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

A Comprehensive Ecosystem for Open-Domain Customized Video Generation

Recent progress in video generation has shown impressive visual synthesis capabilities. However, open-domain customized video generation remains limited by the lack of large-scale, annotated datasets capturing diverse identity-specific attributes. To address this, we introduce PexelsCustom-1M, the first publicly available million-scale dataset for identity-preserving video generation, containing one million curated triplets across 8,000+ categories. Leveraging this, we propose CustoMDiT, a parameter-efficient framework that adapts a pretrained multimodal Diffusion Transformer into a customized video generator with only 8% additional learnable parameters. Our method surpasses prior state-of-the-art. However, benchmarks such as DreamBooth cover only 100 classes, which is insufficient for real-world applications. To overcome this, we construct OpenCustom, a new benchmark with 1,000+ categories, created via cross-dataset knowledge fusion from ImageNet and MS-COCO. Extensive experiments confirm the advantages of both our dataset and model. We will open-source the entire ecosystem–including dataset, pipeline, benchmark, and implementations–to support further research.

02.
arXiv (quant-ph) 2026-06-24

Compressed Quantum Operators and Roots of Hermite Polynomials

arXiv:2606.24792v1 Announce Type: new Abstract: The fundamental position and momentum operators of quantum mechanics are unbounded, but finite rank compressions of the operators can be considered to obtain partial information on the operators and their properties. Motivated by problems in photonic quantum computing, we bring together results from quantum theory and the theory of orthogonal polynomials to show that a natural finite rank compression of the position and momentum operator representation on Fock space Hilbert space has eigenvalues given by roots of the classical Hermite polynomials. We discuss the corresponding compressed displacement operators and potential applications in approximate quantum error correction.

03.
arXiv (CS.AI) 2026-06-19

FundaPod: A Multi-Persona Agent Pod Platform with Knowledge Graph Memory for AI-Assisted Fundamental Investment Research

arXiv:2605.27864v4 Announce Type: replace Abstract: Large language models (LLMs) are increasingly applied in finance, yet most existing work emphasizes trading signals or financial NLP tasks centered on prediction. Institutional fundamental research, by contrast, requires human analysts or AI agents to gather evidence, identify business drivers, compare competing viewpoints, and generate investment memos. Its broader goal is not merely to predict outcomes, but to produce investment plans that are transparent, reusable, and verifiable, while contributing to the cumulative development of investment knowledge. We present FundaPod, a multi-persona agent platform for AI-assisted fundamental investment research. We argue that fundamental research is a human-centric decision-support task that is qualitatively distinct from trading-signal generation, and is therefore better served by an independence-preserving architecture. In FundaPod, AI agents with different personas, such as value investors or macro strategists, conduct research independently under a shared provenance contract. Their disagreements are then surfaced post hoc for adjudication by the human portfolio manager (PM) through a knowledge-graph memory system. This paper contributes five design principles for human-AI hybrid systems supporting fundamental research, grounded in design-science practice and theories of cognitive isolation and human-machine coordination. It also describes four architectural mechanisms: a persona distillation pipeline that turns public investor materials into deployable agents; a declarative skill registry that lets the planner derive typed task graphs; a grounded evidence model that links memo claims to verifiable sources; and a knowledge-graph "second brain" that connects tickers, memos, analysts, and themes. We demonstrate the architecture through a complete case study and a persona-based memo comparison.

04.
arXiv (CS.AI) 2026-06-18

A Distributionally Robust Reinforcement Learning Framework for Constrained Urban EV Dispatch

