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

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

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

02.
arXiv (CS.CV) 2026-06-11

Echoes of the Prior: A Computational Phenomenology of Forgetting

Memory is not merely the storage of data; it is the scaffolding of reality. When biological memory fades, the world does not simply turn black; it regresses into an unrecognizable chaos. Echoes of the Prior is an interactive installation that attempts to visualize this subjective phenomenology of forgetting. By inducing controlled synaptic decay within a Feed-Forward 3D Reconstruction model, we create an artistic analogy for the erosion of the brain's predictive priors. We position the Neural Network not as a tool for engineering, but as a cognitive proxy - a silicon brain whose structural degeneration evokes the disorienting, poetic, and terrifying experience of losing one's grip on the world. Ultimately, we offer this framework as a catalyst, inviting the wider community to explore the uncharted potential of neuromorphic aesthetics in visualizing the fragility of intelligence. Interactive demo see https://decart-4d.github.io/.

03.
arXiv (CS.AI) 2026-06-17

Optimism Stabilizes Thompson Sampling for Adaptive Inference

arXiv:2602.06014v2 Announce Type: replace-cross Abstract: Thompson sampling (TS) is widely used for stochastic multi-armed bandits, yet its inferential properties under adaptive data collection are subtle. Classical asymptotic theory for sample means can fail because arm-specific sample sizes are random and coupled with the rewards through the action-selection rule. We study adaptive inference for Thompson sampling with Gaussian randomized indices in $K$-armed stochastic bandits with independent sub-Gaussian reward noises, and identify optimism as a key mechanism for restoring stability, meaning that each arm's pull count concentrates around a deterministic scale. This stability yields asymptotically valid Wald inference despite adaptive sampling. First, we prove that variance-inflated TS is stable for any $K \ge 2$, including the challenging regime where multiple arms are optimal, with asymptotically uniform allocation over optimal arms and sharp logarithmic pull-count asymptotics for suboptimal arms. This resolves the $K$-armed extension question raised by \citet{halder2025stable}, using new winner-map and Lyapunov-drift techniques to control allocation among multiple optimal arms. Second, we analyze an alternative optimistic modification that keeps the Gaussian index variance unchanged but adds an explicit mean bonus to the index center, and establish a similar stability conclusion. In summary, suitably implemented optimism stabilizes Thompson sampling and enables asymptotically valid Wald inference in multi-armed bandits, while incurring only a mild additional regret cost.

04.
arXiv (CS.AI) 2026-06-11

The Art of Interrogation: Consistency Amplifies Factuality in Spatial Reasoning

arXiv:2606.11918v1 Announce Type: new Abstract: Current Large Reasoning Models (LRMs) exhibit remarkable general capabilities but significantly underperform in spatial reasoning tasks. Existing approaches treat this gap as a knowledge deficit, relying on supervised fine-tuning (SFT) to ingest labeled spatial data from external vision sources or synthetic engines. In contrast, we argue that for many tasks, spatial reasoning capabilities are already present in pre-trained LRMs but require alignment through logical coherence under geometric 2D and 3D constraints. In this work, we propose a self-supervised reinforcement learning (RL) framework that targets the internal reasoning process without requiring ground-truth annotations. By formalizing the notion of consistency verifiers – reward functions that check for geometric and semantic consistency under transformations – we demonstrate that models can improve their spatial reasoning abilities. We use both image transformations, like flipping, and textual transformations, like swapping the order of objects in the question, and propose a new optimal transport-based RL strategy, OT-GRPO, which is a minimal-matching variant of group relative policy optimization tailored to pairwise verifiers. We show that this label-free consistency training approaches the accuracy of models trained with ground-truth supervision and achieves similar generalization across diverse tasks and data domains.

05.
arXiv (CS.CL) 2026-06-15

Beyond Perplexity: UTF-8 Validity in Byte-aware Language Models

Byte-level tokenization enables language models to handle any Unicode input, but models can generate invalid UTF-8 sequences when encountering rare or unseen characters. We investigate the relationship between training scale and UTF-8 generation reliability with a 355M parameter model trained on 80B tokens from a balanced multilingual corpus of English, Japanese, Korean, and Chinese. We introduce multiple evaluation protocols that isolate UTF-8 structural validity from language modeling. UTF-8 validity convergence lags perplexity by a roughly a factor of two: perplexity stabilizes after 2.1B tokens, but UTF-8 validity requires 4.2B tokens. In context-free generation, rare characters achieve higher structural validity than common characters, suggesting over-specialization of frequent character representations. Through experiments, we observed that reliable UTF-8 generation is a distinct capability requiring evaluation beyond perplexity.

