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

BadWorld: Adversarial Attacks on World Models

Visual world models (VWMs) synthesize interactive, action-conditioned rollouts from a single context image. However, it remains an open question how robust these models are to adversarial perturbations. Standard adversarial attacks fail to assess this vulnerability because attackers lack ground-truth future videos and cannot predict subsequent user controls. We introduce BadWorld, a label-free adversarial framework tailored for autoregressive VWMs that systematically overcomes both constraints. First, to bypass the need for future supervision, we propose a self-supervised velocity attack that directly disrupts the early denoising dynamics of the model. Second, to ensure the attack generalizes across unpredictable user actions, we formulate a trajectory-adaptive bi-level optimization that actively mines hard control sequences to forge control-agnostic perturbations. Evaluated on representative VWMs with continuous and discrete controls, BadWorld exposes severe structural fragility. Visually indistinguishable adversarial images reliably trigger catastrophic degradation in future rollouts, leading to incomplete denoising, structural collapse, and control inconsistency. These findings reveal critical risks for deploying VWMs in safety-critical systems while highlighting a practical mechanism for privacy protection.

02.
arXiv (CS.AI) 2026-06-16

Discovering Symmetry Groups with Flow Matching

arXiv:2512.20043v3 Announce Type: replace Abstract: Symmetry is fundamental to understanding physical systems and can improve performance and sample efficiency in machine learning. Both pursuits require knowledge of the underlying symmetries in data, yet discovering these symmetries automatically is challenging. We propose LieFlow, a novel framework that reframes symmetry discovery as a distribution learning problem on Lie groups. Instead of searching for the symmetry generators, our approach operates directly in group space, modeling a symmetry distribution over a large hypothesis group $G$. The support of the learned distribution reveals the underlying symmetry group $H \subseteq G$. Unlike previous works, LieFlow can discover both continuous and discrete symmetries within a unified framework, without assuming a fixed Lie algebra basis or a specific distribution over the group elements. Experiments on synthetic 2D and 3D point clouds, ModelNet10 and a real-world MI-Motion dataset show that LieFlow accurately discovers continuous and discrete subgroups, significantly outperforming a state-of-the-art baseline, LieGAN, in identifying discrete symmetries.

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

Cumulant expansion approach to the decay dynamics of interacting Mössbauer nuclei after strong impulsive excitation

arXiv:2510.00970v2 Announce Type: replace Abstract: Recent progress in accelerator-based x-ray sources brings higher excitation of ensembles of Mössbauer nuclei closer to experimental feasibility. Yet, a theoretical modeling of the decay dynamics of the interacting nuclear ensemble after the impulsive excitation is still an open challenge. Here, we derive a set of nonlinear equations which is capable of efficiently modeling large nuclear ensembles for arbitrary degrees of excitation. As key signature for higher excitation, we identify a non-linear time-evolution of the nuclear dipole phase, which can be tuned via the scattering geometry, and interferometrically be measured. Furthermore, we identify interesting finite-size effects in the nuclear dynamics of small ensembles. Our results provide important guidance for future experiments aiming at the non-linear excitation of nuclei. We further envision the exploration of finite size-effects in Mössbauer spectroscopy with highest spatial resolution, i.e., small sample volumes.

04.
arXiv (quant-ph) 2026-06-12

Supersymmetry of dissipative Bose-Fermi systems with application to Jaynes-Cummings and Dicke models

arXiv:2606.12682v1 Announce Type: new Abstract: We demonstrate how supersymmetries of Hamiltonians for coupled Bose-Fermi systems can be used to place the Hamiltonians of the Jaynes-Cummings model and Dicke model under the rotating wave approximation in matrix form and provide explicit analytic solutions for their eigenvalues. We then use this supersymmetry to place the Liouvillians of the associated Markovian open systems in matrix form and provide explicit solutions for their eigenvalues. These results are a consequence of the fact that the Hamiltonian of the Jaynes-Cummings model commutes with the linear Casimir invariant of the superalgebra $u(1|1)$ and that the Hamiltonian of the Dicke model commutes both with the linear invariant of $\sum_{i} u_{i}(1|1)$ and with the invariant of an additional $su(2)$ algebra. Our methods apply to various coupled Bose-Fermi systems with $u(1|1)$ and more generally with $u(n|m)$ dynamical superalgebras, and may provide efficient tools for studying more complicated examples.

