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01.
arXiv (CS.AI) 2026-06-11

Agents All the Way Down; A Methodology for Building Custom AI Agents from Substrate to Production

arXiv:2606.11869v1 Announce Type: cross Abstract: Custom AI agents areagents that live inside their own application, talk to their own data and tools, enforce their own security boundaries, and carry their own brand and audit trail. What separates them from the general-purpose tier is fit, not capability: each is built for one job, by the engineer who will maintain it. No published practice sets out how to build one end to end. The pieces are everywhere (function-calling APIs, the Model Context Protocol, code agents to pair with), but the practice that chains them lives in podcasts, blogs, and leaked system prompts. This paper writes that practice down as a methodology, Agents All the Way Down: two preconditions crossed once and kept, then three practices repeated for the agent's life. The preconditions are (P1) Substrate, the LLM as a software component, framed as tools, then system, then messages under prompt-caching; and (P2) Building blocks: function calling, MCP, CLI orchestration, the liteshell pattern, the agent loop, skills, characters, hooks, and scaffolding. The practices are (P3) prototype with a general-purpose agent; (P4) harvest, fold, and ship the result as a CLI, the Turtle pattern; and (P5) agent-tests-agent, in which a general-purpose agent drives it through behavioural scenarios, a complement to classical testing, not a replacement. The working loop is P3 to P4 to P5 and back, and one corollary falls out for free: multi-agent orchestration is just CLI composition. The methodology is framework-free by construction. It was distilled from the AAC, a custom agent for the open-source LAMB platform, built in about ten days by one developer with an AI pair-programmer and in production . We present it as a transferable practice, independent of any language or framework.

02.
arXiv (CS.LG) 2026-06-17

A tensor network approach for chaotic time series prediction

arXiv:2505.17740v2 Announce Type: replace Abstract: Making accurate predictions of chaotic time series is a complex challenge. Reservoir computing, a neuromorphic-inspired approach, has emerged as a powerful tool for this task. It exploits the memory and nonlinearity of dynamical systems without requiring extensive parameter tuning. However, selecting and optimizing reservoir architectures remains an open problem. Next-generation reservoir computing simplifies this problem by employing nonlinear vector autoregression based on truncated Volterra series, thereby reducing hyperparameter complexity. Nevertheless, the latter suffers from exponential parameter growth in terms of the maximum monomial degree. Tensor networks offer a promising solution to this issue by decomposing multidimensional arrays into low-dimensional structures, thus mitigating the curse of dimensionality. This paper explores the application of a previously proposed tensor network model for predicting chaotic time series, demonstrating its advantages in terms of accuracy and computational efficiency compared to conventional echo state networks. Using a state-of-the-art tensor network approach enables us to bridge the gap between the tensor network and reservoir computing communities, fostering advances in both fields.

03.
arXiv (CS.CV) 2026-06-15

Spectrum Aware Illumination Estimation Using Multispectral Image

Multispectral (MS) imaging extends beyond conventional RGB imaging by capturing more spectral bands, thereby improving illuminant spectrum estimation (ISE). However, existing methods often fail to fully exploit spectral information, resulting in suboptimal performance under diverse lighting conditions and across different sensor domains. Hence, we propose a deep learning framework with a spatio-spectral feature extraction block, which incorporates spectral attention mechanisms to enhance spectral correlation and preserve illuminant-relevant spatial features. Through the inclusion of an illuminant prior (IP), our approach prioritizes specific channels that provide more meaningful information in an MS image. We also propose a spectral-domain transform across different MS sensor spaces. The results demonstrate that illuminant spectra learned in high-dimensional sensor spaces can be effectively transformed to various lower-dimensional camera sensor spaces without any additional training. To facilitate evaluation, we introduce a real-world MS dataset containing high-dimensional ground-truth illumination spectra captured under diverse lighting conditions. Through extensive experiments, we demonstrate that our method achieves superior accuracy compared to existing models, thus providing a practical solution for real-world ISE. The code and dataset are available at https://github.com/hyejin5/Spectrum-Aware-Illumination-Estimation-Using-Multispectral-Image.

