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01.
arXiv (CS.LG) 2026-06-17

Performance-Driven Environment Abstraction with Multi-Timescale Learning

arXiv:2606.17377v1 Announce Type: new Abstract: We study performance-driven environment abstraction for decision-making in large Markov decision processes. Rather than preserving geometric or topological structure, we seek abstractions that directly optimize decision quality. We model abstraction as a controlled approximation obtained by aggregating the state space and enforcing a shared action distribution within each aggregated state. For a fixed partition, we establish a performance guarantee that separates value-function approximation error from the loss introduced by action sharing. Guided by this analysis, we develop a multi-timescale reinforcement learning framework that jointly adapts the policy and a tree-structured environment abstraction. The resulting algorithm refines and coarsens regions of the state space based on Q-value discrepancies, balancing performance against abstraction size and complexity. Empirical results demonstrate substantial state compression, improved sample efficiency, and faster replanning compared to actor-critic baselines.

02.
arXiv (math.PR) 2026-06-17

Time and Killed Resolvents in Reflected Optimal Stopping with a Max Payoff

arXiv:2606.18214v1 Announce Type: cross Abstract: We study infinite-horizon optimal stopping for normally reflected two-dimensional diffusions in the positive quadrant with max payoff \(G(x_1,x_2)=x_1\vee\alpha x_2\). The non-smooth payoff produces a singular stopping-gain measure on the kink set \(\Delta=\{x_1=\alpha x_2\}\). We prove $\displaystyle \Gamma^\Delta(dx) = -\frac{n^\top a(x)n}{2\sqrt{1+\alpha^2}}\,\sigma_\Delta(dx)$, with $n=(1,-\alpha)$, so the diagonal component is non-positive and strictly negative under local ellipticity. This implies that every interior kink point lies in the continuation region. We further show that the correct value representation uses the resolvent killed at first entry into the stopping set, $\displaystyle V=G-R_r^{\mathcal C}\Gamma$, and give a closed-form reflected Brownian counter-example showing that the unrestricted reflected resolvent is generally wrong. A reflected Brownian benchmark and numerical experiments illustrate the local-time, resolvent-gap, and diagonal-avoidance mechanisms.

03.
medRxiv (Medicine) 2026-06-17

Characterizing the genetic basis of Cardio-Renal-Metabolic multimorbidity using multivariate genomic modelling

Cardio-renal-metabolic multimorbidity (CRMM) encompasses interrelated conditions affecting the heart, kidneys, and metabolic systems. Although the genetics of individual components are well studied, their shared architecture remains unclear. Here, we performed the largest multi-ancestry multivariate GWAS of CRMM across seven biobanks, including individuals of European (EUR; neff = 353,130), African (AFR; neff = 75,436), and East Asian (EAS; neff = 164,373) ancestry. We identified 287 lead loci in EUR, 30 in AFR, and 202 in EAS. Cross-ancestry analyses revealed ancestry-specific signals and 24 shared loci mapping to FTO and TCF7L2. Drug-repurposing highlighted candidates used for type 2 diabetes and hypertension. Mendelian randomization supported causal links with diverse diseases, while polygenic risk scores showed improved prediction across ancestries. Collectively, these findings advance understanding of CRMM genetics and inform precision medicine.

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

AGDN: Learning to Solve Traveling Salesman Problem with Anisotropic Graph Diffusion Network

arXiv:2606.19185v1 Announce Type: new Abstract: The Traveling Salesman Problem (TSP) is a cornerstone of combinatorial optimization and arises in many practical scenarios. Although graph-based learning approaches have been explored for TSP, the question of how to exploit graph structure more effectively remains open. We present the Anisotropic Graph Diffusion Network (AGDN), a new Graph Neural Network framework designed to solve TSP. Our method tackles two central difficulties: (1) the lack of informative topological prior in fully connected TSP graphs, and (2) losing connected nodes in the optimal solution after the commonly used graph sparsification techniques. To overcome these issues, we construct a MixScore transition matrix that merges node similarity with pairwise distance, and we develop an anisotropic graph diffusion strategy that supports efficient information exchange across multiple hops. Comprehensive experiments spanning diverse instance sizes and node distributions show that AGDN consistently outperforms existing methods while keeping computation time competitive. Furthermore, AGDN generalizes well to problem sizes and distributions beyond those seen during training. The implementation is publicly available at: https://github.com/LabRAI/AGDN.

