Large language models (LLMs) concentrate substantial knowledge in specialized domains due to extensive pretraining and instruction tuning, and they are now central to commercial and scientific practice. Yet access is usually limited to costly, rate-limited interfaces, which motivates methods that can extract targeted domain knowledge with minimal querying effort. A further challenge is that the target domain may be unknown in advance, so naive or generic prompts waste queries and fail to expose the underlying concepts and relations that structure the domain. In this work, we introduce a query-efficient approach for domain-specific knowledge stealing from black-box language models. Rather than issuing random questions or generic templates, our framework performs self-directed exploration that lets the model find the direction and mine domain knowledge by itself. Starting from a small and diverse seed, it discovers salient domain entities and induces their relations through structured question families that elicit definitional, functional, and compositional information. A feedback-driven controller analyzes the errors and uncertainty of the extracted surrogate model and uses this signal to refine subsequent queries, all without relying on prior domain knowledge or external resources. We evaluate the method in two expert-centric settings, medicine and finance, and observe consistently better performance while requiring significantly fewer queries.

Large language models (LLMs) augmented with external tools have demonstrated remarkable capability in solving complex real-world tasks. However, existing approaches suffer from two key challenges: brittle multi-step and multi-turn reasoning caused by incompatible tool output types and API schemas, and performance degradation under large tool catalogues. To address these, we introduce Tool Primitives, a design that replaces rigid API schema-based invocation with natural language as the interface for tool calling, where each tool is wrapped with an LLM interface that handles schema resolution and execution internally, enabling natural inter-tool communication for nested and multi-turn tool calling. Building on Tool Primitives, we host ToolFace, a centralized repository of 25,519 functions from which LLMs dynamically retrieve only the relevant tools at inference time, eliminating the need to enumerate raw API schemas in context. To orchestrate Tool Primitives and ToolFace reliably in complex settings, we further propose HEART, a Harness Engineering framework via Agent-native, Reusable Tool Primitives, comprising a Planner, Router, and Verifier that jointly support dynamic tool invocation planning, multi-step execution, and feedback-driven recovery. Experiments on five benchmarks demonstrate that HEART outperforms SFT-based models by 10% on average and surpasses GPT-5.4, Claude-4.6-Sonnet, and Gemini-3.1-Pro by 6% on average while reducing API cost by up to 85%. On 50 real-world tasks, HEART achieves 84% task completion, 3.8× the average of three frontier commercial models (22%).

Abstract Background How gene regulatory programs reorganize across space and time is central to development and disease, but current methods infer regulatory structure from single snapshots. The emergence of spatiotemporal transcriptomics calls for methods that resolve regulation along both axes. Results We introduce SpaTemGRN, which jointly models observations from multi-timepoint slides in spatiotemporal transcriptomics to infer time-resolved spatial-unit-specific putative GRNs. Compared with existing methods, SpaTemGRN allows later-stage units to borrow statistical strength from spatially proximate and temporally preceding units. In the App NL−G−F mouse model of Alzheimer’s disease, SpaTemGRN revealed region- and age-dependent strengthening of complement–glia regulatory coupling. An early, broadly distributed complement signature precedes later, spatially focal coupling with astrocytic and microglial responses. In the developing mouse embryonic brain, SpaTemGRN identified progressively sharpening and spatially segregated regulatory programs as the early neural tube regionalizes. Across simulated datasets, SpaTemGRN recovered regulatory edges more robustly than four existing methods and maintained the most stable performance across stages. Conclusions SpaTemGRN provides a flexible hypothesis-generating framework for investigating how spatially localized gene–gene dependencies are remodeled across biological stages. All source code for SpaTemGRN is available at https://github.com/yibingjiang/SpaTemGRN .

Preference-based post-training is usually understood through endpoint behavior, yet the learned update that produces this behavior remains largely opaque. We study RLHF and related preference optimization through the spectral structure of their induced parameter updates. By decomposing effective LoRA updates and reloading their spectral components as plug-in modules, we turn preference-induced updates into objects that can be isolated, recomposed, and directly intervened on. Across model families, optimization algorithms, and supervision regimes, these updates consistently develop a spectral head–tail organization. A compact head emerges early and carries the dominant endpoint shift, while a heterogeneous residual tail remains. The split is functional rather than merely descriptive. Plug-in intervention shows that the head accounts for the visible behavioral departure from the base model, while the tail is weak in isolation. Cross-run recomposition further shows that mixed adapters follow the source of the head, indicating that the head carries run-level solver bias. This endpoint dominance does not imply learning sufficiency. Head-only learning is non-vacuous but fails to recover the full solution, especially on out-of-distribution behavior. Tail-only learning yields little visible gain, yet the full solution is not recovered without the tail. These findings recast preference post-training as structured update reorganization rather than a monolithic behavioral correction, and suggest that alignment gain and coverage loss are tied to how the learned update itself is organized.

