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01.
arXiv (CS.CL) 2026-06-12

Multi-Bitwidth Quantization for LLMs Using Additive Codebooks

As large language models (LLMs) are increasingly deployed across heterogeneous hardware with varying resource constraints, the ability to adaptively manage the trade-off between performance and efficiency without retraining is critical. We propose Drop-by-Drop, a novel multi-bitwidth post-training quantization framework that enables inference-time precision control over LLM weights from a single trained model. Our method is theoretically grounded in information theory and successive refinement. We establish that LLM weights, which commonly follow a Gaussian distribution, can be optimally reconstructed with increasing fidelity as additional bits are incorporated, under a weighted mean squared error distortion motivated by LLM loss functions. To realize this in practice, Drop-by-Drop incorporates Matryoshka-style supervision into the loss function, exploiting the structure of additive codebooks. Drop-by-Drop produces a single model where ordered subsets of codebooks yield accurate partial reconstructions at each precision level. This approach significantly reduces storage and memory overhead by allowing a single checkpoint to serve multiple bitwidths, while maintaining competitive perplexity and accuracy across major architectures, such as Qwen, LLaMA, Gemma, and Mistral.

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

Prototyping an AI-powered Tool for Energy Efficiency in New Zealand Homes

arXiv:2509.05364v2 Announce Type: replace-cross Abstract: Residential buildings contribute significantly to energy use, health outcomes, and carbon emissions. In New Zealand, housing quality has historically been poor, with inadequate insulation and inefficient heating contributing to widespread energy hardship. Recent reforms, including the Warmer Kiwi Homes program, Healthy Homes Standards, and H1 Building Code upgrades, have delivered health and comfort improvements, yet challenges persist. Many retrofits remain partial, data on household performance are limited, and decision-making support for homeowners is fragmented. This study presents the design and evaluation of an AI-powered decision-support tool for residential energy efficiency in New Zealand. The prototype, developed using Python and Streamlit, integrates data ingestion, anomaly detection, baseline modeling, and scenario simulation (e.g., LED retrofits, insulation upgrades) into a modular dashboard. Fifteen domain experts, including building scientists, consultants, and policy practitioners, tested the tool through semi-structured interviews. Results show strong usability (M = 4.3), high value of scenario outputs (M = 4.5), and positive perceptions of its potential to complement subsidy programs and regulatory frameworks. The tool demonstrates how AI can translate national policies into personalized, household-level guidance, bridging the gap between funding, standards, and practical decision-making. Its significance lies in offering a replicable framework for reducing energy hardship, improving health outcomes, and supporting climate goals. Future development should focus on carbon metrics, tariff modeling, integration with national datasets, and longitudinal trials to assess real-world adoption.

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

Realistic noise synthesis reduces bias and improves tissue microstructure estimation with supervised machine learning

arXiv:2606.02044v2 Announce Type: replace Abstract: Diffusion MRI enables non-invasive probing of tissue microstructure, but accurate parameter estimation is challenged by noise-related effects. In supervised machine learning frameworks trained on simulated data, discrepancies between the noise characteristics of simulated and acquired signals introduce a form of covariate shift, whereby the input signal distribution differs between training and inference. We investigated the impact of this mismatch on microstructure parameter estimation and propose a realistic noise synthesis (RNS) framework to mitigate it. RNS incorporates both the Rician expectation and the effective post-processing noise variance into simulated training signals. The Rician expectation was modelled using a noise standard deviation estimated with MPPCA, while the effective standard deviation was derived from spherical harmonic residuals of preprocessed data. The method was evaluated using the cylinder-zeppelin and the SANDI models on simulated datasets across multiple SNR levels and on in vivo diffusion data with repeated acquisitions. Sensitivity to noise misestimation was also assessed. Ignoring magnitude-induced noise effects during training produced systematic, SNR-dependent parameter bias, particularly at low SNR. Incorporating the Rician expectation substantially reduced bias to the level of noise-aware nonlinear least-squares fitting. Modelling the effective standard deviation further improved precision. Performance was largely independent of regression architecture but sensitive to accurate noise estimation. These findings demonstrate that realistic noise modelling in simulated training data mitigates signal-domain covariate shift and is essential for unbiased supervised microstructure estimation, particularly in low-SNR regimes associated with high b-values or high spatial resolution.