arXiv:2604.25848v2 Announce Type: replace Abstract: We study city-scale control of electric-vehicle (EV) ride-hailing fleets where dispatch, repositioning, and charging decisions must respect charger and feeder limits under uncertain, spatially correlated demand and travel times. We formulate the problem as a hex-grid semi-Markov decision process (semi-MDP) with mixed actions – discrete actions for serving, repositioning, and charging, together with continuous charging power – and variable action durations. To guarantee physical feasibility during both training and deployment, the policy learns over high-level intentions produced by a masked, temperature-annealed actor. These intentions are projected at every decision step through a time-limited rolling mixed-integer linear program (MILP) that strictly enforces state-of-charge, port, and feeder constraints. To mitigate distributional shifts, we optimize a Soft Actor-Critic (SAC) agent against a Wasserstein-1 ambiguity set with a graph-aligned Mahalanobis ground metric that captures spatial correlations. The robust backup uses the Kantorovich-Rubinstein dual, a projected subgradient inner loop, and a primal-dual risk-budget update. Our architecture combines a two-layer Graph Convolutional Network (GCN) encoder, twin critics, and a value network that drives the adversary. Experiments on a large-scale EV fleet simulator built from NYC taxi data show that PD-RSAC achieves the highest net profit, reaching \$1.22M, compared with \$0.58M-\$0.70M for strong heuristic, single-agent RL, and multi-agent RL baselines, including Greedy, SAC, MAPPO, and MADDPG, while maintaining zero feeder-limit violations.

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

SciR: A Controllable Benchmark for Scientific Reasoning in LLMs

arXiv:2606.13020v1 Announce Type: new Abstract: Three paradigmatic forms of inference recur across scientific reasoning: deduction, induction, and causal abduction. Reliably evaluating LLMs on these in scientific settings is currently out of reach: scientific benchmarks built on human annotations are costly and lack mechanistic ground truth, while synthetic logical-reasoning benchmarks do not resemble real scientific documents. We introduce SciR, a benchmark that combines multi-paradigm reasoning with controllable scientific rendering, anchored on three paradigmatic scientific problems. Tasks are generated from formal objects (deduction tree, inductive rule hypothesis, causal graph) to guarantee verifiable answers, then rendered into multi-document scientific discourse via per-track domain-tuned genres. The construction lets us independently vary two difficulty axes: how hard it is to extract the key information needed for inference, and how hard the principled inference itself is. We test six models. Both axes hurt every model, and their effects compound. The rendering even hurts neurosymbolic pipelines, which hand inference to a verified solver. The two axes yield a per-model extraction-vs-inference profile: for instance, reasoning models like deepseek-r1 mostly surpass non-reasoning instruct models on the inference axis. To our knowledge, SciR is the first multi-paradigm scientific-reasoning benchmark with parametric control on both extraction and inference difficulty.

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

Surveying GenAI-based Automation in Printed Circuit Board Design and Test

arXiv:2606.17074v1 Announce Type: cross Abstract: Generative artificial intelligence (GenAI) is increasingly used for applications in the hardware and software domains. It purports to reduce the manual effort involved in the development and testing of complex systems before release. Within the hardware space, most tasks have focused on design automation of integrated circuits, particularly with hardware description languages. However, other types of hardware also exist! In this survey, we instead examine how GenAI has been and is being across the printed circuit board (PCB) design life cycle. This includes everything from supply chains, system specification, circuit design, layout and optimisation, validation and test, and PCB assembly and distribution. Through this lens we present a taxonomy of discovered works, categorising them according to their intent and contributions. This survey also identifies key technical challenges that GenAI faces in this space, such as domain-specific data scarcity and limited support for integration with existing PCB tools. Finally, future research directions are discussed: our survey shows that there are many opportunities remaining when considering how GenAI may be integrated into various tasks in PCB design and test.

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

HKVM-RAG: Key-Value-Separated Hypergraph Evidence Organization for Multi-Hop RAG

Multi-hop RAG poses a data-engineering problem beyond passage matching: under fixed retrieval budgets, a system must organize retrieved text into evidence units that expose answer chains. Dense retrievers score passages independently, while graph-based memories make associations explicit but often rely on pairwise or entity-centered keys that fragment multi-hop evidence. We present HKVM-RAG, a key-value-separated evidence-organization layer. It assembles answer-path hyperedges from cached passage-level LLM evidence tuples and uses them as retrieval keys, while retaining passage text as answer values. To isolate key-space design, our fixed-substrate protocol holds the tuple cache, candidate passages, reader, and evaluation budget constant across pairwise graph and hypergraph variants. Weighted hypergraph key-value retrieval improves over KG-PPR by +3.426 F1 on 2WikiMultiHopQA and +3.592 F1 on MuSiQue; HotpotQA shows that higher structured support coverage need not yield standalone answer-F1 gains. We therefore study WHG-KV as an evidence-control signal rather than a dense-retrieval replacement. Oracle and train-to-dev analyses identify support selection as repairable, and a dense-aware controller combines frozen ColBERTv2 and HKVM rank/score features using out-of-fold HKVM predictions. It reaches 88.846, 65.073, and 85.810 F1 on the three benchmarks, improving over ColBERTv2 by +11.084, +6.763, and +5.966 F1. Source-level ablations show that matched non-WHG structured signals do not match the WHG-KV gains. These results provide bounded evidence that key-value-separated hypergraph organization can serve as a reusable evidence-control mechanism for multi-hop RAG.