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

Variational Graph Neural Networks for Uncertainty Quantification in Inverse Problems

arXiv:2603.29515v2 Announce Type: replace Abstract: The increasingly wide use of deep machine learning techniques in computational mechanics has significantly accelerated simulations of problems that were considered unapproachable just a few years ago. However, in critical applications such as Digital Twins for engineering or medicine, fast responses are not enough; reliable results must also be provided. In certain cases, traditional deterministic methods may not be optimal as they do not provide a measure of confidence in their predictions or results, especially in inverse problems where the solution may not be unique or the initial data may not be entirely reliable due to the presence of noise, for instance. Classic deep neural networks also lack a clear measure to quantify the uncertainty of their predictions. In this work, we present a variational graph neural network (VGNN) architecture that integrates variational layers into its architecture to model the probability distribution of weights. Unlike computationally expensive full Bayesian networks, our approach strategically introduces variational layers exclusively in the decoder, allowing us to estimate cognitive uncertainty and statistical uncertainty at a relatively lower cost. In this work, we validate the proposed methodology in two cases of solid mechanics: the identification of the value of the elastic modulus with nonlinear distribution in a 2D elastic problem and the location and quantification of the loads applied to a 3D hyperelastic beam, in both cases using only the displacement field of each test as input data. The results show that the model not only recovers the physical parameters with high precision, but also provides confidence intervals consistent with the physics of the problem, as well as being able to locate the position of the applied load and estimate its value, giving a confidence interval for that experiment.

07.
Science (Express) 2026-04-16

Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) are widespread bacterial anti-phage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6 Å resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.

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

MeshPad: Interactive Sketch-Conditioned Artist-Reminiscent Mesh Generation and Editing

We introduce MeshPad, a generative approach that creates 3D meshes from sketch inputs. Building on recent advances in artist-reminiscent triangle mesh generation, our approach addresses the need for interactive mesh creation. To this end, we focus on enabling consistent edits by decomposing editing into 'deletion' of regions of a mesh, followed by 'addition' of new mesh geometry. Both operations are invoked by simple user edits of a sketch image, facilitating an iterative content creation process and enabling the construction of complex 3D meshes. Our approach is based on a triangle sequence-based mesh representation, exploiting a large Transformer model for mesh triangle addition and deletion. In order to perform edits interactively, we introduce a vertex-aligned speculative prediction strategy on top of our additive mesh generator. This speculator predicts multiple output tokens corresponding to a vertex, thus significantly reducing the computational cost of inference and accelerating the editing process, making it possible to execute each editing step in only a few seconds. Comprehensive experiments demonstrate that MeshPad outperforms state-of-the-art sketch-conditioned mesh generation methods, achieving more than 22% mesh quality improvement in Chamfer distance, and being preferred by 90% of participants in perceptual evaluations.

09.
arXiv (CS.AI) 2026-06-11

Sample-Efficient Hypergradient Estimation for Decentralized Bi-Level Reinforcement Learning

arXiv:2603.14867v4 Announce Type: replace-cross Abstract: Many strategic decision-making problems, such as environment design for warehouse robots, can be naturally formulated as bi-level reinforcement learning (RL), where a leader agent optimizes its objective while a follower solves a Markov decision process (MDP) conditioned on the leader's decisions. In many situations, a fundamental challenge arises when the leader cannot intervene in the follower's optimization process; it can only observe the optimization outcome. We address this decentralized setting by deriving the hypergradient of the leader's objective, i.e., the gradient of the leader's strategy that accounts for changes in the follower's optimal policy. Unlike prior hypergradient-based methods that require extensive data for repeated state visits or rely on gradient estimators whose complexity can increase substantially with the high-dimensional leader's decision space, we leverage the Boltzmann covariance trick to derive an alternative hypergradient formulation. This enables efficient hypergradient estimation solely from interaction samples, even when the leader's decision space is high-dimensional. Additionally, to our knowledge, this is the first method that enables hypergradient-based optimization for 2-player Markov games in decentralized settings. Experiments highlight the impact of hypergradient updates and demonstrate our method's effectiveness in both discrete and continuous state tasks.

