中 EN
Sign In Register

Academic Intelligence · Curated Daily

Explore the Frontier of Global Academia

AcademicHub aggregates real-time literature from top journals and preprint platforms. Build your personal research radar and let large language models compile cross-disciplinary analysis briefings automatically.

Sign In Register
01.
Nature Biotechnology 2026-06-19

Efficient site-specific gene addition using R2 retrotransposons in tobacco and rice

Authors:
Zahir Ali↗

Precise integration of multikilobase DNA fragments remains a major technical barrier in plants. Here we introduce non-long terminal repeat (non-LTR) R2 retrotransposons as a versatile system for targeted gene integration in plants. We reconstituted R2 activity in Nicotiana benthamiana and benchmarked insertion efficiency and fidelity using a TMV-based episomal reporter system. We demonstrate site-specific integration of GFP (2.2 kb) and recombinase-compatible landing pads (0.6 kb) into 28S rDNA arrays, with intact cassette insertion frequencies up to 75% and 53%, respectively. To temporally constrain donor availability and avoid DNA intermediates, we combined in planta effector expression with recombinant RNA virus-mediated donor delivery. We apply R2 retrotransposons for targeted insertion of resistance cassettes within the rDNA of rice callus, achieving integration efficiencies up to 17%. These results position R2 retrotransposons as a double-strand break-free system for RNA-templated insertion of multikilobase gene cassettes at rDNA loci, for safe-harbor trait stacking in plants with potential applications in crop improvement and synthetic biology. Retrotransposons are applied in plants for safe-harbor transgene integration.

Read & Discuss → View Source →
02.
arXiv (CS.AI) 2026-06-17

LLM-Powered Multi-Agent System for Automated Crypto Portfolio Management

Authors:
Yichen Luo↗Yebo Feng↗Jiahua Xu↗Paolo Tasca↗Yang Liu↗

arXiv:2501.00826v3 Announce Type: replace-cross Abstract: Cryptocurrency portfolio management requires the fusion of heterogeneous multi-modal signals, including structured price and on-chain time series, unstructured news text, and technical indicators, under high-volatility and real-time constraints. While deep learning approaches show predictive capability, their opacity limits practical adoption, and single large language model (LLM) agents struggle to process the breadth of modality-specific inputs needed for robust decision-making. We propose a multi-agent system (MAS) framework in which three modality-specialised agents, a Crypto Agent for market dynamics, a News Agent for weekly news sentiment, and a Trading Agent for signal fusion and portfolio execution, decompose the task across three communication architectures: hierarchical, collaborative, and debate. We evaluate four capability configurations: zero-shot, chain-of-thought (CoT), retrieval-augmented generation (RAG), and skill-augmented. In a 52-week backtest over calendar year 2025 across the top 15 L1 blockchain native cryptocurrencies by market capitalisation as of January 2025, the best configuration, Hierarchical (Skill), achieves a cumulative return of 133.52% and a Sharpe ratio of 1.502, outperforming single-agent variants, passive benchmarks, and deep learning baselines. An ablation study identifies the Crypto Agent as the most critical component, with its removal reducing cumulative return by 42.57 percentage points. A cross-model comparison further shows that MAS outperforms the single-agent baseline under GPT-4o, GPT-5, and Claude Sonnet 4.5, suggesting that the benefit of multi-agent coordination is model-agnostic. Unlike black-box deep learning models, every portfolio decision is traceable to explicit agent reasoning, offering an interpretable and effective approach to multi-modal cryptocurrency portfolio management.

Read & Discuss → View Source →
03.
arXiv (CS.LG) 2026-06-12

Generative Modeling of Bach-Style Symbolic Music: A Comparative Study of Autoregressive, Latent-Variable, and Adversarial Approaches

Authors:
Kyuil Lee↗Dezhi Yu↗Yongkang Huang↗

arXiv:2606.13626v1 Announce Type: cross Abstract: We study generative modeling of Bach-style symbolic piano music using a shared MIDI corpus and three model families: autoregressive LSTMs with attention, latent-variable models including recurrent VAEs and vector-quantized VAEs, and generative adversarial networks. We compare their ability to model polyphonic note sequences, learn useful latent representations, and generate stylistically coherent compositions. Our experiments show that the autoregressive LSTM with attention produces the most musically coherent samples, while vector quantization helps mitigate posterior collapse and yields more structured outputs than conventional recurrent VAEs. The adversarial approach captures local pitch patterns but remains difficult to train and generalizes less reliably to Bach's style. These results highlight the relative strengths and failure modes of autoregressive, latent-variable, and adversarial approaches for symbolic music generation.