08.
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.

09.
arXiv (CS.CL) 2026-06-18

Continual Adaptation for Pacific Indigenous Speech Recognition

Speech foundation models struggle with low-resource Pacific Indigenous languages because of severe data scarcity. Furthermore, full fine-tuning risks catastrophic forgetting. To address this gap, we present an empirical study adapting models to real-world Pacific datasets. We investigate the impact of data volume, adaptation strategies, and representational drift on speech foundation models for various Pacific languages. Additionally, we analyze a continual learning framework for sequential language acquisition. Empirical results across three distinct Pacific Indigenous languages demonstrate that adapting to these linguistically distant languages induces severe internal representational drift. Consequently, these models face a strict plasticity and stability dilemma. While LoRA adapts well initially, it suffers from catastrophic forgetting during sequential learning. Ultimately, this study highlights the urgent need for robust adaptation strategies tailored to underrepresented languages.

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

ConsistencyPlanner: Real-time Planning with Fast-Sampling Consistency Models

arXiv:2606.11569v1 Announce Type: cross Abstract: Closed-loop planning in complex, real-world driving scenarios presents a critical challenge for autonomous driving systems. While traditional rule-based methods are interpretable, their predefined heuristics lack the adaptability for dynamic traffic environments. Learning-based approaches have shown considerable promise. Conversely, learning-based approaches, despite their promise, struggle to balance the modeling diverse and multimodal driving behaviors and real-time planning, often leading to indecisive or unsafe actions. To address this limitation, we propose Consistency Planner, a real-time planning framework with fast-sampling consistency models. Our approach is built upon two key technical contributions. Efficient Multimodal Sampling: We employ fast-sampling consistency models to generate a diverse set of plausible future trajectories. This enables efficient, real-time exploration of multimodal actions, overcoming the computational bottlenecks of previous iterative generative methods. Heterogeneous Feature Fusion: We introduce an attention-enhanced decoder that dynamically integrates heterogeneous input features (including scene feature and action token) into a cohesive representation for robust planning. Extensive evaluation in the Waymax simulator demonstrates superior performance in safety metrics compared to existing methods, with particularly strong results in challenging dynamic scenarios.

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

Agent Economics: An Entropy-Controlled Pluralistic Alignment Framework for Preventing Artificial Hivemind in Autonomous Agents

arXiv:2606.09039v2 Announce Type: replace Abstract: This study proposes the Behavioral Protocol Framework (BPF), an entropy-controlled pluralistic alignment framework designed to address two critical challenges in autonomous agent economies: the hivemind effect arising from excessive strategic convergence among agents and the lack of transparency in autonomous decision-making processes. The proposed BPF consists of three core modules: Mentalizing-based Social Intelligence (MbSI) grounded in Theory of Mind (ToM), Pluralistic Alignment (PA), and a Verifiable Execution Kernel (VEK). These modules are organically integrated within a closed-loop architecture that governs the entire lifecycle of agent behavior, from decision-making and execution to verification and feedback. To evaluate the proposed framework, a simulation environment implemented in Python and a Streamlit-based user interface will be developed. Through empirical experimentation, the study aims to examine whether the entropy-control mechanism of the PA module can effectively preserve strategic diversity among agents and mitigate collective convergence, while the VEK module provides a comprehensive and transparent audit trail of the decision-making process. The anticipated results are expected to demonstrate that the proposed framework can simultaneously enhance the stability, efficiency, and trustworthiness of autonomous agent economies. Consequently, this research offers a practical approach for developing robust, transparent, and accountable agent-native economic systems.

