remains a significant challenge. Here we present a publicly accessible AI-powered tool that mines the ClinicalTrials.gov registry to identify approved drugs with under-explored therapeutic potential in high-value disease areas. The tool integrates natural language processing, mechanism-of-action pathway analysis, and trial density scoring to surface candidates where biological plausibility is high and clinical trial coverage is sparse. We demonstrate the tool's utility across six cross-therapeutic case studies spanning oncology, cardiology, neurology, rare diseases, immunology, and infectious disease. Key findings include: the identification of Zonisamide as an under-explored combination candidate for obesity alongside GLP-1 receptor agonists; mechanistic validation of SGLT2 inhibitors in heart failure with preserved ejection fraction (HFpEF); and a novel cross-domain mapping of anti-TNF biologics to early-stage neurodegeneration via shared neuroinflammatory pathways. The tool is freely accessible and designed to lower the barrier for academic and industry researchers to systematically pursue repurposing opportunities.