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

Revisiting LLM Adaptation for 3D CT Report Generation: A Study of Scaling and Diagnostic Priors

Recent advances in multimodal learning, including large language models (LLMs) and vision-language models (VLMs), have demonstrated strong adaptability to natural images. However, extending their use to the medical domain, particularly for volumetric (3D) images, is challenging due to high computational complexity, volumetric dependencies and the semantic gap between visual features and clinical terminology. Naively fine-tuning LLMs on limited medical data often leads to overfitting and clinical hallucination, where linguistic fluency is prioritized over clinical factuality. In this study, we investigate parameter-efficient adaptation strategies for volumetric CT report generation and introduce RAD3D-Prefix, a lightweight diagnostic-prior conditioning framework that minimizes the need for extensive parameter training. This module integrates image embeddings with multi-label diagnostic classification logits, preserving critical clinical details while bridging the semantic gap. By keeping the LLM frozen, our method requires minimal trainable parameters and mitigates the risk of overfitting on small, domain-specific datasets. Through a systematic study spanning LLMs from 96.1M to 1.6B parameters, we find that fine-tuning is most beneficial for smaller LLMs, whereas freezing larger (~1B+ LLMs and training only lightweight projection layers provides a superior trade-off between performance, generalization, and computational efficiency. Across multiple automatic metrics and a clinical reader study, RAD3D-Prefix outperforms comparable parameter-efficient baselines and demonstrates strong out-of-domain generalization while using substantially fewer trainable parameters than fully fine-tuned alternatives.

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

Spectral Retrieval-Augmented Time-Series Forecasting

arXiv:2606.19412v1 Announce Type: new Abstract: Time series forecasting leverages historical patterns to predict future values, but traditional methods face challenges when dealing with complex, non-stationary patterns that are difficult to memorize during training. Retrieval-augmented approaches have emerged as promising solutions by retrieving similar historical patterns to enhance predictions. However, existing retrieval methods suffer from two fundamental limitations: spectral blindness, which overlooks critical frequency-domain characteristics that capture underlying periodic structures, and temporal recency, which treats all historical data equally without emphasizing recent, more relevant patterns. In this paper, we propose SpecReTF, a novel retrieval method that addresses these issues by converting time series into windowed frequency representations, measuring similarity with a combined metric that captures both amplitude and phase information. To balance recency and historical context, we apply an exponential moving average weighting scheme that emphasizes recent windows. Extensive experiments on benchmark datasets demonstrate that SpecReTF outperforms time-domain retrieval methods, achieving superior forecasting accuracy across diverse, non-stationary time series.

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

SEDULity: A Proof-of-Learning Framework for Distributed and Secure Blockchains with Efficient Useful Work

arXiv:2512.13666v2 Announce Type: replace-cross Abstract: The security and decentralization of Proof-of-Work (PoW) have been well-tested in existing blockchain systems. However, its tremendous energy waste has raised concerns about sustainability. Proof-of-Useful-Work (PoUW) aims to redirect the meaningless computation to meaningful tasks such as solving machine learning (ML) problems, giving rise to the branch of Proof-of-Learning (PoL). While previous studies have proposed various PoLs, they all, to some degree, suffer from security, decentralization, or efficiency issues. In this paper, we propose a PoL framework that trains ML models efficiently while maintaining blockchain security in a fully distributed manner. We name the framework SEDULity, which stands for a Secure, Efficient, Distributed, and Useful Learning-based blockchain system. Specifically, we encode the template block into the training process and design a useful function that is difficult to solve but relatively easy to verify, as a substitute for the PoW puzzle. We show that our framework is distributed, secure, and efficiently trains ML models. We further demonstrate that the proposed PoL framework can be extended to other types of useful work and design an incentive mechanism to incentivize task verification. We show theoretically that a rational miner is incentivized to train fully honestly with well-designed system parameters. Finally, we present simulation results to demonstrate the performance of our framework and validate our analysis.