04.
arXiv (CS.CV) 2026-06-12

OpenMedQ: Broad Open Pretraining for Medical Vision-Language Models

We present OpenMedQ, a medical vision-language model pretrained on the broadest fully-open medical mix to date: 14 datasets totaling ~3.35M pretraining samples spanning pathology, radiology, microscopy, and text-only clinical QA. OpenMedQ reaches state-of-the-art BLEU-1 on PathVQA (75.9), beating Med-PaLM M variants up to 562B parameters (~80x larger), and matches the best reported VQA-MED BLEU-1 (64.5). Its vision encoder, transferred to 8 unseen medical classification benchmarks under an identical downstream recipe, obtains the highest average macro-F1 (0.757) among BiomedCLIP (0.745), PMC-CLIP (0.745), PubMedCLIP (0.746), and a from-scratch baseline (0.616). We release our code and an interactive demo is publicly available as a reproducible baseline for the community.

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

Public transit gains and spatially uneven travel demand changes after NYC congestion pricing

arXiv:2606.17530v1 Announce Type: cross Abstract: New York City implemented the nation's first cordon-based congestion pricing program in January 2025, providing an opportunity to evaluate how system-wide urban mobility responds to large-scale pricing interventions. Because such policies generate spillovers across modes and locations, credible control groups are difficult to construct. We address this challenge using time series foundation models to generate probabilistic counterfactual demand forecasts with calibrated uncertainty. Applying this framework to bus, subway, and aggregate trip volume data, we find that post-policy bus and subway ridership increased significantly relative to expected no-policy demand, while overall travel demand decreased modestly. The effects are spatially heterogeneous: while reductions in overall travel demand are concentrated within the Congestion Relief Zone, transit gains extend beyond Manhattan's core. Socio-demographic analyses further reveal uneven adaptation across neighborhoods, highlighting spatial equity implications. Our framework provides a scalable approach for the uncertainty-aware evaluation of system-wide urban interventions when clean control groups are unavailable.

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

Visualizing Uncertainty: Spatial Maps of Missing and Conflicting Evidence in Deep Learning

arXiv:2606.15767v1 Announce Type: cross Abstract: Understanding when and why deep neural networks are uncertain is crucial for deploying reliable machine learning systems in safety-critical domains. While existing uncertainty quantification methods provide scalar measures of model confidence, they offer limited insight into which spatial regions of an input contribute to different types of uncertainty. We propose a novel visualization framework, Uncertainty Activation Map (UAM), that combines Evidential Deep Learning (EDL) with Full-Gradient Class Activation Mapping (FullGrad) to generate interpretable spatial uncertainty activation maps. Our approach distinguishes between two fundamental types of uncertainty: vacuity, representing lack of evidence, and dissonance, capturing conflicting evidence between competing hypotheses. By leveraging the complete gradient decomposition property of FullGrad and the principled uncertainty quantification of Subjective Logic, our method produces theoretically grounded visualizations that highlight specific image regions responsible for model uncertainty. With this framework, vacuity and dissonance activation maps are generated by computing belief-weighted attributions, enabling identification of where models lack knowledge versus where they encounter ambiguous evidence. Extensive evaluations across multiple benchmark datasets demonstrate that the proposed framework effectively addresses the critical gap between uncertainty quantification and explainability, providing intuitive visual feedback to assess model reliability in complex visual recognition tasks.

07.
arXiv (CS.CV) 2026-06-11

Spatially Coupled Phase-to-Depth Calibration for Fringe Projection Profilometry

In fringe projection profilometry (FPP), depth is commonly recovered by fitting a phase-to-depth relation independently at each camera pixel. Although such pixel-wise calibration achieves high local accuracy, neighboring pixels can acquire markedly different calibration functions even when they observe the same smooth surface, producing spatially inconsistent geometry and structured surface artifacts. We propose a spatially coupled phase-depth transformation in which all pixels share a single low-dimensional mapping-global phase scalars combined with affine spatial terms on the undistorted reference-camera grid-rather than independent per-pixel fits, optionally augmented by a bounded, spatially smooth correction field. We further introduce a native-grid pairing scheme that constructs phase-depth calibration pairs directly on the reference-camera grid: when depth supervision comes from a rectified active-stereo pipeline, planes are fitted in stereo 3D and sampled back onto the camera grid along native rays, so the phase maps are never rectified. On a dental target with high-resolution scanner ground truth, the proposed model attains point-to-surface RMSE comparable to an active-stereo reference (about 12{\mu}m aggregate) while substantially improving spatial coherence over pixel-wise polynomial and rational calibration, and reduces the runtime mapping to a few element-wise operations per pixel with negligible parameter storage.

