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01.
arXiv (math.PR) 2026-06-12

Voronoi Percolation: Topological Stability and Giant Cycles

arXiv:2601.00793v2 Announce Type: replace Abstract: We study the topological stability of Voronoi percolation in higher dimensions. We show that slightly increasing p allows a discretization that preserves increasing topological properties with high probability. This strengthens a theorem of Bollobás and Riordan and generalizes it to higher dimensions. As a consequence, we prove a sharp phase transition for the emergence of i-dimensional giant cycles in Voronoi percolation on the 2i-dimensional torus.

02.
arXiv (quant-ph) 2026-06-17

Hybrid Ferromagnet-SNSPDs: Single photon induced order-to-disorder transition in ferromagnets coupled to thin film superconductors

arXiv:2606.17177v1 Announce Type: cross Abstract: The development of midwave and longwave infrared single photon detectors is crucial for their emerging applications in spectroscopy, remote sensing, exoplanet detection, and free space quantum communications. However, existing sensors need to be operated at extremely low temperatures (0.08-0.9K) to reduce dark noise and hence require the use of advanced cryogenics such as dilution refrigerators or $^3$He cryogens, significantly limiting applications. Here we propose a vortex-engineering approach based on a hybrid phase transition in a ferromagnet/superconductor bilayer to increase the operating temperature of infrared single photon detectors up to 3.75K. We show that the introduction of a ferromagnetic layer produces a local magnetic field which impedes vortex crossing in the superconductor, reducing dark noise. When a single photon is incident, the photon-induced hotspot causes an order-to-disorder transition in the ferromagnet, leading to a vortex-induced phase transition in the superconducting layer. By engineering the ferromagnet's Curie temperature to be close to the device's operating temperature, single photon sensitivity can be achieved at increased operating temperatures. We predict at midwave/longwave infrared wavelengths (3-14$\mu$m) the operating temperature can be raised to 3.25-3.75K, enabling significantly simpler cooling systems.

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

DCD: Domain-Oriented Design for Controlled Retrieval-Augmented Generation

arXiv:2604.07590v2 Announce Type: replace-cross Abstract: Retrieval-Augmented Generation (RAG) is widely used to ground large language models in external knowledge sources. However, when applied to heterogeneous corpora and multi-step queries, Naive RAG pipelines often degrade in quality due to flat knowledge representations and the absence of explicit workflows. In this work, we introduce DCD (Domain-Collection-Document), a domain-oriented design to structure knowledge and control query processing in RAG systems without modifying the underlying language model. The proposed approach relies on a hierarchical decomposition of the information space and multi-stage routing based on structured model outputs, enabling progressive restriction of both retrieval and generation scopes. The architecture is complemented by smart chunking, hybrid retrieval, and integrated validation and generation guardrail mechanisms. We describe the DCD architecture and workflow and discuss evaluation results on synthetic evaluation dataset, highlighting their impact on robustness, factual accuracy, and answer relevance in applied RAG scenarios.

04.
arXiv (CS.AI) 2026-06-16

Decision-Weighted Flow Matching for Contextual Stochastic Optimization

arXiv:2606.16790v1 Announce Type: cross Abstract: Conditional generative models are increasingly used as scenario generators for stochastic optimization, but standard training objectives emphasize uniform distributional fit rather than the downstream decisions induced by generated scenarios. This creates an objective mismatch: errors in statistically common regions may have little effect on decision regret, whereas errors in decision-sensitive regions can substantially change the optimal action. We propose Decision-Weighted Flow Matching (DW-FM), a regret-aligned training framework that preserves the simplicity of standard flow matching while reweighting its velocity-regression objective using decision-sensitive endpoint information. Theoretically, we connect downstream regret to pathwise velocity mismatch through a loss-induced decision discrepancy and an adjoint transport argument, yielding an ideal regret-aligned surrogate and practical endpoint-weighted objectives with regret guarantees. Empirically, we demonstrate the effectiveness of DW-FM on three CVaR-based contextual stochastic optimization benchmarks spanning synthetic portfolio, semi-real financial, and traffic-CVaR tasks, where DW-FM improves downstream regret over standard baselines.

