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

Constrained Variable Projection for Structured Problems

arXiv:2606.23939v1 Announce Type: cross Abstract: Variable projection is a classical technique for separable nonlinear least-squares problems, in which variables that enter linearly are eliminated exactly, yielding a reduced nonlinear problem. By expressing this framework as a particular instance of a broader class of bilevel optimization problems, we develop a constrained variable-projection framework for data-science models, where the remaining variables are subject to convex constraints and the eliminated variables arise from a lower-level least-squares problem. In particular, by interpreting variable projection as a collapsed bilevel optimization problem, we derive exact reduced-gradient formulas compatible with automatic differentiation and propose a conditional-gradient algorithm for the resulting constrained reduced problem. We establish convergence guarantees under standard smoothness and compactness assumptions, and discuss extensions to structured lower-level variables. Numerical experiments on sparse autoencoding, dictionary learning, blind deconvolution, and few-shot learning suggest that the method can improve wall-clock efficiency and data efficiency relative to natural joint-optimization baselines.

02.
bioRxiv (Bioinfo) 2026-06-23

Model-based inference of gene expression noise from single-cell RNA-sequencing data

The heterogeneity of expression levels among genetically identical cells, termed gene expression noise, is a property of the gene expression process whose importance in the biology of organisms and their evolution is increasingly recognized. Measuring gene expression noise requires single-cell expression data, as obtained from single-cell RNA sequencing (scRNASeq). Its estimation, however, is challenging owing to (i) the presence of technical noise in addition to biological noise, and (ii) the heterogeneity of cell types in the sampled population. We propose a maximum-likelihood framework to infer biological noise from scRNASeq data, while accounting for technical noise, dropout probabilities, and distinct cell sequencing depths. We demonstrate the parameter identifiability using simulations and that the resulting noise estimates are uncorrelated from the mean gene expression, and therefore do not need extra correction in downstream analyses, easing intra- and inter- genome comparisons. Using two technical replicates of scRNASeq data from the wild yeast *Saccharomyces paradoxus*, we show that expression noise can be inferred in a reproducible manner.

03.
arXiv (quant-ph) 2026-06-15

Dissipation-induced superradiance in matter coupled to a self-interacting cavity

arXiv:2606.14526v1 Announce Type: new Abstract: Light-matter interactions are often modeled via the Dicke model, namely, by two-level systems coupled to a cavity mode. Alas, the threshold for superradiance is often experimentally inaccessible or hindered by light's diamagnetic term. Here, within the Dicke setting, we consider self-interacting light in a cavity, modeled by a photonic Kerr nonlinearity. We show that negative Kerr nonlinearity gives rise to a low-threshold superradiant phase with spin inversion. While unstable in a closed system, cavity dissipation stabilizes this lit phase, opening avenues for lasing and bath-engineered phases.

04.
arXiv (quant-ph) 2026-06-12

Coulomb crystallization of xenon highly charged ions in a laser-cooled Ca+ matrix

arXiv:2512.12266v2 Announce Type: replace-cross Abstract: We report on the sympathetic cooling and Coulomb crystallization of xenon highly charged ions (HCIs) with laser-cooled Ca$^+$ ions. The HCIs are produced in a compact electron beam ion trap, then charge selected, decelerated, and finally injected into a cryogenic linear Paul trap. There, they are captured into $^{40}$Ca$^+$ Coulomb crystals, and co-crystallized within them, causing dark voids in their fluorescence images. Fine control over the number of trapped ions and HCIs allows us to realize mixed-species crystals with arbitrary ordering patterns. By investigating Xe$^{q+}$–Ca$^+$ strings, we confirm the HCI charge states, measure their lifetime and characterize the mixed-species motional modes. Our system effectively combines the established quantum control toolbox for Ca$^+$ with the rich set of atomic properties of Xe highly charged ions, providing a resourceful platform for optical frequency metrology, searches for signatures of new physics, and quantum information science.

