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01.
arXiv (CS.CL) 2026-06-24

FALCON: Transforming Cyber Threat Intelligence into Deployable IDS Rules with Self-Reflection

Signature-based Intrusion Detection Systems (IDS) detect malicious activity by matching network or host events against predefined rules. Security analysts manually develop these rules from Cyber Threat Intelligence (CTI). As threats evolve, this manual pipeline faces two bottlenecks. Before authoring a new rule, an analyst must reconcile the incoming CTI with the existing rule base and determine whether to create, update, or retire one. This process is challenging due to the representational differences between the CTI and Rule formats. This gap limits the effectiveness of keyword- and embedding-based search, making rule reconciliation cognitively demanding and, in turn, contributing to "rule bloat". Second, automated verification of a new rule is inherently difficult as zero-day threats lack ground truth from simulated testing. Hence, standard metrics cannot prove that a rule semantically adheres to the CTI, and the use of LLMs leads to non-deterministic behavior. To address these challenges, we introduce FALCON, an agentic framework for CTI-grounded rule retrieval, generation, and validation. At its core, a novel CTI-Rule semantic scorer, quantifies the functional alignment between a CTI and a rule; the same signal drives a retriever that surfaces relevant deployed rules and a ground-truth-free validator that scores generated ones. Around it, a generation pipeline produces deployable rules from CTI in real time and refines them through self-reflective syntactic, semantic, and performance validators. Across network (Snort) and host-based (YARA) platforms on a purpose-built CTI-Rule dataset, FALCON attains a mean relevance of 0.72 (approx), with 84% inter-rater agreement among cybersecurity analysts, underscoring the promise of real-time security automation.

02.
arXiv (CS.AI) 2026-06-15

FAConformer: Frequency-Aware Convolutional Transformer for Auditory Attention Decoding

arXiv:2606.14120v1 Announce Type: cross Abstract: Auditory attention decoding (AAD) aims to infer the attended speaker from neural responses in multi-speaker acoustic environments and is a key problem for neuro-steered hearing systems. Although recent studies have achieved encouraging progress, existing AAD models still do not fully exploit frequency domain electroencephalography (EEG) information. In particular, most approaches introduce multi-band information through handcrafted feature extraction or direct cross-band feature concatenation, which mainly exploit frequency information at a shallow level and may overlook band-specific patterns and cross-band interactions. To address these limitations, this paper proposes FAConformer, a frequency-aware CNN-Transformer framework for AAD that explicitly integrates band-specific encoding and adaptive cross-band interaction. Specifically, FAConformer first decomposes EEG signals into multiple frequency bands and assigns each band to an independent CNN-Transformer encoder for band-specific modeling. The resulting band-wise features are then adaptively fused by a carefully designed frequency-aware attention (FAA) module that models cross-band dependencies by treating band-wise features as tokens. Further, band-wise auxiliary supervision (BAS) is introduced to prevent weakly contributing branches from being under-optimized during joint training. In this way, FAConformer performs frequency-aware modeling that more effectively exploits frequency domain information. Extensive experiments on two public AAD datasets with three decision-window lengths demonstrated that FAConformer consistently outperformed 12 competitive baselines, surpassing the current state-of-the-art model by 4.9%. Further analyses of band importance, ablation, and parameter sensitivity verify the effectiveness, robustness, and interpretability of the proposed framework. Code is available at https://github.com/wzwvv/FAConformer.

03.
arXiv (math.PR) 2026-06-16

Free energy of non-convex multi-species spin glasses with centered Ising spins

arXiv:2606.16636v1 Announce Type: new Abstract: We identify the limit free energy of all multi-species spin glasses with centered $\pm 1$ spins. The result was previously known only under a convexity assumption on the covariance function of the Hamiltonian. We also obtain a one-species reduction of the formula for balanced multi-species models.

