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01.
arXiv (CS.CL) 2026-06-16

HyDRA: Hybrid Dynamic Routing Architecture for Heterogeneous LLM Pools

Production LLM deployments increasingly maintain heterogeneous model pools spanning order-of-magnitude cost differences. Existing routers make binary strong-vs-weak decisions and couple learned parameters to specific model identities, requiring retraining whenever the catalog changes. We present HyDRA (Hybrid Dynamic Routing Architecture), a framework that predicts fine-grained, multi-dimensional capability requirements per query and matches them against configuration-defined model profiles via shortfall matching. A ModernBERT encoder with K=4 independent sigmoid heads scores each query along reasoning, code generation, debugging, and tool use; a shortfall-matching algorithm then selects the cheapest model whose capabilities meet the predicted requirements. The deployed predictor runs at 86 ms median CPU inference latency in production, and is fully decoupled from the model catalog – adding or removing models requires only a configuration change, with zero retraining. On SWE-Bench Verified (5-model pool: GPT-5.4-mini, Claude Haiku 4.5, GPT-5.3 Codex, Claude Sonnet 4.6, GPT-5.4), HyDRA's tunable shortfall threshold spans three regimes: peak-quality exceeds the always-strong Claude Sonnet 4.6 baseline (75.4% vs. 74.2% resolution) at 12.9% cost savings; iso-quality matches Sonnet at 54.1% cost savings, a 6x improvement over our prior in-house binary router at 9.1%; aggressive pushes savings to 72.5% for a 3.2-point quality trade. Results generalize across LiveCodeBench, BigCodeBench, and tau-bench. HyDRA is deployed to all users in GitHub Copilot's VS Code Chat auto-mode and – to our knowledge for the first time in the LLM routing literature – demonstrates language-invariant routing across CJK, European, and other script families.

02.
arXiv (CS.AI) 2026-06-15

DIFF-ERO: A Conformance-Aware Loss for Deep Learning in Process Mining

arXiv:2606.14283v1 Announce Type: cross Abstract: Deep learning has driven many recent advances in process analytics, especially for predictive and prescriptive monitoring. However, standard objectives such as cross-entropy optimize local next-step likelihoods and only implicitly capture control-flow structure. As a result, models can achieve high token-level accuracy while permitting imprecise global behaviour. We introduce DIFF-ERO, a conformance-aware loss function for deep learning models on process data. DIFF-ERO is a differentiable formulation of entropy-based stochastic conformance that incorporates control-flow information during training. Our approach constructs batch-level stochastic transition matrices with soft edge memberships, allowing structural precision and recall signals to directly inform backpropagation. The loss is model-agnostic and can be applied whenever the final representation parametrizes stochastic transitions. We instantiate DIFF-ERO in transformer encoder-decoder pipelines for next-activity prediction and use it jointly with cross-entropy to analyse its theoretical components with respect to convergence. Across benchmarks comparing other loss functions and targets, DIFF-ERO shows improved predictive performance where structure matters most while maintaining parity elsewhere. At the same time, the learned stochastic automaton converges towards the structural ground truth, indicating that the network internalizes process model structure.

03.
arXiv (quant-ph) 2026-06-17

Breaking the bicycle frame: Coset-based quantum LDPC codes

arXiv:2606.17268v1 Announce Type: new Abstract: Generalizing the construction of two-block group algebra (2BGA) codes, we introduce a family of two-block quantum LDPC codes constructed using the action of a group on the cosets of its subgroup. This replaces the regular group actions of the earlier two-block constructions and significantly expands the search space, yielding new quantum LDPC codes outside the 2BGA family. Through a computer search, we identify several new quantum LDPC codes, including weight-6 codes with parameters $[[48,8,6]]$, $[[96,8,10]]$, and $[[224,12,16]]$, as well as weight-8 codes with parameters $[[84,16,8]]$, $[[112,16,10]]$, $[[128,16,12]]$, and $[[168,16,15]]$. Furthermore, we introduce a maximally packed syndrome extraction schedule of depth $w+2$, including initialization and measurement steps, for any code with a maximum stabilizer weight of $w$ from our family. Under a standard circuit-level noise model, our codes, when decoded using BP-OSD, perform competitively with BB codes, achieving thresholds of $\approx0.65\%$ for the weight-6 family and $\approx0.35\%$ for the weight-8 family. Finally, we introduce a group-theoretic framework to generate sequences of graph-based covers of 2BGA codes, recovering and extending recent results on code constructions of this type.