12.
arXiv (CS.AI) 2026-06-24

DynamicPO: Dynamic Preference Optimization for Recommendation

arXiv:2605.00327v3 Announce Type: replace-cross Abstract: In large language model (LLM)-based recommendation systems, direct preference optimization (DPO) effectively aligns recommendations with user preferences, requiring multi-negative objective functions to leverage abundant implicit-feedback negatives and sharpen preference boundaries. However, our empirical analyses reveal a counterintuitive phenomenon, preference optimization collapse, where increasing the number of negative samples can lead to performance degradation despite a continuously decreasing training loss. We further theoretically demonstrate that this collapse arises from gradient suppression, caused by the dominance of easily discriminable negatives over boundary-critical negatives that truly define user preference boundaries. As a result, boundary-relevant signals are under-optimized, weakening the model's decision boundary. Motivated by these observations, we propose DynamicPO (Dynamic Preference Optimization), a lightweight and plug-and-play framework comprising two adaptive mechanisms: Dynamic Boundary Negative Selection, which identifies and prioritizes informative negatives near the model's decision boundary, and Dual-Margin Dynamic beta Adjustment, which calibrates optimization strength per sample according to boundary ambiguity. Extensive experiments on three public datasets show that DynamicPO effectively prevents optimization collapse and improves recommendation accuracy on multi-negative preference optimization methods, with negligible computational overhead. Our code and datasets are available at https://github.com/xingyuHuxingyu/DynamicPO.

13.
arXiv (CS.CL) 2026-06-24

AI Fiction in the Wild

Some professional authors are beginning to use AI tools to help produce their fiction writing. Are readers using AI to generate fiction, too? Drawing on over 500,000 anonymized, English-language ChatGPT-user conversations (arXiv:2405.01470), we find that more than one third of the conversations involve some form of fiction generation – including original stories, roleplay, fanfiction, and erotica. This AI-generated fiction is notably dominated by power users. We identify common fiction generation patterns and profiles among these users, including what we call "infinite story demanders," who repeatedly request and revise variations of the same or similar narratives over extended periods of time. We show that users especially gravitate toward fanfiction and erotica, and that they are broadly drawn to generic forms, repetition, immediacy, and niche combinations of story elements. Our findings motivate two theoretical provocations. First, we argue that AI technologies may lead to a shift in the conventional relationship between the author and reader, potentially producing what we call a "solipsistic reader-writer," who both generates and consumes fiction within a closed conversational loop, interacting with a machine rather than a human other. Second, we note that LLMs enable interactivity, play, and permutation in ways that are seemingly pleasurable for users, raising questions about where AI will fit into contemporary storytelling and entertainment ecosystems. We situate these developments within broader transformations in literature and media, including self-publishing, fanfiction, and pornography, and suggest that AI-generated fiction shares structural affinities with on-demand, personalized, and repetitive cultural forms.

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

Decentralised AI Training and Inference with BlockTrain

作者:

arXiv:2606.24722v1 Announce Type: new Abstract: Frontier AI training is increasingly shaped by access to dense, centrally controlled accelerator clusters. This creates a structural advantage for hyperscalers and large centralized laboratories, and makes open or independent AI efforts depend on scarce capital, privileged infrastructure, and data-center geography. We present Spheroid BlockTrain, a decentralized training protocol in which a model is partitioned into independently trainable blocks, each optimized on a local objective derived from the same global target and composed at inference into one model. On byte-level WikiText, BlockTrain reaches cross entropy 1.359 (perplexity 3.89), within about 0.04 CE of a same-setup end-to-end Transformer reference, while each active worker trains only one block and avoids full-model optimizer state. A shared six-worker block training run reaches CE 1.385 by averaging same-block updates into one assembled model. HTTP/TCP transport experiments move real serialized checkpoints and updates, including a public-IP three-host run that improves CE from 5.580 to 1.811 while moving 15.22 GB. For inference, the current BlockTrain path uses one block-stack traversal per full output and serves over direct TCP across three public-network GPU hosts up to a 75.80B-parameter logical fp16 shape, outperforming a matched plain-autoregressive TCP pipeline baseline because it emits a full sequence per WAN pipeline traversal rather than one token per traversal.