04.
arXiv (quant-ph) 2026-06-12

SAT, MaxSAT, and SMT for QLDPC Distance Computation: A Large-Scale Empirical Study

arXiv:2606.12445v1 Announce Type: new Abstract: Exact distance computation for quantum LDPC (QLDPC) codes plays a central role in validating candidate fault-tolerant quantum-code constructions, yet the computational structure of this problem remains poorly understood. Despite substantial recent progress in QLDPC design, it remains unclear which algorithmic principles govern the practical scalability of exact distance computation and which classes of exact solvers are best suited to this task. To address these questions, we conduct a systematic study of SAT- and MaxSAT-based formulations for exact QLDPC distance computation across representative codes. We further compare these formulations against several established exact-distance approaches in order to better understand the algorithmic landscape of exact QLDPC distance computation. Our study challenges and refines several prevailing intuitions about exact QLDPC distance computation. First, despite the XOR-rich structure of QLDPC parity checks, practical scalability appears to be governed more by the handling of cardinality constraints and optimization bounds than by parity reasoning alone. Accordingly, XOR-aware reasoning does not provide a systematic advantage across our benchmark suite. Second, Brouwer-Zimmermann-style search, long regarded as the benchmark paradigm for exact distance computation in sparse classical codes, no longer maintains its traditional scalability advantage in the QLDPC setting. This finding challenges the expectation that techniques successful for sparse classical codes remain dominant for QLDPC codes. Third, substantial qualitative differences arise even among MaxSAT solvers themselves. Branch-and-bound MaxSAT significantly outperforms unsat-core-based MaxSAT on challenging benchmarks, demonstrating that solver architecture and optimization strategy play a decisive role in practical scalability.

05.
arXiv (CS.AI) 2026-06-11

Automated Mediator for Human Negotiation: Pre-Mediation via a Structured LLM Pipeline

arXiv:2606.11379v1 Announce Type: new Abstract: Pre-mediation, the preparatory phase preceding direct human negotiation, plays a critical role in achieving mutually beneficial agreements, yet is often omitted due to cost, time, and limited access to trained mediators. We introduce an automated mediator for human negotiation, implemented as a structured pipeline of LLM modules, that supports pre-mediation in integrative negotiation settings. The pipeline decomposes preparation into specialized modules for dialogue, preference prediction, response-level critique, and structured summarization, separating inference, generation, and evaluation to address limitations of monolithic single-prompt approaches. We use the term "agent" for each module following common LLM-systems terminology, but the components are not autonomous and do not interact peer-to-peer; outputs are passed forward in a fixed sequence. We evaluate the system in two controlled human-subject experiments comparing AI-based pre-mediation with professional human mediators in a multi-issue negotiation scenario. On short-term self-reported measures, the automated mediator achieves preparation outcomes broadly comparable to human mediators, including trust in the mediator and confidence in reaching mutually beneficial agreements, while achieving substantially lower error on the preference-inference task under our scenario and prompts (36% lower RMSE). A second study shows that targeted prompt refinements reduce excessive affirmation patterns from 36.6% to 16.8%, matching human mediator baselines. Our findings suggest that structured LLM pipelines can provide scalable, low-effort pre-mediation support broadly comparable to human mediators on short-term self-reported preparation outcomes. The pipeline's single-party design mirrors how human mediators run pre-mediation today and enables parallel deployment across all parties to a dispute, supporting scalability.

06.
medRxiv (Medicine) 2026-06-10

Frozen elephant trunk repair in heritable thoracic aortic disease: Impact of genetic aortopathy on long-term outcomes - A multicenter analysis