04.
arXiv (CS.AI) 2026-06-17

Like a Hammer, It Can Build, It Can Break: Large Language Model Uses, Perceptions, and Adoption in Cybersecurity Operations on Reddit

arXiv:2604.09998v2 Announce Type: replace-cross Abstract: Large language models (LLMs) have recently emerged as promising tools for augmenting Security Operations Center (SOC) workflows, with vendors increasingly marketing autonomous AI solutions for SOCs. However, there remains a limited empirical understanding of how such tools are used, perceived, and adopted by real-world security practitioners. To address this gap, we conduct a mixed-methods analysis of discussions in cybersecurity-focused forums to learn how a diverse group of practitioners use and perceive modern LLM tools for security operations. More specifically, we analyzed 892 posts between December 2022 and September 2025 from three cybersecurity-focused forums on Reddit, and, using a combination of qualitative coding and statistical analysis, examined how security practitioners discuss LLM tools across three dimensions: (1) their stated tools and use cases, (2) the perceived pros and cons of each tool across a set of critical factors, and (3) their adoption of such tools and the expected impacts on the cybersecurity industry and individual analysts. Overall, our findings reveal nuanced patterns in LLM tools adoption, highlighting independent use of LLMs for low-risk, productivity-oriented tasks, alongside active interest around enterprise-grade, security-focused LLM platforms. Although practitioners report meaningful gains in efficiency and effectiveness in LLM-assisted workflows, persistent issues with reliability, verification overheads, and security risks sharply constrain the autonomy granted to LLM tools. Based on these results, we also provide recommendations for developing and adopting LLM tools to ensure the security of organizations and the safety of cybersecurity practitioners.

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

ReSum: Synergizing LLM Reasoning and Summarization with Reinforcement Learning

arXiv:2606.13316v1 Announce Type: new Abstract: Reinforcement Learning with Verifiable Rewards (RLVR) is a central technique for improving long-horizon reasoning in Large Language Models (LLMs). However, existing RLVR methods often encourage unnecessarily long reasoning rollouts, which can degrade reasoning coherence and exhaust the available context budget. Existing approaches to long-context organization often depend on external mechanisms to organize rollouts, rather than enabling the model to manage its own reasoning trajectory. To address this limitation, we propose ReSum, a novel RLVR framework that enables LLMs to compress and organize their reasoning trajectories through self-summarization. Our pilot studies show that self-summarization stabilizes generation by lowering token-level entropy, and that introducing a ``summarization'' phrase can substantially mitigate errors propagated from an incorrect rollout prefix. Motivated by these findings, ReSum adopts a summarization-aware adaptive rollout mechanism that contrastively evaluates whether self-summarization benefits the ongoing reasoning process. Specifically, when the model spontaneously triggers self-summarization, ReSum masks the summarization phrase to create a contrastive branch; for non-summarization positions, it instead randomly injects the phrase to create a matched branch. We further design a summarization-aware advantage to enable finer-grained comparison between contrastive rollout trajectories. Extensive experiments show that ReSum improves performance at an average of 4\% while reducing rollout length by 18.6\%.

06.
arXiv (CS.LG) 2026-06-19

MassSpecGym in the Wild: Uncovering and Correcting Evaluation Pitfalls in AI-Driven Molecule Discovery

arXiv:2606.19624v1 Announce Type: new Abstract: Reliable benchmarking is critical for developing machine learning models for tandem mass spectrometry (MS/MS) based molecule discovery. Subtle issues in experimental design and model evaluation procedures can degrade the trustworthiness of such benchmarks and lead to erroneous conclusions. We conduct a thorough review of model evaluation issues in the recent MS/MS machine learning literature, using the standard MassSpecGym benchmark suite as a case study to illustrate the impact of these issues. We find evaluation issues in at least 17 of 26 papers reporting MassSpecGym benchmark results in the first year of its adoption. We isolate three classes of failures: (i) data leakage, (ii) shortcut learning, and (iii) implementation bugs and metric divergence. Through extensive experimentation and code replication, we quantify the impact of these issues and show how they corrupt the evaluation standards MassSpecGym was designed to enforce. We distill our findings into recommendations generalizable to MS/MS challenges, benchmarks, and custom evaluation setups. We also release MassSpecGym v1.5, an implementation of our recommendations in the MassSpecGym benchmarking suite which addresses the failure modes identified in this audit. MassSpecGym v1.5 is publicly available at https://github.com/pluskal-lab/MassSpecGym.