Large language models are increasingly deployed in settings where reliability matters, yet output-level uncertainty signals such as token probabilities, entropy, and self-consistency can become brittle under calibration–deployment mismatch. Conformal prediction provides finite-sample validity under exchangeability, but its practical usefulness depends on the quality of the nonconformity score. We propose a conformal framework for LLM question answering that uses internal representations rather than output-facing statistics: specifically, we introduce Layer-Wise Information (LI) scores, which measure how conditioning on the input reshapes predictive entropy across model depth, and use them as nonconformity scores within a standard split conformal pipeline. Across closed-ended and open-domain QA benchmarks, with the clearest gains under cross-domain shift, our method achieves a better validity–efficiency trade-off than strong text-level baselines while maintaining competitive in-domain reliability at the same nominal risk level. These results suggest that internal representations can provide more informative conformal scores when surface-level uncertainty is unstable under distribution shift.

Synthetic data generation using large language models (LLMs) demonstrates substantial promise in addressing biomedical data challenges and shows increasing adoption in biomedical research. This study systematically reviews recent advances in synthetic data generation for biomedical applications and clinical research, focusing on how LLMs address data scarcity, utility, and quality issues with different modalities. We conducted a scoping review following PRISMA-ScR guidelines and searched literature published between 2020 and 2025 through PubMed, ACM, Web of Science, and Google Scholar. A total of 59 studies were included based on relevance to synthetic data generation in biomedical contexts. Among the reviewed studies, the predominant data modalities were unstructured texts (78.0%), tabular data (13.6%), and multimodal sources (8.4%). Common generation methods included LLM prompting (74.6%), fine-tuning (20.3%), and specialized models (5.1%). Evaluations were heterogeneous: intrinsic metrics (27.1%), human-in-the-loop assessments (44.1%), and LLM-based evaluations (13.6%). However, limitations and key barriers persist in data modalities, domain utility, resource and model accessibility, and standardized evaluation protocols. Future efforts may focus on developing standardized, transparent evaluation frameworks and expanding accessibility to support effective applications in biomedical research.

While existing multi-agent systems (MAS) can handle complex problems by enabling collaboration among multiple agents, they are often highly task-specific, relying on manually crafted agent roles and interaction prompts, which leads to increased architectural complexity and limited reusability across tasks. Moreover, most MAS communicate primarily through natural language, making them vulnerable to error accumulation and instability in long-context, multi-stage interactions within internal agent histories. In this work, we propose Agent Primitives, a set of reusable latent building blocks for LLM-based MAS. Inspired by neural network design, where complex models are built from reusable components, we observe that many existing MAS architectures can be decomposed into a small number of recurring internal computation patterns. Based on this observation, we instantiate three primitives: Review, Voting and Selection, and Planning and Execution. All primitives communicate internally via key-value (KV) cache, which improves both robustness and efficiency by mitigating information degradation across multi-stage interactions. To enable automatic system construction, an Organizer agent selects and composes primitives for each query, guided by a lightweight knowledge pool of previously successful configurations, forming a primitive-based MAS. Experiments show that primitives-based MAS improve average accuracy by 12.0-16.5% over single-agent baselines, reduce token usage and inference latency by approximately 3×-4× compared to text-based MAS, while incurring only 1.3×-1.6× overhead relative to single-agent inference and providing more stable performance across model backbones.

