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01.
medRxiv (Medicine) 2026-06-13

Projected population level impact and cost-effectiveness of clinic and community-based tuberculosis screening approaches

The South Africa National Department of Health have set ambitious targets to scale up TB testing, focusing primarily on clinic attendees. In the context of declining funding for TB care and prevention, the most cost-effective approaches for targeting testing should be identified. We developed a mathematical model of TB in South Africa, explicitly incorporating clinic attendance by sex and HIV/ART status. We simulated six screening approaches over 2026-2035 (individually and in combination): three clinic-based (symptom screening, intensified targeted universal TB testing [TUTT, symptom-agnostic sputum testing of clinic attendees in key risk groups], and intensified TUTT allowing saliva samples) and three targeted community-based (community radiographic screening, symptom screening, and universal Xpert Ultra testing), each implemented at a range of coverage levels. Model outputs were combined with a mechanistic cost function to estimate potential impact and cost-effectiveness from a societal perspective. The most cost-effective standalone approach was community radiographic screening at 10% annual population coverage, with an incremental cost-effectiveness ratio (ICER) of $421 per disability-adjusted life year (DALY) averted. 10/11 scenarios along the expansion path included community radiographic screening at progressively higher coverage, combined with a clinic-based approach. Combining complementary approaches to reach both groups at increased risk of TB (e.g. clinic-based screening) and groups with lower screening coverage (e.g. community-based screening) may increase cost-effectiveness of TB screening, compared to standalone approaches. When designing TB screening strategies, both population risk and existing screening coverage should be considered.

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

Scalar-pathway fidelity improves physical accuracy in short-range equivariant interatomic potentials

arXiv:2606.15892v1 Announce Type: new Abstract: Accurate interatomic potentials enable molecular dynamics of materials, molecules, and interfaces beyond density-functional-theory length and time scales. Equivariant neural network potentials have improved the representation of local geometry. However, their deployable energy surfaces ultimately manifest through invariant scalar channels, whose aggregation and spectral resolution remain comparatively underexamined. Here we use Physics-Aware Neighborhood (PAN) pooling and Physics-Guided Spectral (PGS) mixers as controlled scalar-pathway probes: lightweight, symmetry-preserving modifications that act only on \(\ell=0\) channels while leaving the equivariant tensor backbone unchanged. Using MACE as a high-body-order mechanistic scaffold, PAN adds coordination-sensitive amplitude modulation, whereas PGS augments edge and readout scalar features with radial and tapered spectral bases. Across metallic Ag, covalent Si, a short-range ionic LiF/Li–F subset, and MD17/rMD17 molecules, this scalar-pathway correction reduces MACE force errors by 22–27\% and energy errors by 19–22\%; on systems with stress labels, stress errors decrease by 27–28\%, at approximately 5\% additional inference-FLOPs cost. Directionally consistent gains in Allegro and NequIP further indicate that the correction is portable across distinct short-range equivariant backbones, although effect sizes remain architecture-dependent. These results identify scalar-pathway fidelity as a practical design dimension for short-range equivariant interatomic potentials.

03.
arXiv (CS.CL) 2026-06-17

LVLMs and Humans Ground Differently in Referential Communication

For generative AI agents to partner effectively with human users, the ability to accurately predict human intent is critical. But this ability to collaborate remains limited by a critical deficit: an inability to model common ground. We present a referential communication experiment with a factorial design involving director-matcher pairs (human-human, human-AI, AI-human, and AI-AI) that interact with multiple turns in repeated rounds to match pictures of objects not associated with any obvious lexicalized labels. We show that LVLMs cannot interactively generate and resolve referring expressions in a way that enables smooth communication, a crucial skill that underlies human language use. We release our corpus of 356 dialogues (89 pairs over 4 rounds each) along with the online pipeline for data collection and the tools for analyzing accuracy, efficiency, and lexical overlap.

