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02.
Nature Medicine 2026-06-15

Blood signatures of cell type-specific aging forecast disease risk and resilience

Authors: Unknown Author

By measuring thousands of proteins in blood samples from over 60,000 people, we built molecular ‘clocks’ to estimate how fast cells age. Our analyses show that cell types age at different rates within the same person. Accelerated aging of specific cell types is associated with increased disease risk, whereas slower aging of others is linked to protection and improved survival.

03.
arXiv (CS.CV) 2026-06-16

Open-World Video Segmentation

While video segmentation has advanced rapidly on short clips and closed-set benchmarks, open-world video segmentation remains largely unexplored. The challenge is twofold: (1) existing methods are not designed to support object discovery and identity maintenance in long videos of dynamic ego-motion, and (2) existing evaluation protocols rely on a rigid 1:1 matching that unfairly penalizes semantically valid predictions with mismatched granularity. To address both gaps, we introduce Savvy, a practical and strong system for zero-shot open-world long-horizon video segmentation. Savvy combines hierarchical mask discovery, deferred admission, and track consolidation to support persistent object discovery, safe track promotion, and stable long-range identity maintenance. We further propose OGA, a granularity-aware evaluation suite for open-world video segmentation. Built on a Granularity-Agnostic (GA) matching protocol, OGA relaxes conventional 1:1 matching to an n:1 mapping, but still enforces temporal rigor by detecting support discontinuities through sever points and scoring each reference object through its dominant coherent fragment. This prevents fragmented or flickering support from being over-rewarded while enabling GA-adapted metrics and structural diagnostics: identity persistence (IP), and identity concentration (IC). On VIPSeg, we show that standard 1:1 evaluation substantially underestimates open-world methods, whereas GA evaluation recovers much of their suppressed performance. On the more realistic long-horizon benchmarks: ScanNet and HM3D, Savvy consistently outperforms strong baselines across both classical and proposed metrics, including STQ, VPQ$_\infty$, IP and IC. Together, these results establish a practical benchmark and a strong baseline for open-world long-horizon video segmentation.

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

HeteRo-Select: Informativeness as the Participation Driver in Heterogeneous Federated Learning

arXiv:2508.06692v2 Announce Type: replace Abstract: Federated learning systems typically allocate gradient compression by link speed. This is sensible when bandwidth and data informativeness align. However, under non-IID data, these signals often decorrelate or invert. A bandwidth-driven allocator then risks compressing the most informative gradients hardest. We propose HeteRo-Select, a framework that replaces bandwidth with a per-client informativeness score as the primary driver of compression. The score jointly governs three decisions per round: client selection, compression ratio, and server aggregation weight, with bandwidth retained only as a hard ceiling. Score-proportional selection provably reduces the effective heterogeneity of the chosen subset; score-proportional compression provably lowers aggregate top-$k$ error at fixed traffic. Under the exact FedCG simulation protocol, HeteRo-Select delivers a $1.78\times$ speedup and an $18.2\%$ reduction in traffic on CIFAR-10. The same configuration, unchanged, scales from a $7{,}850$-parameter logistic regression to an $11.27$M-parameter ResNet-18, hitting the accuracy target on three of four benchmarks. When bandwidth and informativeness are deliberately anti-correlated, the method still achieves the target accuracy with less traffic than the normal-bandwidth run.

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

When Does Delegation Beat Majority? A Delegation-Based Aggregator for Multi-Sample LLM Inference

arXiv:2606.08098v2 Announce Type: replace Abstract: Majority voting over sampled answers is the dominant unsupervised aggregator for multi-sample LLM inference. In this paper, we show a delegation-based aggregator (Propagational Proxy Voting, PPV; Sakai et al., 2025) yields an unsupervised consensus rule that beats majority on MMLU-Pro by +1.5 pp overall and +2.24 pp on the non-trivial subset (paired McNemar p ~ 1.0e-14, n = 8,099). Majority discards two signals that every sample carries: within-group letter entropy and between-group reasoning geometry. PPV exposes per-voter levers that consume exactly these two signals: When (how much weight a voter keeps on its own pick) and Whom (how it splits the remainder across peers). We drive When with letter entropy and Whom with per-question-centered embedding cosine. Our method needs no gold labels and no auxiliary training: per-question, we partition 128 sampled generations into 16 groups, compute each group's letter-level semantic entropy and reasoning embedding centroid, and feed both into a stochastic delegation matrix whose stationary distribution selects the consensus answer. We walk through an example in which PPV overturns a clear 10-6 majority for the wrong letter: the 10-voter majority cluster is geometrically incoherent (mean within-cluster cosine -0.02) while the 6-voter minority is tight (+0.26), so propagated delegation mass concentrates on the minority's answer even though entropy alone would keep the majority ahead. We further report delegation strategies with negative results that constrain the design space for unsupervised LLM aggregation. No within-question ensemble of confidence modes closes the oracle gap.