Recent advancements in Large Vision-Language Models (LVLMs) have shown groundbreaking capabilities across diverse multimodal tasks. However, these models remain vulnerable to adversarial jailbreak attacks, where adversaries craft subtle perturbations to bypass safety mechanisms and trigger harmful outputs. Existing white-box attacks methods require full model accessibility, suffer from computing costs and exhibit insufficient adversarial transferability, making them impractical for real-world, black-box settings. To address these limitations, we propose a black-box jailbreak attack on LVLMs via Zeroth-Order optimization using Simultaneous Perturbation Stochastic Approximation (ZO-SPSA). ZO-SPSA provides three key advantages: (i) gradient-free approximation by input-output interactions without requiring model knowledge, (ii) model-agnostic optimization without the surrogate model and (iii) lower resource requirements with reduced GPU memory consumption. We evaluate ZO-SPSA on three LVLMs, including InstructBLIP, LLaVA and MiniGPT-4, achieving the highest jailbreak success rate of 83.0

Recent advances in LLM agents enable systems that autonomously refine workflows, accumulate reusable skills, self-train their underlying models, and maintain persistent memory. However, we show that such self-evolution is often non-monotonic: adapting to new task distributions can progressively degrade previously acquired capabilities across all major evolution channels. We identify this phenomenon as capability erosion under self-evolution and show that it consistently emerges across workflow, skill, model, and memory evolution. To mitigate this issue, we propose Capability-Preserving Evolution (CPE), a general stabilization principle that constrains destructive capability drift during continual adaptation. Across all four evolution dimensions, CPE consistently improves retained capability stability while preserving adaptation performance. For example, in workflow evolution, CPE improves retained simple-task performance from 41.8% to 52.8% under GPT-5.1 optimization while simultaneously achieving stronger complex-task adaptation. Our findings suggest that stable long-horizon self-evolving agents require not only acquiring new capabilities, but also explicitly preserving previously learned ones during continual adaptation.

Prompt quality plays a critical role in the performance of large language models (LLMs), motivating a growing body of work on prompt optimization. Most existing methods optimize prompts over a fixed dataset, assuming static input distributions and offering limited support for iterative improvement. We introduce SIPDO (Self-Improving Prompts through Data-Augmented Optimization), a closed-loop framework for prompt learning that integrates synthetic data generation into the optimization process. SIPDO couples a synthetic data generator with a prompt optimizer, where the generator produces new examples that reveal current prompt weaknesses and the optimizer incrementally refines the prompt in response. This feedback-driven loop enables systematic improvement of prompt performance without assuming access to external supervision or new tasks. Experiments across question answering and reasoning benchmarks show that SIPDO outperforms standard prompt tuning methods, highlighting the value of integrating data synthesis into prompt learning workflows.

We introduce self-jailbreaking, a threat model in which an aligned LLM guides its own compromise. Unlike most jailbreak techniques, which often rely on handcrafted prompts or separate attacker models, self-jailbreaking requires no external red-team LLM: the target model's own internal knowledge suffices. We operationalize this via Self-Jailbreaking via Lexical Insertion Prompting (SLIP), a black-box algorithm that casts jailbreaking as breadth-first tree search over multi-turn dialogues, incrementally inserting missing content words from the attack goal into benign prompts using the target model as its own guide. Evaluations on AdvBench and HarmBench show SLIP achieves 90–100% Attack Success Rate (ASR) (avg. 94.7%) across most of the eleven tested models (including GPT-5.1, Claude-Sonnet-4.5, Gemini-2.5-Pro, and DeepSeek-V3), with only ∼7.9 LLM calls on average, 3–6× fewer than prior methods. We evaluate existing defenses, show that regex-based approaches are evaded by prompt paraphrasing, and propose the Semantic Drift Monitor (SDM) defense that tracks SLIP's embedding-space trajectory, achieving 76% detection at 5% FPR. However, SDM remains insufficient against adaptive attack strategies, underscoring the need for more advanced defense mechanisms tailored to the self-jailbreaking threat surface. We release our code for reproducibility.

Large language models (LLMs) are highly sensitive to the prompts used to specify task objectives and behavioral constraints. Many recent prompt optimization methods iteratively rewrite prompts using LLM-generated feedback, but the resulting prompts often become longer, accumulate narrow sample-specific rules, and generalize poorly beyond the training distribution. We study this failure mode as prompt distributional overfitting and argue that it reflects a lack of representation control in discrete text-space optimization. We formalize this view through representational inefficiency, a dual-factor measure that decomposes prompt inefficiency into capacity cost and scope narrowness, attributing distributional prompt overfitting to their coupled growth during optimization. We propose TextReg, a regularization framework that realizes a soft-penalty objective through regularized textual gradients, combining Dual-Evidence Gradient Purification, Semantic Edit Regularization, and Regularization-Guided Prompt Update. Across multiple reasoning benchmarks, TextReg substantially improves out-of-distribution (OOD) generalization, with accuracy gains of up to +11.8

