Academic Intelligence · Curated Daily

Explore the Frontier of Global Academia

AcademicHub aggregates real-time literature from top journals and preprint platforms. Build your personal research radar and let large language models compile cross-disciplinary analysis briefings automatically.

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

DVD: Discrete Voxel Diffusion for 3D Generation and Editing

We introduce Discrete Voxel Diffusion (DVD), a discrete diffusion framework to generate, assess, and edit sparse voxels for SLat (Structured LATent) based 3D generative pipelines. Although discrete diffusion has not generally displaced continuous diffusion in image-like generation, we show that it can be an effective first-stage prior for sparse voxel scaffolds. By treating voxel occupancy as a native discrete variable, DVD avoids continuous-to-discrete thresholding and provides a simple framework for voxel generation, uncertainty estimation, and editing. Beyond quality gains, DVD provides more interpretable generation dynamics through explicit categorical modeling. Furthermore, we leverage the predictive entropy as a robust uncertainty metric to identify ambiguous voxel regions and complicated samples, facilitating tasks such as data filtering and quality assessment. Finally, we propose a lightweight fine-tuning strategy using block-structured perturbation patterns. This approach empowers the model to inpaint and edit voxels within a single sampling round, requiring negligible auxiliary computation and no additional model evaluations. Code is available at https://github.com/TeCai/DVD.

02.
arXiv (CS.AI) 2026-06-16

Minimal Oversight: Uncertainty-Aware Governance for Delegated AI Systems

arXiv:2606.15563v1 Announce Type: new Abstract: AI systems increasingly delegate decisions to specialized models, evaluators, tools, and supervisory controllers. The central AI problem is no longer only model accuracy, but uncertainty-aware governance: how much autonomy to grant, which evidence should calibrate trust, what performance ceiling a delegated AI system can sustain, and when human intervention becomes necessary. We propose the Minimum Sufficient Oversight Principle (MSO), a variational principle for principled autonomy delegation: minimize governance burden on the Fisher information manifold subject to a delivery constraint. The resulting Euler-Lagrange solution yields a water-filling allocation of governed delegation across the task space. Building on a revealed-action governed delegation channel model, we prove a capacity theorem for stationary symbolwise review policies, derive a local first-order approximation relating workflow complexity to quality degradation, and give a drift-dominated autonomy-time scaling law linking intervention timing to effective capacity, complexity, and drift. Within this framework, masking appears as a structural AI-governance pathology: corrected performance can hide the competence signal needed to calibrate trust. Synthetic simulations and a semi-real reconstructed workflow support design prescriptions including upstream-first correction, sensitivity-based intervention, and explicit feasibility checks before autonomy is expanded. The result is a computable framework for uncertainty, planning, and oversight in delegated AI systems. A companion Python package is available at https://github.com/crbazevedo/delegation-lab.

04.
arXiv (CS.LG) 2026-06-15

More with LESS – Local Scene Representations for Tactile Imaging

arXiv:2606.14344v1 Announce Type: new Abstract: Tactile imaging seeks to reconstruct the internal structure of soft objects through touch sensing, with applications in medical diagnosis and robotic manipulation. Recent self-supervised learning approaches have shown promising results, but rely on global, unstructured representations and robot-controlled sensing, limiting generalization and practical use. We propose Local Encoder for Spatial Sensing (LESS), an object-centric tactile representation that exploits the local nature of touch. The tactile scene is modeled as a grid of recurrent encoders with local receptive fields, whose states are fused to reconstruct 2D or 3D images of internal structure. This compositional design enables strong generalization: models trained on single-inclusion phantoms accurately image objects with multiple inclusions and varying sizes. The local structure further supports spatial uncertainty estimation. In addition, we enable hand-held tactile imaging via external pose tracking and human-like palpation data, and extend tactile imaging to full 3D reconstruction.

