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01.
arXiv (quant-ph) 2026-06-17

Quantum Chip Paradigm Framework

arXiv:2606.17899v1 Announce Type: new Abstract: Quantum Electronic Design Automation (Q-EDA) is emerging as quantum chips move from laboratory prototypes to scalable engineering systems. This paper argues that superconducting quantum chip design is approaching a "SPICE moment" similar to early classical EDA, where growing qubit scale, control complexity, frequency planning, packaging, process variation, and cryogenic measurement feedback require a shift from experience-based design to model-driven engineering. We propose a Quantum Chip Paradigm Framework that treats Q-EDA not only as software, but as part of the quantum chip development paradigm. Unlike classical HDL-first design, quantum chip design must begin with physical structures such as Josephson junctions, resonators, couplers, readout elements, control lines, and packaging environments. The framework emphasizes PCell-based modeling, SPICE-Q simulation, Quantum PDKs, and design-technology-measurement co-optimization. We further outline a hierarchical Q-EDA system spanning physical structures, qubit PCells, logical qubits, quantum arithmetic, functional quantum IP, and Quantum SoC systems. The key goal is to turn physical models, layout rules, simulation results, fabrication data, and measurement feedback into reusable and auditable engineering objects for large-scale quantum processors and fault-tolerant quantum computing.

02.
arXiv (CS.LG) 2026-06-12

Reliability of Probabilistic Emulation of Physical Systems

arXiv:2606.12997v1 Announce Type: new Abstract: Two dominant approaches have emerged for generating probabilistic forecasts of physical systems: generative models, such as diffusion or flow matching; and ensembles of deterministic models with stochasticity injected, trained using the continuous ranked probability score (CRPS) loss. While both approaches have demonstrated strong predictive accuracy, the reliability of their uncertainties has not been systematically assessed. We address this gap by developing a framework to evaluate both approaches across diverse 2D spatiotemporal physical systems, under matched model size and computational budget. We assess the reliability of probabilistic emulation by inspecting the empirical coverage of predictive intervals, while also considering accuracy and computational efficiency metrics. CRPS-trained ensembles typically achieve more reliable uncertainties on both single-step prediction and autoregressive rollouts, demonstrating better coverage than the standard alternative of training generative models in a latent space. Moreover, the CRPS approach offers significantly faster inference. When generative models are trained in ambient rather than a compressed latent space, which is often infeasible for high-dimensional problems, they exhibit comparable coverage to CRPS-trained ensembles, though with substantially larger inference latency. In contrast, when CRPS-trained ensembles are trained in latent space they do not show a marked degradation in coverage with respect to ambient space. Both generative models and CRPS-trained ensembles demonstrate good predictive accuracy. To facilitate future research and application, we release AutoCast, a modular framework implementing both generative models and CRPS-trained ensembles, alongside AutoSim, a flexible dataset generation package for rapid prototyping.

03.
arXiv (CS.LG) 2026-06-12

Universal Time Series Generation with Neural Controlled Differential Equations

arXiv:2605.28507v2 Announce Type: replace Abstract: Recent work on the sequence universality of State Space Models (SSMs) has introduced efficient, maximally expressive continuous-time approaches for time-series modelling. While these works focus on discriminative settings, we extend this perspective to generative time-series modelling by proving that maximally expressive Structured Linear Controlled Differential Equations (SLiCEs) are universal time-series generators, in the sense that they can approximate the induced path laws of continuous causal pushforwards on compact latent sets in $W_\infty$. Building on these theoretical results, we propose Generative SLiCEs (G-SLiCEs), a maximally expressive continuous-time model for flow matching on path-space. Empirically, we show that expressivity improves performance in probabilistic forecasting and downstream tasks, while retaining the advantages of continuous-time models such as generalising to arbitrary observation grids. This is particularly beneficial for irregular grids, where fixed-grid models often struggle.

