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.AI) 2026-06-19

Can In-Context Learning Support Intrinsic Curiosity?

arXiv:2606.19476v1 Announce Type: cross Abstract: Effective machine learning depends not only on how we model data, but also on what data we choose to collect. While large sequence models have revolutionized data modeling, the problem of automated data selection, or "intrinsic curiosity", remains a significant challenge. Classic approaches incentivize exploration by rewarding an agent based on its "learning progress", which measures how much a newly acquired observation improves a world model's predictive ability. However, evaluating these rewards traditionally requires expensive inner loops of gradient descent updates within each trajectory, rendering them computationally impractical at scale. In this work, we investigate whether the emergent in-context learning (ICL) capabilities of sequence models can eliminate this bottleneck by serving as immediate, update-free world models. Specifically, we evaluate whether an exploration policy can be trained to maximize learning progress, using solely the prediction errors and counterfactual context manipulations of an in-context learner. We first prove that in general Markov decision processes, this is in fact impossible in an unbiased way: the resulting intrinsic rewards either suffer from nuisance terms that bias their estimation of true learning progress, or they cannot be implemented using an in-context learner's prediction errors. Conversely, we prove a positive result for a broad subclass of non-temporal settings, encompassing active learning and Bayesian Experimental Design: here, ICL-derived rewards successfully bound and asymptotically converge to the true learning progress. We corroborate our theory with controlled experiments across continuous and symbolic environments, demonstrating that our ICL-driven framework successfully trains curious data-collection policies that explore optimally.

02.
arXiv (math.PR) 2026-06-11

Additive Noise, Shift Recovery, and Signed Signals in the Cumulative Distribution Transform

arXiv:2606.11432v1 Announce Type: cross Abstract: The cumulative distribution transform (CDT) is a quantile-based transport representation that exactly linearizes one-dimensional translations of positive densities. We study how this structure behaves under additive perturbations and how it can be exploited for shift recovery. Under a local nondegeneracy condition, we derive a first-order expansion showing that additive noise in physical space induces a nonlocal perturbation in CDT space through the primitive of the noise, weighted by the reciprocal density. This yields an explicit description of transform-domain sensitivity and shows, in particular, that perturbations are amplified in low-density regions. When the physical-space perturbation is modeled as a centered Gaussian random field, the induced first-order CDT perturbation is again Gaussian, with an explicit covariance kernel. We then use this structure to study recovery in CDT coordinates. In the known-template setting, the transport shift is obtained by projection onto the constant mode, giving an explicit estimator together with exactness in the noiseless case and a stability bound under perturbations. In the unknown-template setting, multiple observations permit joint recovery of the shifts and a common template up to the natural constant-mode gauge, leading to a simple de-shift–and–average procedure. We also consider a signed-signal analogue based on the signed cumulative distribution transform (SCDT), where shifts are estimated numerically by feature matching and unknown templates are recovered by alternating alignment and averaging. Numerical experiments validate the perturbation analysis and illustrate effective recovery for both density-valued and signed signals.

03.
arXiv (CS.AI) 2026-06-11

Preregistration for Experiments with AI Agents

arXiv:2606.11217v1 Announce Type: cross Abstract: The proliferation of large language models (LLMs) and autonomous AI agents has given rise to a rapidly growing methodological paradigm: "in silico" behavioral experiments. Originally conceived as a way to use AI agents as proxies for human participants in studies of cognition, decision-making, and social dynamics, this approach has taken on new significance – as AI agents increasingly negotiate, transact, and make consequential decisions on behalf of people and organizations, understanding their behavior has become a research priority in its own right. While these experiments with AI agents offer unprecedented advantages in terms of scalability, cost efficiency, and experimental control, they also inherit, and in some cases amplify, methodological vulnerabilities that have long plagued human subjects research. To address these issues, this paper argues that preregistration practices – central to improving the credibility of human subjects experiments – should now be extended to experiments with AI agents. We systematically catalog the researcher degrees of freedom that experiments with AI agents introduce – model selection, prompt wording, settings, and outcome-contingent redesign, for example – and show how the low cost of iteration and lack of reporting norms make these choices both easy to exploit and difficult to detect. We propose a preregistration template tailored to experiments with AI agents and call on conferences, journals, and funding agencies to make preregistration standard practice for this emerging research paradigm.