Process Reward Models (PRMs) have been proven to be highly effective in guiding test-time scaling (TTS) methods, which significantly boost the capabilities of LLM-based multi-agent systems. However, existing PRMs are text-based: they re-encode the entire trajectory text from scratch. In long multi-agent rollouts, the scoring cost, growing quadratically with respect to sequence length L, creates a severe computational bottleneck, severely limiting PRMs' application in long-context scenarios. To resolve this, we introduce KV-PRM, a highly efficient process reward model that eliminates the heavy text re-encoding by directly reading the KV cache produced naturally during the LLM's generation phase. By processing a single "verify token" against the pre-existing KV cache, KV-PRM reduces the scoring cost from O(L^2) to O(L). We formally prove that the KV cache contains strictly greater information capacity than text, and is more efficient for downstream reward modeling. Empirically, across the MATH, GSM8K, and AIME benchmarks, KV-PRM matches or strictly outperforms text-PRMs under various TTS methods such as Beam Search, MCTS, and Weighted Voting, with up to a 5,000x reduction in scoring FLOPs, a 37x reduction in latency, and a 34x reduction in per-sequence memory footprint compared to text-based PRMs.

Protein co-abundance clusters preserved across tissues can reveal shared disease mechanisms and candidate therapeutic targets, particularly when proteins implicated in organ-confined diseases converge in peripheral or accessible tissues. However, previous cross-tissue studies have focused on biologically pre-selected tissue pairs, leaving most possible combinations and non-obvious relationships unexplored. We present an LLM-agent framework for large-scale, evidence-grounded comparison of tissue-specific protein co-abundance networks. The framework constructs tissue networks, derives pairwise consensus clusters, and integrates evidence from expression atlases, protein interaction and complex databases, pathway annotations, disease catalogues, and literature. Applied to all 820 pairwise combinations of 41 human tissues and fluids, it identified 1,833 conserved co-abundance clusters across 406 tissue pairs. Colon, synovial fluid, blood, cerebrospinal fluid, and bone marrow were the most broadly connected tissues, while the most cluster-rich pairs were dominated by bone marrow. The analysis also highlighted non-obvious relationships: skin-bone marrow exceeded the anatomically adjacent bone-bone marrow pair, while colon-breast contained cancer-relevant clusters involving extracellular-matrix remodeling, lipid metabolism, and immune modulation. Cluster-level analyses generated further mechanistic hypotheses, including a brain-gut extracellular-vesicle/redox/serotonin-cofactor axis and a liver-bone marrow stress-response axis involving genes linked to white matter disease. These results provide a global, comparable landscape of conserved protein co-abundance and a hypothesis-generating resource for mechanistic and therapeutic exploration. Code and data are available at https://github.com/Gry1005/AgenticAI-conserved-cross-tissue-protein-co-abundance.

This paper presents an image dataset of Kazakh banknotes collected for research in computer vision and pattern recognition. The dataset contains photographs of banknotes from seven categories corresponding to the denominations 500, 1000, 2000, 5000, 10,000, 20,000 Kazakhstani tenge, as well as a mixed category containing multiple denominations within a single image. Each denomination folder includes at least 100 images, while the mixed category contains over 1000 images. Images were captured against a wide range of backgrounds and under varying lighting conditions to reflect realistic usage scenarios and environmental diversity.The 5000 tenge denomination is further divided into three subsets that distinguish between old and new banknote designs and between single-note and multiple-note configurations. Most images contain multiple banknotes of the same denomination, except for one subset explicitly designed to include a single banknote per image. All files follow a consistent numeric naming convention.The dataset is intended to support tasks such as banknote classification, object detection, and robustness analysis of deep learning models under background and illumination variation. It may also be reused for transfer learning, dataset bias studies, and comparative evaluations across currency recognition systems.

Online credit card discussions provide a natural setting for studying how consumers communicate about financial products. Simulating these discussions requires more than just generating individual comments, the generated threads should also match how real users express themselves and interact with others. We introduce CARD, a framework for generating realistic credit card discussion threads. Given a credit card post and its matched real thread, CARD uses non-verbatim guidance on reply structure, comment function, stance, tone, and conversational variation. A planner organizes these controls, a writer generates the discussion, and a calibration loop updates comments' populations that contribute to differences between the generated and real thread distributions. We evaluate CARD on real Reddit credit card discussions using lexical, semantic, behavioral, and structural metrics. CARD matches the distributions of real credit card discussions better than simulation baselines across multiple LLMs and also demonstrates smaller effect sizes and distribution distances across metrics. These results show that structured planning and targeted revision can generate the realism of simulated credit card discussions.