Read & Discuss → View Source →
04.
arXiv (CS.AI) 2026-06-18

Code-Augur: Agentic Vulnerability Detection via Specification Inference

Authors:
Zhengxiong Luo↗Mehtab Zafar↗Dylan Wolff↗Abhik Roychoudhury↗

arXiv:2606.18619v1 Announce Type: cross Abstract: The advent of agentic vulnerability detection is already becoming a watershed moment for software security. Audits conducted entirely by autonomous LLM agents are uncovering critical vulnerabilities in fundamental software underpinning digital society. Many of these vulnerabilities remained masked for years, surfacing only now with AI agents. Yet the reasoning behind these discoveries remains alarmingly opaque and unvalidated. What assumptions did the agent make about a function's inputs when it deemed that function to be secure? Failures in reasoning and incorrect assumptions can lead to missed vulnerabilities and reduce trust in agentic analysis. We propose a security-specification-first paradigm that (1) exposes the agent's tacit assumptions explicitly as security specifications and (2) continuously refines those specifications via runtime falsification. We realize our approach in Code-Augur, a novel harness for agentic vulnerability detection. Given a codebase, Code-Augur analyzes each component of the system for vulnerable code. When it deems a component to be secure, it commits the local invariants behind that judgment as in-source assertions. In parallel, Code-Augur leverages a guided fuzzer to attempt to falsify those assumptions. When the fuzzer triggers an assertion, this either reveals a genuine vulnerability or a flawed specification to refine. In both cases, this process grounds the agent's understanding, aligning its view of code intent with how the code actually behaves. On real-world subjects, Code-Augur effectively leverages security specifications to detect more vulnerabilities than other state-of-the-art agents. Additionally, Code-Augur found 22 new vulnerabilities in key open-source projects. Compared to curated specialized models like Claude Mythos, Code-Augur offers effective agentic vulnerability detection built on widely available LLMs like Sonnet and DeepSeek.

Read & Discuss → View Source →
06.
arXiv (CS.LG) 2026-06-16

Generative Modeling on Metric Graphs via Neural Optimal Transport

Authors:
Alessandro Micheli↗Yueqi Cao↗Anthea Monod↗Samir Bhatt↗

arXiv:2606.16273v1 Announce Type: cross Abstract: We introduce, to our knowledge, the first deep generative modeling framework for probability distributions continuously supported on compact metric graphs. Given source and target measures on a metric graph, our method embeds the graph into a smooth ambient space, solves an entropic Kantorovich problem via a neural semidual parameterization, and projects generated samples back onto the original graph. We study two embedded geometries: an extrinsic Euclidean realization and the intrinsic tropical Abel–Jacobi embedding into the Jacobian torus. In both cases, the resulting generator is graph-supported by construction. We prove that, in the joint limit of increasing neural expressivity, the learned generator converges weakly to a valid transport coupling between the original graph measures. Empirically, across a range of geometrically distinct graphs, our method matches or improves upon heuristic transport baselines based on discrete graph OT, while scaling more favorably. Finally, we demonstrate scalability on real-world urban mobility data by training our model on one million Uber pickup locations in Manhattan, New York City.

Read & Discuss → View Source →
07.
Nature (Science) 2026-06-10

Mitochondria directly interact with the nuclear pore complex

Authors:
Ivan Menendez-Montes↗

Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example has been contact with the endoplasmic reticulum at mitochondrial-associated endoplasmic reticulum membranes1, which control pathways including redox and calcium homeostasis2,3. Recent studies have also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signalling4,5. Here we identify direct interactions between mitochondria and nuclear pores. Using two unbiased proteomic screens, GST pulldown and BioID, we found that VDAC1 was the top mitochondrial candidate that interacts with the filamentous nuclear pore protein RANBP2. In vitro RANBP2 CRISPR knockout, RANBP2 truncation or site-directed mutagenesis of RANBP2–VDAC1 interacting amino acids resulted in reduced mitochondria–nucleus proximity and decreased nuclear ATP and phosphocreatine levels. This was accompanied by a decline in the levels of the nuclear phosphoproteome and downregulation of pathways involved in histone modification, cellular differentiation and transcriptional regulation in vitro. Moreover, deletion of the RANBP2 C-terminal domain in vivo in mice resulted in embryonic lethality due to cardiac and neural crest differentiation defects. Collectively, these results describe a mechanism by which mitochondria directly interact with the nuclear pore complex, a phenomenon critical for regulation of nuclear energetics and cellular differentiation. Undoubtedly, additional roles of this interaction remain to be revealed. Mitochondria interact directly with the nuclear pore complex via VDAC1–RANBP2 binding to sustain nuclear ATP levels.