15.
PLOS Computational Biology 2026-06-15

A multilevel hierarchical framework for quantification of experimental heterogeneity in population snapshot data

by David J. Warne, Xiangrun Zhu, Thomas P. Steele, Stuart T. Johnston, Scott A. Sisson, Matthew Faria, Ryan J. Murphy, Alexander P. Browning Biological systems exhibit substantial heterogeneity: that is, variation in specific characteristics of individuals within a population. As a result, it is of critical importance to appropriately account for biological heterogeneity when calibrating mathematical models to infer cellular processes and predict behaviour. Recent approaches consider ordinary differential equations with random parameters to quantify heterogeneity in dynamical processes of cells. In this setting, statistical inference is performed to characterise the distribution of these random parameters within a cell population. One significant limitation of this approach is the tacit assumption that there are no substantial deviations in these distributions across experimental replicates. In this work, we propose a flexible Bayesian hierarchical differential equation modelling framework that quantifies and distinguishes both inter-experimental heterogeneity (heterogeneity between experimental replicates) and intra-experimental heterogeneity (biological heterogeneity within replicate populations). We consider two recent studies that employ mathematical models to interpret flow cytometry snap-shot data and quantify heterogeneity in nano-particle cell interactions and cell internalisation processes. Using simulation data, we demonstrate that substantial inaccuracy in the inferred dynamics can arise when experimental heterogeneity is not accounted for. By contrast, our hierarchical approach is robust to variability in inter-experimental and intra-experimental heterogeneity and our method simplifies to previous methods when inter-experimental heterogeneity is negligible. Our approach is flexible and widely applicable to applications involving replicate populations and snapshot data. We provide open-source implementations of our methods on GitHub.

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

DP-Hype: Federated Differentially Private Hyperparameter Search

arXiv:2510.04902v3 Announce Type: replace Abstract: Tuning hyperparameters in federated machine learning can substantially impact model performance. When hyperparameters are tuned on sensitive data, privacy becomes an important challenge and to this end, differential privacy has emerged as the de facto standard for provable privacy. A standard setting in federated learning is that clients agree on a shared setup, i.e., find a compromise from a set of hyperparameters, like a model's learning rate. Yet, prior work on privacy-preserving hyperparameter tuning is tailored to specific learning tasks, does not account for the privacy leakage of aggregated results, or offers a sub-optimal privacy-utility trade-off. In this work, we present our algorithm DP-Hype, which performs a federated and privacy-preserving hyperparameter search by conducting a federated voting based on local hyperparameter evaluations of clients. In this way, DP-Hype selects hyperparameters that lead to a compromise supported by a majority of clients, while maintaining scalability and independence from specific learning tasks. We prove that DP-Hype preserves the strong notion of differential privacy called client-level differential privacy and, importantly, show that its privacy guarantees do not depend on the number of hyperparameters. We also provide bounds on its utility guarantees, that is, the probability of finding good hyperparameters, and implement DP-Hype as a submodule in the popular Flower framework for federated machine learning. In addition, we evaluate performance on multiple benchmark data sets in iid as well as multiple non-iid settings and demonstrate high utility of DP-Hype even under small privacy budgets.

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

MaskWAM: Unifying Mask Prompting and Prediction for World-Action Models

World Action Models (WAMs) present a promising paradigm for robotic control via video prediction. However, current WAMs suffer from fundamental spatial bottlenecks: standard text inputs introduce referential ambiguity in cluttered scenes, while unstructured RGB predictions lack semantic grounding and remain biased by task-irrelevant backgrounds. To overcome these limitations, we introduce MaskWAM, an object-centric world-action model. By jointly integrating masks as both explicit inputs and predictions via a unified Mixture of Transformers (MoT), MaskWAM unlocks robust policy generalization. This design provides two key benefits: (1) predicting future masks yields object-centric semantic supervision that suppresses visual noise, significantly enhancing even standard text-conditioned WAMs; and (2) coupling this predictive supervision with first-frame visual prompts, such as target object masks, establishes a precise spatial anchor that substantially reduces language ambiguity. Crucially, as WAMs are inherently vision-driven architectures, direct mask conditioning yields substantially stronger guidance than text alone, establishing a precise and robust paradigm for manipulating unseen objects. Evaluations on LIBERO, RoboTwin, and real-world tasks demonstrate that MaskWAM significantly outperforms baselines in both language-clear and language-ambiguous tasks.