11.
medRxiv (Medicine) 2026-06-16

Daily Healthy Eating Index (HEI-2020) scoring reveals diet quality patterns masked by aggregation

The Healthy Eating Index (HEI-2020) is conventionally computed by aggregating intake across days before scoring. Digital food logging enables an alternative: scoring each day and averaging daily scores. These methods are not equivalent. The HEI's density-based structure and component caps cause aggregation to inflate adequacy scores when intake is irregular. Using Food & You data, we show daily HEI correlates more strongly with microbiome diversity, and recommend co-reporting both metrics.

12.
arXiv (CS.LG) 2026-06-16

Bayesian Networks with Latent Time Embedding for Stage-Aware Causal Modeling of Alzheimer's Disease Progression

arXiv:2606.15784v1 Announce Type: new Abstract: Alzheimer's disease (AD) progression is often described through the amyloid-tau-neurodegeneration, or AT(N), cascade. However, most longitudinal models represent this cascade either as a fixed sequence of biomarkers or as a black-box forecasting task. This makes it difficult to determine when biologically guided biomarker relationships influence future regional pathology. In this study, we introduce Bayesian Networks with Latent Time Embedding (BN-LTE), a Bayesian structural framework for stage-aware modeling of AD progression. BN-LTE estimates disease pseudotime from baseline biomarker profiles and constrains directed dependencies according to biologically plausible AT(N) ordering. Posterior spline-varying structural equations are then used to link initial multimodal measurements with future annualized regional tau-PET change. Across repeated subject-disjoint evaluations using ADNI data, BN-LTE shows strong spatial reconstruction of tau progression compared with the included forecasting baselines. Beyond spatial reconstruction, BN-LTE recovers posterior stage-varying AT(N)-constrained effects and identifies a mid-pseudotime window of amyloid sensitivity. This window is supported by model-implied g-formula contrasts, root-adjusted AIPW, mechanism-sensitive ablations, and robustness analyses across spline and prior specifications. Overall, these findings position BN-LTE as a Bayesian structural framework for forecasting tau progression while examining stage-dependent AT(N)-cascade mechanisms in observational longitudinal neuroimaging data. Our code is available at https://github.com/danleneurocom/BN-LTE.

13.
arXiv (CS.LG) 2026-06-12

QoS Improvement in Multi User Cellular-Symbiotic Radio Network Assisted by Active-STAR-RIS

arXiv:2401.08301v2 Announce Type: replace-cross Abstract: In this article, we employ active simultaneously transmitting and reflecting reconfigurable intelligent surfaces (ASRIS) to enhance the quality of 6G cellular network services. The network integrates commensal symbiotic radio (CSR) subsystems to facilitate communication between passive Internet of Things (IoT) users and active users, referred to as symbiotic backscatter devices (SBDs) and symbiotic user equipments (SUEs), respectively. Since the SBDs are passive, transmitting information to the SUEs poses significant challenges. To overcome this challenge, we harness the capabilities of massive multiple input multiple output (MIMO) antennas within the base station (BS) to relay the information transmitted by SBDs with greater power. This scheme uses the non-orthogonal multiple access (NOMA) technique for multiple access among all users, and potential interferences are eliminated using successive interference cancellation (SIC). The primary objective is to maximize the throughput between SBDs and SUEs. To achieve this, we formulate an optimization problem involving variables such as active beamforming coefficients at the BS and ASRIS, phase adjustments of ASRIS, and scheduling parameters between CSR and cellular networks. To solve this optimization problem, we used three deep reinforcement learning (DRL) methods: proximal policy optimization (PPO), twin delayed deep deterministic policy gradient (TD3), and asynchronous advantage actor critic (A3C). These methods were simulated, and the results demonstrate that A3C, TD3, and PPO have the best convergence speeds and achieve the highest increases in network throughput, respectively. Finally, the proposed scheme was evaluated using passive simultaneously transmitting and reflecting RIS (STAR-RIS), which demonstrated poorer performance compared to ASRIS.