04.
arXiv (CS.CV) 2026-06-24

Towards Fast and Effective Long Video Understanding of Multimodal Large Language Models via Adaptive Quasi-Gaussian Sampling

Long video understanding remains a daunting challenge for Multimodal Large Language Models (MLLMs) due to the excessive computation and memory footprint. Thus, keyframe selection is often adopted to mitigate this shortcoming, which however still suffers from low flexibility and high noise due to its hard sampling principle. In this paper, we define video frame selection as a problem of Quasi-Gaussian Sampling, and propose an adaptive and training-free approach termed AdaQ. Inspired by the $3$-$\sigma$ rule of Gaussian distribution, the objective of AdaQ is to achieve the optimal $3$-$\sigma$ interval for different examples, i.e., a smaller $3$-$\sigma$ interval for the local query and a larger one for the global query, thereby facilitating robust and adaptive frame sampling. To validate AdaQ, we apply it to four MLLMs with three embedding models. The extensive experimental results not only show its obvious performance gains over the default MLLMs and the SOTA keyframe selection methods, e.g., helping Qwen3-VL-8B outperform GPT4o by 15.8\% on average by using only 64 frames, but also confirm its superior robustness and high efficiency for long-video understanding, e.g., only 1 hyper-parameter needs to be set. Our code project is given at \href{https://github.com/Zkayovo-xmu/AdaQ}{https://github.com/Zkayovo-xmu/AdaQ}.

05.
arXiv (quant-ph) 2026-06-11

Unifying framework for quantum simulation algorithms for time-dependent Hamiltonian dynamics

arXiv:2411.03180v2 Announce Type: replace Abstract: Recently, there has been growing interest in simulating time-dependent Hamiltonians using quantum algorithms, driven by diverse applications, such as quantum adiabatic computing. While techniques for simulating time-independent Hamiltonian dynamics are well-established, time-dependent Hamiltonian dynamics is less explored and it is unclear how to systematically organize existing methods and to find new methods. Sambe-Howland's continuous clock elegantly transforms time-dependent Hamiltonian dynamics into time-independent Hamiltonian dynamics, which means that by taking different discretizations, existing methods for time-independent Hamiltonian dynamics can be exploited for time-dependent dynamics. In this work, we systemically investigate how Sambe-Howland's clock can serve as a unifying framework for simulating time-dependent Hamiltonian dynamics. Firstly, we demonstrate the versatility of this approach by showcasing its compatibility with analog quantum computing and digital quantum computing. Secondly, for digital quantum computers, we illustrate how this framework, combined with time-independent methods (e.g., product formulas, multi-product formulas, qDrift, and LCU-Taylor), can facilitate the development of efficient algorithms for simulating time-dependent dynamics. This framework allows us to (a) resolve the problem of finding minimum-gate time-dependent product formulas; (b) establish a unified picture of both Suzuki's and Huyghebaert and De Raedt's approaches; (c) generalize Huyghebaert and De Raedt's first and second-order formula to arbitrary orders; (d) answer an unsolved question in establishing time-dependent multi-product formulas; (e) and recover continuous qDrift on the same footing as time-independent qDrift. Thirdly, we demonstrate the efficacy of our newly developed higher-order Huyghebaert and De Raedt's algorithm through digital adiabatic simulation.

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

Multimedia and Visual Analytics in the Agentic Era

arXiv:2504.06138v3 Announce Type: replace-cross Abstract: Professional users need tools to help them gain actionable insights from large multimedia collections. Foundation models and AI agents have rapidly changed the playing field, and improving their accuracy, trustworthiness, and reasoning capabilities are active topics in the computer vision, machine learning, and multimedia communities. Most current research focuses on benchmark driven algorithmic improvements. The multimedia community is the place to go beyond algorithms and consider complete multimedia analytics systems that support professional users in their complex tasks and achieve a true teaming of humans and AI. Supporting users with machine learning and visualizations has been studied for decades in the visual analytics field. In this paper, we propose a framework to bring multimedia and visual analytics together and indicate how it could impact current and new multimedia analytics solutions. Additional information can be found at https://staff.fnwi.uva.nl/m.worring/analytics-model.html