08.
arXiv (CS.CL) 2026-06-11

Grammar-Constrained Decoding Can Jailbreak LLMs into Generating Malicious Code

Large Language Models (LLMs) are increasingly used for code generation, raising concerns that they may be misused to produce malicious code. Meanwhile, Grammar-Constrained Decoding (GCD) has been widely adopted to improve the reliability of LLM-generated code by enforcing syntactic validity. In this paper, we reveal a counterintuitive risk: this reliability-oriented technique can itself become an attack surface. We uncover a new jailbreak attack, termed CodeSpear, that exploits GCD to induce LLMs into generating malicious code. Our experiments show that simply applying a benign code grammar constraint can effectively jailbreak LLMs. To address this vulnerability, we propose CodeShield, a safety alignment approach that robustly preserves safe behavior even under attacker-controlled grammar constraints. CodeShield aligns the model in the code modality by teaching it to generate honeypot code under GCD. Such code is semantically harmless, so it does not implement the malicious request, and structurally diverse, so it is difficult to suppress through grammar tightening. At the same time, CodeShield still preserves natural-language refusals when natural language is available. Experiments on 10 popular LLMs across 4 benchmarks show that CodeSpear outperforms representative jailbreak baselines and increases the attack success rate by more than 30 percentage points on average. CodeShield also restores safety under CodeSpear while preserving benign utility. Our findings reveal a fundamental risk of GCD and call for greater attention to its potential security implications.

09.
arXiv (CS.CV) 2026-06-11

Finding Sparse Subnetworks in One Training Cycle via Progressive Magnitude-Based Pruning

Neural network pruning reduces model size by removing less important parameters while aiming to preserve predictive performance. Although the Lottery Ticket Hypothesis (LTH) shows that sparse subnetworks can match dense networks when trained from suitable initializations, its iterative pruning procedure requires multiple complete training cycles. This work evaluates progressive magnitude-based pruning as a single-cycle alternative. The method gradually increases sparsity during training using a linear schedule and updates pruning masks based on active weight magnitudes. We conduct systematic experiments on CIFAR-10 and MNIST across ResNet, VGG-style, and LeNet architectures, comparing the proposed method with representative iterative and initialization-based pruning baselines, including LTH, SNIP, and GraSP. On CIFAR-10, the method achieves 95.12\% accuracy on ResNet-18 at 72.9\% sparsity, compared with 90.5\% reported for LTH. At extreme sparsity, it achieves 93.13\% accuracy on a VGG-like architecture at 97\% sparsity, compared with approximately 92.0\% for SNIP, and 93.44\% accuracy on VGG-19 at 97.97\% sparsity, compared with 92.19\% for GraSP at 98\% sparsity. A sparsity-accuracy analysis on ResNet-18 further shows that accuracy remains within 0.1 percentage points of the dense baseline across 70–85\% sparsity. These results indicate that progressive magnitude-based pruning provides an effective single-cycle approach for neural network sparsification under the evaluated settings.

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

High-Frequency Pricing at Scale for E-Commerce

arXiv:2606.13741v1 Announce Type: new Abstract: This paper presents the design, development, and implementation of a specialized forecast-then-optimize algorithmic pricing tool for sales campaigns in fashion e-commerce. Sales events present unique challenges for pricing including volatile demand patterns, rapid pricing decisions, and the need to balance short-term revenue with long-term profitability. We describe our approach combining daily-resolution demand forecasting using gradient-boosted trees with a multi-objective optimization framework that maximizes both long-term profit and net merchandise value for more than 5 million articles. Our solution addresses key limitations of existing weekly-granularity systems by implementing a forecast-then-optimize architecture that reduces pricing decision time from hours to minutes. We validate our approach through 23 A/B tests across 12 markets during 2023-2024 sales campaigns at Zalando, one of Europe's leading online fashion retailers. Experimental results demonstrate that the new pricing system achieves approximately 6% higher profit while maintaining equivalent performance on sales and revenue compared to the previous manual-algorithmic hybrid approach. Based on these results, the algorithm was successfully deployed to production and now handles the majority of algorithmic pricing decisions for sales campaigns at the company.

