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01.
arXiv (CS.CL) 2026-06-18

Improve Large Language Model Systems with User Logs

Scaling training data and model parameters has long driven progress in large language models (LLMs), but this paradigm is increasingly constrained by the scarcity of high-quality data and diminishing returns from rising computational costs. As a result, recent work is increasing the focus on continual learning from real-world deployment, where user interaction logs provide a rich source of authentic human feedback and procedural knowledge. However, learning from user logs is challenging due to their unstructured and noisy nature. Vanilla LLM systems often struggle to distinguish useful feedback signals from noisy user behavior, and the disparity between user log collection and model optimization (e.g., the off-policy optimization problem) further strengthens the problem. To this end, we propose UNO (User log-driveN Optimization), a unified framework for improving LLM systems (LLMsys) with user logs. UNO first distills logs into semi-structured rules and preference pairs, then employs query-and-feedback-driven clustering to manage data heterogeneity, and finally quantifies the cognitive gap between the model's prior knowledge and the log data. This assessment guides the LLMsys to adaptively filter out noisy feedback and construct different modules for primary and reflective experiences extracted from user logs, thereby improving future responses. Extensive experiments show that UNO achieves state-of-the-art effectiveness and efficiency, significantly outperforming Retrieval Augmented Generation (RAG) and memory-based baselines. We have open-sourced our code at https://github.com/bebr2/UNO .

02.
arXiv (CS.LG) 2026-06-18

Ensuring Trustworthy Online A/B Testing: Addressing Five Key Questions on CUPED

arXiv:2606.18750v1 Announce Type: cross Abstract: A/B testing has become the gold standard for data-driven decision-making in large-scale online experimentation, providing critical guidance for feature launch, pricing optimization, and user experience enhancement. To maximize statistical sensitivity, many technology companies routinely employ Controlled-experiment Using Pre-Experiment Data (CUPED), a technique that achieves substantial variance reduction while preserving the unbiasedness of estimating the average treatment effect. Despite its widespread adoption, several critical methodological and practical nuances of CUPED remain underexplored. This paper systematically addresses five frequently encountered yet overlooked questions regarding the application of CUPED. First, we provide a comparative analysis of various post-CUPED estimators to identify the optimal adjustment specification. Second, we evaluate the validity of regression-based adjustments and delineate robust variance estimation methods tailored for such frameworks. Finally, we extend our investigation to complex but common scenarios, including multi-arm experiments and two-stage sampling designs. Our findings reveal that in these settings, naive reliance on standard variance estimators can lead to severely misleading inferences. By offering rigorous theoretical insights and extensive experimental validation, this work deepens the conceptual understanding of CUPED. Notably, the recommended methodologies have been successfully deployed and integrated into ByteDance's experimentation platform.

03.
arXiv (CS.CL) 2026-06-16

Understanding the Behaviors of Environment-aware Information Retrieval

Recent retrieval-augmented generation (RAG) approaches have demonstrated strong capability in handling complex queries, yet current research overlooks a critical challenge: different retrievers require fundamentally different query formulation strategies for optimal performance. In this work, we present the first systematic analysis of how LLMs can learn to adapt their query formulation strategies for different retrievers via reinforcement learning (RL). Our empirical study reveals that RL effectively teaches an LLM to tailor its queries to specific retriever characteristics. We discover that different retrievers exhibit surprisingly distinct optimal query styles (e.g., descriptive vs. question-like), suggesting strategies learned for one retriever ineffective for another. We further show that performance can be enhanced by incorporating retriever-specific human guidance and by scaling model size. To facilitate learning over multi-retrieval-step trajectories, we introduce a branching-based rollout technique that improves training stability. Our work provides the first empirical evidence and actionable insights for building truly retriever-aware RAG systems. Code and resources are available at https://github.com/LCO-Embedding/Envs-aware-Information-Retrieval.