07.
arXiv (CS.LG) 2026-06-11

Momentum LMS Theory beyond Stationarity: Stability, Tracking, and Regret

arXiv:2602.11995v2 Announce Type: replace Abstract: In large-scale data processing scenarios, data often arrive in sequential streams generated by complex systems that exhibit drifting distributions and time-varying system parameters. This nonstationarity challenges theoretical analysis, as it violates classical assumptions of i.i.d. (independent and identically distributed) samples, necessitating algorithms capable of real-time updates without expensive retraining. An effective approach should process each sample in a single pass, while maintaining computational and memory complexities independent of the data stream length. Motivated by these challenges, this paper investigates the Momentum Least Mean Squares (MLMS) algorithm as an adaptive identification tool, leveraging its computational simplicity and online processing capabilities. Theoretically, we derive tracking performance and regret bounds for the MLMS in time-varying stochastic linear systems under various practical conditions. Unlike classical LMS, whose stability can be characterized by first-order random vector difference equations, MLMS introduces an additional dynamical state due to momentum, leading to second-order time-varying random vector difference equations whose stability analysis hinges on more complicated products of random matrices, which poses a substantially challenging problem to resolve. Experiments on synthetic and real-world data streams demonstrate that MLMS achieves rapid adaptation and robust tracking, in agreement with our theoretical results especially in nonstationary settings, highlighting its promise for modern streaming and online learning applications.

09.
arXiv (math.PR) 2026-06-19

On creating convexity in high dimensions

arXiv:2502.10382v3 Announce Type: replace-cross Abstract: Given a subset $A$ of $\mathbb{R}^n$, we define \begin{align*} \mathrm{conv}_k(A) := \left\{ \lambda_1 s_1 + \cdots + \lambda_k s_k : \lambda_i \in [0,1], \sum_{i=1}^k \lambda_i = 1 , s_i \in A \right\} \end{align*} to be the set of vectors in $\mathbb{R}^n$ that can be written as a $k$-fold convex combination of vectors in $A$. Let $\gamma_n$ denote the standard Gaussian measure on $\mathbb{R}^n$. We show that for every $\varepsilon > 0$, there exists a subset $A$ of $\mathbb{R}^n$ with Gaussian measure $\gamma_n(A) \geq 1- \varepsilon$ such that for all $k = O_\varepsilon(\sqrt{\log \log(n)})$, $\mathrm{conv}_k(A)$ contains no convex set $K$ of Gaussian measure $\gamma_n(K) \geq \varepsilon$. This result acts as a complement to the recent affirmative resolution of Talagrand's convexity conjecture by Hua, Song, and Tudose, which states that a universal dilation of the threefold Minkowski sum $A+A+A$ of a large set $A$ guarantees a large convex subset. Our approach utilises concentration properties of random copulas and the application of optimal transport techniques to the empirical coordinate measures of vectors in high dimensions.

10.
arXiv (CS.AI) 2026-06-24

Scaling Laws for Task-Specific LLM Distillation

arXiv:2606.24747v1 Announce Type: new Abstract: Large Language Models (LLMs) achieve strong performance across a growing range of domains, yet their scale poses deployment challenges in applications where latency and cost constraints are critical. This paper derives empirical scaling laws for domain-specific LLM compression, quantifying how in-domain and general knowledge performance scale with dataset size, compression ratio, supervision format, and iterative pruning schedule. Using quantitative finance as our application domain, we compare logit-based and LoRA-based distillation under iterative structural pruning, introducing a blended chain-of-thought supervision loss that stabilizes KL-divergence distillation over reasoning traces. In-domain task quality degrades predictably under compression while general-knowledge benchmarks collapse well before the same point; supervision format is the key driver of this tradeoff, with chain-of-thought supervision actively recovering general knowledge that pruning erases. We release the headline dataset FinHeadlineMix, scaling law results, and practical recommendations to provide a reusable framework for domain-specific compression decisions.

11.
arXiv (CS.LG) 2026-06-19

Variational Consensus Monte Carlo for Bayesian Mixture

arXiv:2606.19643v1 Announce Type: cross Abstract: Motivated by the privacy, sensitivity and sharing limitations of health data, we present a comprehensive pipeline for inference of Bayesian mixture models within a federated learning setting, i.e. when data cannot be fully shared or pooled across compute nodes. We adopt a Consensus Monte Carlo (CMC) approach, in which an MCMC algorithm is run independently within each data silo to estimate local posterior distributions, which are then aggregated to approximate the posterior over the full data. The variational CMC approach of Rabinovich, Angelino and Jordan (2015) [1] frames the aggregation step as a variational inference problem, but their application to mixtures assumes the number of clusters and key mixture parameters to be known. Our main methodological contributions are: (i) an extension of variational CMC to over-fitted Bayesian mixture models that infer the number of clusters and all model parameters, without requiring conjugacy; (ii) novel cluster-matching algorithms suitable for cross-silo settings in which not every cluster appears in each local dataset; (iii) a number of inference strategies for the aggregation step, matched to different federated learning constraints; and (iv) guidelines for choosing among these in practice. A comprehensive simulation study validates the framework and allows us to compare to state-of-the-art federated learning alternatives. Notably, we show that when the composition of local datasets reflects the underlying clustering structure in the data, our approach can recover small clusters with greater accuracy than standard MCMC applied to the pooled data. We illustrate the framework on large-scale electronic health record data, identifying multi-morbidity patterns in a British geriatric population.