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

From Frames to Temporal Graphs: In-Context Egocentric Action Recognition with Vision-Language Models

Action reasoning in egocentric video requires capturing fine-grained transitions of hand-object interactions, a task where general-purpose Vision-Language Models (VLMs) often struggle when operating directly on raw pixels. We propose to decouple visual perception from symbolic reasoning by converting videos into Temporal Action Graphs. In a multi-stage prompting pipeline, we first generate dense natural language narratives over short temporal windows as a semantic bottleneck, then formalize them into structured, open-vocabulary graph representations. On the EGTEA and Epic-Kitchens-100 datasets, the symbolic representation unlocks efficient in-context learning: few-shot graph demonstrations yield substantial accuracy gains over zero-shot frame and graph-based inference alike. Even in the zero-shot setting, graph-based reasoning remains competitive with pixel-based inference despite potential pretraining contamination favoring the latter. Across 11 open-weight VLMs from 6 model families ranging from 2B to 235B parameters, our findings indicate that current VLMs are more effective as symbolic reasoners than as direct visual observers. By projecting video into the language domain, we provide a scalable, fine-tuning-free alternative to end-to-end approaches that better leverages these models' latent reasoning strengths. The code will be made public.

09.
Science (Express) 2026-05-28

A Hormone Cell Atlas maps the human endocrine system at cellular resolution | Science

作者: 未知作者

Hormones act across tissues and organs to coordinate physiological functions. Drawing inspiration from the Human Cell Atlas, we analyzed expression of 379 hormone and receptor genes in a transcriptomic dataset comprising 14 million single cells and nuclei across 47 human tissues. Using hormone2cell, we mapped putative hormone-producing and hormone-receiving cell types, defining tissue-specific and cross-tissue endocrine signatures. We predicted non-classical sites of hormone expression, including secretin in plasmacytoid dendritic cells, inferred convergent hormone action and endocrine feedback loops, and implicated cell populations in monogenic endocrine disorders. In a cross-tissue integration of adipocyte datasets, we uncovered dynamic endocrine programs across depots, within adipocyte subtypes and through adipogenic differentiation. Cumulatively, the Hormone Cell Atlas ( hormonecellatlas.org.uk ) provides a comprehensive framework for dissecting hormonal impact on health and disease.

10.
arXiv (CS.AI) 2026-06-12

Intelligence as Managed Autonomy: Failure, Escalation, and Governance for Agentic AI Systems

arXiv:2605.27628v2 Announce Type: replace Abstract: As autonomous and agentic AI systems scale in robotic and human-machine environments, managing hallucination and persistent but unjustified action remains an open challenge. Rather than attributing these failures solely to model or alignment limitations, this paper explores the architectural vulnerability of unbounded autonomy - the presumption that an agent should continue operating regardless of rising uncertainty. It introduces a theory of managed autonomy that defines intelligent behavior through the formal capacity to detect epistemic drift, suspend reasoning, attempt recovery, and ultimately surrender control when reliability diminishes. We instantiate this theory via the SMARt (Self-Managing Multi-tier Autonomous Reasoning with Regulated/Revoked transitions) model, a four-layer framework featuring Stable, Meta-cognitive, Assisted, and Regulated states. By developing a timed, guarded Petri net formulation, we establish theoretically bounded properties for the system, demonstrating how architecture can formally mandate escalation, constrain invalid outputs, and ensure governance reachability under specified conditions. We further analyze how incorporating domain-specific trigger sets across varied operational settings (e.g., healthcare, robotics, etc.) can systematically preserve safety, assuming completeness and soundness criteria are met. Because these triggers are designed to be adaptive, the SMARt model accommodates the safe, controlled expansion of an agent's operational scope over time. We conclude that formalizing failure management within the autonomy lifecycle is a crucial step toward realizing reliable and governed artificial intelligence.

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

MobileFineTuner: A Mobile-Native Framework for On-Device LLM Fine-Tuning in Real-World Embedded AI Applications