05.
arXiv (CS.LG) 2026-06-17

From Drift to Coherence: Stabilizing Beliefs in LLMs

arXiv:2606.17832v1 Announce Type: new Abstract: Large language models (LLMs) are often hypothesized to perform implicit Bayesian inference, yet a key coherence condition, the martingale property of predictive beliefs, has been shown to fail in controlled synthetic in-context learning settings. We revisit this question in a more typical usage regime: generic multiple-choice question answering. Exploiting the discrete answer space, we compute exact predictive distributions and study belief dynamics induced by autoregressive answer resampling. We introduce prompted predictive resampling (PPR), where an LLM generates a sequence of answers to the same question. Empirically, PPR reveals early-stage belief drift, indicating martingale violations. However, after sufficient resampling steps, the belief process self-stabilizes and converges to a coherent predictive distribution. Based on this observation, we further propose (i) a seed-answer prompting strategy to accelerate stabilization, and (ii) a self-consistency loss that amortizes early-stage drift into the model via fine-tuning. Experiments on multiple-choice QA benchmarks show that our methods substantially reduce belief drift and improve predictive coherence without sacrificing accuracy.

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

LOCUS: Local Visual Cue Search for Enhancing Fine-Grained Perception in Multimodal Large Language Models

Multimodal Large Language Models (MLLMs) remain unreliable on fine-grained visual perception, even when high-resolution inputs preserve the necessary local details. We identify this limitation as visual context rot: decisive evidence may exist in the full image, yet fail to be reliably selected and used amid redundant visual context. We propose LOCUS (LOcal visual CUe Search), a training framework that teaches MLLMs to internalize local evidence search through a verifiable proxy task. During training, LOCUS provides a local crop as a visual cue and optimizes the model to recover its spatial support in the full image using an IoU-based reward. The visual cue is used only during training, leaving the standard image-question inference interface unchanged. Experiments across fine-grained perception, hallucination, general understanding, and reasoning benchmarks show that LOCUS improves localization-sensitive visual understanding while preserving broad capabilities. Attention analyses further indicate stronger focus on task-relevant evidence regions, suggesting that training-time visual cue search provides an effective route to internalized fine-grained evidence selection.

07.
arXiv (CS.CL) 2026-06-15

Protean Compiler: An Agile Framework to Drive Fine-grain Phase Ordering

The phase ordering problem has been a long-standing challenge since the late 1970s, yet it remains an open problem due to having a vast optimization space and an unbounded nature, making it an open-ended problem without a finite solution, one can limit the scope by reducing the number and the length of optimizations. Traditionally, such locally optimized decisions are made by hand-coded algorithms tuned for a small number of benchmarks, often requiring significant effort to be retuned when the benchmark suite changes. In the past 20 years, Machine Learning has been employed to construct performance models to improve the selection and ordering of compiler optimizations, however, the approaches are not baked into the compiler seamlessly and never materialized to be leveraged at a fine-grained scope of code segments. This paper presents Protean Compiler: An agile framework to enable LLVM with built-in phase-ordering capabilities at a fine-grained scope. The framework also comprises a complete library of more than 140 handcrafted static feature collection methods at varying scopes, and the experimental results showcase speedup gains of up to 4.1% on average and up to 15.7% on select Cbench applications wrt LLVM's O3 by just incurring a few extra seconds of build time on Cbench. Additionally, Protean compiler allows for an easy integration with third-party ML frameworks and other Large Language Models, and two applications of this two-step optimization show a gain of 10.1\% and 8.5\% speedup w.r.t. -O3 on CBench's Susan and Jpeg applications. Protean compiler is seamlessly integrated into LLVM and can be used as a new, enhanced, full-fledged compiler. We plan to release the project to the open-source community in the near future.