12.
arXiv (CS.AI) 2026-06-16

Closing the Auto-Research Loop: An AI Co-Scientist for Production Search Ranking

arXiv:2603.22376v2 Announce Type: replace-cross Abstract: We present an AI Co-Scientist framework that closes the research loop for the production search-ranking system of a large online travel platform – pairing LLM agents with direct cloud-compute access so that idea generation, code implementation, GPU experimentation, and result analysis iterate end-to-end with a human scientist in the loop. The framework uses a hybrid agent architecture: single-LLM agents handle routine work, while multi-LLM consensus (GPT-5.2, Gemini Pro 3, Claude Opus 4.5) is invoked for higher-stakes decisions. On the production ranking task, a human-designed transformer baseline (V2) yielded $+0.118\%$ over a pre-transformer baseline (V1); the AI Co-Scientist's automated loop on top of V2 contributed an additional $+0.083\%$, for a combined $+0.201\%$ offline gain delivered in roughly one extra week of wall-clock time (single-run numbers; statistical limits discussed in the paper). The most useful AI proposals – unified long-sequence layouts, slot-type embeddings, and multi-phase learning-rate schedules – are standard practice in NLP and Vision but were absent from our production stack, suggesting that LLM agents can serve as cross-disciplinary connectors for ranking teams. We also report deployment context, negative results, and lessons learned.

13.
arXiv (CS.AI) 2026-06-12

Equivariant Flow Matching for Symmetry-Breaking Bifurcation Problems

arXiv:2509.03340v4 Announce Type: replace-cross Abstract: Bifurcation phenomena in nonlinear dynamical systems often lead to multiple coexisting stable solutions, particularly in the presence of symmetry breaking. Deterministic machine learning models are unable to capture this multiplicity, averaging over solutions and failing to represent lower-symmetry outcomes. In this work, we formalize the use of generative AI, specifically flow matching, as a principled way to model the full probability distribution over bifurcation outcomes. Our approach builds on existing techniques by combining flow matching with equivariant architectures and an optimal-transport-based coupling mechanism. We generalize equivariant flow matching to a symmetric coupling strategy that aligns predicted and target outputs under group actions, allowing accurate learning in equivariant settings. We validate our approach on a range of systems, from simple conceptual systems to physical problems such as buckling beams and the Allen–Cahn equation. The results demonstrate that the approach accurately captures multimodal distributions and symmetry-breaking bifurcations. Moreover, our results demonstrate that flow matching significantly outperforms non-probabilistic and variational methods. This offers a principled and scalable solution for modeling multistability in high-dimensional systems.

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

Rethinking Cross-lingual Gaps from a Statistical Viewpoint

Any piece of knowledge is usually expressed in one or a handful of natural languages on the web or in any large corpus. Large Language Models (LLMs) act as a bridge by acquiring knowledge from a source language and making it accessible when queried using target languages. A cross-lingual gap is a drop in accuracy incurred when querying knowledge in a target language rather than the source language. Existing research focused on modeling or training failures leading to cross-lingual gaps. In this work, we take an alternative view to characterize the nature of cross-lingual error, and hypothesize that the variance of responses in the target language is a key cause of this gap. For the first time, we formalize the cross-lingual gap in terms of biased and unbiased errors. We empirically validate our hypothesis through multiple inference-time interventions that control variance and reduce the cross-lingual gap. We demonstrate a few test-time ensemble methods that reduce response variance, and thereby improve source-target transfer scores by up to 12 absolute points yielding relative gains of 8% to over 50% across various LLMs.