11.
medRxiv (Medicine) 2026-06-17

Low-Density Lipoprotein Cholesterol and Dementia Risk: Integrating Mendelian Randomization and Target Trial Emulation Within the Heart-Brain Axis

Background: The heart-brain axis links cardiovascular and neurodegenerative disease through shared vascular and inflammatory mechanisms. Although low-density lipoprotein cholesterol (LDL-C) is an established causal factor in atherosclerotic cardiovascular disease (ASCVD), its relationship with dementia remains uncertain, with midlife elevations associated with increased risk but late-life associations often appearing null or inverse. To address this cholesterol paradox, we integrated mendelian randomization (MR) with an active-comparator new-user target trial emulation. Methods: We applied a triangulated causal inference framework integrating two-sample MR with observational target trial emulation. Genetic variants associated with LDL-C were used as instrumental variables to evaluate Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and any dementia (AnyDem), with causal estimates derived using inverse-variance weighted models and sensitivity analyses for heterogeneity and pleiotropy. In parallel, an active-comparator new-user design compared statin versus ezetimibe initiation among adults aged 60 years or older using propensity score (PS) overlap weighting and Cox proportional hazards models to evaluate cardiovascular and dementia outcomes. Results: Genetically predicted LDL-C was associated with increased risk of DLB (OR 1.65, 95% CI 1.30-2.10; p

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

SAAS: Self-Aware Reinforcement Learning for Over-Search Mitigation in Agentic Search

Agentic search enables LLMs to solve complex multi-hop questions through iterative reasoning and external search. Despite the effectiveness, these systems often suffer from a critical limitation in practice: agents fail to recognize their own knowledge boundaries, blindly triggering searches when internal knowledge suffices and failing to terminate search even when adequate evidence has been collected. The lack of self-awareness leads to severe over-search, incurring substantial inference latency and prohibitive computational cost. To this end, we propose SAAS, a novel RL framework designed to cultivate dynamic self-awareness that precisely regulates search behavior without compromising accuracy. SAAS introduces three key components: (i) a search boundary modeling mechanism, which identifies the search boundary under the evolving policy by contrasting search-disabled and search-enabled rollouts; (ii) a boundary-aware reward module, which translates this boundary awareness into trajectory-level penalties, suppressing unnecessary and redundant searches; and (iii) a stage-wise optimization strategy, which leverages a sequential curriculum to prioritize reasoning over search regularization, thereby avoiding reward hacking. Extensive experiments demonstrate that SAAS substantially reduces over-search, while maintaining accuracy. Our code and implementation details are released at https://github.com/XMUDeepLIT/SAAS.

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

Mechanisms of Introspective Awareness

arXiv:2603.21396v5 Announce Type: replace Abstract: Recent work has shown that LLMs can sometimes detect when steering vectors are injected into their residual stream and identify the injected concept – a phenomenon termed "introspective awareness." We investigate the mechanisms underlying this capability in open-weights models. First, we find that it is behaviorally robust: models detect injected steering vectors at moderate rates with 0% false positives across diverse prompts and dialogue formats. Notably, this capability emerges specifically from post-training; we show that preference optimization algorithms like DPO can elicit it, but standard supervised finetuning does not. We provide evidence that detection cannot be explained by simple linear association between certain steering vectors and directions promoting affirmative responses. We trace the detection mechanism to a two-stage circuit in which "evidence carrier" features in early post-injection layers detect perturbations monotonically along diverse directions, suppressing downstream "gate" features that implement a default negative response. This circuit is absent in base models and robust to refusal ablation. Identification of injected concepts relies on largely distinct later-layer mechanisms that only weakly overlap with those involved in detection. Finally, we show that introspective capability is substantially underelicited: ablating refusal directions improves detection by +53%, and a trained bias vector improves it by +75% on held-out concepts, both without meaningfully increasing false positives. Our results suggest that this introspective awareness of injected concepts is robust and mechanistically nontrivial, and could be substantially amplified in future models. Code: https://github.com/safety-research/introspection-mechanisms.