08.
medRxiv (Medicine) 2026-06-15

Nocturnal Respiratory Rate and Variability Predict Long-term Mortality in Stable Outpatients with Cardiovascular Disease

Background: Respiratory rate (RR) predicts short-term mortality in acute care settings, yet its prognostic significance in clinically stable outpatients remains poorly defined. Objectives: To determine whether the median and variability of nocturnal respiratory rate (NRR) are independently associated with long-term cardiovascular and all-cause mortality in outpatients with cardiovascular disease. Methods: We analyzed overnight chest belt waveforms from elective polysomnography in 5,679 older adults with cardiovascular disease enrolled in the Sleep Heart Health Study (SHHS). NRR was quantified at 30-second resolution, and per-subject median NRR and within-night variability (standard deviation) were derived. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate associations with cardiovascular and all-cause mortality over 3-year and 15-year follow-up periods, adjusting for demographic characteristics, cardiopulmonary comorbidities, and sleep apnea severity. Results: Higher median NRR and greater NRR variability were each associated with increased cardiovascular and all-cause mortality. Combining these metrics identified a high-risk group characterized by elevated median and high variability of NRR, with approximately five-fold higher 3-year all-cause mortality compared with a low-risk group; this association remained significant in Cox models (unadjusted HR: 2.61; 95% CI: 1.65, 4.14; p

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

RoSE: Round-robin Synthetic Data Evaluation for Selecting LLM Generators without Human Test Sets

LLMs are powerful generators of synthetic data, which are used for training smaller, specific models. This is especially valuable for low-resource languages, where human-labelled data is scarce but LLMs can still produce high-quality text. However, LLMs differ in how useful their outputs are for training. Selecting the best LLM as a generator is challenging because extrinsic evaluation requires costly human annotations (which are often unavailable for low-resource languages), while intrinsic metrics correlate poorly with downstream performance. We introduce Round robin Synthetic data Evaluation (RoSE), a proxy metric for selecting the best LLM generator without human test sets. RoSE trains a small model on the outputs of a candidate generator (LLM) and then evaluates it on generated synthetic examples from all other candidate LLMs. The final RoSE score is the mean performance of this small model. Across six LLMs, eleven languages, and three tasks (sentiment, topic, intent), RoSE identifies the optimal generator more often than any other intrinsic heuristics. RoSE outperforms intrinsic heuristics and comes within 0.76 percentage points of the optimal generator baseline. This result is measured in terms of downstream performance, obtained by training a small model on the chosen generator's outputs (optimal vs. proxy metric selected) and evaluating it on human-labelled test data. Additionally, RoSE is the only metric to achieve a positive correlation with performance on human test data.

10.
arXiv (math.PR) 2026-06-11

Continuous stochastic flows driven by white noise and their duals

作者:

arXiv:2606.12143v1 Announce Type: new Abstract: We study a class of continuous stochastic flows driven by a space-time white noise and characterize their dual flows by explicit stochastic differential equations. A key ingredient of the proof is the convergence of solutions under coefficient approximations. As an application, we derive the dual flows in two illustrative examples, the squared Bessel flow and the Jacobi flow. We also introduce a new model of polynomially self-repelling (PSR) flow and show that it enjoys a self-duality property.

11.
bioRxiv (Bioinfo) 2026-06-08

HydraMPP: A lightweight library for distributed massive parallel processing in Python - threading at scale.

We now exist in the era of massive datasets from genomics, large language models, and all the known knowledge of humanity right at our fingertips. Much of this data is becoming more accessible; however, processing such data remains an ongoing issue across systems including high performance computing (HPC) infrastructures. Massively parallel computing (MPP) has solved this using a divide and conquer approach by splitting workloads across independent nodes (i.e., central processing units (CPU) allowing for higher scaling of data). The main engine for this in python is Ray; however, it has many issues including a large code space, security issues, debugging opacity, and memory management issues. Here, we present HydraMPP, a lightweight, ease of use and utilization, with high auditability, and with SLURM ergonomics.