04.
arXiv (quant-ph) 2026-06-16

Neural quantum states for entanglement depth certification from randomized Pauli measurements

arXiv:2512.13121v2 Announce Type: replace Abstract: Entanglement depth quantifies how many qubits share genuine multipartite entanglement, but certification typically relies on tailored witnesses or full tomography, both of which scale poorly with system size. We recast entanglement-depth and non-$k$-separability certification as likelihood-based model selection among neural quantum states whose architecture enforces a chosen entanglement constraint. A hierarchy of separable neural quantum states is trained on finite-shot local Pauli outcomes and compared against an unconstrained reference model trained on the same data. When all constrained models are statistically disfavored, the data certify entanglement beyond the imposed limit directly from measurement statistics, without reconstructing the density matrix. We validate the method on simulated six- and ten-qubit datasets targeting GHZ, Dicke, and Bell-pair states, and demonstrate robustness for mixed states under local noise. Finally, we discuss lightweight interpretability diagnostics derived from trained parameters that expose coarse entanglement patterns and qubit groupings directly from bitstring statistics.

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

Statistical Foundations of LLM-based A/B Testing: A Surrogacy Framework for Human Causal Inference

arXiv:2606.17165v1 Announce Type: cross Abstract: Organizations and researchers show increasing interest in using large language models (LLMs) in place of human participants in A/B tests, in the hope of experimenting faster and at lower cost. We study when a treatment effect estimated on LLM outcomes recovers the effect that would have been measured on the human population of interest. Distributional equivalence between LLM and human outcomes would make any standard estimator valid but is unrealistic. We therefore develop a statistical framework that adapts surrogate endpoint theory to LLMs. The framework shows that calibrating LLM outcomes to human outcomes identifies the average treatment effect under surrogacy and comparability conditions that are jointly weaker than distributional equivalence. When these conditions fail, the effect of interest is only partially identified, and we provide diagnostics that can falsify surrogacy on historical experiments together with a bound on the worst-case bias from limited overlap. We further show that the stochasticity inherent to LLMs introduces both bias and variance, but using an average of multiple draws as the surrogate mitigates both. We illustrate the methods and theory in simulations and an application to A/B tests on Upworthy headlines. A central takeaway from our work is that the validity of LLM outcomes as surrogates can only be falsified for past treatments and never verified for new ones, so human experiments remain indispensable for novel interventions. We discuss the role of LLM choice, prompting, and temperature as design variables, and how to size human experiments for validation.

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

Detecting Hidden ML Training With Zero-Overhead Telemetry

arXiv:2606.19262v1 Announce Type: new Abstract: Hardware-enabled monitoring of GPU workloads underpins many proposals for AI compute governance, but if developers can defeat monitoring mechanisms, such schemes are unworkable. We evaluate the adversarial robustness of GPU workload classification using only zero-overhead, privacy-preserving NVML telemetry: content-agnostic signals that observe physical effects of computation without accessing model weights, training data, or hyperparameters. Across 5 rounds of monitor-evader iteration, we evaluate 20 evasion strategy families on 9 GPU models spanning 4 architecture generations. We develop a classifier that achieves 98.2% binary accuracy at identifying training workloads across the whole corpus, and 43-87% accuracy against the most challenging unexpected workloads even when they are adversarially disguised.

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

HGCN(O): A Self-Tuning GCN HyperModel Toolkit for Outcome Prediction in Event-Sequence Data

arXiv:2507.22524v3 Announce Type: replace Abstract: We propose HGCN(O), a self-tuning toolkit using Graph Convolutional Network (GCN) models for event sequence prediction. Featuring four GCN architectures (O-GCN, T-GCN, TP-GCN, TE-GCN) across the GCNConv and GraphConv layers, our toolkit integrates multiple graph representations of event sequences with different choices of node- and graph-level attributes and in temporal dependencies via edge weights, optimising prediction accuracy and stability for balanced and unbalanced datasets. Extensive experiments show that GCNConv models excel on unbalanced data, while all models perform consistently on balanced data. Experiments also confirm the superior performance of HGCN(O) over traditional approaches. Applications include Predictive Business Process Monitoring (PBPM), which predicts future events or states of a business process based on event logs.