Aims This multicenter study aims to compare outcomes of total aortic arch replacement (TAR) using the frozen elephant trunk (FET) technique in patients with and without heritable thoracic aortic disease (HTAD) and to assess whether HTAD influences postprocedural adverse aortic events (AAEs). Methods From 06/2007 to 05/2024, aortic databases from 13 European centers were screened for HTAD patients undergoing TAR with FET. All consecutive dissection and aneurysm non-HTAD patients from the four core centers served as comparator. The primary outcome was AAE, a composite of diameter progression, distal stent graft induced new entry (dSINE), malperfusion, rupture and pseudoaneurysm at 5 years after FET implantation. Results Of 2739 FET patients, 196 (7.2%) were diagnosed with HTAD. The control group consisted of 867 non-HTAD FET patients. Marfan syndrome was the most common condition (72%), followed by Loeys-Dietz syndrome (11%), vascular Ehlers-Danlos syndrome (5.6%) and Turner syndrome (2.0%). Seventeen (8.8%) patients were diagnosed with ns-HTAD. At 5 years 46 (24%) AAEs occurred in the HTAD group, 169 (20%) in the non-HTAD group (p=0.2). Diameter progression was the most common event (10% vs. 12%; p=0.6), followed by dSINE (5.8% vs. 4.5%; p=0.5), malperfusion (4.2% vs. 3.3%; p=0.5), rupture (2.1% vs. 0.7%; p=0.09) and pseudoaneurysm (0.5% vs. 0.2%; p=0.5). Conclusions The FET technique appears safe and effective for acute and chronic aortic disease in HTAD patients, with outcomes comparable to non-HTAD cases and no increase in graft-related complications, challenging traditional concerns about stent graft use in genetically mediated aortic disease.

07.
arXiv (math.PR) 2026-06-17

A Tanaka-Type Formula for Compact Sets and Equilibrium Measures of L\'{e}vy Processes

arXiv:2606.17472v1 Announce Type: new Abstract: Tanaka's formula is a classical identity for Brownian motion, and Tsukada (2018) extended it to L\'{e}vy processes not necessarily symmetric. From a potential-theoretic point of view, this formula shows that the invariant function for the process killed upon hitting a singleton can be decomposed into the sum of a martingale part and a local time. In this paper, we generalize this singleton setting and derive a Tanaka-type formula for a compact set $B$. To this end, we introduce the equilibrium measure, defined as the rescaled limit of the $q$-capacity measures, and show that the invariant function for the process killed upon hitting $B$ can be represented as the integral, with respect to the equilibrium measure, of the invariant functions associated with processes killed upon hitting singletons, up to an additive constant called the Robin constant. Moreover, when $B$ is an interval, we obtain explicit representations of the equilibrium measure, the Robin constant, and the martingale part for recurrent stable processes as well as for recurrent spectrally negative L\'{e}vy processes. Finally, we discuss how an analogous Tanaka-type formula can also be established for transient L\'{e}vy processes.

08.
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.

09.
arXiv (CS.AI) 2026-06-16

XFlow: An Executable Protocol Programming System for Reliable Multi-Agent Workflows

arXiv:2606.14790v1 Announce Type: cross Abstract: LLM-based multi-agent systems increasingly coordinate planning, reasoning, tool use, and human interaction, yet their reliability remains limited. A central source of this limitation is the underspecified prompt–harness boundary. Current systems lack a principled way to decide which workflow commitments should remain in prompts and which should become harness structure. We present XFlow, an executable protocol programming system for reliable multi-agent workflows, and XPF (XFlow Protocol Format), its domain-specific protocol programming language. XFlow occupies a middle position between prompt-only orchestration and markup-like workflow descriptions. XPF remains readable as a literate protocol, but it is compiled and executed as a program. Its design keeps informal semantic work inside actors while moving selected commitments into harness structure that can be checked, preserved, and enforced. At runtime, XFlow stages uncertainty through lifecycle-governed symbols, which are typed state cells with validation and commit states. Actor outputs are mediated before they become shared state, instead of spreading through prompts, transcripts, or implicit memory. Our experiments cover Constrained Interaction, Long-Context Reasoning, and Agentic Software Engineering. They show that XFlow improves reliability by making constraints, evidence handling, and process requirements explicit and enforceable.