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

SeamEdit: A Black-Box VLM-Agnostic Pipeline for Large-Image Semantic Editing

Semantic region editing for large images must satisfy two requirements at the same time: high generative quality and natural integration with surrounding content. Some related methods rely on white-box models and leave the strong generation capability of closed-source models underexplored. Directly applying closed-source models to tiled editing, however, introduces several failure modes: semantic deformation, canvas-level alignment drift, and visible seam artifacts. This paper presents SeamEdit, a training-free and model-agnostic pipeline that treats any VLM with inpainting capability as a black-box oracle. SeamEdit mitigates these issues through a five-stage post-hoc pipeline: overlay-based tile decomposition, black-box VLM inpainting, geometric and color-consistency correction, seam-risk-based multi-candidate ranking, and dynamic-programming curved seam fusion. The pipeline reduces seam visibility and supports semantic modification of arbitrary tile regions.

13.
arXiv (CS.CV) 2026-06-15

Schrödinger's Navigator: Imagining an Ensemble of Futures for Zero-Shot Object Navigation

Zero-shot object navigation (ZSON) requires robots to find target objects in unseen environments without task-specific fine-tuning or pre-built maps, a key capability for general-purpose service robots. Yet methods that perform well in simulation often degrade in cluttered real-world scenes with severe occlusion and latent hazards, where large unseen regions make single-scene inference brittle and unsafe. We propose Schrödinger's Navigator, a belief-aware framework that reasons at inference time over multiple trajectory-conditioned imagined 3D futures. Given candidate paths, a trajectory-conditioned 3D world model predicts hypothetical observations and maintains a superposition of plausible scene realizations rather than committing to one map. An adaptive occluder-aware sampler directs imagination to uncertainty-critical regions, while a Future-Aware Value Map (FAVM) aggregates imagined futures for robust, proactive action selection. Experiments in simulation and on a physical Go2 quadruped show that Schrödinger's Navigator outperforms strong ZSON baselines, improving hidden-target discovery and risk-aware waypoint selection in occlusion-heavy navigation scenarios. These results highlight imagined 3D futures as a scalable and generalizable strategy for zero-shot navigation in uncertain real-world environments.

14.
arXiv (quant-ph) 2026-06-16

Scheme for Transport-based Global Entanglement Distribution using Quantum Processors

arXiv:2606.15421v1 Announce Type: new Abstract: We propose a scheme for distributing entanglement over global distances in a heralded manner by using satellites to physically transport entangled processor nodes with rare-earth-ion qubits. A full analysis of channel losses, errors and background light is performed to determine the fidelity and number of entangled pairs that can be distributed between two ground stations. We show that the scheme works already with a single satellite and can distribute close to the theoretical maximum number of entangled pairs that can be generated in a satellite overpass. In addition, we argue that in theory transportation-based schemes outperform other satellite-based schemes and can be scaled up to a constellation without additional channel losses. Daytime operation seems feasible as long as the sky is clear, with an EPR pair fidelity ranging from 99.3% at shorter network lengths to 93.9% with global coverage and can be further improved by active error correction or entanglement purification.

15.
arXiv (CS.LG) 2026-06-18

P-K-GCN: Physics-augmented Koopman-enhanced Graph Convolutional Network for Deep Spatiotemporal Super-resolution

arXiv:2606.19303v1 Announce Type: new Abstract: High-fidelity simulation of spatiotemporal dynamics is computationally prohibitive, necessitating efficient super-resolution techniques to reconstruct high-resolution data from coarse-grained inputs. Traditional data-driven methods often lack physical constraints, and simple physics-informed learning struggles with irregular spatial geometries and intricately evolving temporal dynamics. To tackle these challenges, we propose a Physics-augmented Koopman-enhanced Graph Convolutional Network (P-K-GCN) for spatiotemporal super-resolution on irregular geometries. Specifically, a continuous spline-based GCN is first designed to extract spatial dependencies directly from coarse graph, and Koopman operator theory is incorporated to project the nonlinear dynamics into a compact latent space where temporal progression is linearized. Second, we augment the optimization objective with a physics-based loss to force the data-driven reconstructions to adhere to physical laws for improving predictive fidelity and robustness. Finally, we provide a rigorous theoretical analysis, establishing that the physics augmentation and Koopman regularization mathematically guarantees a reduction in super-resolution error by diminishing Rademacher complexity and tightening generalization bounds. We evaluate our framework on reconstructing spatially high-resolution cardiac electrodynamics across a 3D heart geometry from sparse low-resolution measurements. Numerical experiments demonstrate that our method achieves superior accuracy compared to baseline models.