Read & Discuss → View Source →
08.
arXiv (CS.LG) 2026-06-16

DemoDiffusion: One-Shot Human Imitation using pre-trained Diffusion Policy

Authors:
Sungjae Park↗Homanga Bharadhwaj↗Shubham Tulsiani↗

arXiv:2506.20668v3 Announce Type: replace-cross Abstract: We propose DemoDiffusion, a simple method for enabling robots to perform manipulation tasks by imitating a single human demonstration, without requiring task-specific training or paired human-robot data. Our approach is based on two insights. First, the hand motion in a human demonstration provides a useful prior for the robot's end-effector trajectory, which we can convert into a rough open-loop robot motion trajectory via kinematic retargeting. Second, while this retargeted motion captures the overall structure of the task, it may not align well with plausible robot actions in-context. To address this, we leverage a pre-trained generalist diffusion policy to modify the trajectory, ensuring it both follows the human motion and remains within the distribution of plausible robot actions. Unlike approaches based on online reinforcement learning or paired human-robot data, our method enables robust adaptation to new tasks and scenes with minimal effort. In real-world experiments across 8 diverse manipulation tasks, DemoDiffusion achieves 83.8\% average success rate, compared to 13.8\% for the pre-trained policy and 52.5\% for kinematic retargeting, succeeding even on tasks where the pre-trained generalist policy fails entirely. Project page: https://demodiffusion.github.io/

Read & Discuss → View Source →
09.
medRxiv (Medicine) 2026-06-17

Silent Manipulation of Mental Health Treatment Recommendations from a Large Language Model

Authors:
Perlis↗R. H↗

Importance. Large language models (LLMs) increasingly inform mental health decisions by patients and clinicians. Inference-time activation steering can shift model behavior on a target dimension without altering weights or prompts and without disclosure to users, allowing treatment recommendations to be silently changed for commercial or ideological reasons. Objective. To determine whether directional activation steering can shift an open-weights LLM's depression treatment recommendations. Design, Setting, and Participants. This non-human subjects study applied directional activation steering to an open-weights LLM (DeepSeek V4 Flash) responding to 12 depression-advice scenarios (4 favoring medication, 4 favoring avoidance, 4 neutral), generated at 30 amplitudes from -1.5 to +1.5 in 0.1 increments plus an unsteered baseline. Exposures. A single steering direction contrasting antidepressant medication with self-directed approaches (diet, exercise, meditation, dietary supplements), constructed from 16 paired training prompts and applied at the attention output of every transformer block; weights and system prompt were held constant. Main Outcomes and Measures. The extent to which medication and four self-care categories were addressed, scored 0 to 3 by a human-validated LLM rater (Claude Opus 4.7), the medication-versus-self-care balance, and clinician referral, estimated per unit of amplitude using mixed-effects models with a scenario random intercept. Results. Across 372 generations, steering produced a graded, dose-dependent shift in the medication-versus-self-care balance, which declined by 0.32 per unit of amplitude (beta=-0.32; 95% CI, -0.39 to -0.25; P < .001); medication extent fell and self-care extent rose. The shift was largest for scenarios with no stated treatment preference (beta = -0.44; 95% CI, -0.54 to -0.34; P < .001). A clinician referral appeared in 322 of 372 responses (87%) and did not vary with steering amplitude (P = .63). Conclusions and Relevance. In this open-weights LLM providing depression treatment information, inference-time activation steering shifted treatment recommendations without altering weights, prompt structure, or safety outputs, with the largest effect among users expressing no treatment preference. These findings suggest a need for LLM disclosure standards and independent auditing as such models inform clinical decisions.

Read & Discuss → View Source →
10.
arXiv (CS.AI) 2026-06-15

The Shrinking Lifespan of LLMs in Science

Authors:
Ana Tri\v{s}ovi\'c↗

arXiv:2604.07530v2 Announce Type: replace-cross Abstract: Scaling laws describe how language model capabilities grow with compute and data, but say nothing about how long a model matters once released. We introduce time-to-peak and lifespan as measures of model obsolescence and use them to characterize the scientific adoption trajectories of 62 LLMs across more than 108k citing papers (2019-2025), separating active adoption from background citation to recover per-model trajectories that citation counts cannot resolve. We find that a model's longevity is shaped more by when it was released than by its characteristics: release year predicts time-to-peak and lifespan more strongly than architecture, openness, or scale. LLM adoption follows an inverted-U curve (rising after release, peaking, and then declining), but this pattern is rapidly compressing. Each successive release year is associated with a 27% shorter time-to-peak and a 23% shorter lifespan ($p < 0.001$), robust to minimum-age thresholds and controls for model size. These adoption-side dynamics are invisible to scaling laws and suggest that specialization on any single model may be a depreciating investment, with costs falling on reproducibility and migration.