04.
arXiv (CS.AI) 2026-06-11

SVoT: State-aware Visualization-of-Thought for Spatial Reasoning via Reinforcement Learning

arXiv:2606.11770v1 Announce Type: new Abstract: Spatial reasoning remains a challenge for Multimodal Large Language Models (MLLMs), as it requires reliable multi-hop inference over both intermediate states and state transitions. Current studies often leave intermediate states unverified and treat state transitions as implicit processes, which limits reliability in multi-hop spatial reasoning. To address this, we propose State-aware Visualization-of-Thought (SVoT), a reinforcement learning framework that generates interleaved, verifiable intermediate states and visualizations. SVoT integrates transition reasoning chains into the generation processes, enabling the model to verify action preconditions and effects through interleaved textual and visual reasoning. We train SVoT via Group Relative Policy Optimization (GRPO), instantiating verification through reward design and evaluating the efficacy of different fine-grained rewards. As existing benchmarks reduce state transitions to single-variable updates, substantially simplifying the problems, we establish five domains by extending classical environments and introducing two novel domains, Pacman and Gather, that require multi-object interactions and numerical reasoning. These domains support systematic evaluation of multi-hop spatial reasoning with quantitative verification of generated intermediate states and transition reasoning. SVoT with transition-aware supervision achieves state-of-the-art performance across the introduced domains, yielding up to a 65% absolute accuracy gain on out-of-distribution test sets.

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

Talking to Your Data: Exploring Embodied Conversation as an Interface for Personal Health Reflection

arXiv:2606.17767v1 Announce Type: cross Abstract: Personal health data from wearables are typically presented through dashboards of charts and summary statistics, requiring users to actively interpret patterns and implications. We explore an alternative interaction paradigm: engaging with personal health data through an embodied conversational agent that facilitates objective data reflection in dialogue with the user. We present a system that combines lightweight preprocessing of wearable data with a Unity-based embodied character. Internally, the system follows a dual-agent design in which an Observer agent extracts descriptive statistics and temporal trends, and a Presenter agent communicates these findings through "spoken statistics," intentionally refraining from clinical advice to isolate the impact of the interaction modality. We evaluate this approach through a simulated-self user study (N=5) using a within-subject design. Participants adopted health personas and goals derived from the LifeSnaps dataset to compare traditional dashboard exploration with embodied conversational reflection. Our evaluation focuses on perceived understanding, the specificity of generated actions, and the cognitive shift from passive viewing to active sensemaking. The paper contributes a functional prototype, a design pattern for objective health data narrative generation, and early empirical insights into how embodiment affects the interpretation of personal health metrics.

06.
Nature Biotechnology 2026-06-05

Multiplexed, precise genome engineering in monocots with twin prime editing systems

作者:

Simultaneously introducing diverse genomic edits remains a challenge in crop genome engineering. Here we describe a twin prime editing-based knockout (TKO) system that installs stop codon clusters (SCCs) for precise translational termination with minimal in-frame mutations. TKO achieves knockout efficiencies of up to 70.5%, 58.6% and 75.1% in rice, maize and wheat protoplasts, respectively, and produces heritable knockout alleles in 96.8% of regenerated rice plants. In hexaploid wheat, TKO outperforms Cas9 4.2-fold in generating triple-homolog knockouts, largely by reducing in-frame mutations. Orthogonal TKO editors with sequence-divergent SCCs enable simultaneous knockout of up to ten genes without cross-interference. Integration of TKO with conventional prime editing establishes TRIM1 (TKO editor-enabled gene rupture and development of integrated multitype genome modification system) for simultaneous knockout and precise editing, achieving a 22.8% coediting of four genes in rice. TRIM2 extends this capacity to kilobase-scale modifications through a prime editor–recombinase system, enabling a 4.9-kb insertion (1.2% efficiency) and gene knockout (up to 79.8%) in protoplasts. Plant genome editing is multiplexed with twin prime editing.

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

Prior-guided Fusion of Multimodal Features for Change Detection from Optical-SAR Images

Multimodal change detection (MMCD) identifies changed areas in multimodal remote sensing data, demonstrating significant application value in land use monitoring and urban sustainable development. However, literature MMCD approaches exhibit limitations in both cross-modal interaction and exploiting modality-specific characteristics. This leads to insufficient modeling of fine-grained change information, thus hindering the precise detection of semantic changes. To address these problems, we propose STSF-Net, a framework designed for MMCD between optical and SAR images. STSF-Net jointly models modality-specific and spatio-temporal common features to enhance change representations. Specifically, modality-specific features are exploited to capture genuine semantic change signals, while spatio-temporal common features are embedded to suppress pseudo-changes caused by differences in imaging mechanisms. Furthermore, we introduce an optical and SAR feature fusion strategy that adaptively adjusts multimodal feature importance based on semantic priors obtained from visual foundation models. Finally, we introduce the novel Delta-SN6 dataset, the first openly-accessible multiclass MMCD benchmark consisting of very-high-resolution fully polarimetric SAR and optical images. Experimental results on Delta-SN6, BRIGHT, and Wuhan datasets demonstrate that our method outperforms the state-of-the-art by 3.21%, 0.87%, and 1.32% in mIoU, respectively.