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

GOOSE-M2F: Adapting Mask2Former for High-Fidelity, Long-Tailed Fine-Grained Semantic Segmentation in Unstructured Outdoor Terrain

We present GOOSE-M2F, a task-specific adaptation of Mask2Former for the GOOSE 2D Fine-Grained Semantic Segmentation (FGSS) Challenge at ICRA~2026. The GOOSE benchmark spans 64 fine-grained classes across unstructured outdoor terrain with a severely long-tailed distribution, where rare classes occupy fewer than 50 pixels per image. We extend the Swin-Large Mask2Former baseline with three targeted contributions: (1)200 Object Queries to eliminate representational saturation; (2)a Feature Refinement Module (FRM) combining ASPP-lite and CBAM dual-attention; and (3)an Auxiliary Supervision Head that delivers direct per-pixel gradients for rare classes. A multi-stage training strategy pairs Distribution-Balanced loss, Rare-Class Copy-Paste augmentation, dynamic IoU-aware re-weighting, and EMA. At inference, a dense sliding-window engine with 2D Gaussian kernel blending and 4-scale TTA adds +10.57\%. GOOSE-M2F achieves 70.08\% Official Composite mIoU (63.55\% fine, 76.61\% coarse), placing 3rd on the GOOSE 2D FGSS leaderboard. Code and trained models are publicly available at: \href{https://github.com/Aditya-Lingam-9000/GOOSE-M2F}{Github GOOSE-M2F Code} and \href{https://huggingface.co/XYZ9843/GOOSE-M2F}{Hugging Face GOOSE-M2F}.

16.
arXiv (quant-ph) 2026-06-24

Coherence-gated quantum devices via real-time weak measurement

Authors:

arXiv:2604.18662v3 Announce Type: replace Abstract: Single-photon routers in cavity and circuit QED direct photons by the qubit's energy eigenstate – a projective decision that destroys coherence. We propose a different primitive: coherence-gated routing, where the decision depends on the magnitude of the qubit's quantum coherence, estimated in real time from simultaneous weak measurements of $\sigma_x$ and $\sigma_z$. A photon is accepted if the coherence score $S(T) = \sqrt{\langle\sigma_x\rangle_c^2 + \langle\sigma_y\rangle_c^2}$, extracted from the conditional density matrix via the stochastic master equation, exceeds a tunable threshold $S_{\mathrm{th}}$. Certifying coherence at emission enables two applications conventional heralded sources cannot: (i) a quantum random number generator with min-entropy bounded by Bloch-sphere geometry, $H_\infty \geq -\log_2\!\bigl(\frac{1+\sqrt{1-S_{\mathrm{th}}^2}}{2}\bigr)$, and (ii) a phase-tracked photon source whose two-node coherence certification bounds the matter-matter entanglement fidelity after Bell-state measurement. The estimator is itself a security primitive. Benchmarking seven configurations, we find that underestimating detector efficiency ($\eta_{\mathrm{a}} < \eta_{\mathrm{true}}$) both stabilizes the numerics and suppresses overcertification. We trace this via a purity-monotonicity result, identify a geometric loophole amplifying purity undercertification into coherence overcertification by an order of magnitude ($\sim$40$\times$), and prove two complementary tail bounds: an Ornstein-Uhlenbeck comparison giving $4.5\%$ raw overcertification (empirical $3.7\%$ from $10^6$ trajectories) and an exponential supermartingale establishing structural exponential decay.