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

EmoZone-Talker: Regional Semantic Control of Audio-Driven 3DGS Talking Heads via Facial Action Units

3D Gaussian Splatting (3DGS) has shown strong potential for high-fidelity talking head synthesis. However, enabling fine-grained, interpretable, and editable facial expression control remains fundamentally challenging due to intrinsic conflicts between speech-driven facial dynamics and explicit expression signals. Existing methods rely on implicit multimodal fusion, leading to spatial entanglement and temporal instability. We present EmoZone-Talker, a novel framework that reformulates audio-driven facial animation as a structured spatial-temporal coordination problem under cross-modal conflicts. Our approach introduces an explicit spatial disentanglement and temporal dynamics modeling of facial motion. Specifically, we propose Synergy Zones with Prioritized Attention Bias (SZ-PAB) to explicitly decouple modality contributions via region-wise constraints guided by anatomical priors, and a Channel-Independent Temporal AU Encoder (CIT-AE) to model temporally coherent AU dynamics. By integrating these representations into 3D Gaussian deformation, EmoZone-Talker enables precise and interpretable control over facial expressions. Extensive experiments demonstrate that our method improves expression controllability and realism, with notable gains in upper-face accuracy and temporal coherence, while preserving high rendering quality and accurate lip synchronization. Code will be publicly released to facilitate reproducibility and further research.

17.
medRxiv (Medicine) 2026-06-15

Toward a National Registry for Inborn Errors of Immunity in Peru: A Qualitative Implementation Study

Background: Peru lacks an integrated information system for patients with Inborn Errors of Immunity (IEI). Although disease registries are essential tools for data management and health planning, their success depends on implementation science approaches that account for local contextual factors. This study reports Phase I of a three-phase mixed-methods implementation project to design and develop a national IEI registry. Methods: Phase I consisted of a phenomenological qualitative study exploring stakeholder perspectives. Semi-structured focus groups and in-depth interviews were conducted with 29 key stakeholders across four groups: policy-makers, clinical experts, end-users (immunologists, residents, allied health personnel), and patient organization representatives. Interviews followed a guide structured around four a priori domains (structure, navigation, feasibility, and perception of existing systems). Discussions were conducted in Spanish, audio-recorded, transcribed verbatim, and coded using ATLAS.ti. A hybrid thematic analysis combining deductive and inductive coding was performed. Data elements proposed for the registry were triangulated with qualitative findings. Results: Thirty-six initial codes were consolidated into 15 categories, which were further integrated into four overarching themes conceptualized as pathways toward intention to use: (1) Environment, where governance, regulatory backing, and sustainable financing were identified as key enablers, while limited interoperability emerged as a structural barrier; (2) Technical Dimension, emphasizing usability, alignment with clinical workflow, and a hierarchical data architecture (demographic, clinical, therapeutic); (3) Users, highlighting clinical leadership, protected time, digital readiness, and perceived usefulness as stronger motivators than financial incentives; and (4) Patients, underscoring data protection, transparency, trust, and advocacy as essential for legitimacy and sustainability. Conclusions: A national IEI registry in Peru is perceived as necessary and feasible if implemented with strong regulatory foundations, interoperable design, robust data security, and user-centered architecture. These findings informed the development of an initial functional prototype and the operational plan for Phase II, focused on usability evaluation.

18.
arXiv (quant-ph) 2026-06-12

Positive Conserved Quantities in the Klein-Gordon Equation

作者:

arXiv:2410.04666v3 Announce Type: replace Abstract: We introduce an embedding of the Klein-Gordon equation into a pair of coupled equations that are first-order in time. The existence of such an embedding is based on a positivity property exhibited by the Klein-Gordon equation. These coupled equations provide a more satisfactory reduction of the Klein-Gordon equation to first-order differential equations in time than the Schrodinger equation. Using this embedding, we show that the ``negative probabilities" associated with the Klein-Gordon equation do not need to be resolved by introducing matrices as Dirac did with his eponymous equation. For the case of the massive Klein-Gordon equation, the coupled equations are equivalent to a forward Schrodinger equation in time and a backward Schrodinger equation in time, respectively, corresponding to a particle and its antiparticle. We show that there are two positive integrals that are conserved (constant in time) in the Klein-Gordon equation and thus provide a concrete resolution of the historical puzzle regarding the previously supposed lack of a probabilistic interpretation for the field governed by the Klein-Gordon equation. A significant consequence is that the Schrodinger equation is given a relativistic formulation, which does not require creation and annihilation operators, i.e. quantum fields. Physically, this corresponds to a theory in which the positive and negative energy parts do not directly interact, hence there will be no annihilation events–for example, particle-antiparticle collisions which do not result in photon emission. Thus, one practical consequence of this relativistically consistent theory is a simple explanation for dark matter.

19.
arXiv (CS.CV) 2026-06-16

SLU-2K: A Question-Based Benchmark for Semantic Evaluation of Sign Language Translation

Sign Language Translation (SLT) is typically evaluated with surface-form metrics such as BLEU and ROUGE, which reward lexical overlap but do not directly measure whether a translation preserves the meaning of the source sign sequence. This is in contrast with the final objective of integrating SLT in assistive technology. In this work, we shift the focus from Sign Language Translation (SLT) to Sign Language Understanding (SLU), with particular emphasis on semantic understanding. Specifically, we evaluate systems based on their ability to correctly recover, from the input video, key semantic aspects of the original sentence, such as actions taking place and facts about people and objects. To enable this evaluation systematically, we propose SLU-2K, a dataset of 2,350 closed-ended video question-answer pairs based on the popular PHOENIX-2014T and CSL-Daily datasets. To obtain SLU-2K, we propose and extensively evaluate an automated data generation pipeline which produces questions across 7 categories, namely actions, locations, numbers, objects, people, time, and weather conditions. We show the potential of SLU-2K by evaluating popular Multimodal Large Language Models (MLLMs) and two representative state-of-the-art systems, MMSTL and SpaMo. Our results show that MLLMs reach near-random performance, highlighting the need for a more systematic integration of SLU in current AI systems. Furthermore, state-of-the-art translation systems carefully fine-tuned on in-domain data still exhibit a substantial semantic gap, with results ranging from 56.7% to 75.2%. These findings suggest that current SLT evaluation protocols overestimate true understanding and that future progress should be measured not only by fluency and n-gram overlap, but also by semantic correctness. Code, prompts, and benchmark files are available at https://github.com/ZenoTsT/SLU-2K

20.
arXiv (CS.CL) 2026-06-11

Toward Preference-aligned Large Language Models via Residual-based Model Steering

Preference alignment is a critical step in making Large Language Models (LLMs) useful and aligned with (human) preferences. Existing approaches such as Reinforcement Learning from Human Feedback or Direct Preference Optimization typically require curated data and expensive optimization over billions of parameters, and eventually lead to persistent task-specific models. In this work, we introduce Preference alignment of Large Language Models via Residual Steering (PaLRS), a training-free method that exploits preference signals encoded in the residual streams of LLMs. From as few as one hundred preference pairs, PaLRS extracts lightweight, plug-and-play steering vectors that can be applied at inference time to push models toward preferred behaviors. We evaluate PaLRS on various small-to-medium-scale open-source LLMs, showing that PaLRS-aligned models achieve consistent gains on mathematical reasoning and code generation benchmarks while preserving baseline general-purpose performance. Moreover, when compared to models aligned with DPO and SimPO, they perform better with great time-savings. Our findings highlight that PaLRS offers an effective, much more efficient and flexible alternative to standard preference optimization pipelines, offering a training-free, plug-and-play mechanism for alignment with minimal data.