07.
arXiv (CS.AI) 2026-06-19

SPOT-E: Test-Time Entropy Shaping with Visual Spotlights for Frozen VLMs

arXiv:2606.20244v1 Announce Type: cross Abstract: Vision-language models (VLMs) often underperform on evidence intensive tasks because decisive visual evidence are small, localized, and easy to overlook, leading to failures in evidence readout even when high-level reasoning is intact. Prior inference-time visual interventions can improve grounding without retraining, but they are largely open-loop and lack a mechanism to verify whether highlighted evidence is actually used. We study answer-span prediction entropy as a model-internal feedback signal and show that naive entropy minimization is ambiguous, since low entropy may arise from evidence-grounded confidence or shortcut collapse. To resolve this ambiguity, we introduce low-entropy anchors and an entropy-shaping objective that reduces answer uncertainty while preserving baseline high-confidence tokens. We instantiate this principle in SPOT-E, a plug-and-play test-time method that produces question-conditioned spotlights, optimized per instance via light-weight tuning based on Group Relative Policy Optimization (GRPO). Across all benchmarks and different VLM families, SPOT-E yields consistent gains and improved robustness under visual corruptions. Code is publicly available at: \url{https://github.com/YinBo0927/SPOT-E}

08.
arXiv (CS.AI) 2026-06-12

Toward Instructions-as-Code: Understanding the Impact of Instruction Files on Agentic Pull Requests

arXiv:2606.13449v1 Announce Type: cross Abstract: AI-agents (e.g., GitHub Copilot) collaborate as teammates in different software engineering tasks, including code generation proposed through pull requests (Agentic-PRs). For better agent efficiency, developers create instruction files that guide the AI-agents, including how to navigate the project, locate the right components, run tests, respect best practices, and more. In this paper, we investigate the relationship between the creation of these instructions and the performance of AI-agents in creating better pull requests, which have a higher chance of success (i.e., the merge rate), address more complex tasks (e.g., code churn), and require less effort to be merged (e.g., time to merge). To this end, we analyze 15,549 agentic PRs from 148 projects in the AIDev dataset. Using the three dimensions, we compare each project before and after the creation of the instruction files. We find that specifying instructions for AI-agents does not necessarily lead to better results. With the instruction files, 27.7\% of the projects increased their merge rate by at least 20\%, while 26.35\% decreased it. The same observation is seen with the amount of changes (e.g., code churn, number of modified files) and with the efforts to merge an agentic PR (e.g., merge time and number of comments). From a first exploration, we find that projects that managed to increase their merge rate have substantially longer instruction files, which are also well structured into a higher number of sections and sub-sections. Our results motivate the need for research to assist practitioners in framing the development of instruction files as a software engineering activity (aka, Instructions-as-Code).

09.
arXiv (CS.CL) 2026-06-19

DeXposure-Claw: An Agentic System for DeFi Risk Supervision

Decentralized finance exposes supervisors to fast-moving, networked credit risks. General-purpose LLM agents fit this setting poorly: they over-read weak evidence and recommend high-stakes interventions, while existing evaluations offer no regulator-aligned way to measure the resulting false alarms. We introduce DeXposure-Claw, a forecast-grounded agentic supervision system that routes LLM decisions through structured evidence: (1) DeXposure-FM, a graph time-series foundation model, forecasts future exposure networks; (2) deterministic monitors and stress scenarios then turn those forecasts into typed alerts, attribution signals, and scenario evidence; and (3) data-health and confidence gates constrain escalation before DeXposure-Claw emits auditable supervisory tickets with rationales. We further develop DeXposure-Bench, a six-axis evaluation harness, whose decision axis scores tickets against a regulator-aligned absolute-loss ground truth and an explicit false-intervention rate. Experiments on five years of weekly real data fully support our system. Code is at https://github.com/EVIEHub/DeXposure-Claw.