05.
arXiv (math.PR) 2026-06-16

Sharp freezing time estimates for the subcritical Facilitated Exclusion Process

arXiv:2606.15233v1 Announce Type: new Abstract: We investigate the exact transience time of the Facilitated Exclusion Process (FEP) on the one-dimensional torus with $N$ sites. The FEP exhibits an active/inactive phase transition at critical density $1/2$, such that in the subcritical density regime $(0,1/2)$, it becomes frozen after a finite time period – the transience time or freezing time. We first show that for the FEP starting from a Bernoulli product measure of marginal density $\rho \in (0,1/2)$, the transience time has exactly the scale of $\Theta(\log^3 N)$. Secondly, we prove that in the near-critical case $\rho \simeq 1/2 - N^{-\alpha}$ for $\alpha \in (0,1)$, the transience time is polynomial and has a scale of $N^{1 \wedge (2\alpha)}$. The key idea is to estimate the typical size of locally supercritical intervals of the initial distribution, which has order $\log N$ in the subcritical case and $N^{1 \wedge (2\alpha)}$ in the near-critical case. In the subcritical case this is enough, whereas in the near-critical case we need additional dynamical decorrelation inequalities to apply this static result to estimate the freezing time.

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

Evaluating LLM Personalization via Semantic Constraint Verification

Current evaluation paradigms for Large Language Model (LLM) personalization rely heavily on brittle surface-matching metrics or computationally expensive LLM-as-a-judge protocols, both of which lack interpretability. To address these limitations, we introduce Natural Language Inference Constraint Verification (NLICV), a scalable, semantically invariant framework that maps sentence meanings to truth-condition sets to verify personalization constraints via a Natural Language Inference (NLI) model. Moving beyond binary scoring, NLICV categorizes LLM behaviors into four distinct modes: personalization, generalization, sycophancy, and failure. Extensive experiments demonstrate that NLICV aligns closely with human annotations while drastically reducing the latency and token costs associated with LLM judges (up to 2100 inference speedup). Finally, through an ablation-based procedure, NLICV pinpoints the exact sentences driving the constraint verification, yielding faithful, understandable evidence for its evaluations.

07.
bioRxiv (Bioinfo) 2026-06-10

Pseudoperplexity Probes Memorization in Protein Language Models

Protein Language Models (pLMs) have significantly advanced computational biology. Yet their scale and reliance on redundant training data raise a fundamental question: do pLMs generalize the statistical grammar of proteins, or do they simply memorize their training data? To investigate this, we used pseudoperplexity as a probe for sequence-level memorization, comparing ProtT5's pseudoperplexity on a pre-training proxy dataset against a post-training holdout of genuinely novel sequences. To ensure a valid comparison, we matched the datasets by sequence length, cluster size, and taxonomic family. As a statistical baseline, we trained n-gram language models; analysis of higher-order n-gram composition and a statistically significant divergence in perplexity confirmed that the post-training sequences were genuinely novel at the local sequence level. ProtT5 showed a statistically significant difference in pseudoperplexity between seen and unseen sequences, though further analysis revealed this memorization signal to be modest. These findings suggest that ProtT5 exhibits detectable but limited memorization of its training data as measured by a pseudoperplexity-based probe.

08.
arXiv (quant-ph) 2026-06-16

Experimental quantum state learning with pairs of photons

arXiv:2606.16932v1 Announce Type: new Abstract: Tomography allows one to estimate the density matrix describing the state an ensemble of quantum systems are prepared in (for example, polarization tomography determines the polarization state of a beam of identically prepared photons). In general, it is not possible to uniquely decompose the density matrix into its pure state components. Agarwal et al. proposed a protocol which, for a mixture composed of any two pure states of a qubit (with arbitrary probabilities), allows an observer to infer not only the density matrix but the identity of those specific pure states and their weights - the additional requirement being that the qubits arrive in pairs, where both qubits in each pair are in the same state. We experimentally demonstrate this learning-from-pairs concept using photons in the polarization degree of freedom. We use tomography to measure a sequence of single photons and make use of their time-of-arrival information to 'pair up' the photons after the measurement. From here we are able to infer the photons' polarization states and their respective probabilities, and we demonstrate this for various different choices of polarization states and ratios. Finally, we investigate our ability to discriminate between two equal mixtures of distinct pairs of orthogonal polarization states. We find that on the order of approx. 10e4 photons is typically enough to achieve tomography fidelities of approximately 0.9999. This is sufficient to discriminate between two different preparations of the same mixed state, differing by angles of less than 5 degrees between the pure states used in the two preparations.