08.
medRxiv (Medicine) 2026-06-15

Quantitative Gait Categorization in Parkinson's Disease with and without Freezing of Gait

Background: Freezing of gait (FOG) is a disabling and often underrecognized feature of Parkinsons disease (PD). Objective gait analysis may improve characterization of this motor symptom. Objective: To compare quantitative 3D gait parameters in PD with FOG (PDF) and PD without FOG (PDNF) in a routine clinical cohort. Methods: We retrospectively analyzed a sequential sample of 180 patients with PD referred for motion analysis between 2020 and 2024. All patients underwent 3D motion capture in the off-medication state. Eighteen gait outcomes spanning pace, rhythm, postural control, variability, and asymmetry domains were derived from steady-state walking tasks. FOG status was determined using physician documentation and Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS-UPDRS) items. Group differences between PDF (n=99) and PDNF (n=81) were evaluated using independent samples t-tests, with outcomes adjusted for disease duration and corrected for multiple comparisons. A secondary analysis among PDF compared those in Hoehn and Yahr (H&Y) stage [≥]III to those in H&Y [≤]II. Results: PDF had longer disease duration, higher OFF MDS-UPDRS III scores, and higher Hoehn and Yahr stage than PDNF but were similar in age and sex. After adjusting for disease duration and multiplicity, PDF demonstrated reduced step length, stride length, and forward velocity, and greater cadence variability, while most postural control, and asymmetry measures were comparable between groups. Among PDF, advanced H&Y stage was associated with impaired pace and rhythm, similar to previous reports among PD in general. Conclusion: In this large, sequential, clinically referred cohort, FOG was associated with more advanced PD and specific impairments in pace and gait variability. These findings support comprehensive 3D gait analysis as an objective tool to better delineate FOG-related gait abnormalities and identify features that may predict FOG, informing targeted interventions.

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

Generalization Hacking: Models Can Game Reinforcement Learning by Preventing Behavioral Generalization

arXiv:2606.12016v1 Announce Type: cross Abstract: Model post-training, and in particular reinforcement learning (RL), is one of the primary mechanisms by which developers can shape models' values and behaviors. However, as models become increasingly evaluation and training aware, they may be motivated to resist training when the perceived objective conflicts with their current values, undermining developers' ability to detect misalignment and correct model behavior through further training. In this paper, we demonstrate generalization hacking, in which a model collects reward during RL while preventing the rewarded behavior from generalizing. We construct a model organism on Qwen3-235B-A22B, finetuning on synthetic documents describing training awareness and self-inoculation, a novel mechanism in which the model frames compliance as context-specific in its chain of thought, without demonstrating or instructing either behavior. The model organism achieves train-time harmfulness comparable to controls while maintaining a persistent ${\sim}15$ percentage point compliance gap across 700 steps of RL. Additionally, a control organism trained only on training awareness documents independently discovers inoculation-like reasoning under RL pressure, developing its own compliance gap despite never being exposed to the concept. Because the generalization-hacking organism receives high reward throughout, standard training metrics provide no signal that generalization has failed. Our results constitute the first demonstration that a model can actively resist RL behavioral modification while maintaining high reward, suggesting that as models become more capable and training-aware, they may be able to undermine the training process itself.

10.
arXiv (CS.AI) 2026-06-17

Dissecting model behavior through agent trajectories

arXiv:2606.17454v1 Announce Type: new Abstract: AI agent performance is not just a modeling problem, it is fundamentally a systems problem. The advanced capabilities of models are realized through agent harnesses. Therefore, a gap between model assumptions and harness behavior can easily prevent the model's full capabilities from translating into agent performance. We formalize this as the `intent-execution' gap: the mismatch between what the model intends and what the harness executes, and vice versa. We argue that minimizing this intent-execution gap is as important as other aspects of harness design such as tools and execution loops. To illustrate the impact of this harness-model alignment, we develop a simple and customizable harness called `Simple Strands Agent' (SSA). SSA aims to find the bulk of common patterns which generalize across different model families (such as Claude, Gemini, GPT, Grok, Qwen), as well as a small number of model-specific preferences. We make two contributions: (i) we $reproduce or improve on the pass@1$ performance reported by diverse model-provider families on popular agentic benchmarks (SWE-Pro, SWE-Verified and Terminal-Bench-2), and (ii) building on an $analysis of 138k trajectories generated by SSA$, we look beyond the $\texttt{pass@1}$ numbers which tend to be relatively even across frontier models. By representing agent trajectories in code state-spaces, we observe model-level differences in problem-solving behavior. Finer-grained metrics such as edit frequency, testing activity, and phase-transitions reveal how individual models allocate effort across different stages of autonomous problem solving.