14.
arXiv (CS.CV) 2026-06-16

Comparing Human Gaze and Vision-Language Model Attention in Safety-Relevant Environments

Human visual attention plays an important role in how people perceive and respond to environments containing potential risks. This study investigates whether large vision-language models can identify the same regions of a scene that attract human attention in safety-relevant environments. Eye-tracking data were collected from ten participants viewing 33 scene images representing environments with varying levels of potential risk using Pupil Invisible wearable glasses. Gaze coordinates were mapped onto stimulus images to generate population-averaged human gaze heatmaps. In parallel, GPT-4o was prompted through the OpenAI Vision Application Programming Interface (API) to generate spatial predictions of visual attention, which were converted into saliency maps for comparison with human gaze patterns. Spatial alignment between human gaze heatmaps and model-generated saliency maps was evaluated using four complementary metrics: Pearson correlation (r = 0.515 +- 0.117), Normalised Scanpath Saliency (NSS = 0.988 +- 0.323), Kullback-Leibler divergence (KL = 1.766 +- 0.844), and Area Under the Receiver Operating Characteristic Curve using the Judd formulation (AUC-Judd = 0.806 +- 0.076). A cross-model comparison with Gemini Pro, Gemini Flash, and Claude showed that all models exceeded the AUC-Judd chance baseline of 0.5 and achieved positive NSS scores. Gemini Pro demonstrated the strongest spatial localisation according to three of the four metrics, whereas GPT-4o produced the closest distributional match to human attention as measured by KL divergence. These findings suggest that large vision-language models can identify regions that broadly correspond to where humans direct visual attention in safety-relevant scenes without requiring eye-tracking training data. The results highlight the potential of vision-language models as a scalable tool for approximating human attentional patterns.

15.
arXiv (CS.CL) 2026-06-11

Beyond Third-Person Audits: Situated Interaction Auditing for User-Centered LLM Bias Research

Research on bias in large language models (LLMs) has predominantly focused on third-person audits, which study how models represent or evaluate demographic groups as external subjects. However, this paradigm overlooks a structural blind spot because the user is absent from the audit. In practice, LLMs are used in open-ended, personal interactions, during which the model implicitly represents the user and adjusts its responses accordingly. When identical requests yield different responses depending on who is asking, bias manifests not in how the model describes others but in how it treats its interlocutor. We propose Situated Interaction Auditing (SIA), a user-centered framework for studying how user profile signals – implicit sociodemographic markers, writing style, and stated identity – systematically shape LLM response quality, content, and tone. We demonstrate the framework through a case study that intersects gender and socioeconomic status signals across multiple task domains and outline a research agenda for SIA as a new mission for natural language processing.

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

VideoSketcher: Sequential Sketch Generation Using Video Model Priors

Sketching is inherently sequential: strokes are drawn progressively to explore and refine ideas. Yet most generative approaches treat sketches as static images, ignoring the temporal process underlying creative exploration. Modeling this sequential structure remains challenging: prior methods either rely on large-scale human-drawn datasets with limited diversity, or use large language models (LLMs) to produce drawing instructions, often at the cost of visual fidelity. We present VideoSketcher, a method for generating high-quality sketching processes by adapting pretrained text-to-video diffusion models to the sparse, continuous nature of sketch formation. Our key insight is that LLMs and video diffusion models offer complementary strengths: LLMs act as semantic planners that decompose concepts into step-by-step instructions, while video diffusion models serve as powerful "renderers" that translate them into temporally coherent sketch sequences. We introduce a two-stage fine-tuning strategy that decouples temporal structure from visual appearance: stroke ordering is learned from synthetic shape compositions, while style is distilled from as few as seven hand-drawn examples. Despite minimal supervision, our method can generate diverse, high-quality sequential sketches that faithfully follow specified drawing orders. Our framework naturally extends to brush style control and autoregressive generation, supporting artistic applications.