21.
arXiv (quant-ph) 2026-06-12

The table maker's quantum search

arXiv:2601.13306v2 Announce Type: replace Abstract: We show that quantum search can be used to compute the hardness to round an elementary function, that is, to determine the minimum working precision required to compute the values of an elementary function correctly rounded to a target precision of $n$ digits for all possible precision-$n$ floating-point inputs in a given interval. For elementary functions $f$ related to the exponential function, quantum search takes time $\tilde O(2^{n/2} \log (1/\delta))$ to return, with probability $1-\delta$, the hardness to round $f$ over all $n$-bit floating-point inputs in a given binade. For periodic elementary functions in large binades, standalone quantum search yields an asymptotic speedup over the best known classical algorithms and heuristics. We then estimate the resources required for a fault-tolerant implementation of the proposed algorithm for the $\sin$ and $\cos$ functions in double precision. We find that, although the algorithm can in principle compete with the fastest known practical method for computing the hardness to round over all binades in the format, it requires qubit coherence times that are unrealistically long for present technology.

22.
Science (Express) 2026-04-16

Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) are widespread bacterial anti-phage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6 Å resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.

23.
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.

24.
Nature (Science) 2026-06-10

Mutation-dependent responses to sleep and exercise in clonal haematopoiesis

Clonal haematopoiesis (CH) activates inflammation and increases the risk of atherosclerosis1,2. Whether lifestyle alters CH clone expansion or the phenotypic programming of CH mutant cells, thereby affecting atherosclerosis, is unknown. Here, in humans and mice and across mutations in Jak2, Tet2, Trp53 and Dnmt3a, we demonstrate mutation-dependent responses to sleep and exercise in CH and show that mutant cells are uniquely sensitive to lifestyle. In two human datasets, moderate-to-vigorous physical activity was associated with lower prevalence of non-DNMT3A-driven CH. In atherogenic mice with Jak2V617F or Tet2 loss of function (LOF), but not Trp53 LOF or Dnmt3aR878H CH, uninterrupted sleep or exercise curtails clone expansion. In CH with the Jak2V617F mutation, sleep and exercise reduces clone expansion by selectively reprogramming mutant, but not cohabitant wild type, haematopoietic progenitor cells towards antiproliferative and metabolically healthy phenotypes by tempering bone marrow macrophage–haematopoietic progenitor cell IL-1β signalling. Sleep or exercise also lessens Jak2V617F-driven, Tet2 LOF-driven and Trp53 LOF-driven, but not Dnmt3aR878H-driven, atherosclerosis by locally reprogramming mutant vascular macrophages, independent of peripheral clone dynamics. In Jak2V617F, but not adjacent wild type, aortic macrophages, uninterrupted sleep blunts CLEC4E-dependent inflammasome activation, consequently diminishing lesions. Exercise, meanwhile, activates PAC1+ neurons in the locus coeruleus, raising the levels of peripheral noradrenaline, which signals through adrenergic receptor β2 (ADRβ2) whose expression is preserved by exercise in Jak2V617F, but not cohabitant wild type, aortic macrophages, selectively repressing their inflammatory programming and atherosclerosis. Our findings establish that healthy lifestyles gene-specifically diminish CH and selectively reprogram mutant haematopoietic progenitor cells and macrophages to maintain cardiovascular health. Sleep and exercise can slow clonal haematopoiesis and limit mutant cell-driven atherosclerosis.

25.
arXiv (quant-ph) 2026-06-16

3D Ising criticality with Platonic lattice superconducting qubits

arXiv:2606.16854v1 Announce Type: new Abstract: The three-dimensional (3D) Ising model is a foundational model in statistical physics and critical phenomena, yet its analytical intractability has long impeded the precise determination of universal critical exponents. While high-precision estimates have been obtained through classical numerical methods and conformal bootstrap techniques, a direct quantum simulation of the 3D Ising criticality remains challenging, requiring nontrivial connectivity, sufficient system size, and high spectral resolution. In this work, assisted by the state-operator correspondence of conformal field theory, we perform a digital quantum simulation of the 3D Ising critical exponents using a multiply-connected 9-qubit superconducting quantum processor with a Platonic lattice geometry. Employing an extended variational quantum eigensolver equipped with a phase-based loss function, we variationally prepare the low-energy eigenstates of the transverse-field Ising model on a cubic Platonic lattice encoded in an 8-qubit register. The four lowest eigenenergies are extracted via Fourier-transform analysis and high-precision numerical fitting, agreeing with the exact diagonalization values up to +/- 0.001. The resulting scaling dimension Delta_epsilon = 1.5850 and critical exponent nu = 0.7067 match well with theory.