10.
arXiv (math.PR) 2026-06-17

Optimal Impulse Control for Cyber Risk Management

arXiv:2410.17706v2 Announce Type: replace-cross Abstract: We explore an optimal impulse control problem wherein an electronic device owner strategically calibrates protection levels against cyber attacks. Utilizing epidemiological compartment models, we qualitatively characterize the dynamics of cyber attacks within the network. We determine the optimal protective measures against effective hacking by formulating and solving a stochastic control problem with optimal switching. We demonstrate that the value function for the cluster owner constitutes a viscosity solution to a system of coupled variational inequalities associated with a fully coupled reflected backward stochastic differential equation (BSDE). Furthermore, we devise a comprehensive algorithm alongside a verification procedure to ascertain the optimal timing for network protection across various cyber attack scenarios. Our findings are illustrated through numerical approximations employing deep Galerkin methods for partial differential equations (PDEs). We visualize the optimal protection strategies in the context of two distinct attack scenarios: (1) a constant cyber attack, (2) an exogenous cyber attack strategy modeled with a Poisson process.

11.
arXiv (CS.LG) 2026-06-19

How to sketch a learning algorithm

Authors:

arXiv:2604.07328v3 Announce Type: replace Abstract: How does the choice of training data influence an AI model? This broad question is of central importance to interpretability, privacy, and basic science. At its technical core is the data deletion problem: after a reasonable amount of precomputation, quickly predict how the model would behave in a given situation if a given subset of training data had been excluded from the learning algorithm. We present a data deletion scheme capable of predicting model outputs with vanishing error $\varepsilon$ and failure probability $\delta$ in the deep learning setting. Our precomputation and prediction algorithms are only $\tilde{O}(\log(1/\delta)/\varepsilon^2)$ factors slower than regular training and inference, respectively. The storage requirements are those of $\tilde{O}(\log(1/\delta)/\varepsilon^2)$ models. Our proof is based on an assumption that we call stability. In contrast to the assumptions made by prior work, stability appears to be fully compatible with learning powerful AI models. In support of this, we show that stability is satisfied in a minimal set of experiments with microgpt. Our code is available at https://github.com/SamSpo1/microgpt-sketch. At a technical level, our work is based on a new method for locally sketching an arithmetic circuit by computing higher-order derivatives in random complex directions. Forward-mode automatic differentiation allows cheap computation of these derivatives.

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

OSCS-SupCon: Orthogonal Sigmoid-based Common and Style Supervised Contrastive Learning for Robust Feature Disentanglement

Supervised Contrastive Learning (SupCon) has achieved strong performance by explicitly modeling pairwise relationships among samples. However, existing SupCon-based methods suffer from two key limitations: negative-sample dilution induced by the standard InfoNCE loss, and feature-space entanglement caused by the lack of explicit constraints separating category-relevant (common) and category-irrelevant (style) features. These limitations reduce feature discriminability and generalization ability. To address these issues, we propose OSCS-SupCon (Orthogonal Sigmoid-based Common and Style Supervised Contrastive Learning), a unified framework that combines a sigmoid-based pairwise contrastive objective with explicit orthogonality constraints. Specifically, we introduce a sigmoid-based contrastive loss with two learnable parameters, temperature and bias, which adaptively modulate pairwise decision boundaries and alleviate negative-sample dilution. Furthermore, we enforce orthogonality between common and style feature subspaces via a linear projection with ReLU nonlinearity, thereby reducing feature overlap and improving disentanglement of style-irrelevant representations. Extensive experiments on six benchmark datasets demonstrate that OSCS-SupCon consistently outperforms state-of-the-art supervised contrastive learning methods across multiple backbone architectures. In particular, on the fine-grained CUB200-2011 dataset with a ResNet-18 backbone, the proposed method achieves a 3.4% improvement in classification accuracy over CS-SupCon, highlighting its robustness and generalization capability. Ablation studies further confirm the effectiveness of each component.

13.
arXiv (quant-ph) 2026-06-19

Indefinite Quantum Causality

arXiv:2606.19438v1 Announce Type: new Abstract: In recent years, operational approaches to quantum foundations have been developed as a means of understanding the core principles and distinctive features of quantum theory. Such approaches typically view physical processes as sequences of operations, with earlier operations serving as causes of later effects. However, a growing literature is emerging on the possibility of relaxing this assumption and allowing for quantum indefiniteness in the causal order. This development stems from a variety of motivations, both fundamental and applied, including exploring the role of causality in quantum theory, the interplay between quantum theory and general relativity, and higher-order quantum computing. A prominent offshoot of this development is the emergence of indefinite causal order as a feasible resource for quantum information processing. This review provides an overview of the current state of the art in the field, covering the methodology underlying indefinite quantum causality within the so-called "process matrix formalism", outlining key results and experimental implementations, and discussing recent advances.