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

Real-space spectral functions of three-dimensional billion-size topological non-Hermitian matter with tensor networks

arXiv:2606.16424v1 Announce Type: cross Abstract: Non-Hermitian systems host a wide range of unconventional topological phenomena while large-scale simulations in finite three dimensional systems remain challenging because of the rapidly growing number of sites. In particular, higher-order topological corner modes are often studied only in small lattices, where strong finite-size effects can mask their intrinsic behavior. Here, we develop a tensor-network framework that combines quantics tensor cross interpolation with the kernel polynomial method, enabling compact representations of large non-Hermitian tight-binding Hamiltonians and direct calculations of real-space spectral functions for systems exceeding one billion lattice sites. Using this approach, we investigate three-dimensional non-Hermitian higher-order topological insulators with with structured real-space geometries. The unprecedented system size enables direct access to the macroscopic regime and allows corner-mode spectral responses to be resolved in genuinely three-dimensional systems.By tuning the loss strength, we identify distinct in-gap corner modes across weak- and strong-loss regimes.Our results establish tensor-network algorithms as a powerful strategy to perform real-space spectral calculations in exceptionally large non-Hermitian systems.

20.
arXiv (CS.LG) 2026-06-15

Neural ARFIMA model for forecasting BRIC exchange rates with long memory

arXiv:2509.06697v3 Announce Type: replace-cross Abstract: Exchange rate forecasting remains a challenging problem, particularly for emerging economies, where the observed time series exhibit pronounced long-memory dependence, nonlinear dynamics, and sensitivity to macro-financial drivers. Classical models such as ARFIMA capture long-range persistence but fail to adequately represent nonlinear relationships, while modern machine learning approaches often neglect the underlying long-memory structure in macroeconomic series. To address this gap, we propose a Neural AutoRegressive Fractionally Integrated Moving Average (NARFIMA) model that integrates ARFIMA-based long-memory modeling with neural networks for nonlinear function approximation, while incorporating exogenous macroeconomic and uncertainty indicators. The framework provides a unified approach for capturing persistence, nonlinear dynamics, and external shocks. We establish asymptotic stationarity of the NARFIMA process and develop conformal prediction intervals for distribution-free uncertainty quantification. Empirical results for BRIC exchange rates show that NARFIMA consistently outperforms a broad range of forecasting benchmarks across multiple horizons, underscoring the importance of explicitly modeling long-memory dependence in exchange rate dynamics. The `narfima' R package provides an implementation of our approach.

21.
bioRxiv (Bioinfo) 2026-06-12

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.

22.
medRxiv (Medicine) 2026-06-16

Using visual biofeedback to reduce step length error at fast walking speeds is feasible after stroke

Background and Purpose: Walking after stroke is often characterized by persistent biomechanical impairments and reduced walking capacity. While visual biofeedback can improve gait mechanics and fast walking can enhance capacity, it is unclear whether individuals post-stroke can effectively use biofeedback at higher walking speeds to address both deficits simultaneously. This study examined the effects of walking speed on the ability of participants with chronic stroke to reduce step length (SL) errors using visual biofeedback. Methods: Sixteen individuals with chronic stroke walked on a treadmill at slow, self-selected, and fast speeds with and without visual SL biofeedback. Absolute SL error relative to individualized targets was calculated for paretic and non-paretic limbs. Linear mixed-effects models with piecewise linear splines assessed the effects of speed, limb, and feedback condition. Post hoc comparisons were performed for significant interactions. Results: At lower speeds, increasing speed reduced SL error in both limbs (p < 0.001). At higher speeds, the effects of speed were dependent on limb and condition (p < 0.001). Paretic SL error increased with speed without feedback but remained stable with feedback (p < 0.001). Non-paretic SL error decreased with speed regardless of condition. SL error was greater in the paretic limb overall (p < 0.001). Discussion and Conclusions: Fast walking alone did not reduce paretic SL errors. Participants with chronic stroke can effectively use visual biofeedback to reduce paretic SL errors at higher speeds, supporting its integration into high-intensity gait training to simultaneously treat biomechanical impairments and walking capacity deficits after stroke.