04.
arXiv (quant-ph) 2026-06-15

Inhomogeneous Light-Matter Coupling as a Resource for Noiseless Quantum Memories

arXiv:2605.26783v3 Announce Type: replace Abstract: Inhomogeneous ensembles of two-level systems are central to both fundamental light-matter physics and quantum-network applications. Understanding and optimizing ensemble-based quantum memories and entanglement protocols requires a unified framework that describes how to store quantum states of light as collective matter excitations and retrieve them on demand. Here we develop such a framework, the waveguide model, by mapping the dark collective modes of the ensemble onto an effective waveguide with well-defined input-output relations, valid in both the weak-excitation regime and near population inversion. This model reveals that inhomogeneous coupling – often regarded as a limitation – is instead the physical origin of noisy-echo suppression by adiabatic pulses, a key ingredient for realizing noiseless quantum memories. For entanglement generation, the same mechanism exposes a previously unexplored shortcoming of robust control pulses and leads to a new composite-pulse protocol that overcomes it. These results establish the waveguide model as a practical bridge between fundamental collective physics and quantum-network protocol design, recasting inhomogeneous coupling from an obstacle into a control knob for collective emission.

05.
bioRxiv (Bioinfo) 2026-06-21

OracleScreen-LILRB4: Machine Learning-Guided Discovery of Myeloid Immune Checkpoint Binders Validated in Patient-Derived Cells

The identification of small molecule modulators of immune checkpoint proteins remains a significant challenge in drug discovery due to the flat, featureless nature of protein-protein interaction interfaces and the characteristically low hit rates observed in conventional high-throughput screening campaigns. Here we report OracleScreen-LILRB4, an ensemble machine learning framework trained on quantitative biophysical screening data from two structurally diverse compound libraries (19,800 compounds total) screened against the myeloid immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4/ILT3). By formulating binding prediction as a regression task targeting continuous {Delta}Fnorm values rather than binary hit classifications, OracleScreen-LILRB4 achieved a mean Spearman R of 0.61 and ROC-AUC of 0.86 under scaffold-aware cross-validation. Prospective virtual screening of a 45,760-member compound library and experimental validation of the top 200 predictions yielded a 28.5% hit rate, representing a 15.0-fold enrichment over baseline, with 16 compounds demonstrating nanomolar-affinity LILRB4 (ILT3) engagement. Lead compounds ORS-22 and ORS-14 restored anti-tumor immune activity across patient-derived colorectal cancer and acute myeloid leukemia co-culture systems, reversing SCG2-mediated immunosuppression and recovering cytotoxic T-cell function. These findings establish OracleScreen-LILRB4 as an effective computational framework for accelerating small molecule discovery against non-enzymatic immune checkpoint targets.

06.
arXiv (CS.CV) 2026-06-17

LADBench: A Benchmark for Logical Fault Detection in Images

Large Vision Language Models (VLMs) excel at visual question answering and semantic grounding, but their capacity for autonomous logical reasoning remains underexplored. Existing anomaly benchmarks emphasize visual errors or direct prompting rather than the physical and social common sense needed for open-world deployment. To address this, we introduce LAD-bench, a benchmark of more than 1,000 curated synthetic images with logical anomalies across four domains: Residential, Urban, Collaborative, and Nature. We further propose a Tiered Prompting Protocol based on progressive disclosure, which measures how much explicit assistance a model needs to localize and reason about a logical fault. Evaluating leading foundation models reveals substantial weaknesses: even the best achieves only 70.11% overall accuracy, showing that implicit logical fault detection remains unsolved. Crucially, models often fail to identify anomalies even after receiving explicit hints in deeper tiers. By surfacing these limitations in sequential multimodal reasoning, LAD-Bench offers a rigorous framework for advancing the safety, reliability, and cognitive alignment of autonomous visual systems. Dataset and Code: https://huggingface.co/datasets/SahasraK/LADBench

07.
arXiv (CS.AI) 2026-06-18

As You Wish: Mission Planning with Formal Verification using LLMs in Precision Agriculture

arXiv:2606.18519v1 Announce Type: cross Abstract: Though robotic systems are now being commercialized and deployed in various industries, many of these systems are highly specialized and often require an advanced skill set to operate and ensure they perform as instructed. To mitigate this problem, we recently introduced a mission planner leveraging LLMs to synthesize mission plans in precision agriculture based on mission descriptions provided in natural language. While the system demonstrates impressive performance, it also suffers from the inherent ambiguities of natural language. In this paper, we extend our system to address this issue by introducing multiple feedback loops in the planning architecture that leverage linear temporal logic (LTL) to ensure the mission planning system meets the specifications formulated by the user while still using natural language. To mitigate potential bias, this is achieved by using two different commercial LLMs in charge of the specification and verification subtasks. Through extensive experiments, we highlight the strengths and limitations of integrating mission verification into a fully autonomous pipeline, particularly regarding an LLM's ability to generate valuable LTL formulas, and show how our proposed implementation addresses and solves these challenges.