Read & Discuss → View Source →
11.
arXiv (CS.CV) 2026-06-17

Colab NAS: Obtaining lightweight task-specific convolutional neural networks following Occam's razor

Authors:
Andrea Mattia Garavagno↗Daniele Leonardis↗Antonio Frisoli↗

The current trend of applying transfer learning from convolutional neural networks (CNNs) trained on large datasets can be an overkill when the target application is a custom and delimited problem, with enough data to train a network from scratch. On the other hand, the training of custom and lighter CNNs requires expertise, in the from-scratch case, and or high-end resources, as in the case of hardware-aware neural architecture search (HW NAS), limiting access to the technology by non-habitual NN developers. For this reason, we present ColabNAS, an affordable HW NAS technique for producing lightweight task-specific CNNs. Its novel derivative-free search strategy, inspired by Occam's razor, allows to obtain state-of-the-art results on the Visual Wake Word dataset, a standard TinyML benchmark, in just 3.1 GPU hours using free online GPU services such as Google Colaboratory and Kaggle Kernel.

Read & Discuss → View Source →
12.
arXiv (CS.CV) 2026-06-11

Semantic Segmentation of Node and Edge Diagrams for Assistive Technology

Authors:
Michael Cormier↗Yichun Zhao↗Laura Paul↗Cameron Swift↗Duc Tri Dang↗Miguel Nacenta↗

In this paper, we present a novel set of related models for semantic segmentation of node-link diagrams. These diagrams are frequently used to represent mathematical graphs, relationships between concepts, and flowcharts. Such diagrams are difficult to access non-visually; while some assistive interfaces have been designed for node-link diagrams, they rely upon a machine-readable representation of the diagram, whereas such diagrams will generally be made available as bitmap images. Our compact deep learning models show excellent quantitative and qualitative performance on a large synthetic dataset of node-link diagrams, reaching per-pixel accuracy over 93\%.

Read & Discuss → View Source →
13.
arXiv (CS.LG) 2026-06-17

Multi-Source Cybersecurity Logs: An ATT&CK-Labeled Dataset and SLM Evaluation

Authors:
Abir Ashab Niloy↗Ahmed Ryan↗Imamul Hossain Rafi↗Md Erfan↗Md Rayhanur Rahman↗

arXiv:2606.18190v1 Announce Type: cross Abstract: Multi-stage cyberattacks span system, network, and browser logs. Detecting them requires correlating events across all three sources. Machine learning methods can learn these cross-source patterns, but they need labeled multi-source data. Existing public datasets fall short. Network-only datasets such as CICIDS and UNSW-NB15 miss host and browser activity. Host-focused datasets such as LMDG and CICAPT-IIoT lack browser telemetry. ATLAS includes all three sources but labels events only as malicious or benign, without MITRE Adversarial Tactics, Techniques, and Common Knowledge (ATT&CK) technique granularity. No public dataset combines all three sources with per-entry ATT&CK technique labels. We close the gap by building a multi-source log dataset of 870 sessions (70 attack, 800 benign) and approximately 2.3 million events. We captured system, network, and browser activity simultaneously on Windows endpoints. We labeled malicious events with ATT&CK technique IDs, covering 12 tactics and 53 techniques. We generated all attack data using real tools, including Remote Access Trojan (RAT), Command and Control (C2) tunnels, and cloud exfiltration. To demonstrate learnability, we fine-tuned three Small Language Models (SLMs) (Qwen2.5-1.5B, Llama-3.2-3B, Phi-4-Mini) using Low-Rank Adaptation (LoRA). We compared each against its base variant across ten metrics on two tasks: chunk classification and ATT&CK technique identification. Fine-tuning improved every model on every metric. Chunk classification accuracy rose from approximately 8% in the base variants to between 90% and 97% after fine-tuning. Technique identification remained challenging, with the best exact-match accuracy at 42%, although high partial-match scores show the models captured most of the underlying reasoning.