14.
arXiv (CS.CL) 2026-06-17

Reading between the Lines: Leveraging Large Language Models for Global Dementia and Depression Assessment from Clinical Interviews

Dementia and depression are the most prevalent neuropsychiatric disorders in geriatric populations, and their overlapping symptoms pose major challenges for differential diagnosis. In this study, we investigate open-weights Large Language Models (LLMs) for predicting dementia and depression severity from speech samples collected during standardized history taking interviews with 154 German-speaking subjects. We introduce an observer-based Global Depression Scale (GDS-D) aligned with the established Global Deterioration Scale (GDS), enabling parallel global staging of affective and cognitive symptoms. We compare three LLMs (Mistral 3.1, DeepHermes, Qwen3) in two settings: (1) zero-shot prediction and (2) LLM-based feature extraction for Support Vector Regression, using human and pause-enriched transcripts. Results show that LLMs effectively predict depression severity in zero-shot settings (best MAE of 0.60), while dementia assessment benefits substantially from structured feature extraction (best MAE of 0.78), reducing errors by up to 35% over zero-shot baselines. Pause-enriched transcripts achieve competitive performance with human transcriptions, demonstrating the viability of fully automatic screening pipelines for differential neuropsychiatric assessment.

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

An Open-Source Monitoring Framework for Data Exploration and Progress Tracking in Multi-Center Radiology Studies

Multi-center studies are crucial for advancing medical and radiological research. Data exploration, collaboration discovery, and study progress monitoring are essential for maximizing their potential. However, in practice these processes often rely on manual communication and shared tables, which quickly become outdated and hinder efficient coordination in large distributed studies. This highlights the need for dedicated monitoring solutions that provide transparent and up-to-date insights into study progress. We propose a lightweight, open-source monitoring architecture for multi-center studies based on the widely used Grafana-Prometheus stack. The framework collects aggregated monitoring metrics from distributed study sites and visualizes them through configurable dashboards. As a real-world deployment example, the framework is integrated into the medical imaging platform Kaapana and evaluated within a large multi-center research network. By deploying our solution within the Germany-wide RACOON consortium, we demonstrate its ability to enable privacy-preserving data exploration and study progress monitoring across all 38 German university clinics. The monitoring framework supports transparent coordination of distributed research activities and can facilitate more efficient management of large-scale multi-center studies. The source code and Kaapana integration are publicly available at https://github.com/MIC-DKFZ/study-monitoring-kaapana.

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

A biological vision inspired framework for machine perception of abutting grating illusory contours

Higher levels of machine intelligence demand alignment with human perception and cognition. Deep neural networks (DNN) dominated machine intelligence have demonstrated exceptional performance across various real-world tasks. Nevertheless, recent evidence suggests that DNNs fail to perceive illusory contours like the abutting grating, a discrepancy that misaligns with human perception patterns. Departing from previous works, we propose a novel deep network called illusory contour perception network (ICPNet) inspired by the circuits of the visual cortex. In ICPNet, a multi-scale feature projection (MFP) module is designed to extract multi-scale representations. To boost the interaction between feedforward and feedback features, a feature interaction attention module (FIAM) is introduced. Moreover, drawing inspiration from the shape bias observed in human perception, an edge detection task conducted via the edge fusion module (EFM) injects shape constraints that guide the network to concentrate on the foreground. We assess our method on the existing AG-MNIST test set and the AG-Fashion-MNIST test sets constructed by this work. Comprehensive experimental results reveal that ICPNet is significantly more sensitive to abutting grating illusory contours than state-of-the-art models, with notable improvements in top-1 accuracy across various subsets. This work is expected to make a step towards human-level intelligence for DNN-based models.