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

Generativism: Toward a Learning Theory for the Age of Generative Artificial Intelligence

arXiv:2606.12441v1 Announce Type: cross Abstract: The four dominant learning theories of behaviorism, cognitivism, constructivism, and connectivism show significant conceptual limitations as generative artificial intelligence (AI) proliferates in educational settings. These frameworks were formulated before the emergence of AI systems capable of generating, synthesizing, and reasoning about knowledge. This article critically examines each learning theory and identifies assumptions challenged by generative AI's affordances. Drawing on research in distributed cognition, extended mind, human-AI collaboration, AI literacy, cognitive offloading, and metacognition, the article proposes Generativism as a learning theory for the generative AI age. Generativism posits that learning increasingly occurs through the iterative co-construction of knowledge between human learners and AI systems. The proposed framework is organized around four principles: epistemic partnership, distributed agency, generative literacy, and adaptive metacognition. The framework offers a foundation for rethinking instructional design, learning, assessment, and expertise development in contexts where generative AI plays an integral role in cognition.

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

Imitating What Works: Simulation-Filtered Modular Policy Learning from Human Videos

The ability to learn manipulation skills by watching videos of humans has the potential to unlock a new source of highly scalable data for robot learning. Here, we tackle prehensile manipulation, in which tasks involve grasping an object before performing various post-grasp motions. Human videos offer strong signals for learning the post-grasp motions, but they are less useful for learning the prerequisite grasping behaviors, especially for robots without human-like hands. A promising way forward is to use a modular policy design, leveraging a dedicated grasp generator to produce stable grasps. However, arbitrary stable grasps are often not task-compatible, hindering the robot's ability to perform the desired downstream motion. To address this challenge, we present Perceive-Simulate-Imitate (PSI), a framework for training a modular manipulation policy using human video motion data processed by paired grasp-trajectory filtering in simulation. This simulation step extends the trajectory data with grasp suitability labels, which allows for supervised learning of task-oriented grasping capabilities. We show through real-world experiments that our framework can be used to learn precise manipulation skills efficiently without any robot data, resulting in significantly more robust performance than using a grasp generator naively.

07.
arXiv (CS.AI) 2026-06-12

Humor Style Drives Laughter, Topic Shapes Acceptability: Evaluating Bilingual Personal and Political Robot-Delivered AI Jokes

arXiv:2606.13256v1 Announce Type: cross Abstract: Humor plays a central role in human social relationships, and recent advances in computational humor create new opportunities for integrating humor into human-robot interaction (HRI). While large language models (LLMs) can generate diverse forms of humor, it remains unclear how humor style, joke content, and language preference shape perceptions of robot-delivered humor in group settings. In this exploratory study, we employed a mixed factorial design in which participants evaluated AI-generated jokes delivered by a robot in a university classroom. We examined the effects of humor type (Affiliative, Self-Enhancing, Aggressive, Self-Defeating) and joke content (person-related vs. political) on perceived funniness and appropriateness, as well as preferred language. Results show that humor type significantly influences funniness, with Aggressive and Affiliative humor rated higher, while joke content primarily affects appropriateness, with person-related jokes preferred over political ones. Language preference was shaped by both joke content and participants' self-reported fluency and humor practices.

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

Beyond Text-to-SQL: An Agentic LLM System for Governed Enterprise Analytics APIs

Enterprise analytics aims to make organizational data accessible for decision-making, yet non-technical users still face barriers when using traditional business intelligence tools or Text-to-SQL systems. While recent Text-to-SQL approaches based on Large Language Models (LLMs) promise natural language access to structured data, they fall short in enterprise settings where analytics pipelines rely on governed APIs rather than raw databases. In practice, these APIs encapsulate complex business logic to ensure consistency, auditability, and security. However, delegating mathematical or aggregation logic to an LLM introduces reliability and compliance risks. To this end, we present Analytic Agent, an LLM-based agentic system that translates natural language intents into secure interactions with enterprise analytics APIs. Evaluated on 90 real enterprise use cases constructed by domain experts, it reliably interprets user goals, validates permissions, executes governed queries, and generates compliant visualizations through multi-step reasoning and policy-aware orchestration.