arXiv:2512.08211v2 Announce Type: replace Abstract: Large language models (LLMs) are moving from cloud-centric services toward on-device embedded AI, where models interact with private, longitudinal signals sensed from users and their physical environments. Mobile phones are a natural platform for such applications because they are continuously carried by users, connected to wearable sensors, and deeply integrated with daily mobile applications. However, practical LLM fine-tuning on commodity phones remains difficult. Existing fine-tuning frameworks are largely Python-based and server-oriented, making them hard to deploy inside mobile applications. We present MobileFineTuner, a mobile-native open-source framework for end-to-end LLM fine-tuning on commodity mobile phones. MobileFineTuner is implemented in C++ and provides a reusable training stack. To make fine-tuning feasible under mobile resource constraints, MobileFineTuner integrates a resource-aware training runtime with memory-efficient attention, activation checkpointing, gradient accumulation, parameter sharding, and energy-aware scheduling. We evaluate MobileFineTuner on real mobile phones using GPT-2, Gemma 3, and Qwen2.5 models across multiple fine-tuning tasks. The results show that MobileFineTuner reproduces standard Full-FT and LoRA fine-tuning behavior, substantially reduces memory pressure and improves executability on memory-constrained phones. We further demonstrate MobileFineTuner through a private campus health-agent application, where a local LLM is fine-tuned on user-specific wearable-sensing records to provide more personalized responses while keeping raw records on the phone. These results establish MobileFineTuner as a practical toolkit for studying and building on-device LLM fine-tuning applications in embedded AI and sensing systems.

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

PolicyGuard: Towards Test-time and Step-level Adversary Defense for Reinforcement Learning Agent

arXiv:2606.12896v1 Announce Type: cross Abstract: While real-world applications of reinforcement learning (RL) are becoming increasingly popular, the security of RL systems deserve more attention and exploration. In particular, recent work has revealed that RL agents are vulnerable to backdoor attacks, where a victim agent behaves normally under standard conditions but executes malicious actions when a specific trigger is activated. Existing backdoor defenses for RL either require access to the agent's internal parameters, operate only at the model or trajectory level, or are limited to specific attack types. To ensure the security of RL agents, we propose \texttt{PolicyGuard}, a test-time step-level backdoor defense which leverages Gaussian Process (GP) posterior variance and adapts pseudo trajectories to enable uncertainty computation for individual time step. Besides, we also provide theoretical foundations to explain the efficacy of GP posterior variance. Extensive experiments across seven RL games demonstrate that PolicyGuard achieves state-of-the-art detection performance in most cases, with average AUROC of 0.856 for perturbation-based attacks and 0.859 for adversary-agent attacks.

13.
arXiv (CS.LG) 2026-06-11

On Regret Bounds of Thompson Sampling for Bayesian Optimization

arXiv:2603.09276v2 Announce Type: replace-cross Abstract: We study a widely used Bayesian optimization method, Gaussian process Thompson sampling (GP-TS), under the assumption that the objective function is a sample path from a GP. Compared with the GP upper confidence bound (GP-UCB) with established high-probability and expected regret bounds, most analyses of GP-TS have been limited to expected regret. Moreover, whether the recent analyses of GP-UCB for the lenient regret and the improved cumulative regret upper bound can be applied to GP-TS remains unclear. To fill these gaps, this paper shows several regret bounds: (i) a regret lower bound for GP-TS, which implies that GP-TS suffers from a polynomial dependence on $1/\delta$ with probability $\delta$, (ii) an upper bound of the second moment of cumulative regret, which directly suggests an improved regret upper bound on $\delta$, (iii) expected lenient regret upper bounds, and (iv) an improved cumulative regret upper bound on the time horizon $T$. Along the way, we provide several useful lemmas, including a relaxation of the necessary condition from recent analysis to obtain improved regret upper bounds on $T$.

14.
arXiv (math.PR) 2026-06-16

Exact Label Recovery in Euclidean Random Graphs

arXiv:2407.11163v3 Announce Type: replace-cross Abstract: In this paper, we propose a family of label recovery problems on weighted Euclidean random graphs. The vertices of a graph are embedded in $\mathbb{R}^d$ according to a Poisson point process, and are assigned to a discrete community label. Our goal is to infer the vertex labels, given edge weights whose distributions depend on the vertex labels as well as their geometric positions. Our general model provides a geometric extension of popular graph and matrix problems, including submatrix localization and $\mathbb{Z}_2$-synchronization, and includes the Geometric Stochastic Block Model (proposed by Sankararaman and Baccelli) as a special case. We study the fundamental limits of exact recovery of the vertex labels. Under a mild distinctness of distributions assumption, we determine the information-theoretic threshold for exact label recovery, in terms of a Chernoff-Hellinger divergence criterion. Impossibility of recovery below the threshold is proven by a unified analysis using a Cramér lower bound. Achievability above the threshold is proven via an efficient two-phase algorithm, where the first phase computes an almost-exact labeling through a local propagation scheme, while the second phase refines the labels. The information-theoretic threshold is dictated by the performance of the so-called genie estimator, which decodes the label of a single vertex given all the other labels. This shows that our proposed models exhibit the local-to-global amplification phenomenon.