10.
arXiv (quant-ph) 2026-06-15

Efficient Simulation of Szegedy Quantum Walk Formulations and Algorithms

arXiv:2606.14226v1 Announce Type: new Abstract: Quantum walks provide a versatile framework for quantum algorithms across a wide range of applications. We develop efficient classical simulation methods for Szegedy quantum walks that avoid explicit construction of the full unitary evolution operator. Unlike previous approaches restricted to a particular walk formulation, our framework is built from fundamental update and reflection operators, enabling the simulation of a broader class of Szegedy walk formulations. We further extend these methods to phase-estimation-based algorithms coupled to the walk, including implementations suitable for large sparse graphs. The resulting methods achieve optimal $O(N^2)$ complexity for dense graphs with $N$ nodes. For sparse graphs, the computational cost scales linearly with the number of edges, which is $O(N)$ in many cases. We implement the framework in the Python package SQWLib and illustrate its capabilities through simulations of representative algorithms, including quantum simulated annealing and quantum search on graphs. These results provide a practical tool for studying Szegedy-walk-based algorithms numerically beyond purely analytical treatments.

11.
arXiv (CS.AI) 2026-06-18

UPLOTS: A Unified Pretrained Language Model for Constrained Time-series Generation

arXiv:2606.10466v2 Announce Type: replace-cross Abstract: In time-series generation, existing approaches typically handcraft ortrain a separate model for each dataset, which hinders their scalability and fails to leverage shared temporal structures across domains. To address this fragmentation, we propose UPLOTS, a Unified, Prompt-guided Language model framework fOr constrained Time-Series Generation across diverse domains. Instead of building task-specific models, UPLOTS leverages a single pre-trained transformer backbone guided by learned constraint prompts, enabling on-demand generation with precise pattern control. One key innovation is our dynamic multi-dataset loss re-weighting and prompt-to-pattern mapping, which allows UPLOTS to internalize diverse temporal structures during training and conditionally generate them at inference. We evaluate UPLOTS on four real-world benchmarks and multiple constraint settings, including peak-period, calendar, load-level, and volatility patterns. Additional held-out constraint-combination and downstream forecasting experiments further demonstrate that UPLOTS generalizes beyond the original peak-pattern setting and improves data augmentation under scarce real-data regimes. Our code and baselines are available at anonymous github repo: https://anonymous.4open.science/r/UPLOTS-6C36.

12.
arXiv (CS.CV) 2026-06-16

GridVQA-X: A Framework for Evaluating Multimodal Explainability Methods

With the increasing development of Vision-Language Models, it becomes imperative that their predictions are readily explainable to relevant stakeholders. However, the field of explainability has not kept pace with the multimodal surge. While recent Multimodal Explainable AI (MxAI) methods generate explanations to attribute the interaction between different modalities, current evaluation protocols lack the ground truth required to distinguish between true cross-modal reasoning (e.g., spatial composition) and shallow cross-modal shortcuts (e.g., Bag-of-Words attribute matching). It remains unknown whether MxAI methods faithfully capture synergistic interactions or merely hallucinate reasoning on models acting as simple feature detectors. In this paper, we introduce GridVQA-X, the first diagnostic framework specifically designed to evaluate cross-modal explainability. Unlike natural datasets, GridVQA-X leverages a closed-world synthesis logic to generate unique, mathematically guaranteed explanations. We utilize this controlled environment to train paired ground-truth models on identical architectures: $M_{pure}$, which learns robust spatial-relational reasoning and $M_{spur}$, which is structurally forced to rely on cross-modal shortcuts. This behavioral divergence creates a rigorous testbed: a faithful explainer must report distinct reasoning pathways for each model. Our findings reveal that widely used methods fail to distinguish between models relying on genuine spatial-relational reasoning and those exploiting cross-modal shortcuts, highlighting a critical gap in capturing true cross-modal synergy and misrepresenting how multimodal models actually make decisions.

13.
arXiv (quant-ph) 2026-06-16

Sharp Transitions for Subsystem Complexity

arXiv:2510.18832v2 Announce Type: replace-cross Abstract: The circuit complexity of time-evolved pure quantum states grows linearly in time for an exponentially long time. This behavior has been proven in certain models, is conjectured to hold for generic quantum many-body systems, and is believed to be dual to the long-time growth of black hole interiors in AdS/CFT. Achieving a similar understanding for mixed states remains an important problem. In this work, we study the circuit complexity of time-evolved subsystems of pure quantum states. We find that for greater-than-half subsystem sizes, the complexity grows linearly in time for an exponentially long time, similarly to that of the full state. However, for less-than-half subsystem sizes, the complexity rises and then falls, returning to low complexity as the subsystem equilibrates. Notably, the transition between these two regimes occurs sharply at half system size. We use holographic duality to map out this picture of subsystem complexity dynamics and rigorously prove the existence of the sharp transition in random quantum circuits. Furthermore, we use holography to predict features of complexity growth at finite temperature that lie beyond the reach of techniques based on random quantum circuits. In particular, at finite temperature, we argue for an additional sharp transition at a critical less-than-half subsystem size. Below this critical value, the subsystem complexity saturates nearly instantaneously rather than exhibiting a rise and fall. This novel phenomenon, as well as an analogous transition above half system size, provides a target for future studies based on rigorous methods.