09.
arXiv (CS.CV) 2026-06-16

CEVAR: Centerline Embedding Extraction for Endovascular Aneurysm Repair

Long-term mortality rates after endovascular aneurysm repair (EVAR) remain elevated due to post-EVAR rupture caused by loss of seal in stent graft sealing zones. Structured CT review using centerline measurements improves detection, but current workflows require manual centerline editing and expert operators. We propose a transformer framework for automated, protocol-driven sealing zone assessment that combines 3D centerline tracking with embedding-based geometric prediction. Two state-of-the-art image-to-graph models are evaluated for aorto-iliac centerline extraction from follow-up CT and for measurement of stent position, vessel diameters, and seal lengths according to EVAR4C protocol. Across the full test set and a challenging no-contrast subset, the proposed fully automatic method outperforms the commercial semi-automatic workflow.

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

Navigating Gigapixel Pathology Images with Large Multimodal Models

Recent advances in large multimodal models have allowed for the development of interactive chat models that can converse and reason about pathology whole-slide images (WSIs). However, existing slide-level chat systems are often highly specialized, typically compressing WSIs into fixed slide-level embeddings or relying on multi-component pipelines, which can lose multi-scale detail and limit generalizability beyond the target task. We present GIANT (Gigapixel Image Agent for Navigating Tissue), a simple, training-free approach that lets general-purpose multimodal models navigate WSIs on their own, iteratively selecting multi-magnification crops and aggregating evidence over time. To evaluate generalizability in WSI question answering and to promote reproducibility, we introduce MultiPathQA, a benchmark suite spanning five clinical challenges and 934 questions over 868 unique WSIs. This includes a new set of 128 pathologist-authored multiple-choice questions designed to mirror real diagnostic search and multi-scale reasoning. Using GPT-5, GIANT outperforms models specialized for pathology question answering, achieving state-of-the-art performance on four out of five benchmarks.

12.
arXiv (CS.CV) 2026-06-25

PolicyTrim: Boosting Intrinsic Policy Efficiency of Vision-Language-Action Models

Vision-Language-Action (VLA) models provide a unified paradigm for robotic manipulation, yet their real-world deployment is often bottlenecked by execution efficiency. While existing efforts predominantly focus on compute-centric efficiency to reduce per-step inference latency, the intrinsic policy efficiency of these models remains largely unexplored. Policy efficiency is fundamentally affected by two factors, namely the effective executable length of predicted action chunks and the total physical steps required to complete a task. These two factors jointly determine the total number of forward inference calls during execution. We observe that current VLA policies struggle with planning unreliability and action redundancy, suffering from severe prediction degradation at the tail of action chunks and tending to generate unnecessarily redundant physical steps. To address this, we propose PolicyTrim, a reinforcement learning-based post-training framework that extends the reliable action chunk length and reduces redundant physical steps. For reliable chunk extension, we employ a dynamic exploration strategy that explicitly rewards the successful completion of longer executable lengths, progressively pushing the trustworthy prediction horizon to its empirical limit. For step efficiency, we design a redundancy-aware reward that directly favors successful task completions with fewer steps while penalizing unreproducible shortcuts, effectively eliminating redundant physical actions. Extensive experiments across three benchmarks and three VLA models demonstrate that PolicyTrim improves action chunk utilization by 3$\times$ and reduces physical execution steps by 51.4\%. Ultimately, our framework delivers up to a 5.83$\times$ end-to-end deployment speedup without compromising task success rates.

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

Physics-Informed Neural Networks and Radial Basis Functions for PDEs with Dirac Delta Sources

arXiv:2606.12735v1 Announce Type: new Abstract: Physics-Informed Neural Networks (PINNs) are a machine learning method for solving forward and inverse Partial Differential Equations (PDEs). When applied to PDEs with Dirac delta functions in the forcing terms, boundary conditions, or initial conditions, PINNs require approximating them with smooth surrogate functions, a practice that can introduce significant modeling errors. In this work, we exploit the interpretation of PINNs as Residual Least Squares (RLS) methods and show that this perspective enables direct treatment of Dirac delta terms by integrating the weak-form equation. Among RLS formulations other than PINN, we focus on the Radial Basis Function (RBF) expansion (also known as a single-layer RBF Network). We show that while integrating out the Dirac delta in PINNs causes residuals to fail to converge to zero, RBF-RLS consistently provides good forward and inverse solutions to transport problems. We explain this finding using the Neural Tangent Kernel (NTK) theory. We test both approaches on linear PDEs that represent groundwater flow and transport in porous media and rivers. We solve inverse problems to fit synthetic data, noisy synthetic data, and real-world measurements.