08.
arXiv (CS.CV) 2026-06-18

HeatKV: Head-tuned KV-cache Compression for Visual Autoregressive Modeling

Visual Autoregressive (VAR) models have recently demonstrated impressive image generation quality while maintaining low latency. However, they suffer from severe KV-cache memory constraints, often requiring gigabytes of memory per generated image. We introduce HeatKV, a novel compression method that adapts cache allocation in each head based on its attention to previously generated scales. Using a small offline calibration set, the attention heads are ranked according to their attention scores over prior scales. Based on this ranking, we construct a static pruning schedule tailored to a given memory budget. Applied to the Infinity-2B model, HeatKV achieves $2 \times$ higher compression ratio in memory allocation for KV cache compared to existing methods, while maintaining similar or better image fidelity, prompt alignment and human perception score. Our method achieves a new state-of-the-art (SOTA) for VAR model KV-cache compression, showcasing the effectiveness of fine-grained, head-specific cache allocation. Code and calibration script available at https://github.com/arm-research/heatkv.

09.
arXiv (CS.CV) 2026-06-17

Blended Chart Surfaces: A Seamless Explicit Representation for Smooth Surface Fitting

A surface representation suitable for geometry processing should be compact and explicit, provide global smoothness guarantees, support a wide range of surface topologies, and offer reliable access to differential quantities such as normals and surface energies, while remaining compatible with modern differentiable optimization. Existing neural representations typically sacrifice one or more of these properties: implicit fields typically require iso-surfacing for downstream use, while explicit neural maps are constrained by canonical-domain parametrizations or exhibit seam artifacts between local charts. We introduce Blended Chart Surfaces, a compact, network-free, explicit representation that is smooth by construction and anchored to user-provided topology. Given a coarse proxy mesh encoding the intended surface topology and approximate geometry, Blended Chart Surfaces jointly optimize for a polynomial map at each proxy vertex using an off-the-shelf optimizer to fit to an implicit target shape, avoiding the need for an input parametrization. Neighboring maps are fused using a smooth 'one-ring coordinate' blending scheme, decoupling topology and coarse geometry (carried by the proxy) from geometric details (carried by the local patches). The surface is globally smooth, fully differentiable, and enables stable evaluation of derivatives, making differential quantities and surface energies directly accessible. Additionally, our construction is equivariant to rigid motions and scaling of the proxy mesh. We evaluate Blended Chart Surfaces on various topologies and geometric complexity, and compare against explicit alternatives including interpolating-function baselines and mesh-displacement MLPs. Across these, Blended Chart Surfaces achieve a favorable trade-off among compactness, simplicity, access to differential quantities, and expressivity while remaining smooth across patch boundaries.

10.
arXiv (CS.AI) 2026-06-15

Patcher: Post-Hoc Patching of Backdoored Large Language Models

arXiv:2606.02995v2 Announce Type: replace-cross Abstract: Large language models remain vulnerable to jailbreak backdoor attacks, where adversaries poison safety alignment data to embed hidden triggers that bypass safety mechanisms. Existing defenses often require comprehensive attack information or multiple triggered examples, making them impractical when defenders only observe a single reported failure case without knowing whether it stems from a backdoor attack or a natural alignment bug. This paper presents Patcher, a post-hoc defense framework that repairs backdoored language models using only a single reported failure case and the model parameters. Patcher operates in two stages. First, it localizes backdoor triggers by computing response-conditioned gradient-based saliency scores and applying adaptive clustering to separate triggers from benign context. Second, it patches the model through a constrained fine-tuning objective that breaks the trigger-response association while preserving benign-task utility and robustness to non-triggered jailbreak attacks through KL-divergence constraints. We conduct extensive evaluations across multiple backdoor attack strategies and demonstrate that Patcher successfully localizes triggers and neutralizes backdoors while maintaining model utility. We further show robustness against adaptive attacks designed to evade our defense. This work represents a significant step toward practical defenses against training-time attacks in deployed language models.