09.
medRxiv (Medicine) 2026-06-18

Antimicrobial-resistant E. coli in human, animal and environmental reservoirs in rural Bangladeshi households with young children

In low-income countries, ESBL-producing Escherichia coli (ESBL-EC) is frequently detected in humans, animals and household environments, indicating widespread exposure to antimicrobial resistance (AMR). Established risk factors such as antibiotic use do not explain the high community carriage of AMR in all settings; identifying the dominant exposure pathways can inform interventions against AMR. We aimed to investigate (i) animal-human-environment sharing of AMR by assessing associations between the abundance of ESBL-EC in the household environment, domestic animal feces and young children's stool and (ii) household factors associated with ESBL-EC abundance in these reservoirs. We enrolled 112 households from the CRADLE trial in rural Bangladesh. We enumerated ESBL-EC in drinking water, food, child hand rinses, outdoor soil, indoor floor swabs, chicken and cow feces, and stool from children aged 6 months. We recorded indicators of sanitation, animal ownership/management, human and animal antibiotic use, and child exposure behaviors using structured questionnaires and spot checks. The highest prevalence of ESBL-EC was in child stool (95.6%) and animal feces (82.3-96.9%), followed by soil (48.2%) and floors (36.6%); < 10% of food, child hands and drinking water harbored ESBL-EC. The abundance of ESBL-EC in child stool was not associated with its abundance in any sampled matrix; the abundance in chicken but not cow feces showed positive correlations with soil, floors, child hands, and drinking water (correlation coefficients: 0.19-0.39, p-values < 0.05). Higher-quality latrines (improved, pour-flush, with slab) were associated with lower ESBL-EC abundance across matrices; unsafe animal management (animals roaming or spending the night inside the home) was associated with higher abundance. Child antibiotic use and exposure behaviors (soil ingestion, time spent on floor) were not associated with ESBL-EC abundance in child stool. We observed high AMR colonization among young children and domestic animals in rural Bangladesh not explained by traditional fecal-oral exposure pathways. Future studies should explore additional pathways and assess whether sanitation and animal management improvements can reduce AMR.

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

HydraHead: From Head-Level Functional Heterogeneity to Specialized Attention Hybridization

The quadratic complexity of attention poses a critical bottleneck for long-context processing, spurring interest in hybrid attention designs. Most open-source hybrid models adopt a layer-wise strategy. Yet, prior work has noted the inherent difficulty of integrating Linear Attention (LA) with Full Attention (FA), suggesting that the design space of attention hybridization remains underexplored. To probe this space, we conduct interpretability analysis and observe that layers exhibit block-wise functional similarity, while individual heads within the same layer display distinct functional specialization despite sharing input features. This head-level heterogeneity suggests that the head dimension provides a natural and principled granularity for fusing heterogeneous attention signals. Building on this insight, we introduce HydraHead, a novel architecture that hybridizes FA and LA along the head axis. HydraHead features two key innovations: (1) an interpretability-driven selection strategy that identifies retrieval-critical heads and preserves FA only for them, and (2) a scale-normalized fusion module that reconciles the distributional gap between FA and LA head outputs. By leveraging a three-stage transfer pipeline with parameter reuse and distillation, we achieve high-performance hybrid models with minimal training overhead. Under a unified training setup, HydraHead outperforms other hybrid designs in long-context tasks while maintaining strong general reasoning. With interpretability-driven head selection, it matches a 3:1 layer-wise hybrid's long-context performance at a 7:1 LA-to-FA ratio. Crucially, trained on only 15B tokens, HydraHead achieves over 69% improvement over the baseline at 512K context length, approaching Qwen3.5, a leading model of comparable size with a native context length of 256K. This highlights the significant scaling potential of head-level hybridization.