14.
arXiv (CS.AI) 2026-06-25

Semantic Consistency Policy Optimization for Reinforcement Learning of LLM Agents

arXiv:2606.25852v1 Announce Type: cross Abstract: Group-based reinforcement learning effectively post-trains LLM agents for long-horizon, sparse-reward tasks by deriving step-level credit from trajectory outcomes. However, this ties a step's credit to its rollout's final outcome: semantically near-identical intermediate steps receive opposite credit depending on whether their trajectory eventually succeeded or failed. Such semantic credit inconsistency sends conflicting gradients to similar actions and wastes the partially-correct progress inside failed rollouts. Motivated by this, we propose Semantic Consistency Policy Optimization (SCPO), a value-free reward-shaping method that mitigates this inconsistency by recovering step-level credit from successful siblings in the same rollout group. Concretely, SCPO scores each failed step against a successful sibling and adds positive step-level credit for new progress along that sibling. On ALFWorld and WebShop, SCPO matches or exceeds strong group-based baselines, reaching 93.7+/-4.1 percent success on ALFWorld and 74.8+/-2.0 percent on WebShop at 1.5B parameters, with gains concentrated on the hardest multi-step tasks.

15.
arXiv (math.PR) 2026-06-16

Pathwise structure of the three-dimensional attractive one-point interaction diffusion

作者:

arXiv:2606.08008v2 Announce Type: replace Abstract: We study the pathwise behavior of the three-dimensional attractive one-point interaction diffusion whose law was constructed by Cranston, Koralov, Molchanov and Vainberg, corresponding to the singular Schrödinger Hamiltonian \[ \frac12\Delta+\frac{\beta}{2}\delta_0, \qquad \beta>0. \] We identify a local stochastic differential equation satisfied by the process away from the origin and use it to construct a natural submartingale whose increasing component in the Doob-Meyer decomposition is supported on the set of times at which the process visits the origin. In particular, we show that the process visits the origin with positive probability and that the law conditioned on avoiding the origin is three-dimensional Wiener measure.

17.
arXiv (CS.CL) 2026-06-16

Do Safety Monitors Stay Reliable After an Update? Benchmarking and Predicting Activation-Monitor Staleness

作者:

Activation monitors-lightweight probes trained on a language model's internal representations-are an increasingly common layer in deployment safety stacks. Deployed models however are rarely static: they are quantized, fine-tuned, adapted with LoRA, or served with merged adapters while the monitor remains frozen. We present the first systematic test of whether this implicit contract holds: whether activation monitors trained on a base model remain reliable after these routine model updates. Across multiple safety-relevant monitors, model depths, update families, and open-weight models, we find a sharp split: quantization-style updates largely preserve frozen probe performance, while fine-tuning-style updates frequently make probes stale. Fragility is highly monitor-dependent, with privacy/PII probes most affected and refusal-compliance probes comparatively stable, showing that retraining a behavior need not stale its corresponding monitor. QLoRA is especially damaging despite NF4 quantization alone being relatively benign, suggesting that quantization becomes riskier when combined with adaptation. We further show that degradation is predictable from pre-deployment features, enabling revalidation budgets to be triaged toward the monitors most likely to fail. These results suggest that fine-tuning should trigger activation-monitor revalidation by default, while prediction can help prioritize which monitors to check first.