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

BRICKS-WM: Building Reusability via Interface Composition Kinetics for Structured World Models

arXiv:2606.16489v1 Announce Type: new Abstract: Model-based Reinforcement Learning (MBRL) has achieved remarkable success in continuous control by leveraging latent world models. However, prevailing approaches typically rely on monolithic latent dynamics, entangling environment dynamics into a coupled process. This coupling severely limits reusability: altering the agent necessitates retraining the entire world from scratch, even if the environment remains constant. To address this, we introduce BRICKS-WM (Building Reusability via Interface Composition Kinetics for Structured World Models), a framework for the modular assembly of structured world models. Driven by the insight that the physical world is composed of independent entities, we posit that global dynamics can be modeled as a composition of distinct dynamical modules interacting via latent interfaces. As a minimal instantiation, we factorize the latent state space into an actuated Agent module and an external Background module, bridged by a learned latent interface. Unlike prior object-centric methods that prioritize visual segmentation, BRICKS-WM enforces a functional separation in transition dynamics, ensuring that background dynamics remains agnostic to the agent's dynamics. Empirically, BRICKS-WM achieves control performance comparable to strong monolithic baselines when trained from scratch, and enables the reuse of frozen background dynamics across agents.

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

BoRAD: Bootstrap your Own Representations for Multi-class Anomaly Detection

Reconstruction-based anomaly detection is attractive for industrial inspection, but scaling it from category-specific training to a one-for-all setting is challenging. A single model must reconstruct diverse normal appearances without copying abnormal details, which exposes two coupled failure modes: identical shortcut, where anomalies pass through the reconstruction path, and mis-reconstruction, where normal categories are confused with one another. We propose BoRAD, a label-free training framework that treats this as a representation-capacity allocation problem. BoRAD uses a shared learnable prototype bank to impose two complementary regularizers: spatial prototype alignment contracts local within-prototype variation to suppress anomaly copying, while prototype-relative global alignment preserves between-prototype structure and improves sensitivity to abnormal angular deviations. The prototype bank and prediction heads are used only during training; inference remains a standard teacher-student feature discrepancy pass, with no class labels, negative pairs, memory retrieval, or prototype lookup. BoRAD achieves competitive one-for-all anomaly detection performance, including 86.2\% mAD on MVTec AD, 80.7\% mAD on VisA and 73.1\% mAD on Real-IAD. Diagnostic analyses further show reduced anomaly leakage, improved normal-category separability, and stronger anomaly-normal score separation.

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

FairGen: Preference-Aligned Diffusion for Demographically Equitable Medical Image Synthesis

Medical imaging is central to modern diagnostics, and artificial intelligence (AI) systems are increasingly used to support image-based analysis by improving efficiency, accuracy, and access to care. However, inequities in healthcare access and differential disease prevalence create severe demographic imbalances in clinical image data. Such imbalances are compounded by the fact that diseases can manifest with distinct features across demographic groups, rendering certain phenotypic presentations naturally rare. AI models trained on such imbalanced data risk perpetuating diagnostic bias and widening healthcare disparities. Here we introduce FairGen, a fairness-aware diffusion framework that synthesizes demographically balanced medical images while preserving pathology-relevant visual features. By embedding physician-aligned preferences into the generation process, FairGen improves subgroup coverage during synthesis and downstream classification. Applied to dermatology, radiology, and neuroimaging benchmark tasks, FairGen achieves fairness improvements of 95.9% for skin images, 80.0% for chest radiography, and 35.2% for brain MRI, while maintaining competitive diagnostic accuracy relative to models trained on original clinical data. Clinician-facing expert review and external validation on independent cohorts further support that these gains extend beyond standard fidelity metrics and are not confined to the original in-distribution datasets.

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

Sensor-Conditioned Representation Learning via Scene-Relevant Observation Quotients