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

FUSE: Quantifying Uncertainty in Vision-Language Models by Bayesian Fusing Epistemic and Aleatoric Uncertainty

Vision-language models (VLMs) are playing an increasingly important role across multiple domains. In many applications, such as robotics, it is crucial to quantify the uncertainty in the output of these models. } We develop FUSE, a probabilistic framework for capturing two complementary sources of uncertainty in vision-language modeling: (i) aleatoric embedding-level uncertainty derived from input data vision-language ambiguity, and (ii) epistemic model-level uncertainty estimated from the semantic response diversity of VLMs. Our approach formulates a Bayesian fusion mechanism that analytically combines these uncertainty sources to produce a scalar measure of uncertainty. This measure can be used to reliably predict the model's output correctness for downstream applications. We demonstrate that our method outperforms baselines and achieves SOTA uncertainty calibration.

16.
arXiv (quant-ph) 2026-06-15

Quantum Simulation of Spin-Dependent Electron Transfer in a Synthetic Chiral Lattice with a Trapped Ion

arXiv:2606.13930v1 Announce Type: new Abstract: Electron transfer through chiral structures can exhibit spin asymmetry, known as the chiral-induced spin selectivity effect, whose microscopic origin remains an open question. While path-interference within the chiral moiety has been proposed as a key mechanism, its experimental validation requires precise and versatile tunability of system parameters. Here we implement a programmable quantum simulation of spin-dependent electron transfer in a donor–chiral-bridge–acceptor model using a trapped ion. The bridge is encoded in internal states of the ion with tunable nearest- and next-nearest-neighbor couplings, while donor and acceptor states are coupled via a spectator bosonic motional mode. We observe spin-dependent interference within the bridge, and further reveal spin-dependence in donor-to-acceptor transfer dynamics, controlled by amplitude and phase of the coupling parameter. Our results identify interference among spin-dependent pathways as a microscopic origin of spin-dependent transfer, and open a route toward quantum simulations of complex chiral lattices with multi-level and bosonic degrees of freedom.

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

Beyond Static Endpoints: Tool Programs as an Interface for Flexible Agentic Web Services

arXiv:2606.19992v1 Announce Type: cross Abstract: In the agentic web era, LLM-based agents increasingly invoke web services as tools, yet most interfaces remain static endpoints that poorly express long-horizon workflows with loops, conditionals, joins, and retries. We present ToolPro, which represents an agent's tool intent as an executable tool program that compactly encodes multi-step service interactions with explicit effect types. ToolPro combines constraint-guided program construction, effect-aware replay for exactly-once state-modifying calls, and a profile-driven policy that decides when program execution outperforms stepwise calling. We instantiate ToolPro over MCP-style services with WebAssembly sandboxing and evaluate it on diverse workflows of real-world applications. ToolPro reduces end-to-end latency by up to 53.4\% and client-side traffic by up to 96.1\%, with larger gains under higher network latency and workflow complexity.

18.
arXiv (quant-ph) 2026-06-12

Candidate overtone shear horizontal SAW resonators in thin-film lithium niobate for intermodal acousto-optic modulation

arXiv:2606.12853v1 Announce Type: cross Abstract: The merits of thin-film surface acoustic wave (SAW) devices are pivotal to develop the high-performance intermodal acousto-optic modulators. In this work, we have proposed shear-horizontal (SH) SAW resonators for anticipated intermodal acousto-optic modulation on the thin-film lithium niobate platform. Through optimization of the cut angle of LN films, the SAW wavelength, and the thickness of interdigital transducer (IDT) electrodes, the calculated acousto-optic overlap factors utilizing SH0 modes are improved by more than an order of magnitude compared with those of Rayleigh modes. Furthermore, we have fabricated and characterized three kinds of proof-of-principle SH0 mode devices without/with grating reflectors. The electromechanical coupling coefficients (keff^2) and quality factors (Q) in the overtone resonators with grating reflectors are systematically evaluated, featuring the highest Q of 843 with the compromised keff^2 of 0.96%-4.72%. The results reveal that the temperature coefficients of frequency (TCF) of Rayleigh modes vary across various overtones, whereas the SH0 modes exhibit TCFs in the range of 32.3-68.9 ppm/C. Our fabricated SH0-mode overtone resonators demonstrate the capability of operating at power levels up to 29 dBm without electrode damage, offering a promising paradigm for robust and high-efficiency intermodal acousto-optic modulators with potential applications in integrated optical signal processing, microwave photonics,and quantum information technologies.