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

Stochastic Thermodynamics and SDE-based Generative Models

作者:

arXiv:2606.18290v1 Announce Type: cross Abstract: SDE-based generative models, including diffusion models and the Schrödinger bridge, have found broad applications in signal processing tasks such as speech enhancement, image restoration, and time-series generation. This note presents a modeling framework for such models within the context of stochastic thermodynamics. The main results of this note are trajectory-level definitions of work, heat, and entropy production, along with a generalized Jarzynski identity and a second-law-like inequality. The proposed framework extends the original Jarzynski setup to accommodate time-dependent bath temperature and nonconservative driving forces. This thermodynamic perspective may deepen our understanding of diffusion models and the Schrödinger bridge from a nonequilibrium statistical mechanics viewpoint.

19.
medRxiv (Medicine) 2026-06-11

Maternal deaths associated factors in the Conflict-Affected North West Region of Cameroon. Lessons from a cross-sectional survey

Background Maternal mortality is a significant global public health crisis, particularly in sub-Saharan Africa and conflict-affected regions. Cameroon's maternal mortality ratio is high at 406 deaths per 100,000 live births, while the ongoing Anglophone conflict has further exacerbated maternal healthcare delivery in the North West Region (NWR){middle dot} Despite the evidence-based interventions like partographs, obstetric kits, birth preparedness plans, and active management of the third stage of labour, implementation gaps persist across health facilities. Objective The study aimed to assess factors related to preventable maternal deaths in the NWR of Cameroon by exploring maternal health service usage, implementation of obstetric measures, demand-side challenges, accessibility barriers, and health system weaknesses. Methodology The study employed a quantitative descriptive cross-sectional survey design{middle dot} Data was collected with structured questionnaires from postpartum women and healthcare workers in selected health facilities and catchment communities in the NWR{middle dot} Also, a multistage sampling technique was adopted, and Cochran's formula generated a sample size of 109 respondents{middle dot} In addition, data were analysed using SPSS version 27 and Stata version 18, employing descriptive and inferential statistics. Results In this study, while 70{middle dot}64 percent of females attended at least 4 ANC visits, only 38{middle dot}53 percent met WHO ANC adequacy requirements. Facility delivery was 96{middle dot}33 percent, yet only 38{middle dot}46 percent received completed delivery plans. Conflict-related challenges affected access, with 44{middle dot}95 percent reporting insecurity-associated movement difficulties, while 44{middle dot}95 percent reported increased transportation expenses due to the conflict. Near-miss complications were reported among 27.52 percent of participants. Delivery record reviews indicated that obstetric kits were utilised in 81{middle dot}76 percent of deliveries, partographs were accessible in 86{middle dot}49 percent of records but correctly filled in just 60{middle dot}81 percent , while oxytocin administration was 95{middle dot}95 percent. Integrated Health Centres showed poorer adherence with intrapartum interventions compared with District and Regional Hospitals (p

20.
arXiv (CS.AI) 2026-06-15

Hierarchical ODE: Learning Continuous-Time Physical Prototypes for Early Link Failure Detection

arXiv:2606.14284v1 Announce Type: cross Abstract: Time series prototype learning is fundamentally challenged by observational ambiguity. Discrete architectures fail to resolve this, as they lack the capacity to decouple stochastic noise from continuous dynamics. Furthermore, rigid closed-set assumptions fail to capture unseen diversity. To address these limitations, we propose a hierarchical ordinary differential equation clustering network, which utilizes neural ordinary differential equation to model latent state evolution as a continuous integral curve. This formulation enforces temporal continuity to effectively disentangle smooth feature trends from stochastic noise, while our adaptive hierarchical mechanism autonomously determines the appropriate number of prototypes without rigid prior constraints. Validated on the early link failure detection task with irregularly sampled time series, the proposed method effectively extracts underlying physical prototypes, thereby enabling robust failure detection. Our code is available at https://github.com/NJ-LNN/Hierarchical-ODE.

21.
arXiv (CS.CL) 2026-06-11

Improving Cross-Format Robustness in Language Models with Multi-Format Training

Large language models often remain sensitive to answer format: a question solved correctly in one form may fail in another semantically equivalent form. To study this gap, we define cross-format robustness as the extent to which a model answers the same underlying question consistently across formats. We then compare full-format training with FormatMix, which expands only a subset of training items into multiple equivalent formats using either random or targeted selection. Across GLM4 and Llama-3.1, multi-format supervision consistently improves both task performance and cross-format robustness, whereas Multiple-choice question (MCQ)-only supervision alone brings little benefit and can even reduce robustness. We further find that expanding only about 30% of the training set into multiple formats often recovers most of the gain from full-format training, and this effect appears across the model families and sizes we study. These results suggest that format diversity, rather than additional supervision alone, is the key driver of robustness. That lightweight multi-format augmentation is a practical way to make LLMs less sensitive to answer format without changing the base model.