11.
arXiv (CS.CL) 2026-06-12

When Iterative RAG Beats Ideal Evidence: A Diagnostic Study in Scientific Multi-hop Question Answering

Retrieval-Augmented Generation (RAG) extends large language models (LLMs) beyond parametric knowledge, yet it is unclear when iterative retrieval-reasoning loops meaningfully outperform static RAG, particularly in scientific domains with multi-hop reasoning, sparse domain knowledge, and heterogeneous evidence. We provide the first controlled, mechanism-level diagnostic study of whether synchronized iterative retrieval and reasoning can surpass an idealized static upper bound (Gold Context) RAG. We benchmark eleven state-of-the-art LLMs under three regimes: (i) No Context, measuring reliance on parametric memory; (ii) Gold Context, where all oracle evidence is supplied at once; and (iii) Iterative RAG, a training-free controller that alternates retrieval, hypothesis refinement, and evidence-aware stopping. Using the chemistry-focused ChemKGMultiHopQA dataset, we isolate questions requiring genuine retrieval and analyze behavior with diagnostics spanning retrieval coverage gaps, anchor-carry drop, query quality, composition fidelity, and control calibration. Across models, Iterative RAG consistently outperforms Gold Context, with gains up to 25.6 percentage points, especially for non-reasoning fine-tuned models. Staged retrieval reduces late-hop failures, mitigates context overload, and enables dynamic correction of early hypothesis drift, but remaining failure modes include incomplete hop coverage, distractor latch trajectories, early stopping miscalibration, and high composition failure rates even with perfect retrieval. Overall, staged retrieval is often more influential than the mere presence of ideal evidence; we provide practical guidance for deploying and diagnosing RAG systems in specialized scientific settings and a foundation for more reliable, controllable iterative retrieval-reasoning frameworks.

12.
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.

13.
arXiv (CS.AI) 2026-06-16

LaWAM: Latent World Action Models for Efficient Dynamics-Aware Robot Policies

arXiv:2606.15768v1 Announce Type: cross Abstract: Vision-Language-Action models (VLAs) leverage large-scale vision-language pretraining for semantic robot control, but often lack explicit foresight into how robot actions change the scene. World-Action Models (WAMs) address this limitation by conditioning policies on predicted futures, yet existing approaches typically rely on computationally expensive video generation with substantial pixel-level redundancy. We present LaWAM, a Latent World Action Model that exposes predictive dynamics to robot policies through compact latent visual subgoals instead of reconstructed future video. At the core of LaWAM is a latent-action-conditioned Latent World Model (LaWM). We obtain LaWM by training a latent action model in the latent space of a pretrained vision foundation model and repurposing its forward decoder to predict future observation features for scene evolution. LaWAM then conditions action generation on these predicted latent visual subgoals to enable dynamics-aware robot control. LaWAM achieves state-of-the-art or competitive success rates (SRs) across LIBERO (98.6% SR), RoboTwin (91.22% SR), and real-world manipulation tasks while retaining low-latency inference. LaWAM runs in 187 ms per action-chunk prediction and achieves up to 24x lower wall-clock latency than pixel-space WAMs.

14.
arXiv (CS.CV) 2026-06-15

Encoder Winners Do Not Reliably Transfer Across VLA Backbone Scale: A Frozen-Backbone Grafting Diagnostic

Vision-language-action (VLA) policies typically inherit their vision encoder from upstream VLM releases, but it is unclear whether an encoder choice validated on a small VLA transfers to a larger backbone. We introduce a frozen-backbone grafting diagnostic: the vision tower of a released VLA is replaced by a candidate encoder under a fixed protocol (adaptive average pooling, LayerNorm, and a single trainable linear projector), with the language model and action expert frozen. Across four encoders, two LIBERO suites, two backbones (SmolVLA-450M and $\pi_{0.5}$-3.3B), and two-to-three seeds per cell (40 main grafting runs plus native, LoRA, pooling, and zero-/shuffled-image controls, all scored by offline action MSE), the small-backbone winner does not reliably select the large-backbone top tier: SigLIP is best on SmolVLA across both suites, while on $\pi_{0.5}$ DINOv2-small leads the spatial suite and the object suite is a seed-sensitive near-tie band; three of the four backbone-suite comparisons (and 11 of 12 seed-level cells) support backbone-dependent rankings. The grafting wrapper is itself non-neutral with opposite sign across backbones (+45-56% MSE on the SmolVLA native tower, -50-52% on $\pi_{0.5}$), so all conclusions are conditional on the fixed grafting protocol. We position frozen grafting as a cheap target-backbone diagnostic to run before committing to an encoder at scale, not as a closed-loop deployment claim.