17.
arXiv (quant-ph) 2026-06-16

Suppressing Intrinsic Spin-Phonon Errors in Trapped-Ion Quantum Simulation

arXiv:2606.15518v1 Announce Type: new Abstract: Trapped-ion quantum simulators realize programmable spin models through phonon-mediated interactions. For Hamiltonians with noncommuting terms, however, the same phonon bus generates intrinsic spin-phonon errors that strongly distort the target dynamics. Because these errors are governed by the full time history of the spin-dependent phonon motion, they survive standard loop-closing control and limit simulation accuracy. Using a sequence of frame transformations, we isolate the residual error dynamics and show that this intrinsic error can be strongly suppressed while preserving programmable Ising couplings. Full spin-boson simulations of multi-ion chains demonstrate orders-of-magnitude lower error than both constant-drive and conventional loop-closing protocols. These results remove a central precision barrier in trapped-ion analog quantum simulation and enable accurate programmable simulation of noncommuting many-body Hamiltonians and dynamical protocols.

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

Denoising Implicit Feedback for Cold-start Recommendation

arXiv:2606.19658v1 Announce Type: new Abstract: Implicit feedback is widely used in recommender systems due to its accessibility and generality, yet it usually presents noisy samples (e.g., clickbait, position bias). Meanwhile, recommenders inevitably face the item cold-start problem due to the continuous influx of new items. We identify that cold items are more prone to noisy samples due to the aforementioned factors, and researchers often overlook the significance of denoising implicit feedback for cold items. Previous denoising studies usually identify noisy samples based on heuristic patterns, such as higher loss values, and mitigate noise through sample selection or re-weighting. However, these methods have limited adaptability and are ineffective in cold-start scenarios. To achieve denoising implicit feedback for cold-start recommendation, we propose a model-agnostic denoising method called DIF. First, user preferences for content remain stable, which allows us to infer pseudo-labels indicating whether a user is interested in a cold item through content-similar warm items. Furthermore, to improve pseudo-label accuracy, we model the confidence of pseudo-labels based on the content similarity between the cold item and warm items, and then aggregate multiple pseudo-labels for each sample. Finally, we explicitly estimate the uncertainty of the noisy sample label by considering its relative entropy and the cold-start status of the item, which adaptively guides the role of pseudo-labels to correct the noisy labels at the sample level. DIF's superiority is supported by both theoretical justification and extensive experiments on real-world datasets. The method has been deployed on a billion-user scale short video application Kuaishou and has significantly improved various commercial metrics within cold-start scenarios.

19.
PLOS Medicine 2026-05-08

Optimal minimal residual disease threshold in pediatric acute myeloid leukemia: A retrospective cohort study based on the TARGET database

Authors:

by Xiong-yu Liao, Hong Zheng, Jian-pei Fang, Dun-hua Zhou, Kun-yin Qiu Background Minimal residual disease (MRD) monitoring is a cornerstone of risk stratification in pediatric acute myeloid leukemia (AML), with a threshold of 0.1% conventionally defining positivity by flow cytometry. Advances in flow cytometric technologies, enabling detection of leukemic cells with higher sensitivity and specificity, warrant a reevaluation of whether a lower threshold improves prognostic accuracy. Methods and findings We conducted a retrospective cohort study using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-AML initiative. The study population comprised 1,205 pediatric patients with de novo AML treated across Children’s Oncology Group (COG) clinical trial centers. Patients were enrolled between September 1996 and December 2016, with a median follow-up of 6.2 years (range: 0.5–20.1 years). The primary objective was to compare the prognostic performance of the traditional MRD threshold (≥0.1%) with a lower threshold (≥0.05%) after induction courses 1 and 2. The main outcome measure was 5-year event-free survival (EFS). Analyses included Kaplan−Meier survival estimates, Cox proportional hazards models to calculate hazard ratios (HR) with 95% confidence intervals (CI), receiver operating characteristic (ROC) curves, and net reclassification improvement (NRI). The optimal threshold for predicting 5-year EFS, determined by ROC analysis, was 0.05% after both induction course 1 (AUC: 0.840, 95%CI[0.76,0.88]) and course 2 (AUC: 0.854, 95%CI[0.78,0.89]). The 0.05% threshold demonstrated higher HR for the first event than the 0.1% threshold (after course 1: HR = 2.8, 95%CI[2.3,3.3]; P 