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

Stochastic dominations for FK percolation and sharp thinning thresholds for the Ising energy field

arXiv:2606.13648v1 Announce Type: new Abstract: At first glance, one would imagine that the energy field of the Ising model, the set of edges whose endpoints share the same spin, is stochastically monotone as a function of the coupling constants. However, this is not generally the case. In this paper, we introduce two weaker notions of stochastic domination that make this result true: $p$–weak and $p$–weak$^\dagger$ domination. Both of these notions depend on a parameter $p$ and we find the optimal values $p$ and $p^\dagger$ so that these dominations hold. One of the key ingredient to obtain some of the results is a new stochastic domination relating FK percolations with different parameters $q,\tilde{q}\geq 1$ that is of independent interest.

07.
arXiv (CS.LG) 2026-06-12

Dense Supervision, Sparse Updates: On the Sparsity and Geometry of On-Policy Distillation

arXiv:2606.13657v1 Announce Type: new Abstract: On-policy distillation (\textsc{OPD}) has recently become a prominent post-training recipe as it combines two desirable ingredients: on-policy student trajectories and dense teacher supervision, yet how this hybrid changes a model's parameters remains unclear. Across several language and vision-language model pairs and use cases, our analysis yields two main findings. On sparsity, \textsc{OPD}-style updates are small and coordinate-sparse. They are distributed across layers and are usually FFN-heavy. This sparse structure is operationally useful: training only the discovered subnetwork recovers nearly the same performance as full \textsc{OPD}. However, the sparsity-inducing SGD optimizer underperforms AdamW in our optimizer ablation, likely because dense teacher supervision preserves heterogeneous coordinate-wise gradient scales where AdamW's adaptive scaling remains useful. On geometry, the updates are numerically full-rank but spectrally concentrated; they lie mostly away from the principal singular subspaces of the source weights and fall disproportionately on coordinates where the source weights are close to zero. These findings suggest that dense teacher supervision does not turn \textsc{OPD} into ordinary dense parameter rewriting; instead, \textsc{OPD} retains important geometric signatures of on-policy post-training.

08.
arXiv (CS.LG) 2026-06-19

A Solver-Free Training Method for Predict-then-Optimize

arXiv:2606.19587v1 Announce Type: cross Abstract: We propose a scalable method for training prediction (machine learning) models in the predict-then-optimize paradigm, where model outputs serve as coefficients for a subsequent linear optimization task. Directly minimizing the empirical decision regret is intractable for linear programming and combinatorial optimization since the decision mapping is piecewise constant, and the gradients are zero almost everywhere. While existing methods address this by smoothing the differentiation process, they suffer from scalability issues, since a computationally expensive solver call is required for every gradient evaluation. To address this, we propose a decision-focused learning pipeline based on a measure transformation principle, which yields a new surrogate loss that is completely optimization-solver-free during training. We establish theoretical guarantees, including Fisher consistency and excess risk bounds. Empirically, our method achieves decision quality competitive with state-of-the-art methods while reducing training time by orders of magnitude.

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

Principled RL for Flow Matching Emerges from the Chunk-level Policy Optimization

Recent Progress in post-training flow matching for text-to-image (T2I) generation with Group Relative Policy Optimization (GRPO) has demonstrated strong potential. However, it is hindered by a critical limitation: inaccurate advantage attribution. In this work, we argue that aggregating consecutive steps into a coherent 'chunk' and shifting the policy optimization paradigm from GRPO's step level to the chunk level can effectively mitigate the negative impact of this issue. Building on this insight, we propose Group Chunking Policy Optimization (GCPO), the first chunk-level reinforcement learning approach for post-training flow matching. Extensive experiments demonstrate that GCPO achieves superior performance on both standard T2I benchmarks and preference alignment, with up to 43% relative gains over GRPO, highlighting the promise of chunk-level policy optimization. The code is available on https://github.com/xingzhejun/GCPO.