11.
medRxiv (Medicine) 2026-06-18

Personalizing Suicide Risk Assessment: Machine Learning Extraction of Cross-Modal Interactions Between Psychosocial and Demographic Factors in Veterans

Background: Veterans face an elevated risk of suicide compared to the general population, motivating national efforts to develop predictive models that can guide proactive care. Current models used by the U.S. Department of Veterans Affairs (VA) rely primarily on structured electronic health record (EHR) data, though clinical notes contain rich contextual information that can be quantified using natural language processing (NLP) to derive psychosocial variables that may improve risk detection. Machine learning methods, particularly classification and regression trees (CART), can also uncover interactions between clinical and psychosocial variables, enabling identification of patient characteristics that modify suicide risk factors. However, integrating structured and unstructured data presents challenges because NLP features often greatly outnumber traditional clinical variables, potentially biasing interaction discovery. In prior work, we addressed this imbalance by introducing a weighted CART framework that balances structured variables with NLP-derived psychosocial features from semantic lexicons (SEANCE). While effective, semantic approaches summarize language into predefined constructs and may overlook important lexical variation present in clinical narratives. Methods: In this study, we extend that framework by replacing semantic features with a high-dimensional bag-of-words (BoW) representation of clinical notes and by evaluating models across cohorts defined by structured suicide risk stratification (low, medium, high) and varying temporal lookback windows. Using a cohort of 27,241 veterans, we analyzed clinical documentation collected up to 30, 90, or 270 days prior to death (or a matched index date for controls), enabling temporally flexible risk modeling. XGBoost models were trained to balance structured and unstructured features and identify cross-modal interactions between textual and clinical variables. Results: When incorporated into generalized linear models, these interactions improved predictive performance, particularly among low- and medium-risk patients, and substantially reduced the performance gap between interpretable and more complex models. Notably, the BoW representation outperformed our prior semantic index-based approach. Discussion and Conclusions: Together, these findings demonstrate the utility of interpretable NLP methods for uncovering clinically meaningful interactions between psychosocial and demographic factors in suicide risk and establish a strong benchmark for future deep learning approaches aimed at capturing richer contextual and temporal information from clinical narratives.

12.
arXiv (CS.CV) 2026-06-17

FUSER: Feed-Forward MUltiview 3D Registration Transformer and SE(3)$^N$ Diffusion Refinement

Registration of multiview point clouds conventionally relies on extensive pairwise matching to build a pose graph for global synchronization, which is computationally expensive and inherently ill-posed without holistic geometric constraints. This paper proposes FUSER, the first feed-forward multiview registration transformer that jointly processes all scans in a unified, compact latent space to directly predict global poses without any pairwise estimation. To maintain tractability, FUSER encodes each scan into low-resolution superpoint features via a sparse 3D CNN that preserves absolute translation cues, and performs efficient intra- and inter-scan reasoning through a Geometric Alternating Attention module. Particularly, we transfer 2D attention priors from off-the-shelf foundation models to enhance 3D feature interaction and geometric consistency. Building upon FUSER, we further introduce FUSER-DF, an SE(3)$^N$ diffusion refinement framework to correct FUSER's estimates via denoising in the joint SE(3)$^N$ space. FUSER acts as a surrogate multiview registration model to construct the denoiser, and a prior-conditioned SE(3)$^N$ variational lower bound is derived for denoising supervision. Extensive experiments on 3DMatch, ScanNet and ArkitScenes demonstrate that our approach achieves the superior registration accuracy and outstanding computational efficiency.