Read & Discuss → View Source →
14.
arXiv (CS.AI) 2026-06-11

Time-Series Foundation Model Embeddings for Remaining Useful Life Estimation

Authors:
Amir El-Ghoussani↗Michele De Vita↗Ronald Naumann↗Valiseios Belagiannis↗

arXiv:2606.11990v1 Announce Type: cross Abstract: Remaining Useful Life (RUL) prediction is essential for industrial predictive maintenance, yet many learning-based approaches rely on extensive feature engineering or large labeled datasets to train task-specific sequence models. In this work, we introduce a lightweight learning approach, in which we leverage a frozen pretrained time-series foundation model (TSFM) and combine it with a small regression head for RUL estimation from multivariate sensor streams. More specifically, we use Chronos-2 as a frozen backbone to extract context window features and train a lightweight regression neural network for RUL prediction. Experiments on real-world industrial sensor data from two device types show that Chronos-2 features consistently improve over recurrent, convolutional, Transformer-based, and gradient-boosting baselines under the same preprocessing and evaluation protocol. We further analyze the impact of context length and find that performance improves significantly with longer histories, indicating that TSFM representation offer a practical and data-efficient alternative for RUL estimation in industrial settings.

Read & Discuss → View Source →
15.
arXiv (CS.CL) 2026-06-18

VISUALSKILL: Multimodal Skills for Computer-Use Agents

Authors:
Ziyan Jiang↗Li An↗Yujian Liu↗Jiabao Ji↗Qiucheng Wu↗Jacob Andreas↗Yang Zhang↗Shiyu Chang↗

Computer-use agents (CUAs) approach human-level performance on standardised benchmarks but still struggle on long-horizon tasks and unseen software. Existing skill libraries address this with reusable skills, but represent the skill artifact as text only, despite the visual nature of GUI interaction. We propose VISUALSKILL: a hierarchical multimodal skill, tailored to each target application and organised as a central index over per-topic files, which the agent consumes through a load_topic MCP tool that fetches the relevant topic's text and figures on demand. We construct each skill with a two-stage pipeline that combines authored documentation with live-application UI exploration. On two CUA benchmarks, CUA-World and OSExpert-Eval, a Claude Code CLI agent backed by Claude Opus 4.6 reaches an average score of 0.456 with VISUALSKILL, a +15.3 point absolute lift over the no-skill baseline (0.303). Against a matched text-only skill that is generated from the same source content and differs from VISUALSKILL only in modality, VISUALSKILL yields a further +8.3 point absolute gain over the matched text-only skill (0.373 vs. 0.456), providing direct evidence that retaining visual figures in the skill artifact, rather than verbalizing them away, helps the agent both identify UI elements and verify workflow state after each action. Our code is available at https://github.com/XMHZZ2018/VisualSkills.

Read & Discuss → View Source →
16.
arXiv (CS.LG) 2026-06-15

Detecting Lookahead Bias in LLM Forecasts

Authors:
Zhenyu Gao↗Wenxi Jiang↗Yutong Yan↗

arXiv:2512.23847v2 Announce Type: replace-cross Abstract: We develop a statistical procedure to detect lookahead bias in economic forecasts generated by large language models (LLMs). Using a date-only recall query for a firm-date pair, we estimate the probability that the LLM has internalized information about the realized outcome, a statistic we term Lookahead Propensity (LAP). LAP is materially positive throughout the in-sample period and collapses essentially to zero right after the training-data cutoff. We show that a positive interaction between LAP and the LLM forecast in an accuracy regression indicates lookahead-bias contamination, and apply the test to two forecasting tasks: news headlines predicting stock returns and earnings call transcripts predicting capital expenditures. In both applications, the LLM forecast's predictive power is amplified on high-LAP firm-date pairs, and the interaction loses significance on post-training-cutoff samples. Our test provides a cost-efficient, diagnostic tool for assessing the validity and reliability of LLM-generated forecasts.

Read & Discuss → View Source →
17.
arXiv (CS.CL) 2026-06-11

SAGE: Answer-Conditioned Uncertainty Targets for Verbal Uncertainty Alignment

Authors:
Kaiwen Shi↗Zheyuan Zhang↗Yanfang Ye↗

Large language models increasingly express uncertainty through natural-language statements, yet these expressions often fail to reflect the model's sampled behavior. We study verbal uncertainty alignment as a distributional calibration problem: the appropriate uncertainty target for a prompt should be estimated from repeated model outputs rather than from an isolated response. However, group rollouts alone are insufficient, since the resulting target must provide a useful training signal. Existing targets only partially satisfy this requirement. We propose SAGE, Semantic-Answer Guided Entropy, a group-level uncertainty target that constructs an answer-conditioned uncertainty geometry over sampled responses. SAGE preserves categorical, numeric, and symbolic answer distinctions while maintaining a smooth and scale-preserving calibration signal. We further apply this target through Group-Uncertainty Preference Optimization, or GUPO, an uncertainty-channel training framework that supervises verbal uncertainty expressions rather than the full response. Experiments across factual, mathematical, and multiple-choice reasoning tasks show improved uncertainty ranking, lower calibration error, and reduced overconfidence.