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

Last But Not Least: Boundary Attention CalibratiON for Multimodal KV Cache Compression

Multimodal Large Language Models (MLLMs) achieve strong vision-language reasoning, but long visual contexts enlarge the KV cache and increase decoding latency. Existing compression methods rely on observation window attention for stable token-importance estimation, yet this aggregation can dilute sparse visual evidence and discard answer-critical tokens under aggressive compression. Therefore, we identify last-query attention as a complementary source for recovering such evidence, but its answer-irrelevant signals can mislead retention. We propose BACON, a plug-and-play method that calibrates observation window attention with last-query evidence and suppresses isolated noise via intra-layer coherence and inter-layer persistence. Across diverse benchmarks, models, budgets, and compression methods, BACON improves multimodal KV compression by 7.5% on average under the most aggressive budget, with gains up to 30.9%.

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

CONCORD: Asynchronous Sparse Aggregation for Device-Cloud RAG under Document Isolation

arXiv:2606.15179v1 Announce Type: new Abstract: Retrieval-augmented generation (RAG) has emerged as a pivotal technique for improving language models by incorporating external knowledge at inference time. As device-cloud collaborative inference makes it feasible to deploy small language models on edge devices, a new setting arises in which private documents remain on the device and public knowledge resides in the cloud. Privacy and policy constraints often forbid raw document exchange, creating a document-isolated dual-end RAG setting. However, existing methods rely on frequent remote synchronization and dense evidence transfer, limiting throughput under realistic latency and bandwidth conditions. To address this issue, we propose CONCORD, an asynchronous sparse aggregation framework for dual-end RAG under document isolation. CONCORD treats the cloud as an asynchronously arriving evidence source rather than a continuously synchronized co-generator. Specifically, we introduce waiting debt control to decide whether each decoding step should continue waiting for remote participation based on the observed return of waiting. We also design a certificate-guided minimal supplementation mechanism that requests only the remote evidence needed to determine the current greedy decision. Steps that consult the cloud preserve the same greedy token as dense dual-end aggregation, while the remaining steps commit locally without remote evidence. Experiments on Natural Questions and WikiText-2 show that CONCORD improves end-to-end throughput over baselines by $1.66\times$ and $2.15\times$, respectively, while reducing per-token communication by over two orders of magnitude and maintaining comparable answer quality and perplexity.

10.
medRxiv (Medicine) 2026-06-11

Decoding the Genetic Architecture of Autistic Traits in the Aging Population

Autism research has mostly focused on diagnostic frameworks in childhood. However, autistic traits including social skills, communication, attention switching, attention to detail, and imagination may also vary in many undiagnosed individuals beyond childhood, and the genetic architecture of autistic traits in undiagnosed aging adults remains poorly understood. Here, we performed an exome-wide association study of autistic traits in adults aged >=40 from the UK Biobank (n = 161,269) and independently validated key findings in the SPARK cohort (n = 142,357). We identified exome-wide significance at 17q21.31, represented by a lead variant associated with social skills (rs199533, beta = 0.081, P = 2.04e-11). In addition, we identified an independent signal for communication (rs12632110, beta = 0.042, P = 3.07e-12) and two independent signals for attention switching (rs690733, beta = 0.046, P = 4.26e-12; rs2164272, beta = -0.047, P = 1.73e-12). Gene-based analyses further implicated loss-of-function variation in ZSCAN2 (beta = 1.00, P = 2.44e-6), which was associated with communication differences. Enrichment analyses revealed preferential expression of implicated genes in the cerebral cortex, while phenotypic and neuroimaging analyses linked those variants to cortical brain structure and regional volume. Taken together, these findings delineate the genetic architecture of autistic traits in the aging population and link genetic variation to downstream molecular and neuroanatomical mechanisms.