10.
bioRxiv (Bioinfo) 2026-06-22

When Less Is Not More: DICEPro Mitigates the Impact of Incomplete Reference Matrices on Cellular Frequency Deconvolution.

Cellular deconvolution aims to estimate the frequencies of different cell populations from gene expression measurements in a biological sample. Supervised approaches, such as CIBERSORTx and DISSECT, critically depend on the reference signature matrix, which encodes the gene expression profiles of cell-types based on prior knowledge. Despite numerous deconvolution methods, the impact of missing cell populations in the reference matrix remains understudied. Here, we evaluate the robustness of state-of-the-art deconvolution approaches using simulations based on real dataset examples combined with statistical modeling, validated against published data, and multiple real benchmark datasets. Results show that deconvolution performance remains stable when the reference matrix includes most cell-types, but declines sharply as the matrix becomes incomplete, especially for abundant cell populations. To address the limitations of incomplete reference matrices, we introduce DICEPro, an optimization-based framework designed to enhance existing deconvolution methods. By systematically adjusting the reference signatures, DICEPro better accounts for missing or underrepresented cell populations, leading to improved precision and robustness. We show that DICEPro consistently boosts deconvolution performance across both simulated datasets, derived from real data examples, and multiple real biological datasets, offering a practical solution when standard methods are hindered by incomplete references.

11.
arXiv (CS.AI) 2026-06-17

FacProcessTwin: An LLM-Based System for Process Twin Development

arXiv:2606.17666v1 Announce Type: cross Abstract: Process twins provide real-time representations of entire production processes. By capturing how process steps interact, rather than monitoring a single machine in isolation as an asset-based digital twin does, they have the potential to drive efficiency gains across the whole process. However, developing a process twin is costly. It requires accurately modelling the entire production process: its process steps, the equipment and product-specific settings each step uses, and its process variations. The resulting model must then be bound to live operational data. We present FacProcessTwin, a system that leverages a large language model (LLM) to reduce this development time, building a process twin from a plant's process documentation and natural-language input from an operator. FacProcessTwin generates this complete process model and then automatically binds its process steps to live operational data. The generated model and its data bindings are rendered as an interactive process diagram through which manufacturing personnel can monitor and correct the system's autonomous decisions, such as resolving uncertainty at safety-critical binding steps. We evaluate FacProcessTwin through a real-world case study of an Australian food manufacturer, covering 16 production process flows that span chilled, frozen, and aseptic shelf-stable product categories and include process variations within the same product. The results show that FacProcessTwin generates these process models accurately (a mean F1 of 95.2% against ground truth) and builds each twin in roughly a sixth of the manual time. Its human-in-the-loop governance then keeps the safety-critical bindings correct: at ambiguous tags where a single-pass baseline silently mis-binds 75.0% of the time, FacProcessTwin defers to the operator and mis-binds none.

12.
arXiv (CS.CV) 2026-06-19

An Angular-Temporal Interaction Network for Light Field Object Tracking in Low-Light Scenes

High-quality 4D light field representation with efficient angular feature modeling is crucial for scene perception, as it can provide discriminative spatial-angular cues to identify moving targets. However, recent developments still struggle to deliver reliable angular modeling in the temporal domain, particularly in complex low-light scenes. In this paper, we propose a novel light field epipolar-plane structure image (ESI) representation that explicitly defines the geometric structure within the light field. By capitalizing on the abrupt changes in the angles of light rays within the epipolar plane, this representation can enhance visual expression in low-light scenes and reduce redundancy in high-dimensional light fields. We further propose an angular-temporal interaction network (ATINet) for light field object tracking that learns angular-aware representations from the geometric structural cues and angular-temporal interaction cues of light fields. Furthermore, ATINet can also be optimized in a self-supervised manner to enhance the geometric feature interaction across the temporal domain. Finally, we introduce a large-scale light field low-light dataset for object tracking. Extensive experimentation demonstrates that ATINet achieves state-of-the-art performance in single object tracking. Furthermore, we extend the proposed method to multiple object tracking, which also shows the effectiveness of high-quality light field angular-temporal modeling.