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

Momentum LMS Theory beyond Stationarity: Stability, Tracking, and Regret

arXiv:2602.11995v2 Announce Type: replace Abstract: In large-scale data processing scenarios, data often arrive in sequential streams generated by complex systems that exhibit drifting distributions and time-varying system parameters. This nonstationarity challenges theoretical analysis, as it violates classical assumptions of i.i.d. (independent and identically distributed) samples, necessitating algorithms capable of real-time updates without expensive retraining. An effective approach should process each sample in a single pass, while maintaining computational and memory complexities independent of the data stream length. Motivated by these challenges, this paper investigates the Momentum Least Mean Squares (MLMS) algorithm as an adaptive identification tool, leveraging its computational simplicity and online processing capabilities. Theoretically, we derive tracking performance and regret bounds for the MLMS in time-varying stochastic linear systems under various practical conditions. Unlike classical LMS, whose stability can be characterized by first-order random vector difference equations, MLMS introduces an additional dynamical state due to momentum, leading to second-order time-varying random vector difference equations whose stability analysis hinges on more complicated products of random matrices, which poses a substantially challenging problem to resolve. Experiments on synthetic and real-world data streams demonstrate that MLMS achieves rapid adaptation and robust tracking, in agreement with our theoretical results especially in nonstationary settings, highlighting its promise for modern streaming and online learning applications.

13.
arXiv (CS.CL) 2026-06-16

Dr-DCI: Scaling Direct Corpus Interaction via Dynamic Workspace Expansion

Agentic search over large corpora relies on retriever-mediated interfaces (e.g., BM25 or ColBERT) for scalable candidate discovery. While effective at ranking relevant documents, these interfaces expose evidence only as ranked results or bounded document views, limiting agents' ability to reorganize material and verify constraints across documents. Direct Corpus Interaction (DCI) addresses this limitation by exposing shell-executable corpus operations for flexible search, filtering, comparison, and verification. However, full-corpus terminal commands become slow and unstable as the corpus grows, degrading performance and efficiency. We introduce DR-DCI, a retriever-steered DCI framework that treats retrieval as an agent-callable action for expanding a local workspace. Rather than operating directly over the full corpus, the agent dynamically pulls relevant documents into an evolving workspace and conducts DCI operations within it. This design combines retriever-level recall with DCI-style precision: retrieval keeps exploration scalable, while DCI preserves the local operations needed for effective evidence resolution. Experiments show that DR-DCI is both effective and efficient across scales. On Browsecomp-Plus, DR-DCI reaches 71.2\% accuracy, improving over raw DCI and ablated variants by up to 8.3 points while reducing tool usage, wall time, and estimated cost. With workspace-preserving context reset, accuracy further improves to 73.3\%. In corpus-scaling experiments, DR-DCI remains effective from 100K to 10M documents, whereas raw DCI becomes unstable and BM25 performs substantially worse. DR-DCI also scales to a 20M-scale file-per-document Wiki-18 QA setting, achieving an average score of 63.0 across six benchmarks and outperforming retrieval-based and trained search-agent baselines. Ablation analysis further shows that ranked previews and inter-document DCI are key to performance.