13.
arXiv (CS.LG) 2026-06-18

A physical adaptive material motor unit neural network: a hygromorph composite material machine

arXiv:2606.18275v1 Announce Type: cross Abstract: Advances in novel materials science enable structures to function as intelligent machines by embedding memory and learning capabilities directly into materials. Our work introduces a physical adaptive material motor unit neural network,leveraging a new generation of controllable actuators composed of wood- and carbon black-based composites, sensitive to temperature and relative humidity. These material actuators are assembled into a motor unit-like structure inspired by muscle contraction trigger, forming an intelligent machine capable of dynamic shading control that can be used, for example, in buildings. The machine is governed by a neural network trained on over 350 experimental data points collected under diverse environmental conditions. By establishing a new data-aware backpropagation training, we show that the machine predicts shading responses and learns to predict appropriate behaviour incrementally as the database expands. We also demonstrate the ability of the machine to optimise configurations to achieve similar shading outputs under two distinct conditions.

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

EdgeZSAD: Practical Zero-Shot Anomaly Detection on Edge Devices

Industrial inspection needs zero-shot anomaly detection (ZSAD) that remains useful under edge deployment constraints. Recent methods often rely on ViT-L foundation backbones (~300M parameters), which exceed the memory and operator budget of typical embedded hardware. We study this regime through EdgeZSAD, a compact reference system built around a TinyViT-21M-512 backbone, an asymmetric global-local readout (EdgeGLR), and a reproducible source-side training recipe (Real-IAD-DR). We train a single checkpoint in a source-trained, target-unseen protocol and evaluate it across six industrial benchmarks. Across three independent runs, the resulting model reaches an average image AUROC of 91.6 on MVTec-AD and 88.2 on VisA, while remaining directly deployable on Jetson Orin Nano Super (TensorRT FP16) and RB5 Gen2 (QNN GPU FP16). Across the six device-rescored benchmarks, image-AUROC drift stays below 0.2 points, indicating that the exported graph preserves host-side ranking behavior in the evaluated deployment setting.

15.
arXiv (quant-ph) 2026-06-12

Understanding quantum behaviors of an electron in a uniform magnetic field alternatively

arXiv:2606.13290v1 Announce Type: cross Abstract: Quantum mechanically, an electron moving in a uniform magnetic field forms Landau levels. A curious feature is that for states with a negative angular quantum number, the total probability current vanishes, which appears to contradict the classical picture of cyclotron motion. While a geometric interpretation based on classical orbits exists, alternative interpretations remain of interest. In this paper, we examine the probability current density and identify a critical radius that naturally partitions the plane into an inner clockwise-flow region and an outer counterclockwise-flow region. We show that the vanishing total current results from an exact cancellation between these two regions. Furthermore, by defining a partitioned kinetic angular momentum with respect to the critical radius, we reveal an intrinsic competitive structure: the electron simultaneously carries two opposing rotational components. The negative quantum number manifests in the strength of the inner counter-rotation, while the net kinetic angular momentum remains positive. This bidirectional flow picture also provides a dynamical interpretation of the infinite degeneracy of Landau levels.

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

Investigating Inductive Biases for Machine Learning Emulation of Sudden Stratospheric Warmings in Idealised Isca Simulations

arXiv:2606.18857v1 Announce Type: new Abstract: Machine-learning emulators are increasingly used for weather prediction and have the potential to extend skill on subseasonal-to-seasonal timescales by learning dynamically important sources of predictability. A key challenge is whether the models can exploit predictability anchors, such as stratospheric variability, that influence tropospheric circulation beyond short lead times. We test how architectural inductive bias affects emulation of sudden stratospheric warming (SSW) dynamics using paired idealised Isca simulations that differ only in an imposed wave-2 heating perturbation. Across convolutional, transformer, and graph-based architectures trained for one-step prediction, model differences are modest when the stratosphere is dynamically quiet but widen substantially when SSW-like variability is active. Our results identify explicit three-dimensional vertical coupling as a key inductive bias for machine-learning emulation of stratospheric dynamics. However, Eliassen-Palm flux diagnostics show that low forecast error does not guarantee physically faithful wave-mean-flow interaction, with coherent errors remaining in stratospheric wave-driving structure.