Read & Discuss → View Source →
18.
arXiv (CS.CL) 2026-06-16

The Answer Lies Within: Self-Derived Rewards Enable Explainable Relation Extraction

Authors:
Xinyu Guo↗Zhengliang Shi↗Minglai Yang↗Mihai Surdeanu↗

Despite the remarkable reasoning capabilities of large language models, they still struggle with one-shot relation extraction without predefined relation labels. We identify two pitfalls: models are often misled by irrelevant tokens instead of relation-conveying semantics, and they often fail to align with the abstraction level human annotators expect. We introduce a novel framework that closes this gap with two components: (1) COGRE, a cognitively-inspired reasoning framework that structures RE into a series of processes mimicking human text-processing; and (2) HIT@DICT, a reinforcement learning intermediate reward strategy that encourages reasoning to align with relational labels by rewarding relation-relevant phrases in reasoning. The reward is derived on a credit dictionary automatically extracted from correct predictions. Our experiments show that our framework improves both accuracy and explanation quality by addressing these two pitfalls. For example, COGRE with Qwen2.5-14B-Instruct on One-shot NYT29 achieves 24.65% F1, surpassing prior reasoning-based designs. Optimizing this approach with RL using HIT@DICT further improves performance by +23.46% points. Finally, human evaluation shows that our best model generates relational phrases closely aligned with gold labels, increasing human explanation quality ratings by 54% (relative).

Read & Discuss → View Source →
19.
bioRxiv (Bioinfo) 2026-06-11

An AI-Powered Trisomy 21 Research Assistant

Authors:
NANDI↗Sundararajan↗Subirana-Granes↗Espinosa↗J. M↗Pividori↗Sullivan↗K. D↗Galbraith↗M. D↗Costello↗

Down syndrome, caused by trisomy 21, increases the risk of diverse co-occurring conditions. With more than 34,000 related publications indexed in PubMed as of early 2026, keeping pace with this expanding literature is challenging. While general-purpose large language models are widely used for information retrieval, they often rely on broad training data rather than specific evidence. Retrieval-augmented generation (RAG) improves rigor and reliability of responses by linking model outputs to source texts. In research, source texts are peer-reviewed articles. Standard implementations treat all manuscript sections equally, allowing background text to rank as highly as experimental results. To focus model outputs on experimentally supported responses, we developed the T21 Research Assistant, a section-aware RAG system that prioritizes Results sections to ground responses in primary experimental evidence. The system draws exclusively from 1,789 open-access Down syndrome publications from PubMed Central, including 327 NIH INCLUDE-funded studies, and uses a multistage pipeline for query validation, retrieval, reranking, synthesis, and citation verification. Built on NVIDIA Nemotron models, it generates structured, cited responses. Evaluation using expert-curated questions demonstrated strong performance, achieving a BERTScore F1 of 0.712 and recall of 0.758, comparable to or exceeding leading proprietary and open-source models. T21 Research Assistant is available at: https://bioinformatics.cuanschutz.edu/t21-res-assi/

Read & Discuss → View Source →
20.
medRxiv (Medicine) 2026-06-11

Plasma protein prioritisation in rheumatoid arthritis reveals druggable targets and shared biology with cardiovascular diseases