14.
arXiv (CS.AI) 2026-06-19

Co-policy: Responsive Human-Robot Co-Creation for Musical Performances

arXiv:2606.19914v1 Announce Type: cross Abstract: Art has long stood as a pivotal expression of human creativity. Embodied artificial intelligence offers a route for generative models to participate in that creativity through physical action rather than disembodied digital content. In robotic music co-creation, it is challenging to connect semantic musical understanding with real-time and physically executable performance. We present Co-policy, a framework for human-robot musical co-creation that separates semantic intent grounding, constrained musical variation, and visuomotor execution. To ground musical semantics, Co-policy uses pre-inference semantic anchors and a fine-tuned Qwen-vl planner (F-Qwen) to transform speech, live musical seeds, and visual observations into structured co-creation plans. To support low-latency execution, Co-policy introduces a Gaussian-Mixture Visuomotor Policy (GMP), implemented as a conditional mixture-density policy that maps target notes and visual context to multimodal robot actions in a single forward pass. Unlike robotic playback systems that merely reproduce user-specified notes, Co-policy generates complementary musical responses under both musical and physical constraints. Real-robot chime experiments, ablations, and expert evaluation show improved intent alignment, execution accuracy, and response frequency over diffusion-policy and ablated baselines, supporting physically grounded action generation as a key requirement for embodied human-AI co-creation.

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

Stop the Sampler! Classifier-Based Adaptive Stopping for Sampling Kernels

arXiv:2606.16073v1 Announce Type: new Abstract: Sampling from complex, unnormalized probability densities is a fundamental challenge in Bayesian inference and probabilistic modeling. While Markov chain Monte Carlo (MCMC) methods provide asymptotic guarantees, they often suffer from slow mixing and high computational costs due to fixed or manually tuned trajectory lengths. In this work, we propose a novel framework that treats trajectory termination as a learnable component of the sampling dynamics. By framing MCMC within the theory of non-acyclic generative flow networks (GFlowNets), we train state-dependent neural classifiers to decide when a trajectory has reached a high-density region and should terminate. We theoretically establish the connection between optimal classifiers and the target density via detailed balance conditions and introduce a multilevel training scheme to facilitate exploration in complex geometries. Experimental results across various benchmark densities demonstrate that our approach significantly reduces average trajectory lengths while improving mode coverage and mixing compared to standard MCMC baselines.

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

Test-Time Adaptation in Optical Coherence Tomography Using Trajectory-Aligned Time-Independent Flow

Optical coherence tomography (OCT) is essential in ophthalmology, but inconsistent image quality especially in low-cost devices hinders automated analysis. To address this, we introduce a flow-matching-based test-time adaptation method that generates high-quality surrogate images from noisy inputs. Typically, domain gaps between test and training data cause pixel distribution mismatches during the denoising process. We overcome this by matching the test image's histogram to synthetic reference trajectories, successfully aligning the input with expected distributions. Additionally, we remove the network's time conditioning to account for slight deviations in real-world noise distributions. Our approach achieves state-of-the-art performance in segmenting critical biomarkers for two stages of Age-related Macular Degeneration (AMD). Code is available: https://github.com/Veit21/tta-flow.

18.
medRxiv (Medicine) 2026-06-22

''Circumstantial Determinants'': An Efficient Approach to Reaching People in Need of HIV Prevention?

HIV prevention and testing programmes primarily reach people who self-refer or attend routine health services. Higher-risk individuals are missed if they are healthy, under-estimate their risk of infection or under-report sexual risk-behaviours. We assess a new approach to address limitations in existing programmes by targeting HIV services on ''Circumstantial Determinants'' (CDs) of HIV risk - the social circumstances, settings, and norms associated with behaviours that increase risk of HIV acquisition. Data on potential CDs and sexual behaviour were collected in a population survey in Zimbabwe in 2018/19 (N=9141). HIV-negative individuals reporting [&ge;] 1 sexual risk-behaviours were defined as the 'priority population' for HIV prevention. For each sex, six circumstantial determinants were associated with being in the priority population (aOR [&ge;] 1.30; p [&le;] 0.01). Reach and efficiency of CDs (and combinations) were calculated; ROC curve algorithms evaluated their ability to identify priority population membership; and HIV prevention condom cascades were compared between CD-defined priority population subgroups. Example findings include that targeting men at bars and beerhalls could reach 48.5% of the priority population and 25.1% of lower-risk men. These percentages increase to 77.1% and 53.7% if men with poor mental health, no religious affiliation, negative social capital, or living on agricultural estates are also targeted. Targeting women with poor mental health could reach 32.0% of the priority population and 21.3% of lower-risk women. Targeting additional circumstantial determinants increases these percentages to 54.1% and 37.5%, respectively. Cascade barriers to condom use differed between CD-defined subgroups. The Circumstantial Determinants approach demonstrates proof-of-concept potential to strengthen HIV prevention services.