14.
medRxiv (Medicine) 2026-06-22

Genetic and Shared Environmental Influences on Cancer Risk and Cross-Cancer Associations in Nordic Twins

The relative contributions of genetic and shared environmental influences to cancer risk and cross-cancer associations remain poorly understood. We analyzed data from 222,530 same-sex twins from Denmark, Finland, Norway, and Sweden in the Nordic Twin Study of Cancer, including 43,060 incident cancers over a median follow-up of 41.6 years. Using a target trial framework, biometric modeling, and competing-risk adjustment, we estimated familial risk, heritability, and shared environmental contributions across 35 cancer sites. Lifetime cancer risk was 36.5%, increasing to 51.4% in monozygotic (MZ) twins and 45.3% in dizygotic (DZ) twins with an affected co-twin. Overall cancer risk was explained by heritable (28%) and shared environmental (40%) influences. Heritability was highest for prostate (42%), non-melanoma skin (24%), and breast (18%) cancers. Cross-cancer analyses revealed extensive overlap in the genetic and shared environmental factors across sites, consistent with widespread pleiotropy and shared environmental susceptibility. Prostate cancer exhibited the strongest genetic overlap with rectum/anus (12%) and kidney (11%) cancers, whereas co-shared environmental influences were most pronounced for breast-lung (11%), prostate-bladder (11%), and prostate-lung (12%) cancers. These findings show pervasive genetic overlap across cancers at different sites and emphasize the importance of incorporating familial shared environmental exposures into cancer risk prediction and prevention strategies.

15.
arXiv (CS.CL) 2026-06-16

Measuring Whether LLM Tutors Teach or Solve: A Diagnostic for Educational Impact

Large language models are increasingly proposed as educational tutors, yet stronger task-solving ability does not necessarily imply stronger learning support. Motivated by recent calls to measure the social impact of NLP systems in practice, we study whether public LLM tutoring benchmarks distinguish learning-supportive behavior from mere answer production. We propose a lightweight diagnostic based on the gap between solving-oriented and pedagogy-oriented benchmark performance. Using public MathTutorBench leaderboard results, we show that these dimensions are only partially aligned: across eight publicly reported models, the correlation between solving and pedagogy composites is 0.421, and several models shift meaningfully in rank when evaluation moves from solving to pedagogy. We then analyze the public TutorBench sample and show that agency-relevant behaviors are explicitly encoded in benchmark rubrics, especially in active-learning settings that reward guiding questions, calibrated hints, and non-disclosive scaffolding. Together, these findings suggest that educational-impact evaluation should not treat task success as a sufficient proxy for learning support. We argue that public tutoring benchmarks can better support positive-impact evaluation by reporting solving-oriented and pedagogy-oriented scores separately and by making disclosure-sensitive, student-agency-preserving criteria more explicit.

16.
arXiv (quant-ph) 2026-06-19

Applications of quantum annealing to magnetic dipole hyperfine structure constants: First results beyond energies for atoms

arXiv:2606.20166v1 Announce Type: new Abstract: We report the first results of the magnetic dipole hyperfine structure (HFS) constants of neutral $\mathrm{Li}$, Li-like $\mathrm{Be}$, neutral $\mathrm{Na}$, and Na-like $\mathrm{Mg}$ using a modified version of the Quantum Annealer Eigensolver (QAE) algorithm on D-Wave's quantum hardware. The results are benchmarked against relativistic configuration interaction with multiconfiguration Dirac Hartree-Fock (MCDHF) calculations using the General-purpose Relativistic Atomic Structure Package (GRASP), and simulated annealing. In our modified QAE, a zooming-and-sigma-annealing approach with a floating-point encoding scheme is adopted to estimate the ground-state eigenvalue and eigenvector of the relativistic Dirac-Coulomb Hamiltonian matrices ($H_{\mathrm{DC}}$) constructed from 11 or fewer configuration state functions (CSFs). For calculations with extended correlation orbital sets, we applied a CSF truncation scheme, retaining only CSFs (up to 12) that make significant contributions to the ground-state wavefunction. Our modified QAE precision is kept limited to three decimal places (up to 10 qubits). Hardware demonstrations on the D-Wave quantum processing unit (QPU) yielded results that were completely consistent with GRASP (at the chosen precision) in determining the magnetic dipole HFS constants, with accuracy varying across systems and $H_{\mathrm{DC}}$ matrix dimensions.