arXiv:2606.16210v1 Announce Type: new Abstract: Learned representations in intelligent sensing systems are often evaluated by reconstruction fidelity or downstream prediction accuracy, but these criteria do not specify which latent distinctions are justified by the sensing process. In sensor-conditioned environments, nuisance factors can change measurements without changing the scene, while distinct scenes may be indistinguishable under limited sensing capability. This paper formulates sensor-conditioned representation correctness as preserving sensing-supported scene distinctions while suppressing nuisance-induced and sensor-unsupported variation. We introduce the scene-relevant observation quotient, a representation target induced by sensing-supported distinguishability after nuisance canonicalization, and develop Observation-Quotient Tucker-Structured Autoencoding (OQ-TSAE), a scene-nuisance factorized framework with diagnostics for false distinction, false merge, nuisance sensitivity, and latent ordering consistency. Experiments on a controlled benchmark show that quotient-consistent supervision improves representation-correctness diagnostics over reconstruction-oriented, metric-learning, and contrastive-learning baselines. Sensitivity, perturbation, and ablation studies show the importance of quotient-aligned supervision, reliable quotient relations, and quotient geometry. Complementary real-radar experiments show that a reconstruction-only OQ-TSAE variant retains competitive downstream utility, robustness under observation degradation, and low seed-to-seed variability. These results suggest that sensor-conditioned representations should be evaluated not only by predictive utility, but also by whether their latent geometry preserves sensing-justified scene distinctions.

18.
arXiv (CS.LG) 2026-06-19

Utility-Aware DRL-Based TXOP Adaptation for NR-U and Wi-Fi Coexistence Networks

arXiv:2605.00457v4 Announce Type: replace-cross Abstract: The coexistence of NR-U and Wi-Fi in the unlicensed spectrum introduces a challenging resource management problem, where heterogeneous channel access mechanisms can lead to unbalanced spectrum utilization and severe Wi-Fi performance degradation. To address this issue, this paper proposes a utility-aware deep reinforcement learning (DRL) framework for adaptive transmission opportunity (TXOP) control in NR-U/Wi-Fi coexistence networks. The coexistence process is formulated as a Markov decision process (MDP), in which the NR-U TXOP duration is treated as a controllable variable for regulating post-access channel occupancy. A deep Q-network (DQN) is then employed to learn adaptive TXOP control policies through online interaction with the coexistence environment. A key feature of the proposed framework is the integration of a configurable reward and criterion design, which enables explicit control of the fairness-efficiency-utility tradeoff. Three operating policies are developed, namely absolute fairness, moderate fairness, and utility-oriented moderate fairness, to characterize different coexistence operating points. Simulation results show that the proposed framework achieves a Jain fairness index above 0.9 under strict fairness control. Compared with the absolute fairness policy, the moderate fairness policy improves aggregate throughput by 68.22%, while the utility-oriented policy achieves a 177.6% improvement under the adopted utility evaluation metric. These results demonstrate that the proposed utility-aware DRL framework provides an effective and flexible solution for adaptive TXOP control and tradeoff management in heterogeneous unlicensed coexistence networks.

19.
arXiv (math.PR) 2026-06-18

Functional central limit theorems for non-local branching Markov processes

arXiv:2502.19382v2 Announce Type: replace Abstract: The aim of this paper is to study the fluctuations of a general class of supercritical branching Markov processes with non-local branching mechanisms. We establish functional central limit theorems and show that the limiting behaviour falls into three regimes, determined by the size of the spectral gap associated with the first-moment semigroup of the branching process. The main novelty is to develop a unified functional fluctuation theory for spatial branching Markov processes with non-local reproduction, allowing a general finite-dimensional spectral structure for the first-moment semigroup, including non-simple leading eigenvalues and nilpotent Jordan-type components. In doing so, we extend the classical small, critical and large fluctuation trichotomy beyond the finite-type and local spatial settings, and obtain limiting processes that capture the covariance structure induced by non-local offspring displacement.

20.
medRxiv (Medicine) 2026-06-22

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes

OBJECTIVE To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

21.
arXiv (math.PR) 2026-06-15

On the Poisson Follower Model

arXiv:2309.04864v5 Announce Type: replace Abstract: We introduce a stochastic geometry dynamics inspired by opinion dynamics that captures the essence of modern asymmetric social networks with leaders and followers. Points in the Euclidean space represent opinions, and the leader of an agent is the one with the closest opinion. In this dynamics, each follower updates its opinion by halving the distance to its leader. We demonstrate that this simple dynamics and its iterations exhibit several interesting purely geometric phenomena related to the evolution of leadership and opinion clusters, which resemble those observed in social networks. We also show that when the initial opinions are randomly distributed as a stationary Poisson point process, the spatial frequency of each of these phenomena can be expressed through an integral geometry formula involving semi-algebraic domains. Finally, we analyze numerically the limiting behavior of this follower dynamics. In the Poisson case, the agents fall into two categories: ultimate followers, who continue updating their opinions indefinitely, and ultimate leaders, who adopt a fixed opinion after a finite time. Spatial discrete event simulations support all our findings.