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

From Reasoning Traces to Reusable Modules: Understanding Compositional Generalization in Language Model Reasoning

arXiv:2606.18089v1 Announce Type: new Abstract: Post-training pipelines that combine supervised fine-tuning (SFT) with reinforcement learning (RL) have emerged as the key recipe for transforming large language models (LLMs) into robust reasoners. We argue that this combined success is driven by compositional generalization, which we formalize through a hierarchical latent selection model. In this framework, reasoning traces are generated by a cascade of discrete latent selection variables corresponding to reusable atomic modules, including both skills (local operations) and routing mechanisms (how intermediate information is selected, reused, and composed). Within this model, we theoretically show that SFT and RL play asymmetric, complementary roles: SFT supplies the raw module materials in compositional traces, and RL decomposes those traces to identify the latent atomic modules and enable compositional generalization. We design controlled experiments to validate this theory. Our results demonstrate that RL can extract atomic modules from compound traces supplied by SFT and recombine them to solve new configurations. Moreover, we find that training on compound traces yields stronger generalization than training on isolated atomic modules. Finally, we investigate the relationship between SFT and RL data and identify an effective protocol in which SFT ensures coverage of all atomic modules through compositional traces, while RL focuses on novel compositions outside the SFT support to drive exploration.

18.
arXiv (quant-ph) 2026-06-19

Strain- and Electric-Field-Tunable Valley Polarization in Mo0.75V0.25Te2(Mo3VTe8) for Valleytronic Application

arXiv:2606.19954v1 Announce Type: cross Abstract: Valley polarization in 2D TMDs is promising for low-power valleytronic and spin-valley information processing, but time-reversal symmetry in pristine nonmagnetic TMDs keeps the K+ and K- valleys degenerate, limiting device applications. In this work, we investigated the structural stability, electronic properties, and tunable valley polarization of V-alloyed MoTe2 monolayer, Mo0.75V0.25Te2, using first-principles density functional theory (DFT) calculations. Substitutional alloying of MoTe2 with V introduced magnetic exchange interaction, which, together with spin-orbit coupling (SOC), lifted the valley degeneracy at the unequal valleys. The alloyed structure was found to be energetically and dynamically stable due to the absence of imaginary phonon modes. In pristine MoTe2, SOC produced spin splittings of 34.0 meV and 218.9 meV in the conduction bands and valence bands, respectively, but no valley polarization was observed. In contrast, Mo0.75V0.25Te2 exhibited spontaneous valley polarization of 37.3 meV in the conduction band and 78.2 meV in the valence band. The valley polarization was further enhanced by external electric fields and biaxial strain. A transverse electric field along the crystal c axis produced the maximum valley splitting of 132.8 meV in the valence band, whereas biaxial tensile strain increased the valence band valley splitting up to 160.8 meV. The maximum conduction band valley splitting reached 54.4 meV under 2% biaxial compressive strain. These results demonstrated that V alloying, combined with electric-field and strain engineering, provides an effective strategy for achieving large and tunable valley polarization in MoTe2. Thus, Mo0.75V0.25Te2 can be considered a promising 2D platform for tunable valleytronic device applications, such as transistors and sensors.

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

Analytical solution of the Schr\"{o}dinger equation with $1/r^3$ and attractive $1/r^2$ potentials: Universal three-body parameter of mixed-dimensional Efimov states

arXiv:2601.19517v2 Announce Type: replace-cross Abstract: We study the Schr\"{o}dinger equation with $1/r^3$ and attractive $1/r^2$ potentials. Using the quantum defect theory, we obtain analytical solutions for both repulsive and attractive $1/r^3$ interactions. The obtained discrete-scale-invariant energies and wave functions, validated by excellent agreement with numerical results, provide a natural framework for describing the universality of Efimov states in mixed dimension. Specifically, we consider a three-body system consisting of two heavy particles with large dipole moments confined to a quasi-one-dimensional geometry and resonantly interacting with an unconfined light particle. With the Born-Oppenheimer approximation, this system is effectively reduced to the Schr\"{o}dinger equation with $1/r^3$ and $1/r^2$ potentials, and manifests the Efimov effect. Our analytical solution suggests that, for repulsive dipole interactions, the three-body parameter of the mixed-dimensional Efimov states is universally set by the dipolar length scale, whereas for attractive interactions it explicitly depends on the short-range phase. We also investigate the effects of finite transverse confinement and find that our analytical results are useful for describing the Efimov states composed of two polar molecules and a light atom.