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

Branch-and-Browse: Efficient and Controllable Web Exploration with Tree-Structured Reasoning and Action Memory

Autonomous web agents powered by large language models (LLMs) show strong potential for performing goal-oriented tasks such as information retrieval, report generation, and online transactions. These agents mark a key step toward practical embodied reasoning in open web environments. However, existing approaches remain limited in reasoning depth and efficiency: vanilla linear methods fail at multi-step reasoning and lack effective backtracking, while other search strategies are coarse-grained and computationally costly. We introduce Branch-and-Browse, a fine-grained web agent framework that unifies structured reasoning-acting, contextual memory, and efficient execution. It (i) employs explicit subtask management with tree-structured exploration for controllable multi-branch reasoning, (ii) bootstraps exploration through efficient web state replay with background reasoning, and (iii) leverages a page action memory to share explored actions within and across sessions. On the WebArena benchmark, Branch-and-Browse achieves a task success rate of 35.8\% and reduces execution time by up to 40.4\% relative to state-of-the-art methods. These results demonstrate that Branch-and-Browse is a reliable and efficient framework for LLM-based web agents.

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

Spectro-Temporal Interference Confounds Phase Encoding in Spatial Audio Foundation Models

Recent spatial self supervised audio models achieve high performance on localization tasks, raising questions about their encoding of microsecond interaural phase fine structures. We propose a psychoacoustic benchmark based on the binaural masking level difference to evaluate this. Using an equalization cancellation baseline and a GCC PHAT positive control we evaluate nine frozen audio models spanning binaural SSL, monaural SSL, and neural audio codecs. Four monaural negative controls yield zero BMLD confirming binaural specificity. Two general purpose binaural SSL models exhibit minimal phase sensitivity while dedicated binaural spatial SSL models achieve BMLD comparable to the analytical baseline. Progressive physical ablations show that general purpose binaural SSL models rely on spectro temporal interference textures rather than cross channel phase computation. High detection rates in speech reflect a confounding reliance on broadband envelopes rather than genuine phase encoding.

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

Range-Aware Bayesian Optimization for Discovering Diverse Designs within Target Property Windows

arXiv:2606.11574v1 Announce Type: new Abstract: In many materials and product design problems, desirable candidates exhibit properties that fall within an acceptable range rather than achieve a single optimum. Recovering multiple, distinct solutions that satisfy such specifications is also practically valuable, as some candidates may be preferred for reasons of cost, processability, or robustness that are difficult to encode directly in an objective function. Here, we develop a range-aware Bayesian optimization (BO) framework in which the acquisition function directly scores the posterior probability that a candidate satisfies a target range. The framework naturally extends to parallel pursuit of multiple distinct specifications over a shared candidate space. Across benchmark tasks, range-aware acquisition consistently recovers larger and more diverse sets of valid designs than standard BO baselines and recent goal-seeking methods. Its utility is further demonstrated in two practically motivated design case studies involving optimizing reaction conditions for polymer synthesis and sequence-defined oligomer discovery for prescribed optical absorption bands, supported by quantum chemical calculations. These results suggest that range-aware BO can provide a practical and sample-efficient foundation for specification-driven design, particularly when design flexibility and solution diversity are important considerations.

08.
arXiv (CS.AI) 2026-06-16

Do Large Language Models Have Emotions?

arXiv:2606.14742v1 Announce Type: cross Abstract: Do LLMs have emotions? A recent paper from Anthropic reports finding internal representations of emotion concepts in Claude Sonnet 4.5, concluding that the LLM has 'functional emotions.' We evaluate this claim against what is known about how emotions actually function in biological systems. We argue that emotions serve two core functions: the context-sensitive interpretation of situations, and the reorganization of processing across multiple systems in response to those interpretations. The Anthropic findings offer partial support for the first function, though the consistent, discrete emotional representations identified in Claude sit uneasily with affective neuroscience findings that human emotion is characterized by variable rather than uniform neural signatures. On the second function, the evidence is mixed: Claude's representations modulate output without producing the dynamic reorganization of attention, decision speed, and motivational state that defines emotion in biological systems. We close by proposing what it would take for an LLM to have emotions.

09.
arXiv (math.PR) 2026-06-11

On multidimensional infinite dihedral group extensions of Gibbs Markov maps

arXiv:2601.08961v2 Announce Type: replace-cross Abstract: We obtain a local central limit theorem for cocycles associated with a class of non abelian and non compact group extensions of Gibbs Markov maps. This class consists of multidimensional infinite dihedral groups. Unlike in the set up of the random walks on groups, we cannot use the convolution of measures on the group and instead we resort to an approach based on irreducible representations. Depending on the dimension of the group, we obtain either mixing, and thus ergodicity, or dissipativity. Also, we obtain the asymptotics of the first return time of the group extension to the origin.