13.
arXiv (CS.AI) 2026-06-19

OnDeFog: Online Decision Transformer under Frame Dropping

arXiv:2606.19721v1 Announce Type: cross Abstract: In challenging real-world reinforcement learning applications, communication delays or sensor failures often cause frame dropping, in which the agent cannot receive the dropped states and associated rewards. To address the performance degradation caused by frame dropping, the Decision Transformer under Random Frame Dropping (DeFog) was developed by incorporating additional mechanisms into the decision transformer to tackle frame dropping. Although DeFog can mitigate performance degradation in frame-dropping environments, since DeFog is an offline learning method, it struggles to effectively generalize to novel states not adequately represented in the training dataset. In this study, we propose OnDeFog, which integrates the mechanisms in DeFog with the online decision transformer (ODT), an online reinforcement learning method that learns policies through direct environmental interaction. Comprehensive experimental evaluation demonstrates that our proposed OnDeFog achieves superior performance compared to ODT in environments characterized by high dropping frame rate and outperforms DeFog on datasets containing a large amount of low-reward data.

14.
arXiv (CS.AI) 2026-06-24

ScaleToT: Generalizing Structured LLM Reasoning for Billion-Scale Low-Activity User Modeling

arXiv:2606.24605v1 Announce Type: new Abstract: Accurate user modeling often depends on rich interaction histories, which are unavailable for billions of low-activity users. Large Language Models (LLMs) can infer latent user states from static profiles, but this reasoning becomes unreliable when profiles are sparse, and applying an LLM to billions of users is prohibitively expensive. We present ScaleToT, which learns structured reasoning from a small LLM-processed subset and extends it to the broader low-activity user population. To improve reasoning reliability, ScaleToT constructs typed user-state chains with a bounded entropy-guided Tree-of-Thought (ToT) refinement procedure. To make this structured reasoning usable from sparse profiles, the teacher-curated chains are used to train a student model on static profiles through supervised fine-tuning (SFT) and Outcome-Driven Segment-Aware Implicit Reward Policy Optimization (OSIPO). ScaleToT then transfers the student's reasoning representations to a lightweight profile encoder, providing shared reasoning signals for the remaining users without LLM inference. We evaluate ScaleToT on lifetime value (LTV) prediction in a billion-scale advertising deployment. A randomized online A/B test increased LT30 by 6.738\%, while offline reasoning covered only 7.32\% of the potential population, greatly reducing compute cost compared with full-population reasoning.

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

Metabolic cost of information processing in Poisson variational autoencoders

arXiv:2602.13421v2 Announce Type: replace-cross Abstract: Computation in biological systems is fundamentally energy-constrained, yet standard theories of computation treat energy as freely available. Here, we argue that variational free energy minimization under a Poisson assumption offers a principled path toward an energy-aware theory of computation. Our key observation is that the Kullback-Leibler (KL) divergence term in the Poisson free energy objective becomes proportional to the prior firing rates of model neurons, yielding an emergent metabolic cost term that penalizes high baseline activity. This structure couples an abstract information-theoretic quantity – the *coding rate* – to a concrete biophysical variable – the *firing rate* – which enables a trade-off between coding fidelity and energy expenditure. Such a coupling arises naturally in the Poisson variational autoencoder (P-VAE) – a brain-inspired generative model that encodes inputs as discrete spike counts and recovers a spiking form of *sparse coding* as a special case – but is absent from standard Gaussian VAEs. To demonstrate that this metabolic cost structure is unique to the Poisson formulation, we compare the P-VAE against Grelu-VAE, a Gaussian VAE with ReLU rectification applied to latent samples, which controls for the non-negativity constraint. Across a systematic sweep of the KL term weighting coefficient $\beta$ and latent dimensionality, we find that increasing $\beta$ monotonically increases sparsity and reduces average spiking activity in the P-VAE. In contrast, Grelu-VAE representations remain unchanged, confirming that the effect is specific to Poisson statistics rather than a byproduct of non-negative representations. These results establish Poisson variational inference as a promising foundation for a resource-constrained theory of computation.