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

Bidirectional Tutoring for Developmental Motor Learning in Robots: Co-Developed Interaction Dynamics Support Stable Learning

arXiv:2606.19728v1 Announce Type: cross Abstract: Infants are well known to develop their motor skills through dense interaction with caregivers. Although such social interaction is crucial for human development, motor-skill learning in robots is often treated as a unidirectional process in which robots passively receive demonstrations from tutors. This overlooks a key property of social interaction: it is inherently bidirectional, with tutor and learner dynamically adapting to each other. In such interactions, the robot's past experiences may function as prior constraints that shape the dynamics of their co-developed trajectories. We hypothesize that bidirectional tutoring allows such constraints to guide the formation of consistent behavioral patterns that preserve behavioral coherence and support generalization, whereas unidirectional interaction lacks such constraints and leads to broader, less consistent behavioral patterns. To examine this hypothesis, we conducted two experiments with a physical humanoid robot performing an object manipulation task: one involving human-robot interaction and another employing an AI tutor interacting with the real robot through an adaptive intervention mechanism designed to examine whether similar effects would emerge under more controlled conditions. We implement the developmental learning framework using a free-energy-principle-based neural network extended with generative replay, which supports stable sequence-by-sequence learning from single tutored episodes. Across both settings, bidirectional tutoring fostered consistent behaviors and stage-wise generalization, while the robot gradually required less tutor guidance. These results suggest that bidirectional tutoring, as an embodied and socially grounded approach, provides an effective scaffold for developmental motor learning in robots.

18.
arXiv (CS.CV) 2026-06-16

HanDyVQA: A Video QA Benchmark for Fine-Grained Hand-Object Interaction Dynamics

Hand-object interaction (HOI) inherently involves dynamics where human manipulations produce distinct spatio-temporal effects on objects. However, existing semantic HOI benchmarks focused either on manipulation or on the resulting effects at a coarse level, lacking fine-grained spatio-temporal reasoning to capture the underlying dynamics in HOI. We introduce HanDyVQA, a fine-grained video question-answering benchmark that comprehensively covers both the manipulation and effect aspects of HOI. HanDyVQA comprises six complementary question types (Action, Process, Objects, Location, State Change, and Object Parts), totalling 11.1K multiple-choice QA pairs. Collected QA pairs recognizing manipulation styles, hand/object motions, and part-level state changes. HanDyVQA also includes 10.3K segmentation masks for Objects and Object Parts questions, enabling the evaluation of object/part-level reasoning in video object segmentation. We evaluated recent video foundation models on our benchmark and found that even the best-performing model, Gemini-2.5-Pro, reached only 73% average accuracy, which is far from human performance (97%). Further analysis shows the remaining challenges in spatial relationship, motion, and part-level geometric understanding. We also found that integrating explicit HOI-related cues into visual features improves performance, offering insights for developing future models with a deeper understanding of HOI dynamics.

19.
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.

20.
arXiv (CS.LG) 2026-06-19

Exploring the potential of AlphaEarth and TESSERA embeddings for Fine-scale Local Climate Zone Mapping: A case study across five cities in Switzerland

arXiv:2606.20034v1 Announce Type: new Abstract: Understanding urban spatial morphology is critical for climate modeling, risk assessment, and sustainable urban design, and Local Climate Zone (LCZ) mapping provides the basic framework for this. However, many cities still use coarse ~100-m resolution LCZ records, which are unsuitable for fine-scale urban research. In this study, precomputed embeddings from TESSERA (Feng et al., 2025) and AlphaEarth (Brown et al., 2025) are compared to traditional Sentinel-1/2 (S1S2) composites in five Swiss cities to see if they can upscale coarse LCZ maps to 10-m resolution using an attention-based U-Net. Three experiments assess multi-city transferability, the impact of higher-resolution reference data, and temporal robustness to year-to-year phenology changes. We find that all datasets achieve strong performance with test data Intersection-over-Union (IoU) ranging from 0.59-0.69 and 0.77-0.82 in the first two experiments. TESSERA consistently outperforms both S1S2 and AlphaEarth across both settings As expected, we find that the transfer of embedding-based models from one year to another remains an open challenge. Overall, however, our results demonstrate the promising potential of embeddings derived from EO foundation models to reduce time consuming preprocessing, respectively, manual feature engineering tasks and to guide a universal deep learning-based LCZ mapping workflow. When combined with a simple location-aware attention U-Net architecture, the embeddings enhance regional transferability and scalability, supporting the development of comprehensive and reproducible fine-scale LCZ maps for global urban climate applications Improving reference data quality remains the strongest lever for further accuracy gains.