17.
medRxiv (Medicine) 2026-06-16

Non-invasive Detection of Fasciculation Using Surface EMG with a Wavelet-Based Analytical Method (DEWCS)

Objective: Needle electromyography (nEMG) is essential for diagnosing neuromuscular disorders but is invasive and often painful. We employed single-channel bipolar surface EMG (sEMG) analyzed with a novel wavelet-based analytical approach, Detecting and Extracting Elemental Wave Components based on a Wavelet Coefficient Set (DEWCS) and investigated whether fasciculation-related activity could be identified. Methods: In this prospective study, 28 patients undergoing nEMG for suspected neuromuscular disorders and 13 healthy controls were included. Resting-state sEMG was recorded from selected muscles using single-channel bipolar active electrodes at a high sampling rate. DEWCS was used to extract indices reflecting fast- and slow-type motor unit (MU)-related activity. These standardized indices were evaluated against nEMG-detected fasciculation potentials using generalized estimating equation logistic regression to account for within-subject clustering. Diagnostic performance was assessed by receiver operating characteristic analysis. Results: A total of 67 muscles from 38 participants were analyzed. Indices of fast- and slow-type MU-related activity were significantly associated with fasciculation potentials (slow: OR 5.10, p = 0.0041; fast: OR 2.38, p = 0.0162). The combined model showed excellent discrimination (area under the curve = 0.97), outperforming either index alone. Muscle region had no significant effect. Conclusions: A single-channel bipolar sEMG setup combined with DEWCS detected fasciculation-related activity with promising accuracy. This method may serve as a non-invasive surrogate marker of lower motor neuron involvement. Further validation in larger cohorts is warranted. Significance: This non-invasive sEMG approach may help detect fasciculation-related activity and complement nEMG in neuromuscular diagnostics.

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

libhmm: A Modern C++20 Library for Hidden Markov Models with Correct MLE Emission M-Steps

作者:

arXiv:2605.29208v2 Announce Type: replace-cross Abstract: We describe libhmm, a C++20 library for Hidden Markov Model parameter estimation, sequence decoding, and model selection. libhmm addresses two gaps in existing software: the absence of a well-maintained, zero-dependency C++ HMM library suitable for embedding in production systems, and the widespread use of method-of-moments (MOM) approximations in the emission distribution M-step of the Baum-Welch algorithm. The library implements correct maximum likelihood estimators for sixteen scalar emission distributions, including an ECME algorithm for the location-scale Student-t distribution, Newton-Raphson maximization for Gamma, Beta, Weibull, and Negative Binomial distributions, and the von Mises distribution for circular data. All forward-backward and Viterbi calculations operate in full log-space. SIMD acceleration is provided for AVX-512, AVX2, SSE2, and ARM NEON via compile-time dispatch with scalar fallback. Version 4 adds multivariate observation support via the BasicHmm template, with three multivariate emission families (diagonal Gaussian, full-covariance Gaussian, and independent components) each with correct weighted MLE M-steps. Python bindings are available via the companion package pylibhmm. We compare libhmm against established C and C++ HMM libraries and against published R reference packages on seven real-data benchmarks, and discuss the architectural tradeoffs made in the design.

19.
Nature Biotechnology 2026-06-11

Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT

作者:

Spatially resolved CRISPR screening in vivo has been limited to small perturbation panels and subsets of protein-coding RNAs. We present Perturb-DBiT, a method for co-sequencing of spatial total RNA whole transcriptomes and single guide RNAs (sgRNAs) on the same tissue section in situ. In a human cancer metastatic colonization model, we applied large (80,000+) sgRNA panels across tumor colonies in multiple consecutive tissue sections alongside their corresponding total RNA transcriptomes. We linked perturbations affecting long noncoding RNA covariation, microRNA–mRNA interactions and distinct amino acid-specific tRNA alterations to tumor migration and growth. By integrating transcriptional pseudotime trajectories, we further observed the impact of perturbations on clonal dynamics and cooperation. In an immune-competent syngeneic mouse model, investigation of the tumor immune microenvironment indicated distinct, synergistic effects on immune infiltration and suppression. Perturb-DBiT provides a spatially resolved comprehensive view of perturbation responses in complex tissues, including small and large RNA regulation, tumor proliferation, migration, metastasis and immune interactions. In vivo CRISPR genetic perturbations are spatially mapped at scale.