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

Ternary Mamba: Grouped Quantization-Aware Training of W1.58A16 State Space Models

arXiv:2606.18114v1 Announce Type: cross Abstract: State Space Models (SSMs) such as Mamba-2 offer linear-time inference but their memory footprint limits edge deployment. Prior ternary SSM work (Slender-Mamba) trains from scratch on 150B tokens; we show a pretrained checkpoint suffices, reducing the marginal token budget by 1,000x. Using grouped quantization-aware training (QAT) with knowledge distillation from a frozen FP16 teacher, we compress Mamba-2 1.3B to 3.61x (2,687 to 744 MB) and achieve 48.1% zero-shot accuracy (7-task average) in just 102M tokens (4 GPU-hours, single H100) – approaching Bi-Mamba's 48.4% (within +/-0.9pp CI). This QAT-from-pretrained setting reveals zero-ratio collapse, a novel instability caused by learnable quantization scales that does not arise in from-scratch training. We further show that post-hoc correction strategies effective for Transformers fail for SSMs due to error accumulation through the recurrence. These results demonstrate that ternary SSMs do not require expensive from-scratch training: QAT from pretrained checkpoints with KD is a data-efficient alternative.

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

Performance Analysis and Optimization of 3D Generative Diffusion Models across GPU Architectures

arXiv:2606.19365v1 Announce Type: new Abstract: Diffusion models have become essential for high-fidelity 3D MRI synthesis, yet their deployment remains constrained by substantial GPU resource demands arising from hundreds of U-Net evaluations per sample and a highly heterogeneous kernel behavior. This paper performs a comprehensive performance analysis of the state-of-the-art medical diffusion model, Med-DDPM, across three generations of NVIDIA architectures to study kernel-level runtime breakdowns, instruction-mix characteristics, memory system utilization, warp-level activities, and profiler priority-score estimates. We show that training is overwhelmingly dominated by cuDNN convolution and implicit-GEMM kernels, with inefficiencies arising from memory-access patterns, tensor-layout conversions, and limited Tensor Core utilization. Guided by these insights, we evaluate two architecture-aware optimizations TF32 Tensor Core activation and a 3D channels-last layout and demonstrate that they reduce SM cycles by up to 100x, cut dynamic instructions by 100x, raise Tensor Core utilization from 1.45 to 9.98x, and increase IPC by 7% on A100, all without degrading synthesis quality.

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

Policy-aware Vector Search: A Vision for Fine Grained Access Control in Vector Databases

arXiv:2606.19803v1 Announce Type: cross Abstract: Vector databases are increasingly used in security sensitive contexts with Retrieval Augmented Generation and organizational AI pipelines; however, their security capabilities remain limited. Specifically, Fine-grained Access Control (FGAC) which is required to ensure that data access adheres to user-specific policies is not fully supported in modern vector databases. Unlike relational databases, vector databases combine structured and unstructured attributes to provide semantic, approximate query results, which complicates FGAC implementation. This creates an inherent tension between enforcing FGAC policies correctly, achieving high ANN search recall and maintaining low query latency. In this paper, we present a vision for Policy-aware Vector Search by formalizing the FGAC policy model in vector databases as well as the enforcement problem. We compare various enforcement strategies, present preliminary findings, and identify key open challenges for future research in policy-aware vector search.

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

Ricci flow for the Bures–Helstrom qubit metric

arXiv:2606.19493v1 Announce Type: cross Abstract: The Bures–Helstrom metric is the minimal monotone Riemannian metric on the state space of a qubit. With the quantum Fisher normalization used here, it identifies the Bloch ball with a geodesic hemisphere of the unit round three–sphere. We describe its Ricci flow explicitly. In a general rotationally symmetric gauge the flow is a coupled system for the radial lapse and warping factor; a single scalar equation appears only after a Hamilton–DeTurck gauge choice. In the corresponding moving DeTurck frame the squared warping function $\Psi=\Phi^2$ satisfies the linear forced heat equation \begin{equation*} D_t\Psi=\Psi_{ss}-2, \end{equation*} while the fixed-lapse coordinate form contains the associated transport term. Since the Bures–Helstrom metric is Einstein, the geometric flow itself is the homothetic shrinker \begin{equation*} g(t)=(1-4t)g_{\mathrm{BH}}, \end{equation*} with scalar curvature $6/(1-4t)$ and extinction time $T=1/4$. Thus the metric remains inside the monotone cone for all $t