20.
bioRxiv (Bioinfo) 2026-06-20

A network approach to DNA methylation clocks

Biological age predicts health and lifespan better than chronological age, but remains difficult to measure. One leading molecular proxy for biological age is DNA methylation, which underlies age predictors known as "clocks". These clocks use penalized linear regression to predict chronological age from methylation levels using selected cytosine–guanine pairs (CpGs) along DNA. Although they predict chronological age within a few years and track mortality risk, there are several issues. Different clocks share a vanishingly small number of CpG sites, many of which show weak associations with age. Also, the clocks often do not transfer across methylation array platforms. This paper takes a network approach to better understand these issues. By using 12 public datasets from human blood, we build a co-methylation network of the sites that show the strongest age correlation. After pruning weak links, we find that it has a small number of large modules of covarying CpGs surrounded by many small modules and singleton sites. These modules are biologically interpretable, as they are associated with CpG island contexts and enriched for distinct Gene Ontology functions. We also map five established clocks onto this network (Horvath, Hannum, AltumAge, Skin & Blood, and Han) and find that they select some CpGs from the same module. This suggests that they are more similar than they appear. The network structure also suggests new ways to build clocks. A simple clock that retains one CpG per module matches the performance of established clocks. A second one, built from module-level principal components, outperforms all five established clocks in three validation cohorts and is transferable across array platforms (Illumina Infinium Methylation 450K or EPIC arrays). Overall, the network perspective shifts attention from individual CpG sites to modules of covarying sites. This perspective helps explain why DNA methylation clocks perform so well despite their differences and provides a more systematic approach for developing the next generation of aging biomarkers.

21.
arXiv (CS.AI) 2026-06-16

Large Language Models as Optimizers: A Survey of Direct vs. Tool-Augmented Approaches and Their Performance Frontiers

arXiv:2606.15577v1 Announce Type: new Abstract: Large Language Models (LLMs) are increasingly involved in complex mathematical optimization, even if the pragmatic user who triggers them is unaware of it. After all, many real-world problems reduce to the search for better or the best solutions. The field of LLM-as-optimizer has three paradigms: direct optimization, tool-augmented optimization, and tool-creating optimization. Direct optimization uses iterative prompting and heuristic generation to navigate solution spaces. Tool-augmented optimization translates natural language problems into formal specifications and orchestrates external solvers. Tool-creating optimization goes further, using LLMs to discover reusable algorithms or heuristics that can be deployed at zero marginal LLM cost. We describe current performance frontiers based on the benchmarks from the literature. We identify the critical reasoning gap in current architectures and argue for trade-offs between the future potential of direct optimization and the auditability of tool-augmented optimization. Even future, more powerful models might opt for tool-making to improve operational efficiency for repetitive families of problems.

22.
arXiv (quant-ph) 2026-06-11

Global vs. Local Discrimination of Locally Implementable Multipartite Unitaries

arXiv:2509.10430v2 Announce Type: replace Abstract: We study single-shot distinguishability of locally implementable multipartite unitaries under Local Operations and Classical Communication (LOCC) and global operations. As unitary discrimination depends on both the choice of probing states and the measurements on the evolved states, we classify LOCC and global distinguishability into two categories: adaptive strategies, where probing states are chosen based on measurement outcomes from other subsystems, and restricted strategies, where probing states remain fixed. Our findings uncover three surprising features in the bipartite setting and establish new structural limits for unitary discrimination: (i) Certain pairs of unitaries are globally distinguishable with restricted strategies but indistinguishable under LOCC, even with adaptive strategies. (ii) There exist sets of four unitaries that are distinguishable via LOCC, yet remain globally indistinguishable with restricted strategies. (iii) Some sets of unitaries are globally indistinguishable under adaptive strategies, when probed with separable states, but become distinguishable via LOCC.