20.
arXiv (math.PR) 2026-06-12

Dimension-free Markov–Bernstein inequalities for product measures

作者:

arXiv:2606.13575v1 Announce Type: cross Abstract: We study dimension-free Markov–Bernstein inequalities for polynomials with respect to product probability measures. In the Gaussian case, for $p\ge4$, we prove that \[ \|\nabla f\|_{L^p(\gamma^n)} \le C(p)d^{\frac12+\theta_p} \|f\|_{L^p(\gamma^n)} \] for every polynomial $f$ of degree at most $d$, where $\theta_p\le \frac{2}{3p}$ and $\theta_p=0$ whenever $p$ is an even integer. Thus, for even integer exponents, we establish the sharp dependence on the degree conjectured by Eskenazis–Ivanisvili. For general $p\ge4$, the estimate improves upon their dimension-free inequality. We also obtain dimension-free Markov–Bernstein inequalities with sharp dependence on the degree for even integer exponents beyond the Gaussian setting. We first prove such estimates for the uniform distribution on the unit cube and then extend them to products of absolutely continuous measures with unimodal densities. Finally, we treat products of one-dimensional Freud measures with densities proportional to $e^{-|t|^{2m}}$.

21.
arXiv (CS.LG) 2026-06-17

From Theory to Application: A Practical Introduction to Neural Operators in Scientific Computing

arXiv:2503.05598v2 Announce Type: replace-cross Abstract: This review examines neural operator architectures for learning solution operators of parametric partial differential equations (PDEs), with an emphasis on conceptual clarity and practical implementation. The work analyzes key models, including DeepONet, PCANet, and the Fourier Neural Operator, highlighting their underlying representations, computational structures, and comparative performance. These architectures are demonstrated on three canonical PDE problems: the Poisson equation, a linear elasticity problem, and a hyperelasticity problem. To make the presentation self-contained, key foundational topics are introduced, including finite-dimensional representations of function spaces, singular-value decomposition, and sampling from infinite-dimensional function spaces. Beyond forward modeling, the review discusses the use of neural operators as surrogate models within a Bayesian inverse-problem framework, including prior specification, forward-map approximation, and posterior computation. The performance of the three neural-operator architectures is evaluated on in-distribution samples, out-of-distribution samples, and Bayesian inference tasks. The review also discusses challenges related to prediction accuracy and generalization, outlining emerging strategies such as residual-based error correction and multi-level training. The review concludes by positioning neural operators within broader scientific-computing workflows and by identifying directions for reliable, scalable operator learning.

22.
medRxiv (Medicine) 2026-06-17

Differential Determinants of Past Behavior and Future Intention Regarding Voluntary Blood Donation: A Cross-Sectional Study of Knowledge, Attitudes, and Practices in Qingdao, China

Background A persistent gap between motivation and action threatens voluntary blood supply. This study examined the publics knowledge, attitudes, and practices (KAP) regarding blood donation, with a particular focus on identifying the different determinants of past blood donation behavior and future willingness to donate. Methods Convenience sampling was used to conduct a cross-sectional survey among 1,058 eligible people in Qingdao, China, between July and November 2025. Data were collected via a self-designed KAP questionnaire. To find independent characteristics linked to previous behavior and future intention, respectively, multivariable binary logistic regression was used. Results Overall, 37.0% of participants (n=391) had a lifetime donation history, while 39.2% (n=415) intended to donate in the next 12 months. Past behavior was positively associated with older age (36-45 years: OR=6.84; 95% CI: 3.21-14.58), higher education (OR=2.06; 95% CI: 1.33-3.17), and interpersonal interaction channels (OR=1.45; 95% CI: 1.01-2.09) but hindered by safety concerns (OR=0.23; 95% CI: 0.16-0.34). Conversely, future intention was positively correlated with male sex (OR=1.69; 95% CI: 1.24-2.29), prior donation history (OR=2.69; 95% CI: 1.87-3.86), having family members or friends in need of blood (OR=2.75; 95% CI: 1.96-3.85), and traditional media exposure (OR=3.33; 95% CI: 2.18-5.10). Higher education was adversely correlated with future intention (OR=0.55; 95% CI: 0.38-0.79). Conclusion There is a substantial disparity between donation motivation and action. The determinants of past behavior and future intention are asymmetric, suggesting that stage-specific interventions are required, using social mobilization for initiating first-time donations, while employing family reciprocity and authoritative communication to sustain long-term engagement.