10.
arXiv (CS.AI) 2026-06-11

Runtime Enforcement of Hybrid System Properties

arXiv:2606.12022v1 Announce Type: cross Abstract: Runtime enforcement has emerged as a promising approach for ensuring the safety of autonomous and cyber-physical systems operating in uncertain and dynamic environments. Unlike traditional runtime verification, runtime enforcement actively intervenes during execution to prevent property violations by modifying unsafe system behaviors. Existing enforcement frameworks primarily focus on untimed or discrete-time specifications and are often limited to delaying or suppressing events, making them inadequate for reactive systems exhibiting complex continuous dynamics. In this paper, we propose a runtime enforcement framework where safety requirements are modeled using Hybrid Automata (HA). The framework combines discrete-event editing with continuous-time monitoring to support enforcement actions such as suppression, delay, and insertion of events at arbitrary time instants. Upon observing environmental inputs, the automaton is initialized, and runtime reachability analysis is used to synthesize safe corrective actions. We formally define the enforcement problem for safety hybrid automata, establish enforceability conditions, and present an online enforcement algorithm for reactive systems. A detailed case study on an Adaptive Cruise Control (ACC) system demonstrates the effectiveness of the proposed approach in maintaining safety properties under unsafe controller behaviors. Experimental results show that the framework introduces minimal computational overhead while ensuring continuous compliance with safety requirements in real time.

11.
arXiv (CS.CV) 2026-06-16

A Survey on 3D Gaussian Splatting Applications: Segmentation, Editing, and Generation

In the context of novel view synthesis, 3D Gaussian Splatting (3DGS) has recently emerged as an efficient and competitive counterpart to Neural Radiance Field (NeRF), enabling high-fidelity photorealistic rendering in real time. Beyond novel view synthesis, the explicit and compact nature of 3DGS enables a wide range of downstream applications that require geometric and semantic understanding. This survey provides a comprehensive overview of recent progress in 3DGS applications. It first reviews the reconstruction preliminaries of 3DGS, followed by the problem formulation, 2D foundation models, and related NeRF-based research areas that inform downstream 3DGS applications. We then categorize 3DGS applications into three foundational tasks: segmentation, editing, and generation, alongside additional functional applications built upon or tightly coupled with these foundational capabilities. For each, we summarize representative methods, supervision strategies, and learning paradigms, highlighting shared design principles and emerging trends. Commonly used datasets and evaluation protocols are also summarized, along with comparative analyses of recent methods across public benchmarks. To support ongoing research and development, a continually updated repository of papers, code, and resources is maintained at https://github.com/heshuting555/Awesome-3DGS-Applications.

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

When Dynamics Models Read the Wrong Time Steps: Label-Free Event Credit Re-Anchoring for Robust Global Readouts

作者:

arXiv:2606.17572v1 Announce Type: new Abstract: Learned dynamics models often answer global physical questions, such as fault severity or impact stiffness, by pooling a per-step feature sequence into one readout vector. This sequence-to-global interface creates an under-studied temporal credit problem: with only trajectory-level supervision, a model can predict accurately in training conditions while reading from abundant smooth correlates rather than the brief physical events that determine the target. We call this failure temporal credit dilution. It is not exposed by the training loss and is not removed by standard physics-informed residuals, because the error lies in where the global readout assigns functional credit. We introduce Credit-in-Event, an interface-level probe for measuring how much pooled credit lands on event steps, and prove in closed form that a pooled linear reader routes credit to a spurious background channel as the event fraction shrinks. We then propose CREST, a training-free and label-free readout that estimates a transient event core from learned features and re-anchors the pooled representation through event-versus-rest contrast. Across simulated gear and impact systems, recurrent and attention encoders, and public bearing vibration data, CREST reduces out-of-distribution error while restoring event credit. Ablations show that stable-step selection and receptive-field shrinking fail, confirming that the gain comes from event-core credit re-anchoring rather than a generic locality or stability prior.