23.
arXiv (CS.AI) 2026-06-24

DeepBD: A Grounded Agentic Workflow for Variant Prioritization and Diagnosis of Genetic Birth Defects

arXiv:2606.24779v1 Announce Type: cross Abstract: Birth defects are a major cause of fetal loss, neonatal morbidity and long-term disability. In the subset with suspected genetic etiologies, exome and genome sequencing have moved many cases from variant detection to post-sequencing interpretation: clinicians must rank patient-specific candidate variants under incomplete fetal or infant phenotypes and heterogeneous evidence from population genetics, variant-effect prediction, gene-disease validity, phenotype ontologies, cellular and pathway context, protein structure and clinical literature. We present DeepBD, a grounded agentic workflow for variant prioritization and diagnostic interpretation of genetic birth defects. DeepBD organizes the workflow into LLM-assisted case structuring, a pretrained evidence engine, specialist evidence modules and a grounded diagnostic review layer. The evidence engine learns patient-specific variant scores from structured rule evidence, sequence and variant-effect representations and phenotype-conditioned biological context, whereas specialist modules and the agentic layer provide tool-based refinement, candidate-pool review and diagnosis-oriented synthesis from ranked candidates. Developed using an in-house fetal and infant cohort comprising 18,622 cases, DeepBD achieved Recall@1/3/5/10 of 0.658/0.882/0.912/0.929 on an internal held-out solved-case benchmark, outperforming standalone Exomiser, DeepRare and prompted LLM reranking baselines evaluated on Exomiser-derived top-20 candidate variants. Ablation and overlap analyses show that rule evidence, mechanistic context, and specialist refinement provide complementary signals. These findings support a grounded agentic workflow that separates evidence integration, tool-based refinement, and LLM-assisted diagnostic review for retrospective variant prioritization in genetic birth defects.

24.
arXiv (CS.CL) 2026-06-24

ParaPairAudioBench: Paralinguistic Pairwise Audio Benchmark for LALM-as-a-Judge

Large Audio-Language Models (LALMs) have been widely used as judge models for the automatic evaluation of generated speech. However, prior approaches predominantly focus on holistic naturalness, leaving fine-grained paralinguistic distinctions underexplored. We introduce ParaPairAudioBench, a pairwise benchmark of 5,175 audio pairs across five paralinguistic dimensions: Style, Rate, Emphasis, Age, and Gender. Our experiments show that current LALM judges still lag behind human judgments by 32%p on average and exhibit severe calibration failures, particularly in Tie cases where the correct decision is to abstain. To further analyze lexical versus acoustic reliance, the benchmark includes both same-transcript and cross-transcript conditions. ParaPairAudioBench enables multi-dimensional, calibration-aware assessment of the reliability of LALM-as-a-Judge for paralinguistic speech evaluation.

25.
arXiv (math.PR) 2026-06-24

Autoregressive Processes on Riemannian Manifolds

arXiv:2606.24771v1 Announce Type: cross Abstract: This paper introduces a Riemannian autoregressive (R-AR) model of order one, generalising classical discrete-time stochastic processes to manifold-valued data. The model is based on two parameters, a parameter $\mu$ representing the intrinsic central tendency as the Fréchet mean and an autoregressive parameter $\phi$ controlling the stationarity and ergodic properties. Due to the inherent dependence structure of the R-AR process, the estimation procedure for these parameters necessitates new asymptotic results for dependent processes on manifolds. Thus, we establish a strong law of large numbers for the sample Fréchet mean set of ergodic Markov chains in proper metric spaces. By proving this general consistency result, we move beyond the limitations of classical i.i.d. theory to provide the mathematical foundation required for the strong consistency of our proposed estimators. The framework is validated through numerical simulations in the hyperbolic plane and an application to aerosol size distributions on the Fisher-Rao manifold, demonstrating how the proposed model can characterise mean-reverting dynamics in nonlinear geometries.