Process reward models (PRMs) are a cornerstone of test-time scaling (TTS), designed to verify and select the best responses from large language models (LLMs). However, this promise is challenged by recent benchmarks where simple majority voting, which ignores PRM signals, occasionally outperforms standard PRM-based selection. This raises a critical question: How can we effectively utilize verification signals from PRMs for TTS? To address this, we start by developing a theoretical framework for optimally combining signals from both the LLM and the PRM. Our framework reveals that the optimal strategy is a weighted aggregation of responses, a strategy whose effectiveness hinges on estimating weights that capture the complex interplay between the models. Based on our theoretical results, we empirically show that these optimal weighting functions differ significantly across LLM-PRM pairs and, notably, often assign substantial negative weights. Motivated by these insights, we propose efficient pre-computation methods to calibrate these weighting functions. Extensive experiments across 5 LLMs and 7 PRMs demonstrate that our calibration method significantly boosts the TTS efficiency, surpassing the performance of vanilla weighted majority voting while using only $\sim 21.3\\%$ of the computation. Ultimately, our work demonstrates that investing in a more intelligent aggregation strategy can be a more convincing path to performance gains than simply scaling test-time computation.

Long-context question answering (QA) remains challenging for smaller language models even when answer-bearing evidence is already present in the input. Existing within-context retrieval methods localize and expose candidate evidence chunks for the question, but they stop at input-level evidence exposure rather than adapting the query-side attention parameters that control how the model allocates attention over full-context positions. In contrast, lightweight test-time adaptation methods, such as query-only test-time training (qTTT), leave evidence localization unresolved because their generic span-level self-supervised objectives do not identify which context positions support the current answer. In this paper, we propose Evidence-Aligned SElective Test-Time Training (EASE-TTT), a within-context retrieval-augmented test-time training framework that converts selected evidence chunks into a soft attention supervision target over their token positions. Instead of replacing the full context with retrieved chunks, EASE-TTT uses the resulting attention target to guide query-side adaptation, with the adapted model generating the final answer from the original full context. Experiments on six LongBench QA tasks and three small decoder-only language models show that EASE-TTT achieves the strongest macro-average performance among full-context inference, retrieval-only baselines, and qTTT, supporting evidence-aligned test-time adaptation in long-context QA.

Large Language Models (LLMs) are increasingly deployed in finance, where unsafe behavior can lead to serious regulatory risks. However, most red-teaming research focuses on overtly harmful content and overlooks attacks that appear legitimate on the surface yet induce regulatory-violating responses. We address this gap by introducing a controllable black-box multi-turn risk-concealed redteaming framework (CoRT) that progressively conceals surface-level risk while exploiting regulatory-violating behaviors. CoRT contains two key components: (i) a Risk Concealment Attacker (RCA) that generates multiturn prompts via iterative refinement, and (ii) a Risk Concealment Controller (RCC) that predicts a turn-level Risk Concealment Score (RCS) to steer RCA’s follow-up style. We also build a domain-specific benchmark, FinRisk-Bench, with 522 instructions spanning six financial risk categories. Experiments on nine widely used LLMs show that CoRT (RCA) achieves 93.19% average attack success rate (ASR), and CoRT (RCA+RCC) further improves the average ASR to 95.00%. Our code and FinRisk-Bench are available at https://github.com/gcheng128/CoRT.

Multi-agent systems built on large language models have shown strong performance on complex reasoning tasks, yet most work focuses on agent roles and orchestration while treating inter-agent communication as a fixed interface. Latent communication through internal representations such as key-value caches offers a promising alternative to text-based protocols, but existing approaches do not jointly optimize communication with multi-agent reasoning. Therefore we propose DiffMAS, a training framework that treats latent communication as a learnable component of multi-agent systems. DiffMAS performs parameter-efficient supervised training over multi-agent latent trajectories, enabling agents to jointly learn how information should be encoded and interpreted across interactions. Experiments on mathematical reasoning, scientific QA, code generation, and commonsense benchmarks show that DiffMAS consistently improves reasoning accuracy and decoding stability over single-agent inference, text-based multi-agent systems, and prior latent communication methods, achieving 26.7