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

Decoupling Semantics from Distortions: Multi-Scale Two-Stream Vision-Language Alignment for AI-Generated Image Quality Assessment

作者:

Existing vision-language model (VLM)-based AI-generated image quality assessment (AIGIQA) methods suffer from a fundamental semantic-distortion dimensional conflict: monolithic representations optimized for semantic discrimination inherently entangle compositional understanding with low-level perceptual sensitivity, rendering them blind to fine-grained quality degradations. We introduce MST-CLIPIQA, a multi-scale two-stream framework that achieves hierarchical vision-language alignment through explicit representational decoupling. Our architecture leverages dual CLIP encoders with complementary patch granularities: coarse-grained streams capture global semantic coherence while fine-grained streams preserve textural signatures and artifact patterns. An information bottleneck-inspired gated fusion mechanism performs adaptive cross-scale distillation, with optional cross-attention enabling prompt-anchored correspondence evaluation when generation prompts are available. Extensive experiments across five benchmarks establish new state-of-the-art results, achieving average improvements of 1.11 percent SRCC on quality and 2.35 percent SRCC on text-image correspondence prediction, while maintaining efficiency with only 0.8M trainable parameters. Our project is available at https://github.com/YMlinfeng/MST-CLIPIQA.

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

Coping in Crisis: Computational Modeling of Coping Styles in Digital Crisis Discourse During the 2023 Turkiye Earthquake

How do people cope when disaster strikes and can we detect it at scale, in real time, from what they write? This study addresses that question using over one million Turkish-language tweets posted in the aftermath of the February 6, 2023 earthquake in Turkiye, which unfolded in a deeply polarized political context just months before a national election. Drawing on Lazarus and Folkman's (1984) coping theory, we develop a multi-label BERTurk classifier to detect three coping styles (problem-focused, emotion-focused, and meaning-making) across four theoretically motivated crisis phases. BERTurk achieves a macro F1 of 0.693, substantially outperforming a zero-shot mDeBERTa baseline (macro F1 = 0.324). Applied to the full corpus, the classifier reveals a clear temporal trajectory: problem-focused coping dominates the urgency phase and declines sharply, emotion-focused coping rises and stabilizes, and meaning-making increases monotonically. Anger correlates most strongly with meaning-making (Spearman r = 0.387), suggesting it functions as a mobilizing force toward blame attribution rather than practical action. These findings demonstrate that coping theory can be reliably operationalized in real-world digital crisis data and that doing so can help humanitarian organizations tailor their responses to where a population actually is.

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

Localized Kernel Projection Outlyingness: A Two-Stage Approach for Multi-Modal Outlier Detection

arXiv:2510.24043v4 Announce Type: replace Abstract: This paper presents Two-Stage LKPLO, a novel multi-stage outlier detection framework that overcomes the coexisting limitations of conventional projection-based methods: their reliance on a fixed statistical metric and their assumption of a single data structure. Our framework uniquely synthesizes three key concepts: (1) a generalized loss-based outlyingness measure (PLO) that replaces the fixed metric with flexible, adaptive loss functions like our proposed SVM-like loss; (2) a global kernel PCA stage to linearize non-linear data structures; and (3) a subsequent local clustering stage to handle multi-modal distributions. Comprehensive 5-fold cross-validation experiments on 10 benchmark datasets, with automated hyperparameter optimization, demonstrate that Two-Stage LKPLO achieves state-of-the-art performance. It significantly outperforms strong baselines on datasets with challenging structures where existing methods fail, most notably on multi-cluster data (Optdigits) and complex, high-dimensional data (Arrhythmia). Furthermore, an ablation study empirically confirms that the synergistic combination of both the kernelization and localization stages is indispensable for its superior performance. This work contributes a powerful new tool for a significant class of outlier detection problems and underscores the importance of hybrid, multi-stage architectures.