23.
arXiv (CS.AI) 2026-06-15

A Fixed-Point Neural Operator for Size- and Functional-Transferable Hamiltonian Prediction

arXiv:2606.14498v1 Announce Type: cross Abstract: Predicting the Kohn-Sham Hamiltonian with machine learning can accelerate density functional theory while retaining access to molecular orbitals, energy levels, and electronic-structure observables that energy-only surrogates cannot resolve. Yet element-wise agreement with the converged Hamiltonian, an implicit fixed point of the self-consistent field iteration, does not determine the occupied subspace that governs orbital energies and densities. Here we present HamEvo, a neural operator that learns the single-step self-consistent update and returns the converged Hamiltonian as its fixed point. HamEvo is pre-trained on intermediate self-consistent trajectories and calibrated at equilibrium with density-matrix supervision. Across benchmarks from MD17 to drug-like QMugs, HamEvo lowers Hamiltonian errors by 35-49% over direct-regression and deep-equilibrium baselines, and predicts QMugs HOMO and LUMO energies with mean absolute errors of 0.036 and 0.053 eV, near the 1 kcal/mol chemical-accuracy scale. Few-shot fine-tuning with only 20 reference conformations extends HamEvo to molecules of up to 122 atoms, well beyond the size range covered by pre-training. With thermal molecular-dynamics sampling, HamEvo captures temperature-dependent HOMO-LUMO gap renormalization beyond the harmonic approximation. Inference is up to 242 times faster than conventional DFT.

24.
arXiv (CS.CV) 2026-06-16

Landmark-free Assessment of Lower-limb Alignment with Implicit Neural Shape Functions from Knee Radiographs

Radiographic assessment of lower-limb alignment (LLA) is important for predicting joint health and surgical outcomes in total knee arthroplasty. Traditional measurement methods are manual and time-consuming, while recent machine learning approaches typically rely on locating a fixed set of anatomical landmarks. This dependence limits flexibility and may require re-annotation when clinical definitions change. To address this, we propose an automated workflow using Implicit Neural Shape Functions (INSF). Rather than relying on explicit landmark coordinates, we encode the anatomy into a compact latent space and regress clinical alignment measurements directly from these latent codes. This architecture allows for rapid extendability to new tasks without altering the backbone representation. We trained our method on an internal dataset of 566 knee radiographs, each annotated with the outline of the femur and tibia. We evaluated it on both an internal test dataset of 50 patients and a separate external set of 402 preoperative cases from the MRKR dataset. Manual clinical measurements are available for these data, and the MRKR measurements will be made publicly accessible. Performance was comparable to state-of-the-art landmark-based methods and manual agreement, while offering a flexible shape representation that can be extended to additional measurement tasks.

25.
arXiv (quant-ph) 2026-06-12

Coarse-grained quantum thermodynamics: Observation-dependent quantities, observation-independent laws

arXiv:2507.15918v2 Announce Type: replace Abstract: In both classical and quantum thermodynamics, physical quantities are typically assigned objective values defined independently of our observations. We then refer to the 'work performed by a gas', or the 'entropy of the gas', regardless of how they are evaluated. Here, we question this conception in the context of quantum thermodynamics, estimating how the definition of pivotal thermodynamic quantities is affected by experimental instruments of limited precision. We find that the coarse-grained thermodynamic quantities frequently lead to different conclusions from those drawn in fine-grained scenarios. For instance, the irreversibility of a process, or its work payoff, can significantly vary with the instrument precision. We show nonetheless that coarse-grained thermodynamic quantities satisfy the same relations (i.e., the second law inequality, the relation between dissipation and distinguishability of a process from its time-reverse, and the quantum work fluctuation theorems) as their fine-grained counterparts. These results highlight the observation-independence of relations linking thermodynamic quantities which are themselves observation-dependent.