17.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

18.
bioRxiv (Bioinfo) 2026-06-23

VCBench: A Multi-Dimensional Benchmark for Single-Cell Foundation Models

Single-cell foundation models are increasingly positioned as virtual cells, yet their capabilities are assessed by fragmented, largely single-task benchmarks that obscure where these models improve on simple baselines. VCBench addresses this by synthesizing four independent virtual-cell frameworks into seven capability dimensions: perturbation response prediction, cross-species universality, gene regulatory network (GRN) inference, modality integration, temporal dynamics, multi-scale integration, and in silico experimentation. Each dimension is assessed for operational testability under current architectures and datasets: five admit direct or proxy evaluation, while multi-scale integration and in silico experimentation are structurally untestable as end-to-end tasks. We evaluate five foundation models (Geneformer, scGPT, UCE, TranscriptFormer, Arc State) against pre-registered linear and nearest-neighbor baselines across the five testable dimensions, and report three findings. First, the baselines match or exceed every foundation model on four of the five scored dimensions, replicating the reported competitiveness of linear baselines on perturbation prediction and extending it to cross-species transfer, GRN inference, and temporal ordering. Second, TranscriptFormer alone exceeds the strongest baseline on cross-modal RNA-to-protein prediction (53% Pearson improvement, with a documented contamination caveat) and is the only model to reach Level 2 in the pre-registered Virtual Cell (VC) Level rubric; the architectural choice behind this advantage simultaneously causes a spectral collapse that destroys its temporal-ordering performance, a tradeoff invisible to single-task benchmarks. Third, no foundation model publishes a complete cell-level training manifest, leaving data contamination undetectable to users. Alongside the benchmark, VCBench releases a Contamination Reporting Schema and contributes two further methodological tools: a common-label-set protocol that controls for class-count confounds in cross-species transfer, and a spread-error correlation probe for epistemic calibration.

19.
arXiv (CS.AI) 2026-06-24

Evolving Programmatic Skill Networks

arXiv:2601.03509v2 Announce Type: replace Abstract: We study continual skill acquisition in open-ended embodied environments where an agent must construct, refine, and reuse an expanding library of executable skills. We introduce the Programmatic Skill Network (PSN), a framework in which skills are executable symbolic programs forming a compositional network that evolves through experience. PSN defines three core mechanisms instantiated via large language models: (1)~\opreflect for structured fault localization over skill compositions, (2)~progressive optimization with maturity-aware update gating that stabilizes reliable skills while maintaining plasticity for uncertain ones, and (3)~canonical structural refactoring under rollback validation that maintains network compactness. We further show that PSN's learning dynamics exhibit structural parallels to neural network training. Experiments on MineDojo and Crafter demonstrate robust skill reuse, rapid adaptation, and strong generalization across open-ended task distributions.

20.
arXiv (CS.AI) 2026-06-11

Position: Hippocampal Explicit Memory Is the Cornerstone for AGI

Authors:

arXiv:2606.11245v1 Announce Type: new Abstract: Large Language Models (LLMs) have demonstrated remarkable capabilities across various tasks, raising expectations for Artificial General Intelligence (AGI). This position paper argues that integrating explicit memory is the cornerstone for advancing LLMs toward AGI. The key reason is that the underlying learning mechanism of LLMs is highly analogous to human implicit memory. However, higher-order cognitive functions necessary for AGI, such as long-term strategic planning, metacognition, and symbolic reasoning, heavily rely on hippocampal explicit memory and cannot arise solely from implicit statistical learning. Drawing on findings from neuroscience, I advance this perspective and complement it with computational requirements for artificial explicit memory systems, hoping to foster further research and lay the groundwork for explicit memory integration.

22.
bioRxiv (Bioinfo) 2026-06-19

HTS-Oracle v2: Prospective AI-Guided Discovery and Experimental Validation of Small Molecule Modulators Across Multiple Targets

High-throughput screening (HTS) remains the cornerstone of early-phase small molecule discovery yet consistently underperforms against immunotherapy targets, yielding validated hit rates below 0.1%. Here we introduce HTS-Oracle v2, which features rigorous cross-validation that ensures honest performance estimates. HTS-Oracle v2 was trained and validated across four clinically significant immune checkpoint targets (CD28, ICOS, LAG-3, and TIGIT) achieving ROC-AUC values of 0.968, 0.969, 0.875, 0.928 respectively under rigorous cross-validation. For prospective experimental validation, HTS-Oracle v2 was applied to an 8,960-compound Enamine Protein Mimetic Library, selecting only 25 compounds per target for experimental testing using temperature-related intensity change (TRIC) technology, a 99.7% reduction in screening burden. HTS-Oracle v2 identified 4, 5, 4, and 6 validated binders from 25 prospectively selected compounds per target, corresponding to validated hit rates of 16%, 20%, 16%, and 24%, respectively. Notably, 67-80% of all experimentally confirmed hits across the full 8,960-compound library were captured within just 25 model-selected compounds per target. For CD28, this represents a 28-fold improvement over HTS-Oracle v1 (239x versus 8.4x), establishing HTS-Oracle v2 as an efficient platform for AI-guided prospective hit discovery across immunotherapy targets.