11.
arXiv (CS.LG) 2026-06-17

AIMER: Calibration-Free Task-Agnostic MoE Expert Pruning

arXiv:2603.18492v3 Announce Type: replace Abstract: Mixture-of-Experts (MoE) language models increase parameter capacity without proportional per-token computation, yet deployment still requires storing the full expert pool, making expert pruning important for reducing memory and serving overhead. Existing task-agnostic expert-pruning methods are typically calibration-dependent: they estimate expert importance from routing or activation statistics on a calibration set, making pruning decisions sensitive to calibration-data variation while introducing substantial preprocessing cost. We propose AIMER (Absolute mean over root mean square IMportance for Expert Ranking), a simple calibration-free criterion that identifies more distinct experts by capturing the concentration pattern of expert weights, making it well suited for task-agnostic expert pruning. Across 7B to 47B MoE language models with distinct architectures and 16 diverse benchmarks, AIMER consistently delivers stronger capability balance across diverse tasks than existing calibration-free methods. Surprisingly, AIMER also achieves better balance than strong calibration-based expert-pruning baselines calibrated on the widely used task-agnostic C4 corpus, while requiring only 0.22–2.06 seconds to score all experts.

12.
Nature (Science) 2026-06-10

Whole-genome duplication shaped cell-type evolution in the vertebrate brain

作者:

The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution1, but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human2, mouse3, lizard4, lamprey5 and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show one-to-one homology with amphioxus. Moreover, ohnologues, particularly those from the first WGD, were more important than small-scale duplication paralogues for vertebrate cell-type evolution. To explore whether ohnologues are mechanistically important for this process, we predicted ancestral cell-type states and compared them to amphioxus and experimentally investigated macroglia. The findings indicate that ohnologues had a role in early vertebrate cell-type diversification. Moreover, by examining paralogue expression across cell types and species, we show that expression changes were mainly driven by dosage selection and subfunctionalization. We also link ohnologues to cellular diversity at different anatomical and cell-type scales. Our findings demonstrate the importance of WGDs for the evolution of early vertebrate brain complexity and highlight that the resultant ohnologues continued to capacitate cell-type evolution long after they were formed. Analyses of brain single-cell transcriptomes from human, mouse, lizard, lamprey and amphioxus reveal that duplicated genes (ohnologues) played a pivotal part in early vertebrate cell-type diversification.

13.
arXiv (CS.LG) 2026-06-11

Bypassing Prompt Guards in Production with Controlled-Release Prompting

arXiv:2510.01529v4 Announce Type: replace Abstract: Ball et al. recently established that prompt filtering for AI alignment faces a fundamental barrier: under standard cryptographic assumptions, no filter running significantly faster than the protected model can universally distinguish adversarial prompts from benign ones. We investigate whether this impossibility result translates to real-world vulnerabilities in deployed large language model (LLM) systems. We answer affirmatively by introducing controlled-release prompting, a practical instantiation of the theoretical framework that exploits the resource asymmetry between lightweight input filters and the main models they protect. Unlike the theoretical construction, our attack does not require model modification: it generates malicious prompts that are indecipherable by any bounded filter yet remain tractable to the target LLM. We find our attack to be successful on four major chat platforms (Google Gemini, DeepSeek Chat, xAI Grok, and Mistral Le Chat) where baseline methods fail. Additionally, we apply our attack to extract copyrighted data from Gemini. Finally, we provide a systematic evaluation of 14 open-weight prompt guard models, revealing that even reasoning-capable filters cannot reliably detect our attack without incurring prohibitive resource overhead.

14.
arXiv (CS.CV) 2026-06-16

Trusting Right Predictions for Wrong Reasons: A LIME Based Analysis of Deep Learning Interpretability in Lung Cancer Diagnosis

Lung cancer is the leading cause of cancer-related mortality, with approximately 2.5 million new cases and 1.8 million deaths annually, making reliable diagnosis a clinical priority. Although deep learning models have achieved strong performance in lung cancer classification, evaluation has largely focused on predictive accuracy, leaving their decision-making processes insufficiently examined. This study compares three architecturally distinct models: a Convolutional Neural Network (CNN), a pretrained ResNet50, and a Vision Transformer (ViT), trained on the IQ-OTH/NCCD lung cancer CT dataset. Local Interpretable Model-Agnostic Explanations (LIME) were applied to investigate model reasoning. In addition to standard performance metrics, a dual-correlation framework was introduced to measure both prediction agreement and explanation agreement across model pairs. All three models achieved strong classification performance, with ResNet50 attaining 98.61% accuracy, CNN 97.91%, and ViT 93.75%, while all achieved ROC-AUC scores of 0.99. Prediction correlations exceeded 0.99 across all model pairs, indicating highly consistent outputs. However, LIME explanation correlations remained below 0.26, revealing substantial differences in the image regions used to reach those predictions. Analysis of misclassified samples further identified a consistent spatial pattern: incorrect predictions were associated with attention outside the lung parenchyma, whereas correct predictions focused primarily within lung regions. These findings demonstrate that prediction agreement is a poor proxy for reasoning consistency, and that interpretability evaluation must be treated as an independent validation criterion alongside predictive performance in clinical AI systems.

