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A helicase-fused Cas9 improves large-size fragment knockin

By fusing MCM5, a subunit of the eukaryotic MCM2–7 helicase complex, to the N terminus of spCas9 (MCCas), the MCCas fusion protein enhances large-size fragment knockin via homologous recombination, reduces insertions and deletions (indels), and enables efficient large-size fragment insertions in human cells and rabbit embryos.
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Smart Adaptive Computing Across the Continuum: LLMs in IoT-Edge-Cloud Resource Management

arXiv:2609.09348v1 Announce Type: cross Abstract: Managing resources across IoT, edge, and cloud layers calls for continuous, context-aware decisions under constraints that rarely stay fixed. Deep reinforcement learning (DRL) handles this class of problems well, and large language models (LLMs) are increasingly used to augment DRL pipelines, yet the architectural relationship between the two is seldom made explicit. We build on Wang et al.'s taxonomy of Continuum Orchestration Systems employing DRL techniques and extend it with two further dimensions. The AI Augmentation Paradigm measures how LLMs are exploited, while the Feedback channel captures whether and through which system path the execution feedback returns to the LLM in order to close the MAPE control loop at the LLM Orchestration layer. We apply this taxonomy to six recent system architectures and find a common gap, as none combines full LLM orchestration with full agent-layer feedback in a Cloud Continuum setting. We relate this gap to a missing cross-tier feedback abstraction, bridging the incommensurable per-tier signals and the LLM Orchestrator.
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Robust transcriptomic hallmarks targeting intratumor heterogeneity in intrahepatic cholangiocarcinoma

Cell Rep Med. 2026 Mar 30:102708. doi: 10.1016/j.xcrm.2026.102708. Online ahead of print.

ABSTRACT

Intratumor heterogeneity (ITH) undermines transcriptome-based stratification in intrahepatic cholangiocarcinoma (iCCA). Here, we integrate multi-omics data from multi-region, single-region, and single-cell RNA sequencing cohorts to systematically characterize gene expression ITH. We uncover that immune and stromal heterogeneity are primary drivers of ITH, leading to misclassification of a median 27.8% of tumors by existing subtyping systems. To overcome this, we identify a low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set and develop an ITH-insensitive classification system defining five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3). These subgroups exhibit distinct clinical outcomes, molecular features, immune landscapes, and therapeutic vulnerabilities. GPRC5A and VTCN1 serve as robust immunohistochemical biomarkers for SI and SIII tumors, while serum CEA and CA19-9 identify inflammatory iCCA. Therapeutically, HSP90 inhibition synergizes with anti-PD1 in inflammatory iCCA, whereas combined anti-PD1 and anti-TIM3 suppresses neurodegenerative iCCA. Collectively, our study provides a robust molecular framework and actionable therapeutic strategies for iCCA.

PMID:41916296 | DOI:10.1016/j.xcrm.2026.102708

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BIRD-INTERACT: Re-imagining Text-to-SQL Evaluation for Large Language Models via Lens of Dynamic Interactions

arXiv:2510.05318v3 Announce Type: replace Abstract: Large language models (LLMs) have demonstrated remarkable performance on single-turn text-to-SQL tasks, but real-world database applications predominantly require multi-turn interactions to handle ambiguous queries, execution errors, and evolving user requirements. Existing multi-turn benchmarks fall short by treating conversation histories as static context or limiting evaluation to read-only operations, failing to reflect production-grade database assistant challenges. We introduce BIRD-INTERACT, a benchmark that restores this realism through: (1) a comprehensive interaction environment coupling each database with a hierarchical knowledge base, metadata files, and a function-driven user simulator, enabling models to solicit clarifications, retrieve knowledge, and recover from errors without human supervision; (2) two evaluation settings consisting of a pre-defined conversational protocol (c-Interact) and an open-ended agentic setting (a-Interact) where models autonomously decide when to query the user simulator or explore the environment; (3) a challenging task suite covering the full CRUD spectrum for business-intelligence and operational use cases, guarded by executable test cases. Each task features ambiguous and follow-up sub-tasks requiring dynamic interaction. The suite comprises BIRD-INTERACT-FULL (600 tasks, up to 11,796 interactions) for comprehensive performance assessment, and BIRD-INTERACT-LITE (300 tasks with simplified databases) for detailed behavioral analysis and rapid method development. Our empirical results highlight BIRD-INTERACT's difficulty: GPT-5 completes only 8.67% of tasks in c-Interact and 17.00% in a-Interact. Analysis via memory grafting and Interaction Test-time Scaling validates the importance of effective interaction for complex, dynamic text-to-SQL tasks.
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MCP Security Bench (MSB): Benchmarking Attacks Against Model Context Protocol in LLM Agents

arXiv:2510.15994v2 Announce Type: replace-cross Abstract: The Model Context Protocol (MCP) standardizes how large language model (LLM) agents discover, describe, and call external tools. While MCP unlocks broad interoperability, it also enlarges the attack surface by making tools first-class, composable objects with natural-language metadata, and standardized I/O. We present MSB (MCP Security Benchmark), the first end-to-end evaluation suite that systematically measures how well LLM agents resist MCP-specific attacks throughout the full tool-use pipeline: task planning, tool invocation, and response handling. MSB contributes: (1) a taxonomy of 12 attacks including name-collision, preference manipulation, prompt injections embedded in tool descriptions, out-of-scope parameter requests, user-impersonating responses, false-error escalation, tool-transfer, retrieval injection, and mixed attacks; (2) an evaluation harness that executes attacks by running real tools (both benign and malicious) via MCP rather than simulation; and (3) a robustness metric that quantifies the trade-off between security and performance: Net Resilient Performance (NRP). We evaluate nine popular LLM agents across 10 domains and 405 tools, producing 2,000 attack instances. Results reveal the effectiveness of attacks against each stage of MCP. Models with stronger performance are more vulnerable to attacks due to their outstanding tool calling and instruction following capabilities. MSB provides a practical baseline for researchers and practitioners to study, compare, and harden MCP agents. Code: https://github.com/dongsenzhang/MSB
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Order Is Not Layout: Order-to-Space Bias in Image Generation

arXiv:2603.03714v1 Announce Type: cross Abstract: We study a systematic bias in modern image generation models: the mention order of entities in text spuriously determines spatial layout and entity--role binding. We term this phenomenon Order-to-Space Bias (OTS) and show that it arises in both text-to-image and image-to-image generation, often overriding grounded cues and causing incorrect layouts or swapped assignments. To quantify OTS, we introduce OTS-Bench, which isolates order effects with paired prompts differing only in entity order and evaluates models along two dimensions: homogenization and correctness. Experiments show that Order-to-Space Bias (OTS) is widespread in modern image generation models, and provide evidence that it is primarily data-driven and manifests during the early stages of layout formation. Motivated by this insight, we show that both targeted fine-tuning and early-stage intervention strategies can substantially reduce OTS, while preserving generation quality.
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