20.
arXiv (quant-ph) 2026-06-11

Controlled ion-ion interactions and cavity-enhanced emission of a coherent dinuclear Eu$^{3+}$ complex

arXiv:2606.11947v1 Announce Type: new Abstract: Molecular rare-earth-ion complexes offer unique opportunities for quantum technologies by combining the intrinsic coherence properties of rare-earth ions with chemically tunable molecular environments. A crucial capability is the realization of multi-qubit architectures with defined qubit couplings to enable two-qubit quantum gates. Here, we investigate the optical coherence properties and excitation-induced interactions of two Eu$^{3+}$-based molecular complexes, comparing a mononuclear reference system with a dinuclear analogue in which two Eu$^{3+}$ ions are positioned at a well-defined intramolecular distance of about 7 Angstrom. Using cryogenic ensemble spectroscopy, including spectral hole burning, free-induction decay, and photon echo measurements at temperatures down to 100 mK, we demonstrate long optical coherence times $T_{2,o}$ of up to 9 $\mu$s. As a key step toward scalable multi-qubit architectures, a control-target sequence was implemented to probe conditional ion-ion interactions, revealing a stronger interaction-induced dephasing in the dinuclear complex. Finally, we show the integration of the dinuclear complex into a fiber-based optical microcavity, and observe an 380-fold emission enhancement of the $\mathrm{}^5\mathrm{D}_0\rightarrow\mathrm{}^7\mathrm{F}_0$ transition. Together, these results position molecular rare-earth complexes as versatile and chemically tunable building blocks for scalable quantum technologies.

21.
medRxiv (Medicine) 2026-06-22

Histologically validated diffusion MRI signatures of neuroinflammation and neurodegeneration in Alzheimer disease

Noninvasive neuroinflammation measurement remains a major barrier for Alzheimer disease (AD) therapeutics. We present generalized diffusion basis spectrum imaging (g-DBSI), a diffusion MRI framework that decomposes the tissue signal into biologically interpretable microstructural compartments. In postmortem Knight ADRC brains, g-DBSI-derived restricted isotropic fraction (RIF) and restricted anisotropic fraction (RAF) mapped cellularity and neurofilament density, while their ratio (RIF/RAF) tracked inflammatory cell density and peri-plaque amyloid-beta with higher specificity and regional consistency than RIF alone. In 112 living Knight ADRC participants stratified by PET amyloid, g-DBSI metrics showed amyloid-dependent trajectories: in low-amyloid individuals, RIF and RAF rose together with amyloid, consistent with early neuropil expansion and glial elaboration, whereas in high-amyloid individuals, RIF/RAF increased, and RAF declined, indicating established neuroinflammatory remodeling and neurofilament loss. CSF proteomics linked RIF/RAF to glia-enriched immune and vascular pathways, supporting g-DBSI as a clinically compatible MRI biomarker of neuroinflammation and neurodegeneration in AD.

22.
medRxiv (Medicine) 2026-06-11

Large-scale proteomics and timing of hypertensive disorders of pregnancy

Background: Hypertensive disorders of pregnancy (HDP) may first be diagnosed antepartum, during labor, or postpartum. We utilized untargeted large-scale proteomics to identify pathways associated with HDP based on timing of onset. Methods: We performed a nested case-control study comparing differential protein expression, from the SomaScan 7K platform, based on timing of onset of HDP versus controls (referent) using first-trimester samples from the NuMoM2b-Heart Health Study, a multi-site cohort that followed nulliparous individuals from the first trimester. Associations of proteins with timing of onset of HDP, adjusted for co-variates, were assessed using logistic regression q value-based false discovery rates and pathway enrichment and differential expression analysis were conducted. Results: Of 1628 individuals included, 678 had HDP, of which 67% manifested antepartum (AP), 29% intrapartum (IP), and 3% postpartum (PP). After adjusting for co-variates, compared to controls, 698 proteins, 39 proteins, and 144 proteins were differentially expressed in those with HDP according to AP, IP, PP onset, respectively. There was little overlap in individual protein expression based on timing of HDP. Pathway enrichment and graphical summary analyses suggested distinct processes. Specifically, there was downregulation of angiogenic proteins in AP HDP, downregulation of immune-related proteins in IP HDP, and upregulation of complement activation promoting fibrotic changes leading to cardiac dysfunction in PP HDP. Conclusion: There are differences in first-trimester protein expression based on whether HDP first manifests AP, IP or PP. This raises the possibility that there may be distinct mechanistic phenotypes that could uniquely inform diagnostic and therapeutic targets for HDP.