22.
arXiv (CS.AI) 2026-06-15

A fully GPU-based workflow for building physics emulators of hypersonic flows

arXiv:2606.13742v1 Announce Type: cross Abstract: The ability to resolve complex physical phenomena with high fidelity and at low computational cost is central to addressing key challenges in modern engineering. A prime example lies in hypersonic flows, where the precise prediction of the full flowfield topology, in particular with respect to shock wave location and intensity, is critical. Yet supersonic and hypersonic flows continue to be a stumbling block for traditional reduced-order models and neural emulators that struggle to capture steep gradients in flow states with physical consistency in applications of industrial relevance. To that end, we introduce a fully GPU based workflow that integrates accelerated data generation with the training of neural emulators augmented by uncertainty quantification and physics-aware refinement. Our workflow is enabled by a differentiable high-fidelity solver (JAX-Fluids) which we employ for rapid dataset creation and residual-based improvement of the neural emulator to enhance physical consistency. Building on this framework, we first present a suite of model architectures and analyze their scaling behavior to expose their strengths and shortcomings. We then show that residual-based refinement enables training on cases where only mesh and input parameters are available, substantially reducing residuals and improving physical consistency. Together, differentiable simulation and residual-based refinement yield physics emulators that remain reliable beyond their training distribution, a key requirement for deploying surrogates in real-world engineering design loops.

23.
arXiv (CS.AI) 2026-06-18

Detecting High-Potential SMEs with Heterogeneous Graph Neural Networks

arXiv:2602.19591v3 Announce Type: replace-cross Abstract: Small and Medium Enterprises (SMEs) constitute 99.9% of U.S. businesses and generate 44% of economic activity, yet systematically identifying high-potential SMEs remains an open challenge. We introduce SME-HGT, a Heterogeneous Graph Transformer framework that predicts which SBIR Phase I awardees will advance to Phase II funding using exclusively public data. We construct a heterogeneous graph with 32,268 company nodes, 124 research topic nodes, and 13 government agency nodes connected by approximately 99,000 edges across three semantic relation types. SME-HGT achieves an AUPRC of 0.621 0.003 on a temporally-split test set, outperforming an MLP baseline (0.590 0.002) and R-GCN (0.608 0.013) across five random seeds. At a screening depth of 100 companies, SME-HGT attains 89.6% precision with a 2.14 lift over random selection. Our temporal evaluation protocol prevents information leakage, and our reliance on public data ensures reproducibility. These results demonstrate that relational structure among firms, research topics, and funding agencies provides meaningful signal for SME potential assessment, with implications for policymakers and early-stage investors.

24.
Nature Medicine 2026-06-08

Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

Authors:

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0–IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60–1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.

25.
arXiv (CS.CL) 2026-06-11

From Explicit Elements to Implicit Intent: A Predefined Library for Auditable Behavioral Inference

Authors:

We present SemantiClean, a modular framework for extracting structured semantic signals from e-commerce session data and driving pluggable inference targets including purchase intent, customer segmentation, and product affinity through a shared element library. Unlike conventional end-to-end predictors that optimise solely for accuracy, SemantiClean prioritises auditability, structural governance, and sigma=0 reproducibility, explicitly trading marginal predictive gains for element-level transparency and defensible decision trails. Built upon the Online Shoppers Purchasing Intention (OSPI) dataset, the framework organises twenty-four behavioural elements into a four-layer architecture (Functional, Interaction, Systemic, Contextual) and enforces signal quality through three anti-inflation mechanisms: RedundancyGroup contribution caps, TieredPenaltyCalculator bias penalties, and AdaptiveConstraintMode cold-start protection.This report introduces the LLM-Integrated Semantic Inference Engine, a fully implemented two-phase LLM-driven inference architecture that leverages complete element metadata at inference time. All quantitative results reported herein are produced by this engine. Deterministic engine outputs remain fully reproducible (sigma=0); LLM-dependent results (E8, E10) are subject to controlled output variability under fixed provider/model/temperature settings. The gender inference target remains non-functional in the current implementation and is excluded from all quantitative results.