23.
arXiv (CS.LG) 2026-06-19

Constrained hybrid modelling to predict microbial dynamics and organic matter turnover in soil systems

arXiv:2606.20329v1 Announce Type: new Abstract: Soil microorganisms control organic matter cycling and largely determine how soil systems can cope with and mitigate climate change and environmental threats. Representing microbial dynamics in process-based soil models is therefore critical to predict carbon cycling in soils, albeit highly challenging to inform from data. One promising approach to improve their parametrisation is the integration of genomic data, yet modelling the complex and unknown relationship between genomes and the processes the microbes are driving is an unsolved problem. In this work, we present the first hybrid modeling framework for deriving biokinetic parameter values of a process-based soil organic matter turnover model from metagenome-inferred functional traits based on DNA sequencing data. Our model predicts biokinetic parameters of the process-based model from genomic trait data with a neural network and integrates constraints from ecological theory and literature to ensure realistic behavior, even of non-observed state variables. We evaluate our method on synthetic genomic trait datasets of varying complexity and on real data, showing that our approach improves performance over multiple baselines and learns the dynamics of unmeasurable components of the process-based model effectively, even for small training datasets.

24.
PLOS Computational Biology 2026-06-17

Combining machine learning and iterative experiments to keep pace with emerging viral variants of concern

by Thomas Sheffield, Ryan C. Bruneau, Stephen Won, Kenneth L. Sale, Brooke Harmon, Le Thanh Mai Pham Modeling and predicting viral mutations before they emerge plays a crucial role in pandemic preparedness, enabling the early identification of emerging variants of concern (VOCs) and guiding timely updates to vaccines, diagnostic tests, and therapeutic strategies. However, existing machine learning models and large-scale experiments lose their predictive power as viral variants evolve further from the original strains in sequence space. Here, we present a scalable framework that integrates random forest and neural network machine learning models with targeted high-throughput experimentation to anticipate and evaluate emerging SARS-CoV-2 receptor-binding domain (RBD) variants. Using public datasets, we trained predictive models for binding to human Angiotensin-converting enzyme 2 (ACE2), RBD expression, and antibody escape, and refined these models through iterative integration of experimental data focused on over 200 variants derived from wild-type (WT) and Omicron strains. Through an indirect transfer learning approach, our machine learning models achieved high accuracy having correlation coefficients of up to 0.79 for antibody binding. The models were also generalizable across diverse antibody types including heavy-chain-only antibodies (HCAbs) by encoding complementarity-determining regions (CDRs) as input features. This dynamic approach enables rapid assessment of emerging variants, facilities prioritization of the therapeutic strategies, and supports a proactive, data-driven response to evolving viral threats.

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arXiv (CS.CV) 2026-06-11

DIRECT: When and Where Should You Allocate Test-Time Compute in Embodied Planners?

Vision-Language Models (VLMs) are increasingly deployed as high-level planners for embodied agents, with an emerging strategy of scaling test-time compute to improve capability. However, we observe that doing so increases latency, token usage, and FLOPs while yielding uneven, often diminishing gains in downstream success, limiting where embodied agents can be deployed. We argue that choosing when and where to spend test-time compute is central to bringing frontier performance to the real world. We introduce DIRECT, a routing framework that uses multimodal scene context to allocate compute per prompt, improving the success–cost Pareto frontier over fixed model selection. Across three dominant scaling axes, namely chain-of-thought depth, model size, and memory history, our experiments on VLABench and RoboMME show that test-time compute is not a uniform lever: different axes yield qualitatively distinct capability gains. We validate these insights on a physical Franka arm in a DROID setup spanning zero-shot manipulation and long-horizon chaining, where our router matches or exceeds a stronger model's success rate at up to 65% lower average latency. Ultimately, our results show that naively scaling test-time compute is wasteful, and that DIRECT can provide frontier-level embodied planning in robotic systems at a fraction of the cost. Project page can be found at jadee-dao.github.io/direct/.