13.
arXiv (CS.LG) 2026-06-17

Softmax as Linear Attention in the Large-Prompt Regime: a Measure-based Perspective

arXiv:2512.11784v2 Announce Type: replace Abstract: Softmax attention is a central component of transformer architectures, yet its nonlinear structure poses significant challenges for theoretical analysis. We develop a unified, measure-based framework for studying single-layer softmax attention under both finite and infinite prompts. For i.i.d. Gaussian inputs, we lean on the fact that the softmax operator converges in the infinite-prompt limit to a linear operator acting on the underlying input-token measure. Building on this insight, we establish non-asymptotic concentration bounds for the output and gradient of softmax attention, quantifying how rapidly the finite-prompt model approaches its infinite-prompt counterpart, and prove that this concentration remains stable along the entire training trajectory in general in-context learning settings with sub-Gaussian tokens. In the case of in-context linear regression, we use the tractable infinite-prompt dynamics to analyze training at finite prompt length. Our results allow optimization analyses developed for linear attention to transfer directly to softmax attention when prompts are sufficiently long, showing that large-prompt softmax attention inherits the analytical structure of its linear counterpart. This, in turn, provides a principled and broadly applicable toolkit for studying the training dynamics and statistical behavior of softmax attention layers in large prompt regimes.

14.
PLOS Medicine 2026-05-21

U = U for all: Advancing equity in HIV prevention

by Thiago S. Torres, Paula M. Luz Suppression of HIV with antiretrovirals eliminates HIV transmission risk, summarized as Undetectable = Untransmittable (U = U). However, U = U literacy remains unevenly understood and shared, and stigmas persist. Equitable and accurate awareness of U = U requires culturally tailored interventions, improved provider education, and supportive policy environments beyond biomedical evidence alone. Suppression of HIV with antiretrovirals eliminates HIV transmission risk, summarized as Undetectable = Untransmittable (U=U). However, U=U literacy remains unevenly understood and shared, and stigmas persist. In this Perspective, Thiago Torres and Paula Luz outline what is needed to improve equity and accuracy in global awareness and education of U=U.

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

Modeling light-matter coupled systems with neural quantum states

arXiv:2606.14352v1 Announce Type: cross Abstract: Recent advances in cold atom manipulation enable the study of many-body systems where short-range interactions between neighboring atoms coexist with long-range interactions mediated by photons. Such a combination of interactions makes a theoretical approach challenging beyond mean-field methods. In this work, we develop a neural quantum state based approach to study these systems numerically. We introduce a neural-network architecture capable of handling hybrid Hilbert spaces with large local bosonic dimensions in strongly interacting spin-photon systems. We benchmark this approach on a model of a two-dimensional lattice of Rydberg atoms coupled to a photon mode. The superradiant ground states found in the large spin-photon coupling regime allow us to demonstrate the efficiency of the method in the presence of high photon occupation. Furthermore, the ability to capture spin-spin and spin-photon correlations leads us to observe quantitative deviations in the ground state phase boundaries with respect to mean-field theory. The method extends to other systems with a similar hybrid Hilbert space structure, such as spin-phonon systems, and provides a scalable framework for investigating their ground state properties.

16.
medRxiv (Medicine) 2026-06-16

Exercise Training Improves Skeletal Muscle Insulin Sensitivity and Reprograms the Adipose Transcriptome in Heavier Monozygotic Twins

Exercise training improves skeletal muscle insulin sensitivity, yet its effects on white adipose tissue remain incompletely understood. We investigated how adiposity and exercise training influence insulin-stimulated glucose uptake in skeletal muscle and abdominal subcutaneous adipose tissue (ASAT), alongside adaptations in gene expression and DNA-methylation. Ten monozygotic twin pairs discordant for BMI underwent [18F]FDG-PET/CT imaging of skeletal muscle (vastus lateralis, VL) and ASAT during a euglycemic-hyperinsulinaemic clamp before and after six months of exercise training. VL and ASAT biopsies were analyzed using mRNA-sequencing and reduced representation bisulfite sequencing. Exercise training improved whole-body and VL insulin sensitivity in leaner and heavier co-twins (p

17.
arXiv (CS.CV) 2026-06-15

Visual Quality Score Assessment of Large White Goods in Remanufacture with Multi-View Deformable-DETR

Remanufacturing large white goods is essential for a circular economy, yet visual quality assessment remains a manual bottleneck for training and pricing. Conventional detection methods require extensive annotation and struggle with small defects in high-resolution multi-view data. We present a multi-view framework based on Deformable-DETR for automated quality scoring that aggregates information across redundant views to extract fine-grained features. To enhance robustness with limited labels, we employ self-supervised pretraining followed by supervised fine-tuning on expert-annotated scores. Additionally, a linear projection over frozen feature maps identifies regions of interest to explain model decisions. Evaluated on an industrial multi-view dataset, our approach delivers precise quality assessments while reducing reliance on manual annotation and per-part customization, enabling scalable and transparent inspection for remanufacturing lines.