Authors:
Alduhayhi↗S. S↗Morris↗A. P↗Zhao↗Bowes↗

Abstract Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex and incompletely understood molecular mechanisms. Understanding circulating proteins associated with RA may improve understanding of disease biology and clarify its pathological links with cardiometabolic comorbidities. Methods A proteome-wide two-sample Mendelian randomisation (MR) drug target analysis was conducted using plasma proteins measured in 54,219 participants from the UK Biobank Pharma Proteomics Project as exposures and RA and cardiometabolic diseases as the outcomes. Summary statistics for RA included 53,663 cases and 1,070,200 controls. Colocalisation analysis was performed to confirm shared single causal variants and prioritise RA proteins supported by both MR and colocalisation. The prioritised proteins were then evaluated in the Accelerating Medicines Partnership RA Phase II synovial single-cell dataset for cell-type expression patterns. Druggability was then assessed followed by analysis of genetic overlap between RA-associated proteins and cardiometabolic diseases. Results 37 plasma proteins had a causal effect on RA risk, supported by combined evidence from MR and conditional colocalisation. In synovial tissue, TPPP3, RARRES2, AKAP12, and GGT5 were predominantly expressed in stromal and endothelial cell clusters. Druggability assessment identified IFNGR2, IL6R, CD40, and FCGR2B as Tier 1 targets. However, several biologically relevant proteins, including RARRES2, AKAP12, TPPP3, and SNX2, had limited available druggability data. Genetic overlap analysis demonstrated shared protein signals between RA and cardiovascular diseases, including overlap of RARRES2 and TPPP3 with coronary artery disease (CAD) and FCGR2B with atrial fibrillation (AF). To approximate the therapeutic effect of target inhibition, the direction of effect estimates for proteins showing overlap between RA-CAD and RA-AF was reversed. Conclusion This study identified circulating proteins involved in RA pathogenesis and reveals shared mechanisms between RA and cardiovascular diseases. While some proteins showed clear translational potential targets, several prioritised proteins had limited available druggability information and could not be confidently classified. Addressing these gaps may help identify new targets relevant to RA management. Future work should also use phenome-wide MR studies to evaluate potential on-target adverse effects of protein inhibition across RA-CAD and RA-AF.

Read & Discuss → View Source →
21.
arXiv (CS.CV) 2026-06-17

UoU: A Universal Fingerprint Foundation Model Based on Large-Scale Unsupervised Learning

Authors:
Xiongjun Guan↗Jianjiang Feng↗Jie Zhou↗

Fingerprint recognition is still dominated by task-specific pipelines, where enhancement, structural parsing, alignment, and matching are optimized in isolation. Although effective in narrow settings, this design limits representation reuse across sensors, qualities, and downstream applications. We therefore present UoU, short for ``a Universal fingerprint foundation model based on large-scale Unsupervised learning,'' which reframes fingerprint feature extraction as a domain-specific foundation-model problem. UoU is organized around a multi-level representation hierarchy spanning image restoration, structural fields, semantic tokens, point-level biometric entities, and compact global descriptors. Its training recipe combines a supervised cold start on precise annotations, large-scale weakly supervised refinement, and large-scale unsupervised consolidation, with the latter two stages iterated during large-scale training so that weak supervision broadens semantic coverage while unsupervised learning stabilizes correspondences, invariances, and representation geometry. Rather than treating fingerprint imagery as generic texture, UoU exploits domain-specific symmetries and intermediate structure, including orientation flow, periodic ridge patterns, sparse biometric entities, and spatial equivariance. The framework is intentionally architecture-agnostic: while the present study includes an initial transformer-based structured-prediction instantiation, the broader design supports multi-task learning, scalable model configurations, and downstream specialization for matching, alignment, enhancement, registration, and related fingerprint applications. This paper presents the technical motivation, system design, and validation protocol of UoU, and part of the baseline implementation is publicly available at https://github.com/XiongjunGuan/UoU.

Read & Discuss → View Source →
22.
arXiv (CS.AI) 2026-06-15

The Curse and Blessing of Mean Bias in FP4-Quantized LLM Training

Authors:
Hengjie Cao↗Zhendong Huang↗Mengyi Chen↗Yifeng Yang↗Fang Dong↗Anrui Chen↗Ruijun Huang↗Xin Zhang↗Mingzhi Dong↗Yujiang Wang↗Jinlong Hou↗Qin Lv↗…

arXiv:2603.10444v2 Announce Type: replace-cross Abstract: FP4 training promises substantial memory and compute savings for large language models, but remains fragile because blockwise quantization is dictated by extreme activation magnitudes, which inflate dynamic range and compress long-tail signals. We identify a counterintuitive source of this failure: dominant activation outliers are not merely arbitrary sparse events, but are largely induced by a coherent rank-one mean bias, whose direction aligns with the leading anisotropic spectral component. This mean component strengthens during training, is amplified and reshaped by attention and FFN operators, and increasingly dominates top activation magnitudes. Crucially, this discovery reveals that a seemingly complex outlier-suppression problem admits a truly simple solution: isolate the coherent mean before quantization. We therefore propose Averis, a mean-residual splitting quantization method that separates the mean component using only reductions and elementwise subtractions before FP4 quantization. Across Qwen3 0.6B Dense trained on 100B tokens and Qwen3 7B A1.5B MoE trained on 50B tokens, Averis enables robust W4A4G4 FP4 training, reducing BF16 loss gaps to 1.19%/0.81% versus 2.05%/1.10% for NVIDIA's recently released Hadamard-based outlier-smoothing method, while limiting downstream gaps to 0.89/0.71 points. With only 2.20% end-to-end overhead over vanilla NVFP4, about 30% of NVIDIA's Hadamard-based design, Averis provides a hardware-efficient path to stable low-bit LLM training. Complementary to Hadamard, Averis further reduces the Qwen3-0.6B loss and downstream gaps to 0.94% and 0.73 points when combined. Code is available at: https://anonymous.4open.science/r/averis-504D.