20.
arXiv (CS.CV) 2026-06-16

HairLRM: Strand-based Hair Modeling via Large Reconstruction Models

The fundamental limitation of traditional strand-based modeling is not simply data scarcity, but the ill-posedness of inferring complex 3D fields from 2D imagery without structural constraints. This unconstrained regression leads to catastrophic failures in resolving both global occlusion (e.g., in ponytails) and local directionality (e.g., in curls), resulting in over-smoothed, plausible-but-incorrect geometries. To resolve this, we integrate the strong geometric priors of Large Reconstruction Models (LRMs) into the strand generation pipeline. Using the LRM mesh as a structural anchor, we employ a novel Dual Orientation AutoEncoder to lift coarse geometry into high-fidelity strands. By resolving vector field singularities through latent-space optimization and surface-guided refinement, our method effectively disentangles complex topological structures, setting a new benchmark for robustness and accuracy in hair reconstruction.

21.
arXiv (quant-ph) 2026-06-16

Hyperinvariant Spin Network States – An AdS/CFT Model from First Principles

arXiv:2510.06602v2 Announce Type: replace Abstract: We study the existence and limitations of hyperinvariant tensor networks incorporating a local SU(2) symmetry. As discrete implementations of the anti de-Sitter/conformal field theory (AdS/CFT) correspondence, such networks have created bridges between the fields of quantum information theory and quantum gravity. Adding SU(2) symmetry to the tensor network allows a direct connection to spin network states, a basis of the kinematic Hilbert space of loop quantum gravity (LQG). We consider a particular situation where the states can be interpreted as kinematic quantum states for three-dimensional quantum gravity. We show that important aspects of the AdS/CFT correspondence are realized in certain quantum states of the gravitational field in LQG, thus justifying, from first principles, a class of models introduced by [F. Pastawski et al., JHEP 06, 149 (2015)]. We provide examples of hyperinvariant tensor networks, but also prove constraints on their existence in the form of no-go theorems that exclude absolutely maximally entangled states as well as general holographic codes from local SU(2)-invariance. We calculate surface areas as expectation values of the LQG area operator and discuss further possible constraints as a consequence of a decay of correlations on the boundary.

22.
arXiv (CS.LG) 2026-06-11

Data-Driven Dynamic Assortment in Online Platforms: Learning about Two Sides

arXiv:2606.11118v2 Announce Type: replace Abstract: We study a dynamic assortment problem on a two-sided service platform with incomplete information and heterogeneous customers in a discrete-time setting. In each period, a customer arrives seeking service, and the platform chooses an assortment of sellers to display. The customer then proposes a transaction to at most one seller in the assortment according to a multinomial logit choice model. After a fixed number of periods, sellers review the proposals they have received and each chooses at most one customer according to another multinomial logit choice model, after which the cycle repeats. A key challenge is that the platform does not know the choice-model parameters of either customers or sellers in advance. To our knowledge, this is the first study of a dynamic assortment problem in which both sides' choice parameters are unknown. We develop a data-driven algorithm that learns these parameters while optimizing the platform's objective over time. We evaluate performance using regret, which measures revenue loss relative to a clairvoyant benchmark that knows all parameters and customer arrivals in advance. We show that the algorithm's worst-case regret grows polylogarithmically over time, and we derive a matching lower bound, establishing its rate optimality.