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

Enhancing Underwater Light Field Images via Global Geometry-aware Diffusion Process

This work studies the challenging problem of acquiring high-quality underwater images via 4-D light field (LF) imaging. To this end, we propose GeoDiff-LF, a novel diffusion-based framework built upon SD-Turbo to enhance underwater 4-D LF imaging by leveraging its spatial-angular structure. GeoDiff-LF consists of three key adaptations: (1) a modified U-Net architecture with convolutional and attention adapters to model geometric cues, (2) a geometry-guided loss function using tensor decomposition and progressive weighting to regularize global structure, and (3) an optimized sampling strategy with noise prediction to improve efficiency. By integrating diffusion priors and LF geometry, GeoDiff-LF effectively mitigates color distortion in underwater scenes. Extensive experiments demonstrate that our framework outperforms existing methods across both visual fidelity and quantitative performance, advancing the state-of-the-art in enhancing underwater imaging. The code will be publicly available at https://github.com/linlos1234/GeoDiff-LF.

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

VinQA: Visual Elements Interleaved Long-form Answer Generation for Real-World Multimodal Document QA

Real-world documents combine text with tables, charts, photographs, and diagrams arranged in diverse layouts, yet existing research on multimodal large language models (MLLMs) for document QA predominantly produces text-only responses, underutilizing these visual elements. We introduce VinQA, a dataset for long-form answer generation where cited visual elements are explicitly interleaved with their supporting text and grounded in relevant document pages. To support this task, we study two encoding methods for feeding raw document page images into an MLLM, along with their visual-element citation mechanisms: (1) Page Encoding, which directly encodes full-page images with bounding boxes of visual elements and treats these boxed regions as citable units; and (2) Modality Encoding, which parses each page to extract text and crop visual elements, encodes them separately, and uses these cropped elements as citable units. In our experiments, we propose M-GroSE, a multimodal evaluation framework extending GroUSE to assess answers along four dimensions: completeness, answer relevancy, faithfulness, and unanswerability. We additionally report Visual Source F1 to directly measure visual citation accuracy. Although proprietary frontier models still achieve the best overall scores on the VinQA test split, fine-tuning open Qwen2.5-VL models on the training split substantially improves their performance and narrows this gap. Modality Encoding is initially more robust for complex documents with long text, many visual elements, and diverse citation requirements. After training on VinQA, however, Page Encoding reaches a comparable level, competing effectively even without the explicit parsing used in Modality Encoding. Finally, Visual G-Eval, an MLLM-based judge, confirms that fine-tuned models insert visual elements at semantically appropriate positions with faithful supporting text.

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

Dealing with locality in QAOA

arXiv:2606.14447v1 Announce Type: new Abstract: Shallow-depth QAOA on sparse, high-diameter MaxCut instances faces a locality bottleneck: at depth \(p\), local observables can depend only on a bounded neighborhood of the circuit interaction graph. We propose a transport-augmented QAOA that keeps the MaxCut cost Hamiltonian unchanged but enriches the mixer with optimized, unweighted shortcut couplings (scheduled \(XX+YY\)) to collapse the effective interaction-graph diameter. Using exact finite-depth support recursions, we relate optimal shortcut placement to bounded-diameter graph augmentation, and show in benchmarks that (unlike ma-QAOA) performance becomes effectively size-invariant once the diameter is reduced. For bipartite families (base diameter 4), reducing the interaction path to \(d=1\) raises the ensemble-averaged approximation ratio from 0.7378 (ma-QAOA) to 0.9767 at \(p=1\) (\(\sigma=0.0251\), nine system sizes); on random trees (base diameter 10), at \(p=2\) it improves from 0.9226 to 0.9997 (\(\sigma=0.0001\)).