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

Non-Gaussian Phase Transition and Cascade of Instabilities in the Dissipative Quantum Rabi Model

arXiv:2507.07092v3 Announce Type: replace Abstract: The open quantum Rabi model describes a two-level system coupled to a harmonic oscillator. A Gaussian phase transition for the nonequilibrium steady states has been predicted when the bosonic mode is soft and subject to damping. We show that oscillator dephasing is a relevant perturbation, which leads to a non-Gaussian phase transition and an intriguing cascade of instabilities for $k$-th order bosonic operators, as well as a jump in the steady-state qubit polarization. For the soft-mode limit, the equations of motion form a closed hierarchy and spectral properties can be efficiently studied. To this purpose, we establish a fruitful connection to non-Hermitian Hamiltonians. The results for the phase diagram, stability boundaries, and relevant observables are based on mean-field analysis, exact diagonalization, perturbation theory, and Keldysh field theory.

20.
arXiv (quant-ph) 2026-06-17

Full-state information-disturbance tradeoff for direction estimation with antiparallel spin-coherent pairs

arXiv:2606.18040v1 Announce Type: new Abstract: We determine the optimal information–disturbance tradeoff for estimating an unknown spatial direction encoded in two antiparallel spins. Rotational covariance reduces the optimization over all instruments to a finite-dimensional Choi problem: a positive seed operator obeys one trace constraint for each irreducible sector of the input representation, while both the directional score and the operation fidelity are linear functionals of this seed. For two antiparallel spin-$1/2$ particles, whose physical representation decomposes as $0\oplus1$, we derive the two-multiplier dual problem and characterize the optimal instrument from the kernel vectors of the dual slack operator. The optimal operation is a covariant filter with scalar–vector coherence and is generally not a convex interpolation between the identity channel and a measure-and-reprepare strategy. At maximum information we recover the Gisin–Popescu score, but the least disturbing output state is optimized independently, giving a smaller disturbance than both the parallel-spin benchmark and antiparallel measure-and-reprepare. We also formulate the parallel benchmark and, as a central extension of the method, treat antiparallel spin-coherent states of arbitrary spin $j$. In this case the signal coherently occupies all sectors $\ell=0,\ldots,2j$ of $j\otimes j$, the endpoint information is governed by nearest-neighbor sector coherences, and the endpoint disturbance is obtained from an explicit finite block-diagonal eigenvalue problem.

21.
PLOS Computational Biology 2026-06-01

Histology-informed spatial domain identification through multi-view graph convolutional networks

作者:

by Huihui Zhang, Jiaxing Chang, Zirong Li, Yue Sun, Pinli Hu, Haoxiu Wang, Hang Yang, Yonglin Ren, Xingtan Zhang, Zehua Chen, Kok Wai Wong, Haojing Shao Identifying spatial domains is crucial in spatial transcriptomics, yet effectively integrating gene expression, spatial location, and histology remains challenging. We present STESH, a Spatial Transcriptomics clustering method that combines Expression, Spatial information and Histology. STESH extracts histological features using a convolutional neural network and generates expression, histology, spatial, and collaborative convolution modules for a multi-view graph convolutional network with a decoder and attention mechanism. We evaluated STESH on multiple tissue types and technology platforms. STESH consistently outperformed ten state-of-the-art methods, achieving superior clustering accuracy with the highest scores in adjusted Rand index, normalized mutual information, and Fowlkes-Mallows index.