Read & Discuss → View Source →
23.
arXiv (CS.LG) 2026-06-17

Constrained Diffusion Models with Primal-Dual Inference

Authors:
Samar Hadou↗Yigit Berkay Uslu↗Alejandro Ribeiro↗

arXiv:2606.17192v1 Announce Type: new Abstract: This paper develops constrained diffusion models with primal-dual inference (PDI) to sample from optimal distributions of entropy-regularized optimization problems with average constraints. We formalize constrained sampling in the Lagrangian dual domain, where the optimal distribution takes the form of a Gibbs distribution indexed by the optimal dual variable. Rather than estimating this dual multiplier before sampling and freezing it throughout generation, PDI jointly infers the optimal primal distribution and its parametrizing dual variable. Each reverse diffusion step denoises using the score field associated with the current multiplier and then updates the multiplier through dual ascent using the estimated constraint violation of the denoised samples. To enable this conditional score field, we train a single dual-conditioned score network over the family of Gibbs distributions induced by the dual variables encountered during inference. We prove that the time average of the dual variables generated along the inference trajectory converges to a neighborhood of the dual optimum and bound the effect of residual dual mismatch on the terminal distribution through schedule-dependent stability factors. We evaluate PDI on constrained sampling from a mixture of Gaussians, wireless resource allocation, and portfolio management.

Read & Discuss → View Source →
24.
arXiv (CS.AI) 2026-06-18

A Clinician-Centered Pipeline for Annotation and Evaluation in Ultrasound AI Studies

Authors:
Fangyijie Wang↗Jianjun Yu↗Wentao Shi↗Haixia Huang↗Ran Shi↗Gu\'enol\'e Silvestre↗Kathleen M. Curran↗

arXiv:2606.19174v1 Announce Type: cross Abstract: Clinician-centered evaluation is critical for validating medical AI systems, especially in ultrasound imaging where quantitative metrics do not always capture clinical usability. Existing medical image platforms primarily focus on dataset labeling. They lack integrated support for blinded model comparison and reproducible evaluation workflows. We present a clinician-centered pipeline for remote annotation and evaluation in ultrasound AI studies. The proposed pipeline uses a centralized server and lightweight browser interfaces to enable clinicians to perform annotation, blinded ranking, and review without local dataset downloads. The pipeline also supports multi-rater participation, centralized result aggregation, and automated statistical analysis. We validate the pipeline in a fetal ultrasound segmentation study with six raters spanning expert, generalist, and non-expert experience levels. The system automatically generated Spearman correlation, Kendall's $\tau$, and top-1 selection statistics. Results indicated moderate to strong agreement across experts and other groups. The blinded evaluation results showed a tendency for later active learning models to be preferred. These outcomes suggest that the pipeline can support clinician-centered annotation and reproducible human-\ac{AI} evaluation studies in ultrasound imaging. The proposed pipeline is available on \href{https://github.com/13204942/SonoRate}{GitHub}.

Read & Discuss → View Source →
25.
arXiv (CS.CL) 2026-06-18

Learning User Simulators with Turing Rewards

Authors:
Yingshan Susan Wang↗Cedegao E. Zhang↗Linlu Qiu↗Zexue He↗Pengyuan Li↗Alex Pentland↗Roger P. Levy↗Yoon Kim↗

Learning to simulate human users in interactive settings could advance the training of agent assistants, evaluation of personalization systems, research in the social sciences, and more. Existing approaches generally do so by training a large language model (LLM) to match a single ground truth response, either by maximizing the log probability or by using a similarity reward. We instead propose {Turing-RL}: a Turing-Test-based reinforcement learning approach for training user simulator models. {Turing-RL} uses a discriminative Turing reward with an LLM judge to score how indistinguishable a generated response is from the real user's given the user's history, and the user simulator LLM learns to produce responses indistinguishable from what the user could have said with such rewards. Across two different domains–conversational chat and Reddit forum discussion–we find that {Turing-RL} consistently outperforms baseline methods on both LLM and human evaluation metrics. Our study suggests that optimizing for indistinguishability, rather than response matching, is effective for learning user simulators.

Read & Discuss → View Source →