21.
medRxiv (Medicine) 2026-06-22

Maternal-Fetal immune networks and viral signatures in the healthy amniotic cavity

The intrauterine environment has traditionally been viewed as a privileged site protected by the placental barrier. However, emerging evidence suggests that early in utero microbial exposure may prime the developing fetal immune system. Here, using target-enriched metagenomics and high-dimensional proteomics, we characterized the intra-amniotic viral landscape and immune networks in 114 healthy pregnancies including both normal and anomalous fetuses. We identify a sparse yet heterogeneous human viral signature in 26% of samples, predominantly composed of Herpesviridae, Polyomaviridae, and Picornaviridae. Although viral reads abundance was associated with fetal abnormalities, viral detection generally did not induce overt inflammatory activation, supporting a state of immune homeostasis within the amniotic cavity. Instead, viral presence was associated with subtle and selective immune modulation, including altered inducible antimicrobial peptide expression (HBD-2 and HBD-3), coupled with an attenuation of regulatory cytokines. Our results further reveal that the amniotic immune environment is primarily governed by gestational age, transitioning from a Th1-predominant "alert" phase to innate-readiness preceding parturition. These findings suggest that fragments of viral genetic material within the amniotic cavity may contribute to fetal immune instruction without triggering overt inflammation, providing a foundational framework for understanding how "silent" viral-exposure during gestation influences the developmental origins of neonatal immunity.

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

How Low Can You Go? Active Learning for Sparse Model Discovery in the Ultra-Low-Data Limit

arXiv:2606.12182v1 Announce Type: new Abstract: Identifying the governing equations of complex dynamical systems remains a fundamental challenge across science and engineering. While early approaches relied on empirical data and heuristics, modern data-driven methods offer greater flexibility and fewer assumptions. However, data acquisition in real-world settings is often expensive. This work addresses this challenge by introducing an active learning strategy for dynamics discovery in the ultra-low data limit. Rather than sampling randomly, our method iteratively prioritizes regions that are most informative for model identification. This approach builds on Sparse Identification of Nonlinear Dynamics (SINDy), and utilizes an ensemble extension, E-SINDy, to estimate epistemic uncertainty and guide the sampling for both ordinary and partial differential equations (ODEs/PDEs). For ODEs, an exhaustive analysis is conducted on the Lorenz system across varying data budgets and noise levels. For PDEs, two systems with contrasting dynamical characteristics are examined: the Burgers' equation, where a sharp shock front creates a distinction between informative and uninformative regions, and the Kuramoto-Sivashinsky equation, which presents a more spatially complex sampling landscape. Across all scenarios, the proposed method accurately identifies the governing dynamics with significantly fewer data samples than random sampling.

24.
arXiv (quant-ph) 2026-06-19

Attosecond Path Qubits in High-Harmonic Generation: Classical Dephasing and Trace-Out Decoherence

arXiv:2606.20372v1 Announce Type: cross Abstract: High-harmonic generation (HHG) is governed by interference between electron trajectories. We propose that the dominant short and long trajectories define an experimentally addressable two-level subsystem: an attosecond path qubit (APQ). We formulate a trajectory-resolved density matrix to identify two distinct coherence-loss mechanisms: classical dephasing from ensemble averaging and quantum decoherence arising from the trace-out of unobserved degrees of freedom. By investigating shot-to-shot fluctuations and unresolved transverse momentum, we demonstrate that while dephasing suppresses coherence through averaging, the ``trace-out'' channel produces mixed states even for fixed driving parameters. We explore how these mechanisms modify APQ purity and show that mode selection and conditioning provide operational routes to isolate them. These results establish a reduced-state framework for diagnosing coherence loss in HHG and for engineering trajectory-based quantum states in attosecond interferometry.

25.
bioRxiv (Bioinfo) 2026-06-22

Drug-Prot: A query system for statistical inference of drug effects and interactions in dynamic proteomic networks

Understanding drug effects and drug-drug interactions is essential for developing combination therapies. We present Drug-Prot, a computational framework that leverages large-scale perturbation proteomics to quantify causal drug effects, drug-drug interactions, and dynamic protein relationships. Using data from 63 single drugs and 59 drug combinations applied to 18 breast cancer cell lines at 6, 24, and 48 hours, Drug-Prot estimates drug effects on protein expression and reconstructs directed temporal protein dependency networks. The publicly available software enables targeted analyses of user-defined protein sets, substantially reducing the multiple-testing burden. Through an interactive web application, users obtain corrected p-values for single-drug and combination effects, directed temporal dependency networks, and downloadable results without requiring access to the underlying proteomic dataset. As a use case, we apply invariance-regularized Random Forests to triple-negative breast cancer cell lines to identify proteins associated with drug response. Querying these proteins in Drug-Prot reveals drug-specific and interaction effects at the protein-network level, illustrating how the framework links candidate causal protein features to actionable drug combinations.