22.
bioRxiv (Bioinfo) 2026-06-16

DynamicDemiLog: A Single Sketch for Ultrafast Similarity, Frequency, and Cardinality Estimation

Probabilistic cardinality estimators (HyperLogLog), similarity sketches (MinHash), and frequency estimators (Count-Min Sketch) are fundamental approximate data structures that each target one primary problem. We present DynamicDemiLog (DDL), a sketch that unifies cardinality estimation, set similarity, containment, element frequency and composition in one tiny data structure built from a single pass over the input stream. Using an inverted index over 200,687 RefSeq sketches (159,567 organisms), DDL performs all-to-all sketch similarity comparison of the full database in 30 seconds (128 threads, indexed) - over 375x faster per query than Mash's brute-force all-to-all comparison of 91,282 sketches, or 31x faster without the index, at double the sketch resolution. DDL extends the LogLog register with a mantissa: each register stores a floating-point-encoded hash value consisting of an integer exponent (the leading-zero count) and a fractional mantissa (the sub-leading-zero bits), rather than the integer leading-zero count alone. This preserves enough hash information for meaningful register-by-register comparison - a property that standard 6-bit registers lack - while improving on LogLog's cardinality estimation machinery, including DynamicLogLog's early exit mask for high-throughput streaming. With a default 10 mantissa bits (16-bit registers, 2,048 buckets, 4 KB), DDL achieves a per-register false-match rate of 0.018% on unrelated random same-size sets (compared to 17.0% for LL6, a basic HyperLogLog implementation), enabling Weighted Kmer Identity (WKID), Average Nucleotide Identity (ANI), containment, and completeness estimation from register comparison alone. A 16-bit per-register observation counter provides element frequency information at trivial additional computation cost, and an additional byte tracks element composition (GC content, for biological data). Furthermore, DDL's high-specificity registers enable an inverted index structure (DDLIndex) that answers similarity queries against a database of N sketches in O(B + M) time, where M is the number of matching index entries, compared to O(NxB) for pairwise comparison.

23.
arXiv (math.PR) 2026-06-15

Trivariate Hypergeometric Series Formulas for Pure Partition Functions of Multiple $3$-SLE$_\kappa$

作者:

arXiv:2606.14038v1 Announce Type: new Abstract: Pure partition functions of multiple SLE are characterized by null-state partial differential equations, Möbius covariance, and boundary asymptotics. After quotienting by Möbius covariance, the case of three curves is the first genuinely multivariable one: the moduli space has three independent variables, naturally represented by the three unoriented cross-ratios of the three pairs of links. We solve this Möbius-normalized three-variable problem for the two basic link-pattern types of multiple \(3\)-SLE\(_\kappa\), namely the rainbow and neighbor patterns. Writing \(\beta=4/\kappa\), we construct explicit trivariate hypergeometric-series normal forms and identify them with the corresponding pure partition functions for all \(\beta>1/2\) in the rainbow case and all \(\beta\ge2/3\) in the neighbor case. Equivalently, these ranges are \(\kappa\in(0,8)\) and \(\kappa\in(0,6]\), respectively. The proof is analytic. The null-state PDEs and Möbius covariance yield recursion relations for the trivariate coefficient arrays. In the rainbow case, coefficient estimates give convergence and boundary regularity on the closed cube. In the neighbor case, Pfaff systems continue the local power series to a neighborhood of \([0,1)^3\), while side-face equations, regular normal estimates, and corner propagation give continuity on \([0,1]^3\) for \(\beta\ge2/3\). The endpoint \(\beta=2/3\), corresponding to \(\kappa=6\), requires a logarithmic normal term. The two-dimensional boundary degenerations are classical Appell \(F_1\) and Horn \(G_2\) functions. The probabilistic identification uses SLE martingale arguments and Itô calculus, together with positivity and boundary regularity. We also discuss boundary degenerations, including heuristic connections with boundary Green's functions.

24.
arXiv (CS.CL) 2026-06-11

Which Speech Representation Better Matches Text-Native Reasoning? A Study of Speech-Text Alignment on Frame Rate and Representation

Spoken dialogue models typically start from text LLM backbones, yet reasoning often degrades when conditioning on speech instead of text. We attribute part of this modality gap to a temporal-granularity mismatch: speech tokens are temporally redundant and far longer than text under matched semantics, diluting per-token semantic density and weakening text-native reasoning dynamics. We study speech token design as a representation selection problem and sweep frame rates under a frozen LLM backbone with a fixed information rate. To make low frame rates feasible, we introduce factorized FSQ and a lightweight non-autoregressive audio LM head, scaling capacity to nearly 300\,bits/frame without sacrificing efficient prediction. With the bottleneck removed, we sweep frame rates (50$\rightarrow$2.08\,Hz) and alignment depth, and observe a consistent best regime for speech QA at 4.17\,Hz with intermediate-layer representation alignment.

25.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

作者:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.