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

On the Smoluchowski-Kramers approximation for the hyperbolic $O(N)$ linear sigma model and its mean-field limit

arXiv:2606.15214v1 Announce Type: cross Abstract: We study the hyperbolic $O(N)$ linear sigma model, i.e. a system of $N$ interacting stochastic damped nonlinear wave equations (SdNLW) with coupled cubic nonlinearities, posed on the two-dimensional torus and indexed by a parameter $\varepsilon > 0$. We show that as $\varepsilon$ goes to zero (Smoluchowski-Kramers approximation) and $N$ goes to infinity (mean-field limit), each component of the solution to the SdNLW system converges to the solution to the stochastic nonlinear heat equation (SNLH) with a mean-field nonlinearity. We prove such convergence via two regimes: first with $\varepsilon$ going to zero to obtain the parabolic $O(N)$ linear sigma model, i.e. a system of $N$ coupled SNLH, and then with $N$ going to infinity; or first with $N$ going to infinity for each component to obtain the mean-field SdNLW and then with $\eps$ going to zero. As a result, we obtain a commutative diagram regarding the convergence from the hyperbolic $O(N)$ linear sigma model to the mean-field SNLH.

16.
arXiv (CS.AI) 2026-06-18

IPSL-AID: Generative Diffusion Models for Climate Downscaling from Global to Regional Scales

arXiv:2604.03275v2 Announce Type: replace-cross Abstract: Effective adaptation and mitigation strategies for climate change require high-resolution projections to inform strategic decision-making. Conventional global climate models, which typically operate at resolutions of 150 to 200 kilometers, lack the capacity to represent essential regional processes. IPSL-AID is a global to regional downscaling tool based on a denoising diffusion probabilistic model designed to address this limitation. Trained on ERA5 reanalysis data, it generates 0.25 degree resolution fields for temperature, wind, and precipitation using coarse inputs and their spatiotemporal context. It also models probability distributions of fine-scale features to produce plausible scenarios for uncertainty quantification. The model accurately reconstructs statistical distributions, including extreme events, power spectra, and spatial structures. This work highlights the potential of generative diffusion models for efficient climate downscaling with uncertainty

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

When Do LLMs Reason? A Dynamical Systems View via Entropy Phase Transitions

Chain-of-thought (CoT) reasoning has become the default strategy for enhancing LLM capabilities, yet its application raises a fundamental question: when is explicit reasoning actually beneficial? Empirical evidence reveals a striking paradox: CoT often provides marginal or even negative gains on factual and open-ended tasks while multiplying token consumption. In this work, we show that LLM reasoning is not a static property of tasks or models, but a dynamic decoding state that emerges during generation. Through systematic analysis, we find early-stage entropy dynamics provide a reliable signal of this state: tasks benefiting from CoT exhibit consistent entropy reduction, while others display unstable or increasing patterns. This behavior can be interpreted as a phase-transition-like shift from a high-entropy exploratory regime to a low-entropy structured reasoning regime. Based on these insights, we propose EDRM (Entropy Dynamics-based Reasoning Manifold), a lightweight and training-free routing framework that leverages early decoding entropy to adaptively select inference strategies. EDRM embeds entropy trajectories into a compact and interpretable manifold representation, enabling both zero-shot deployment and fine-grained instance-level adaptation. Across 15 benchmarks and 4 LLMs of varying scales and architectures, EDRM consistently outperforms static baselines. At the dataset level, EDRM achieves 41–55\% token reduction while improving accuracy with as few as 50 calibration samples. At the instance level, it further improves accuracy by up to 4.7\% while maintaining 27–45\% token savings. These results suggest that reasoning should be invoked selectively rather than by default, and demonstrate the effectiveness of entropy-driven decoding control for efficient and adaptive LLM inference.