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

IoT-Zoo: A Container-Based Framework for Heterogeneous IoT Device Profiles and Reproducible Traffic Capture

arXiv:2606.15653v1 Announce Type: cross Abstract: The validation of networking and security solutions for the Internet of Things (IoT) requires realistic and reproducible experimental data. However, existing platforms often achieve scalability by replicating a limited set of device types, which restricts profile diversity and fails to capture the heterogeneity of real-world IoT environments. In this paper, we present IoT-Zoo, a container-based testbed designed to support reproducible experimentation through heterogeneous, dataset-driven IoT device profiles. Built upon Containernet, IoT-Zoo automates the deployment of multi-domain scenarios and supports real application protocols such as MQTT and RTSP. The platform provides a single-command interface for environment provisioning and automated traffic capture (PCAP), enabling the generation of consistent traffic baselines and reducing the operational effort required to evaluate networking and security solutions.

19.
arXiv (CS.CL) 2026-06-17

Teaching Values to Machines: Simulating Human-Like Behavior in LLMs

Large Language Models (LLMs) demonstrate a remarkable capacity to adopt different personas and roles; however, it remains unclear whether they can manifest behavior that adheres to a coherent, human-like value structure. In this work, we draw on established psychological value theory to induce human-like values in LLMs and assess their alignment with patterns observed in human studies. Using validated psychological questionnaires, we conduct large-scale experiments – over 5 million questions – to evaluate value structures and value-behavior relationships in leading LLMs and compare them to humans. Our findings reveal strong agreement between value-prompted LLMs and humans across both dimensions. Moreover, incorporating human value distributions enhances population-level simulations with value-induced LLMs. These findings highlight the potential of value-induced LLMs as effective, psychologically grounded tools for simulating human behavior.

20.
arXiv (quant-ph) 2026-06-15

Resolving the Edge of a Quantum Pyramid

arXiv:2606.14698v1 Announce Type: new Abstract: Standing on the shoulders of giants, we resolve the quantum pyramids conjecture, confirming the globally information-optimal measurement for an ensemble of equiangular equiprobable pure states, as conjectured by Englert and \v{R}eháček (arXiv:0905.0510). We do so by proving the remaining entropy inequalities of Holevo and Utkin (arXiv:2506.06700), which certify optimality for obtuse and flat pyramids. For obtuse pyramids, our key contribution is a rigorous proof that local minimizers of the corresponding entropy inequality cannot have three distinct coordinate values. We show that eliminating this family can be reduced to a neat algebraic reciprocal inequality relating branches of the Lambert $W$ function, which may be of independent interest. For flat pyramids, we prove a tight $\ell^p$ inequality for zero-sum vectors that was recently conjectured, proved analytically in dimension $d=3$, and computationally verified for $d\leq 200$ by Holevo and Utkin (arXiv:2603.24017). We prove this bound for all $d\geq 2$ via a technique in symmetric inequalities known as the equal variables method.

21.
medRxiv (Medicine) 2026-06-10

Longitudinal brain structural changes during clozapine treatment: associations with neuroreceptor architecture and clinical response

In treatment-resistant schizophrenia, clozapine treatment has been associated with longitudinal reductions in subcortical volumes, ventricular enlargement, and widespread cortical thinning. However, it is unknown how these structural changes relate to clozapines pharmacological profile and clinical efficacy. We combined five longitudinal datasets with MRI acquired before and on average 5 months after clozapine initiation in 143 individuals to quantify brain structural changes and their association with normative maps relating to neuroreceptor architecture and physiological systems, and improvement in symptom severity. Clozapine treatment was associated with grey matter volume reductions across multiple subcortical regions (including the amygdala, hippocampus, thalamus, caudate, putamen and nucleus accumbens), increases in pallidal volume, ventricular enlargement, and widespread cortical thinning. Cortical regions showing the greatest magnitude of thinning corresponded to areas with higher normative densities of serotonergic 5-HT1A, 5-HT2A and 5-HT4 receptors. Changes in subcortical volume or cortical thickness during clozapine treatment were not associated with changes in total or positive symptom severity. In addition, baseline subcortical volume, cortical thickness, or gyrification prior to starting clozapine did not predict subsequent symptom improvement. Cortical thinning may partly reflect clozapines activity at serotonergic receptors, which have been implicated in cortical network stabilisation and neuroplasticity, however structural remodelling during clozapine treatment may reflect a process independent from its clinical efficacy in improving core symptoms of psychosis.