23.
arXiv (CS.AI) 2026-06-16

Edu-Theater: A Data-Efficient Agent Framework for Scalable Learner Behavior Simulation through Staging Roll-Call

arXiv:2606.15225v1 Announce Type: cross Abstract: Large-scale learner-task interaction data are crucial for intelligent educational systems but are costly to collect and constrained by privacy and learner engagement. Learner simulators play a critical role in simulating scalable learner behavior without the need for continuous involvement of real learners. However, existing methods are predominantly individual-centric, pairing a simulator with each learner to iteratively infer latent knowledge states from dense interaction histories, which is both data- and computation-intensive, and fragile in cold-start scenarios. We propose a cohort-aware roll-call simulation paradigm that first constructs cohort-level proficiency priors and refines individual learner states through a small number of targeted diagnostic queries. Based on this paradigm, we introduce Edu-Theater, an LLM-powered agent system that performs cohort-aware learner simulation via a teacher agent and retrospective roll-call probing over learner logs. Edu-Theater enables scalable future behavior simulation without the need for dense per-learner histories. Experiments on two real-world datasets demonstrate that Edu-Theater achieves higher simulation accuracy with significantly fewer LLM calls, producing synthetic data that enhances downstream applications such as adaptive testing.

24.
arXiv (CS.AI) 2026-06-12

Definitional alignment before capability alignment: a Design-Science framework for adjudicating claims about AGI

arXiv:2606.12713v1 Announce Type: new Abstract: Claims that artificial general intelligence has already arrived and claims that it remains decades away are often defended from overlapping evidence. "AGI" lacks a single shared and stable referent and competing operationalizations can return different verdicts on the same system. This article treats that under-specification as a design and governance problem. Following Design Science Research Methodology, it develops DAF-AGI, a second-order conceptual artifact with two coupled components: five ordinal criteria for assessing the adjudicative fitness of candidate definitions and a structured governance audit of authorship, interest, certification, external verification and revision authority. The artifact is demonstrated on five prominent measurement families and one deflationary boundary position in a documented corpus and then stress-tested against a stylized strong arrival claim: that current generative systems constitute AGI because they outperform a well-educated adult on many cognitive tasks. On evidence from the cited 2024-2025 sources, the claim was certifiable only under a performance-based operationalization; capability-ontology, psychometric and skill-acquisition approaches did not certify it, the economic family remains indeterminate and the deflationary position refuses binary adjudication. The contribution is a novel integration and operationalization, not an empirical validation: independent application, inter-rater testing and author-external cases remain necessary. The paper further proposes definitional sovereignty as an enabling component of algorithmic sovereignty: the institutional capacity to contest, certify and revise imported technological categories under public accountability.

25.
bioRxiv (Bioinfo) 2026-06-17

DesignMaster: A Multi-Conditional Diffusion Framework for Rational PROTAC Design

Motivation: Proteolysis-targeting chimeras (PROTACs) enable targeted protein degradation through ternary complex formation with E3 ubiquitin ligase. However, the rational design of PROTACs remains highly challenging due to limited structure-activity relationship data and the vast conformational diversity of linkers. Existing computational approaches can be broadly divided into structure-based ternary modelling methods and fragment-based linker generation models. Although these approaches have advanced PROTAC design, they typically neglect key physicochemical constraints and linker-length control during the generation process, causing the generated PROTACs to lack balanced structural properties required for effective ternary complex formation with drug-like characteristics. Results: To address these limitations, we propose DesignMaster, a diffusion-based generative framework that explicitly incorporates linker length and physicochemical properties as controllable conditioning signals. DesignMaster employs an E(3)-equivariant graph Transformer with a gated multi-condition fusion module to inject linker length and physicochemical constraints throughout the diffusion process, enabling fine-grained and constraint-aware molecular generation. Experiments on PROTAC-DB 2.0 and 3.0 demonstrate that DesignMaster outperforms state-of-the-art baselines, with a 3.2% improvement in validity and a 34.4% improvement in recovery. The Case study shows DesignMaster achieves a 51.78% reduction in RMSD when predicting the linker of PROTAC BCPyr targeting 6W7O, highlighting its potential for practical structure-guided PROTAC design. Availability: The source code and datasets are available at https://github.com/ABILiLab/DesignMaster.