18.
medRxiv (Medicine) 2026-06-22

Development of a Novel Risk Prediction Model for Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD): A Longitudinal Study

Background: Interstitial lung disease (ILD) is one of the most common and potentially most devastating extra-articular complication of rheumatoid arthritis (RA) and is associated with substantial morbidity and mortality. However, reliable tools for the early identification of ILD in patients with RA remain limited. This study aimed to identify plasma protein biomarkers of RA-ILD and develop an interpretable machine learning model for risk prediction using data from the UK Biobank. Methods: We first evaluated the association between baseline RA and the risk of incident ILD in the UK Biobank using Cox proportional hazards models. Mendelian randomization analysis was then performed to investigate the potential causal relationship between RA and ILD. Finally, we analyzed 2,920 plasma proteins measured using the Olink platform in 781 eligible RA patients. Proteins associated with ILD risk were identified using Cox proportional hazards models and subsequently used to construct eight machine learning models. Model performance was assessed using the receiver operating characteristic curve (ROC) and decision curve analysis. The best-performing model was further interpreted using Shapley additive explanations (SHAP) to evaluate feature importance. Results: Compared with participants without RA, Patients with baseline RA had a significantly higher risk of developing ILD (Hazard ratio: 4.425, 95% CI: 3.549,5.518). The MR supported a potential causal association between RA and ILD (Odds ratio: 1.227, 95% CI: 1.121,1.343). Among the eight machine learning models, the CatBoost model showed the best performance, achieving an area under the curve (AUC) of 0.884 (95% CI: 0.773,0.996). The SHAP analysis identified LAG3, NPC2, and LAMP3 are the three most important plasma protein predictors of ILD development in patients with RA. Conclusion: Plasma proteomics combined with machine learning may provide a promising approach for identifying biomarkers and predicting ILD risk in patients with RA. LAG3, NPC2, and LAMP3 may serve as candidate biomarkers for RA-ILD and warrant further validation. Keywords: Rheumatoid arthritis, Interstitial lung disease, Mendelian randomization, Machine learning, Plasma proteins.

19.
Nature (Science) 2026-06-18

Daily briefing: The proteins that protect us from deadly mutations

作者:

Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States. Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States.

20.
arXiv (CS.AI) 2026-06-19

Sovereign Execution Brokers: Enforcing Certificate-Bound Authority in Agentic Control Planes

arXiv:2606.20520v1 Announce Type: cross Abstract: Autonomous agents are increasingly connected to cloud, deployment, and data-control workflows, but production mutation authority should not reside inside non-deterministic reasoning processes. Existing access-control mechanisms authorize identities, while assurance layers certify proposed actions; neither alone provides a mandatory enforcement point for certified authority at the moment of mutation. This paper introduces the Sovereign Execution Broker (SEB), a runtime enforcement boundary for certificate-bound agentic infrastructure. SEB consumes certificates issued by the Sovereign Assurance Boundary (SAB), verifies that the requested mutation matches the certified execution contract, checks validity windows, policy epochs, revocation epochs, and live-state drift, mints scoped execution identity, invokes infrastructure APIs, and records signed decision and outcome records. By separating proposal, admission, and execution, SEB turns certified authority into a short-lived, revocable, auditable runtime capability, provided that production mutation APIs reject non-broker identities. We present the SEB execution model, certificate and replay-verification predicates, scoped identity semantics, bypass-prevention deployment patterns, failure behavior, and a concrete prototype implementation. We evaluate the prototype on AWS and Kubernetes clusters, measuring latency overheads, revocation propagation, drift detection, and security under fault injection.

21.
arXiv (quant-ph) 2026-06-19

Efficient upsampling for tensor-network and quantum-state encoded functions

arXiv:2601.03885v2 Announce Type: cross Abstract: Both tensor trains (TTs) and quantum states provide compressed representations of grid-structured data with potentially exponential compression power. We present a unified framework for upsampling data encoded in vector amplitudes, with efficient realizations in both classical TT and quantum settings. Starting from an \(n\)-core TT or an \(n\)-qubit state on a coarse grid with \(2^n\) points, the construction produces an \((n+m)\)-core TT or \((n+m)\)-qubit state on a finer grid with \(2^{n+m}\) points. In the TT setting, it supports interpolation, quasi-interpolation, augmentation, and synthesis through efficient low-rank contractions, with the added \(m\) cores retaining constant rank. For function-value encodings, the resulting interpolation satisfies an \(\ell^2\)-error bound independent of the number of added grid points, achieves exponential compression at fixed accuracy, and has a logarithmic complexity in the number of grid points. In the quantum setting, the refined state is prepared by a \(\mathrm{poly}(n,m)\)-size circuit using \(\log(p+1)\) ancillas, where \(p\) controls the smoothness of the quasi-interpolant; the corresponding error scales quadratically with the initial grid spacing. We validate our framework for tensor networks in one-, two-, and three-dimensional examples, including functions, derivatives, airfoil masks, and synthetic random fields such as three-dimensional turbulence. In particular, fractal fields can be generated directly in TT format with logarithmic memory and runtime. These results open a practical route to multiscale solvers, generative models, and geometry-aware algorithms on tensor-network and quantum platforms, with potential applications in scientific simulation, imaging, and real-time graphics.