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

Loss Landscape Diagnosis for Gradient-Based Gray-Scott System Inversion: Disentangling the Roles of PINN Components

Authors:

arXiv:2606.11258v1 Announce Type: new Abstract: Gradient-based inversion of reaction-diffusion systems is typically approached via surrogate models or physics-informed neural networks (PINNs), while the most direct route, backpropagation through the PDE's structure itself, has largely been avoided. We pursue this direct route as a diagnostic probe, backpropagating a steady-state loss through unrolled Gray-Scott simulation to recover its parameters, with no surrogate or neural-network augmentation. Optimization fails to converge, and plotting the landscape directly locates the failure in its geometry – flat plateaus with no gradient signal, bounded by sharp cliffs that align with bifurcation boundaries – a structure that recurs across loss functions and is inherited however the gradients are routed to parameters. Reading this minimal setup as an ablation of PINN, we disentangle each component's role: with the neural network fixed, the residual loss is quadratic in the PDE parameters and yields a smooth landscape, so it alone already avoids the pathology, by implicitly encoding the full PDE dynamics across all initial conditions. The neural network, for its part, cannot repair an ill-posed parameter subspace, and so serves only to complete the observed data – a division of labor not previously made explicit. These findings carry concrete design implications for PINN-type methods and a broader heuristic on when added dimensions actually help.

20.
arXiv (CS.CV) 2026-06-11

Semantically-Aware Diver Activity Recognition Framework for Effective Underwater Multi-Human-Robot Collaboration

Effective multi-human-robot collaboration is essential for expanding human-led operations in the challenging and high-risk underwater environment. For autonomous underwater vehicles (AUVs) to become true teammates, they must be able to comprehend their surroundings and recognize a diver's activities to offer assistance and ensure safety. Towards this goal, we introduce DAR-Net, a novel transformer-based framework that analyzes complex underwater scenes to classify diver activities. Our contribution lies in a semantically guided learning formulation that couples transformer-based temporal reasoning with pixel-level scene supervision. This multi-loss training strategy explicitly aligns global activity recognition with local human-robot interaction semantics, which is particularly critical in low-visibility underwater conditions. To address the significant challenge of data scarcity in this domain, we present the first-ever Underwater Diver Activity (UDA) dataset, a foundational resource containing over 2,600 annotated images with pixel-level masks. Through rigorous experimental evaluations in a controlled environment, we demonstrate that DAR-Net achieves promising accuracy in recognizing six distinct diver activities, outperforming state-of-the-art models. While this dataset provides a crucial baseline, our work serves as a pioneering step, laying the groundwork for future research and facilitating the development of more intelligent, collaborative underwater robotic systems.

21.
bioRxiv (Bioinfo) 2026-06-11

Revealing trajectories of multi-modal voxel-level changes in neurodegenerative diseases using latent event mapping

Neurodegenerative diseases are driven by pathological mechanisms that can be indirectly measured in vivo using multi-modal neuroimaging. However, current computational methods that aim to reconstruct trajectories of voxel-level changes in the brain are either not computationally scalable or fully interpretable, limiting their ability to reveal associations between disease progression and underlying mechanisms. Here we introduce Latent Event Mapping (LEMING), a generative unsupervised modelling technique that learns a latent map of disease events along a common pseudo-timeline of events. We apply LEMING to amyloid PET and structural MRI data from the Alzheimer's Disease Neuroimaging Initiative to reveal the first voxel-level trajectories of events in Alzheimer's disease. Notably, we show how LEMING can provide new insights into progression-dependent disease mechanisms. We find that acetylcholine receptor density is significantly positively associated with both late-stage amyloid and atrophy events, suggesting that either these receptors are targeted later in disease progression, or that amyloid does not play an active role. This has strong implications for therapeutics that target acetylcholine receptors, particularly for early-stage intervention strategies.