23.
arXiv (CS.LG) 2026-06-19

A Model-Driven Approach for Developing Families of Reinforcement Learning Environments

arXiv:2606.20324v1 Announce Type: cross Abstract: Virtual training environments are software-intensive systems in which reinforcement learning (RL) agents learn, adapt, and demonstrate meaningful behavior. Virtual training environments offer a safe and cost-efficient alternative to training agents in real-world settings. However, to converge, most realistic RL problems require training in multiple, mostly similar but slightly different environments - i.e., families of environment variants. The typical development process of environment families is a labor-intensive and error-prone manual endeavor that does not scale well. To alleviate these issues, in this paper, we propose a model-driven approach for developing families of RL training environments. To obtain the family of environments, we develop an approach and prototype tool. In our approach, a hybrid genetic algorithm - a combination of population-based global search and heuristic local search - generates environment families. Mutations and constraints are expressed as model transformations and are operationalized into a search process by a state-of-the-art model transformation engine. We demonstrate the soundness of our approach in a wildfire mitigation scenario and curriculum learning - a particular learning paradigm that relies on environment families.

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

Two-Phase Bilevel Search for the Moving-Target Traveling Salesman Problem with Moving Obstacles

arXiv:2606.18730v1 Announce Type: cross Abstract: The Moving-Target Traveling Salesman Problem (MT-TSP) seeks a minimum cost trajectory for an agent that departs from a static depot, visits a set of moving targets, each within one of their assigned time windows, and returns to the depot. In this article, we study the Moving-Target Traveling Salesman Problem with Moving Obstacles (MT-TSP-MO), a generalization of the MT-TSP where the agent trajectory must avoid moving obstacles. We present a Mixed-Integer Conic Programming (MICP) formulation that can be solved using off-the-shelf solvers, as well as a fast and scalable Two-Phase Bilevel Search (TPBS) algorithm that computes high-quality feasible solutions for the problem. We evaluate our approaches against an existing baseline algorithm on a broad range of problem instances with up to 40 targets and 40 obstacles. The results demonstrate that both the proposed methods significantly outperform the baseline with respect to success rates, solution costs, and computation time.

25.
arXiv (CS.LG) 2026-06-12

DiffCoord: Differentiable Coordination for Distributed Multi-Agent Trajectory Optimization

arXiv:2509.01630v3 Announce Type: replace Abstract: Integrating the Alternating Direction Method of Multipliers (ADMM) with Differential Dynamic Programming (DDP) provides a scalable framework for distributed multi-agent trajectory optimization. In practice, ADMM is typically truncated for computational efficiency, tightly coupling parameters that would otherwise separately govern coordination quality and task performance. In this paper, we propose Differentiable Coordination (DiffCoord), a unified framework that jointly meta-learns these coupled parameters for the truncated ADMM-DDP pipeline. These parameters are generated by agent-wise neural networks for task adaptation, and the same networks are shared among isomorphic agents to enable scalability to varying agent counts. We achieve efficient meta-learning by differentiating the ADMM-DDP pipeline end-to-end. Notably, this yields an auxiliary ADMM-LQR distributed gradient solver that computes and coordinates meta-gradients with respect to these parameters. This solver inherits the computational structure of the pipeline, enabling reuse of key computation results and efficient parallelization over agents and along trajectory horizons. We validate DiffCoord through numerical and physical experiments on a cooperative aerial transport system, where it reconfigures quadrotor formations for safe 6-DoF load manipulation in tight spaces. It adapts robustly to varying team sizes and load dynamics, while reducing per-agent gradient computation time by up to 70% compared with state-of-the-art trajectory-gradient methods.