21.
medRxiv (Medicine) 2026-06-15

Long-read sequencing enables high-accuracy mitochondrial heteroplasmy detection in Parkinson's disease

Background: Low-frequency heteroplasmic mitochondrial DNA (mtDNA) variants are associated with aging and neurological diseases, including Parkinson's disease (PD). Targeted deep mtDNA sequencing using PacBio HiFi long reads has the potential to resolve heteroplasmy across the full mitochondrial genome with high accuracy. Methods: To validate Vega PacBio sequencing for detecting mtDNA heteroplasmy, we analyzed four predefined mixtures of two mtDNA haplotypes. We generated a single long-range PCR amplicon covering the entire mitochondrial genome. These amplicons were mixed at predefined ratios (minor mixture haplotype component: 5%, 2%, 1%, and 0.1%). Variant calling was performed using Mutserve2, and accuracy was assessed by calculating the F1 score from comparisons between expected and detected variants. Full-length mtDNA PacBio sequencing was applied to investigate heteroplasmy across fibroblast passages derived from five LRRK2 p.Gly2019Ser variant carriers (n=3 affected with PD and n=2 unaffected carriers). Changes in mtDNA heteroplasmy level and variant load were assessed longitudinally using a linear mixed model. Results: The single-amplicon approach enabled full-length haplotype resolution without amplification bias associated with overlapping PCR strategies. The F1 score of the predefined mixtures was 1.0 for heteroplasmy levels between 5% and 1% and remained high (0.91) at 0.1%. We detected n=10/62 variants discordant with the Illumina reference at the 0.1% mixture, but sensitivity remained very high at 1.00 in that mixture. Detected minor variants closely matched expected heteroplasmy levels, with average variant levels of 0.057 (5%), 0.022 (2%), 0.011 (1%), and 0.001 (0.1%). Across twelve fibroblast passages, we observed fewer mtDNA heteroplasmic variants ({beta}=-3.2, p=0.026). Increased heteroplasmic variant load over time was also associated with older age ({beta}=1.50, p=0.001) and PD affection status ({beta}=5.0, p=1.0 x 10-4) in LRRK2 variant carriers. Notably, we observed distinct patterns of heteroplasmic variants that either increased or decreased in heteroplasmy level across passages. Conclusion: PacBio HiFi sequencing, combined with a single-amplicon strategy, enables accurate full-length mtDNA heteroplasmy detection and longitudinal analysis, providing a valuable tool for studying mitochondrial variation and dynamics in disease.

22.
arXiv (CS.CV) 2026-06-19

HypOProto: Hyperbolic Ordinal Prototypes for Left Ventricular Filling Pressure Classification

Echocardiography (echo) is a widely used imaging modality for assessing cardiac function, with Left Ventricular Filling Pressure (LVFP) serving as a critical physiological marker for conditions such as heart failure. Standard LVFP classification into normal vs elevated categories relies on the Doppler-derived $E/e'$ ratio, which is operator-dependent and often unavailable in resource-limited settings, motivating methods that infer LVFP directly from B-mode echo. Existing deep learning approaches achieve high performance but remain largely black-box, limiting clinical interpretability. We propose HypOProto, a hyperbolic, ordinal prototype-based framework for interpretable LVFP classification using a frozen, explainable foundation model backbone. HypOProto arranges prototypes along the physiological $E/e'$ scale, placing borderline cases near the hyperboloid root where small angular differences separate similar cases, while normal and elevated cases occupy outward positions reflecting increasing diagnostic certainty. This hyperbolic geometry encodes clinically meaningful ordinal relationships and improves interpretability. We also introduce a novel Hyperbolic Prototype Angular Separation (HyperPAS) loss, enforcing inter-class prototype separation in hyperbolic space. HypOProto achieves SOTA performance while maintaining transparency, and highlights clinically relevant regions in visualizations. This work represents the first prototype-based framework for LVFP classification in echo. Our code can be found at https://github.com/DeepRCL/HypOProto.