22.
bioRxiv (Bioinfo) 2026-06-11

DyMoTree decodes early cell state transitions and drivers from single-cell transcriptomes using a tree-structured neural network

Inferring early cell fate from single-cell RNA-sequencing data is essential for identifying cellular origins and fate plasticity in development and disease. However, existing methods often fail to exploit tree-structured lineage trajectories, limiting the accuracy and interpretability of fate mapping. Here we present DyMoTree, a computational framework that models cell fate decisions as nonlinear mappings between progenitor and terminal cell states under explicit lineage constraints. By integrating lineage graphs with a tree-structured neural architecture, DyMoTree learns lineage-resolved cell-state transition maps from single-cell transcriptomes, enabling robust inference of early fate bias and identification of fate-specific progenitor substates and driver genes. Across simulations, lineage-tracing experiments, and in vivo systems, DyMoTree outperformed existing methods in resolving early fate biases. Applications to mouse embryogenesis, lung adenocarcinoma progression, and CAR-T immunotherapy revealed regulatory programs underlying developmental and disease-associated transitions. DyMoTree provides a general framework for modeling lineage-resolved cell-state dynamics underlying development and disease progression.

23.
Nature Biotechnology 2026-06-23

Mapping and engineering the human cell–cell interactome

Efforts to systematically understand how cell interactions tune tissue-level function have motivated transformative advances in single-cell transcriptomics and spatial profiling. Although these technologies can measure molecular states in individual cells and their spatial mapping within tissues, they also reveal that there exists a fundamental knowledge gap of how cells influence each other in context. In this Perspective, we propose an initiative to map and engineer the human cell–cell interactome: a functional atlas of how all major human cell types communicate. We highlight how recent innovations can make this vision achievable. As a first moonshot, we propose the ‘Billion Cell×Cell Project’, which systematically characterizes the outcomes of defined cell–cell dyads across diverse cell types and conditions. We envision this multistage initiative will produce progressively deeper insights and unlock additional avenues for therapeutic discovery. We call on the scientific community to join us in building the tools, datasets and models that will decode and rewrite the language of life between cells. Di Carlo and colleagues discuss technologies required to map and engineer the human cell–cell interactome and the therapeutic avenues such an atlas could unlock.

24.
arXiv (quant-ph) 2026-06-15

Quantum geometrical description of hole spin qubits far away from the $\Gamma$-point

arXiv:2606.14683v1 Announce Type: cross Abstract: Hole spin qubits provide one of the leading platforms for spin-based quantum computing due to their large intrinsic spin-orbit interaction (SOI), which enables fast electrical manipulation. The SOI of planar quantum dots has mostly been investigated in theoretical studies by examining the SOI already present in the two-dimensional hole gas (2DHG). Here, we study the SOI created by the in-plane confinement by deriving non-perturbative effective Hamiltonians numerically for hole spin qubits. We find that the quantum geometry of the 2DHG naturally emerges, leading to a meaningful non-perturbative definition of pseudospin valid far away from the $\Gamma$-point. The SOI of the 2DHG and of the in-plane confinement have different forms; therefore, they cannot be turned off simultaneously, ruining the perfect spin-orbit switch functionality of spin qubits. We construct effective Hamiltonians using the symmetry approach for various low-dimensional hole systems: (i) a heavy-hole confined in a SiGe/Ge/SiGe heterostructure, (ii) a light-hole confined in SnGe/Ge, (iii) a gate-defined nanowire in SiGe/Ge/SiGe, and (iv) a hole confined in a Ge/Si core/shell nanowire. The non-perturbative effective Hamiltonians provide results with excellent agreement with the full Hamiltonians.

25.
bioRxiv (Bioinfo) 2026-06-11

An AI-Powered Trisomy 21 Research Assistant

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/