23.
arXiv (CS.LG) 2026-06-16

One-Step Generalization Ratio Guided Optimization for Domain Generalization

arXiv:2606.16301v1 Announce Type: new Abstract: Domain Generalization (DG) aims to train models that generalize to unseen target domains but often overfit to domain-specific features, known as undesired correlations. Gradient-based DG methods typically guide gradients in a dominant direction but often inadvertently reinforce spurious correlations. Recent work has employed dropout to regularize overconfident parameters, but has not explicitly adjusted gradient alignment or ensured balanced parameter updates. We propose GENIE (Generalization-ENhancing Iterative Equalizer), a novel optimizer that leverages the One-Step Generalization Ratio (OSGR) to quantify each parameter's contribution to loss reduction and assess gradient alignment. By dynamically equalizing OSGR via a preconditioning factor, GENIE prevents a small subset of parameters from dominating optimization, thereby promoting domain-invariant feature learning. Theoretically, GENIE balances convergence contribution and gradient alignment among parameters, achieving higher OSGR while retaining SGD's convergence rate. Empirically, it outperforms existing optimizers and enhances performance when integrated with various DG and single-DG methods.

24.
arXiv (quant-ph) 2026-06-11

Entanglement generation between field modes mediated by a fluctuating conducting wall

arXiv:2606.12338v1 Announce Type: cross Abstract: We consider a movable conducting plate of finite mass, between two fixed ones, whose mechanical degrees of freedom are treated quantum-mechanically and bound to its equilibrium position by a harmonic potential. The movable wall is thus subjected to quantum fluctuations of its position. This creates a system of two sub-cavities separated by the movable fluctuating plate, and two massless one-dimensional scalar fields, one in each sub-cavity. This system is described by an appropriate generalization of the Law Hamiltonian. The presence of the movable wall yields an effective plate-fields interaction, as well as an effective interaction between the field modes. We obtain, at the second order in perturbation theory, the ground state of the interacting system and the reduced density operator of the fields in each sub-cavity by tracing out the wall's degrees of freedom. We calculate the entanglement between two field modes, one in each cavity, by evaluating analytically the negativity; we then evaluate numerically also the total multimode negativity. Our results show that in both cases the fields in the two sub-cavities are entangled, in contrast to the case in which the wall is fixed in space. We discuss the amount of the field entanglement present as a function of relevant physical parameters of the system such as the mass and oscillation frequency of the movable wall, its distance from the fixed walls and the frequencies of the field modes considered.

25.
medRxiv (Medicine) 2026-06-19

Within-host pathogen population diversity predicts treatment response in tuberculosis

Background: Tuberculosis (TB) treatment outcomes remain suboptimal, and standard clinical diagnostics cannot reliably identify patients at high risk of treatment failure or relapse at the time of diagnosis. While within-host Mycobacterium tuberculosis genetic diversity is hypothesized to reflect the viable bacterial burden and adaptive capacity of the infection, its clinical prognostic value remains unknown. Methods: We conducted a prospective cohort study of 364 patients with newly diagnosed, rifampicin-susceptible pulmonary TB in South Africa. Patients received standard 6-month therapy and were monitored for up to two years to ascertain composite unfavorable outcomes (treatment failure, death, or relapse). To accurately detect low-frequency (unfixed) genetic variants and eliminate reference bias artifacts, we mapped medium to high depth short-read sequences against matched, patient-specific long-read assemblies. The association between baseline pathogen genetic diversity and clinical outcomes was evaluated using multivariable Cox proportional-hazards models. Results: After bioinformatic filtering, true unfixed variants were relatively rare but significantly enriched in genes mediating pathogen adaptation and drug tolerance, including transporter proteins and two-component regulatory systems. Within-host bacterial genetic diversity (i.e., the total number of unfixed variants) ranged from 0-20, with a median of 1 per patient. In survival analysis adjusting for known clinical risk factors–including HIV status, prior TB, baseline smear positivity, and radiographic lung involvement–baseline within-host genetic diversity emerged as a strong, independent predictor of unfavorable treatment outcomes. For patients with greater than 3 unfixed variants at diagnosis, each increase of 5 unfixed variants was associated with more than double the risk of a composite unfavorable outcome (adjusted Hazard Ratio, 2.36; 95% CI, 1.27 to 4.39; p=0.007). Conclusions: Baseline within-host pathogen genetic diversity is an independent predictor of unfavorable TB treatment outcomes. As sequencing becomes increasingly integrated into routine diagnostics, quantifying unfixed variants is an accessible approach that promises to risk-stratify patients and guide the duration of individualized regimens.