23.
arXiv (CS.LG) 2026-06-12

When to Align, When to Predict: A Phase Diagram for Multimodal Learning

arXiv:2606.11190v2 Announce Type: replace Abstract: Cross-modal alignment (CA) and cross-modal prediction (CP) are the dominant paradigms for multimodal representation learning, yet there is no systematic understanding of when each succeeds, when each fails, and when cross-modal training helps at all – a gap that leaves practitioners, especially in scientific domains like biomedicine or astrophysics, with heterogeneous instruments and multiple levels of organization and measurement, unable to diagnose why standard methods underperform the best single modality. We develop a unified linear framework that addresses both questions. Under a spiked signal-plus-noise model with structured cross-modal nuisance correlation, we derive separation ratios for both objectives that expose complementary failure modes: alignment whitens each modality and fails when nuisance is strongly correlated across views; prediction encodes whatever is cross-predictable through a one-sided whitening, with recovery governed by source-modality quality. The resulting phase diagram partitions multimodal problems into four regimes: Both, CA only, CP only, and Neither. We present a data-driven procedure to locate real-world datasets in this diagram using a small labeled subsample, identifying the preferred objective and prediction direction before any cross-modal training. Experiments on synthetic data, stereo-vision benchmarks, image-caption pairs, and real astrophysical data validate the predictions in the nonlinear regime, including the Neither regime where cross-modal training is actively harmful. Our framework lets practitioners diagnose their multimodal problem and choose the right objective before committing to training. Code to reproduce the results is available at https://github.com/IlayMalinyak/mm_align_vs_pred.

24.
arXiv (CS.AI) 2026-06-19

PiDR: Physics-Informed Inertial Dead Reckoning for Autonomous Platforms

arXiv:2601.03040v2 Announce Type: replace-cross Abstract: A fundamental requirement for full autonomy is the ability to sustain accurate navigation in the absence of external data, such as GNSS signals or visual information. In these challenging environments, the platform must rely exclusively on inertial sensors, leading to pure inertial navigation. However, the inherent noise and other error terms of the inertial sensors in such real-world scenarios will cause the navigation solution to drift over time. Although conventional deep-learning models have emerged as a possible approach to inertial navigation, they are inherently black-box in nature. Furthermore, they struggle to learn effectively with limited supervised sensor data and often fail to preserve physical principles. To address these limitations, we propose PiDR, a physics-informed inertial dead-reckoning framework for autonomous platforms in situations of pure inertial navigation. PiDR offers transparency by explicitly integrating inertial navigation principles into the network training process through the physics-informed residual component. PiDR plays a crucial role in mitigating abrupt trajectory deviations even under limited or sparse supervision. We evaluated PiDR on real-world datasets collected by a mobile robot and an autonomous underwater vehicle. We obtained more than 29% positioning improvement in both datasets, demonstrating the ability of PiDR to generalize different platforms operating in various environments and dynamics. Thus, PiDR offers a robust, lightweight, yet effective architecture and can be deployed on resource-constrained platforms, enabling real-time pure inertial navigation in adverse scenarios.

25.
medRxiv (Medicine) 2026-06-11

Two modes of aversive control in suicidality: joint computational modelling exposes regime-specific clinical signatures invisible to symptom-based stratification

Suicidal thoughts and behaviours (STBs) are heterogeneous in their proximal dynamics, planning, and stress-sensitivity, yet most subtyping efforts remain symptom-driven and rarely validated across independent datasets. Computational mixture modelling offers a principled alternative: by fitting explicit models of learning and action selection and partitioning individuals by their latent parameter profiles, it can identify mechanistically distinct control strategies invisible to cross-sectional symptom measurement. We applied this approach to aversive Go/NoGo performance, jointly clustering two independently collected STB-enriched samples (N = 50 and N = 184) using tasks with the same structure but different duration, reversal timing, and clinical instrumentation. Two recurrent behavioural regimes emerged: a fast/adaptive regime characterised by rapid policy updating and elevated feedback reactivity, and a slow/perseverative regime characterised by slow updating, high choice determinism, and a pronounced cost following contingency reversal. These regimes were stable across initialisations, recovered more parsimoniously in joint than independent solutions, and were largely orthogonal to symptom-based stratification. Critically, stratification by regime exposed clinical-computational coupling structures substantially attenuated in pooled analyses. Pooled, population-level associations were modest and anchored by a broad affective burden axis. Within the slow/perseverative regime, coupling reorganised around learning dynamics and internalizing burden (depression, hopelessness, and active suicidal ideation) with markedly larger effect sizes. Within the fast/adaptive regime, a dissociation between anxious-compulsive and antisocial-disinhibitory profiles emerged along the same computational axis, invisible at the population level. These findings support a view of suicidality heterogeneity in which clinically similar individuals differ in the control strategies they recruit under aversive uncertainty - variation that symptom measurement alone cannot capture.