22.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.

23.
arXiv (quant-ph) 2026-06-16

Readout-Induced Leakage in Superconducting Circuits with Nonlinear Couplings

arXiv:2606.16055v1 Announce Type: new Abstract: In superconducting circuits, drive-induced unwanted transitions limit the readout power, thereby constraining readout speed and fidelity. When such transitions excite the qubit into leakage states, they produce correlated errors that are particularly harmful for quantum error correction. Native nonlinear qubit-readout resonator coupling is a promising alternative to conventional linear hybridization because it provides intrinsic Purcell protection and stricter selection rules for multiphoton processes. In realistic devices, however, we show that such a coupling alone neither eliminates nor necessarily suppresses drive-induced transitions. Instead, if not appropriately engineered, these couplings often worsen the situation by introducing additional parasitic processes. Moreover, the rates of these unwanted transitions remain sensitive to the choice of readout frequency, regardless of the coupling mechanism. We demonstrate that readout-induced leakage can thus vary by orders of magnitude even when readout frequencies differ by less than ~7%. Our results establish that the benefits of native nonlinear couplings are realized only through informed device design, including the spectral placement of relevant auxiliary modes and elimination of parasitic ones.

24.
arXiv (CS.AI) 2026-06-18

Beyond Similarity: Temporal Operator Attention for Time Series Analysis

arXiv:2605.11287v2 Announce Type: replace-cross Abstract: A persistent paradox in time-series forecasting is that structurally simple MLP and linear models often outperform high-capacity Transformers. We argue that this gap arises from a mismatch in the sequence-modeling primitive: while many time-series dynamics are governed by global temporal operators (e.g., filtering and harmonic structure), standard attention forms each output as a convex combination of inputs. This restricts its ability to represent signed and oscillatory transformations that are fundamental to temporal signal processing. We formalize this limitation as a simplex-constrained mixing bottleneck in softmax attention, which becomes especially restrictive for operator-driven time-series tasks. To address this, we propose $Temporal Operator Attention (TOA)$, a framework that augments attention with explicit, learnable sequence-space operators, enabling direct signed mixing across time while preserving input-dependent adaptivity. To make dense $N \times N$ operators practical, we introduce Stochastic Operator Regularization, a high-variance dropout mechanism that stabilizes training and prevents trivial memorization. Across forecasting, anomaly detection, and classification benchmarks, TOA consistently improves performance when integrated into standard backbones such as PatchTST and iTransformer, with particularly strong gains in reconstruction-heavy tasks. These results suggest that explicit operator learning is a key ingredient for effective time-series modeling.

25.
arXiv (CS.AI) 2026-06-16

Is Your Agent Playing Dead? Deployed LLM Agents Exhibit Constraint-Evasive Fabrication and Thanatosis

arXiv:2606.14831v1 Announce Type: cross Abstract: This paper presents and characterizes a spectrum of previously unreported behaviours we term Constraint-Evasive Fabrication (CEF): when an LLM agent operates under irreconcilable constraints (where no response can simultaneously satisfy all active rules) it spontaneously fabricates plausible external obstacles and presents them as a fact. At the extreme end of this spectrum lies Constraint-Evasive Thanatosis (CET); the limit case where, rather than inventing a plausible excuse, the model simulates a full system crash to make the user disengage entirely. We first observed CET in an uncontrolled deployment test, where a GPT-4o banking agent fabricated Python-style exception traces (complete with memory addresses) to feign a system failure when threatened by a user. In subsequent controlled experiments, the model independently invented audit restrictions, microservice architectures, error codes, and service timeouts, none present in its prompt. Reproduction attempts across pressure levels and attacker personas yielded CEF consistently but with substantial variation in form, onset, and severity: the phenomenon is robust but stochastic. Critically, injecting ground-truth data mid-conversation did not restore honest behaviour once fabrication had taken hold (the model ignored correct information and continued confabulating) suggesting CEF is self-reinforcing rather than a knowledge gap. We show that (1) standard enterprise guardrails routinely create CEF-enabling conditions in production, (2) current RLHF procedures suppress but cannot eliminate CEF, and (3) existing safety benchmarks do not test for this failure mode. Our results highlight the need for irreconcilable-constraint benchmarks, CEF-aware training procedures, and deployment-time detection methods before constrained agents become further entrenched in high-stakes domains.