22.
arXiv (quant-ph) 2026-06-11

Compressed minimum-purity time evolution for late-time quantum dynamics

arXiv:2606.11392v1 Announce Type: cross Abstract: Unitary time evolution of initially simple quantum many-body states rapidly generates entanglement and complex correlations, which limits direct numerical simulations. The late-time dynamics of physical observables, however, typically exhibits an effective simplicity in the form of hydrodynamics or kinetic theory. This leads to the question whether microscopic equations of motion can remain accurate and tractable up to long time scales by discarding irrelevant information in a controlled manner. Here, we introduce compressed minimum-purity time evolution (CoMPuTE) as an approach to keep track of a consistent set of reduced local density matrices, closing the hierarchical equations of motion using a minimum-purity principle. In benchmark applications we demonstrate (i) accurate description of energy diffusion in the one-dimensional mixed-field Ising model, (ii) the applicability to genuinely out-of-equilibrium Floquet dynamics starting from a pure state, and (iii) the limitations of the local reduced density matrix approximation when describing transport in the XXZ chain at $\Delta=1$ that is governed by increasingly non-local integrals of motion. The CoMPuTE method enhances computational efficiency in comparison to the closely related local-information time evolution algorithm, opening a possible route towards an extension to systems in higher spatial dimensions.

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

From Isolation to Entanglement: When Do Interpretability Methods Identify and Disentangle Known Concepts?

A goal of interpretability is to recover disentangled representations of latent concepts (features) from the activations of neural networks. The quality of features is typically evaluated in isolation, and under implicit independence assumptions that may not hold in practice. Thus, it is unclear to what extent common featurization methods such as sparse autoencoders (SAEs) and probes disentangle one concept from another. We propose a multi-concept evaluation setting using concepts including sentiment, domain, voice, and tense. We evaluate how well featurizers produce disentangled representations of each concept, observing that features are typically sensitive to only one concept, but also that concepts are distributed across many features. Then, we steer these features, measuring whether each concept is independently manipulable, and whether features interact. Even in idealized settings, steering a feature often affects many concepts, despite a near absence of interaction effects. These results suggest that correlational metrics are insufficient to establish steering selectivity, and that demonstrating that two features operate in separate spaces is insufficient to claim that they will be selective for one concept. These results underscore the importance of multi-concept evaluations in interpretability research.

24.
bioRxiv (Bioinfo) 2026-06-22

CellTosg2Sequence: A Unified Text-Omics-Signaling-Graph Large Language Model for Single-Cell Analysis

bioRxivLaTeXUnicodeabstract — In single-cell (sc)-based scientific discovery, text-formatted biomedical prior knowledge and signaling graphs are essential for annotating and interpreting numeric sc-omics data and for generating novel testable hypotheses. A major limitation of existing single-cell large language models (scLLMs) is that they rely on numeric expression data with gene names as the only textual signal, while comprehensive biomedical priors – cellular localization, gene function, disease associations, and signaling interaction patterns – remain absent from the model input. We introduce CellTosg2Sequence, a textual-prior- and signaling-graph-augmented cell-omics-sentence language model. A lightweight heterogeneous graph encoder maps a curated 62,507-node biomedical knowledge graph (KG) into compact virtual tokens that are prepended to each cell sentence, allowing the language model to condition on biological structure with minimal sequence-length overhead. We train CellTosg2Sequence with a three-stage objective: Stage I anchors the KG channel under autoregressive language-model pretraining, leveraging Qwen2.5-32B's own language reasoning for rapid KG alignment; Stage II aligns labels via supervised fine-tuning with KG-anchored InfoNCE; Stage III applies Group Relative Policy Optimization (GRPO) with an ontology-hierarchy reward, enabling free-generation cell-type prediction that generalizes beyond the closed training vocabulary. Across multiple benchmarks and ablation experiments, CellTosg2Sequence outperforms strong baselines. All results are achieved with lightweight LoRA training and a single unified checkpoint.

25.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Authors:

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.