22.
arXiv (CS.CL) 2026-06-11

NightFeats @ MMU-RAGent NeurIPS 2025: A Context-Optimized Multi-Agent RAG System for the Text-to-Text Track

We present NightFeats, a structured multi-agent retrieval-augmented generation (RAG) system submitted to the MMU-RAGent competition at NeurIPS 2025, where it was awarded Best Dynamic Evaluation in the text-to-text track. Rather than targeting benchmark maximization, this work proposes a principled pipeline that decomposes knowledge synthesis into three coordinated phases: retrieval, curation, and composition, each governed by explicit intermediate representations and handoff contracts. Inspired by Agentic Context Engineering (ACE), the system introduces temporal-semantic reranking, bounded contradiction reconciliation, and citation-preserving composition as core architectural primitives. Competition results show that NightFeats surpasses proprietary baselines including Claude-SonnetV2 and Nova-Pro on LLM-as-a-Judge and Human Likert evaluations, confirming that architectural transparency and verifiable evidence grounding are better aligned with human preferences than systems optimizing narrowly for automatic similarity metrics.

23.
arXiv (CS.AI) 2026-06-11

Agents All the Way Down; A Methodology for Building Custom AI Agents from Substrate to Production

arXiv:2606.11869v1 Announce Type: cross Abstract: Custom AI agents areagents that live inside their own application, talk to their own data and tools, enforce their own security boundaries, and carry their own brand and audit trail. What separates them from the general-purpose tier is fit, not capability: each is built for one job, by the engineer who will maintain it. No published practice sets out how to build one end to end. The pieces are everywhere (function-calling APIs, the Model Context Protocol, code agents to pair with), but the practice that chains them lives in podcasts, blogs, and leaked system prompts. This paper writes that practice down as a methodology, Agents All the Way Down: two preconditions crossed once and kept, then three practices repeated for the agent's life. The preconditions are (P1) Substrate, the LLM as a software component, framed as tools, then system, then messages under prompt-caching; and (P2) Building blocks: function calling, MCP, CLI orchestration, the liteshell pattern, the agent loop, skills, characters, hooks, and scaffolding. The practices are (P3) prototype with a general-purpose agent; (P4) harvest, fold, and ship the result as a CLI, the Turtle pattern; and (P5) agent-tests-agent, in which a general-purpose agent drives it through behavioural scenarios, a complement to classical testing, not a replacement. The working loop is P3 to P4 to P5 and back, and one corollary falls out for free: multi-agent orchestration is just CLI composition. The methodology is framework-free by construction. It was distilled from the AAC, a custom agent for the open-source LAMB platform, built in about ten days by one developer with an AI pair-programmer and in production . We present it as a transferable practice, independent of any language or framework.

24.
arXiv (CS.CL) 2026-06-11

M4FC: a Multimodal, Multilingual, Multicultural, Multitask Real-World Fact-Checking Dataset

Existing real-world datasets for multimodal fact-checking have multiple limitations: they contain few instances, cover on only one or two languages, focus only on one task, or rely on external news article sets for sourcing true claims. To address these shortcomings, we introduce M4FC, a new real-world dataset comprising 4,982 images paired with 6,980 claims. The images, verified by professional fact-checkers from 22 organizations, represent a diverse range of cultural and geographic contexts. Each claim is available in one or two out of ten languages. M4FC spans six multimodal fact-checking tasks: visual claim extraction, claimant intent prediction, fake image detection, image contextualization, location verification, and verdict prediction. We provide baseline results for all tasks and analyze how combining intermediate tasks affects verdict prediction performance. We make our dataset and code publicly available.

25.
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.