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

UniReason-Med: A Shared Grounded Reasoning Interface for 2D-to-3D Transfer in Medical VQA

We study whether grounded reasoning supervision from abundant 2D medical images can improve 3D medical VQA when both input types are aligned through a common reasoning interface. We introduce UniReason-Med, a single-checkpoint framework that processes either a 2D image or a slice-serialized 3D volume at inference time, generating interleaved textual reasoning and localized visual evidence through shared box syntax, region-token injection, and a common grounded reasoning policy. To train this interface, we construct UniMed-CoT, a 220K instruction-tuning dataset with interleaved textual reasoning and grounded visual evidence, including 170K 2D and 50K 3D samples. Through supervised fine-tuning followed by outcome-level reinforcement learning, UniReason-Med learns to generate grounded reasoning traces without IoU/Dice-based localization rewards during RL. Data-mixture and component ablations show that joint 2D+3D grounded supervision substantially improves 3D reasoning over 3D-only training, while grounding and region-token injection consistently benefit both 2D and 3D tasks. These results suggest that a shared grounded reasoning interface can transfer reasoning structure from 2D images to slice-serialized volumetric medical understanding. The code and data are publicly available at https://github.com/IQuestLab/unireason-med.

05.
medRxiv (Medicine) 2026-06-17

Determinants of non-utilization of insecticide-treated nets among children under five in Rwanda: analyses of the 2024 Rwanda malaria indicator survey

Background Insecticide-treated nets (ITNs) are effective for preventing malaria among children under five years, who bear a disproportionate burden of malaria. This study assessed the prevalence and determinants of ITN non-utilization among children under five in Rwanda using data from the 2024 Rwanda Malaria Indicator Survey (RMIS).Methodology This cross-sectional study utilized nationally representative data from the 2024 RMIS. Analyses were restricted to children under five residing in households that owned at least one ITN. The outcome was non-utilization of ITN, defined as not sleeping under an ITN the night preceding the survey. Survey-weighted descriptive statistics were used to estimate the prevalence of ITN non-utilization. Factors associated with non-utilization were identified using a survey-weighted Poisson regression model. Adjusted prevalence ratios (aPRs), 95% confidence intervals and p-values were reported.Results A total of 1,979 children were included in the study. The weighted prevalence of ITN non-utilization among children under five years was 20.11% (95% CI: 17.81 - 22.63). After adjusting for other factors, children aged 2 - 3 years were associated with an 83% higher prevalence of ITN non-utilization compared with those aged [&le;]1 year (aPR = 1.83, 95% CI: 1.423 - 2.352, p < 0.001). Compared with households that owned only one ITN, children in households with three or more ITNs were associated with a 76% lower prevalence of ITN non-utilization (aPR = 0.24, 95% CI: 0.171 - 0.332, p < 0.001). Children living in households with 5 - 7 members were associated with an 87% higher prevalence of ITN non-utilization compared with those in households with 1 - 4 members (aPR = 1.87, 95% CI: 1.476 - 2.358, p < 0.001).Conclusion The findings suggest that ITN utilization among children is influenced not only by household access to nets but also by household composition and dynamics that shape the allocation and use of available preventive resources.

06.
PLOS Computational Biology 2026-06-01

On real-time calibrated prediction for complex model-based decision support in pandemics: Part 2

by Trevelyan J. McKinley, Daniel B. Williamson, Xiaoyu Xiong, James M. Salter, Robert Challen, Leon Danon, Ben Youngman, Doug McNeall Calibration of complex stochastic infectious disease models is challenging. These often have high-dimensional input and output spaces, with the models exhibiting complex, non-linear dynamics. Coupled with a paucity of necessary data, this results in a large number of non-ignorable hidden states that must be handled by the inference routine. Likelihood-based approaches to this missing data problem are very flexible, but challenging to scale, due to having to monitor and update these hidden states. Methods based on simulating the hidden states directly from the model-of-interest have an advantage that they are often more straightforward to code, and thus are easier to implement and adapt in real-time. However, these often require evaluating very large numbers of simulations, rendering them infeasible for many large-scale problems. We present a framework for using emulation-based methods to calibrate a large-scale, stochastic, age-structured, spatial meta-population model of COVID-19 transmission in England and Wales. By embedding a model discrepancy process into the simulation model, and combining this with particle filtering, we show that it is possible to calibrate complex models to high-dimensional data by emulating the log-likelihood surface instead of individual data points. The use of embedded model discrepancy also helps to alleviate other key challenges, such as the introduction of infection across space and time. We conclude with a discussion of major challenges remaining and key areas for future work.

07.
arXiv (CS.LG) 2026-06-19

CAGE: Curvature-Aware Gradient Estimation For Accurate Quantization-Aware Training

arXiv:2510.18784v3 Announce Type: replace Abstract: Despite significant work on low-bit quantization-aware training (QAT), there is still an accuracy gap between such techniques and native training. To address this, we introduce CAGE (Curvature-Aware Gradient Estimation), a new QAT method that augments the straight-through estimator (STE) gradient with a curvature-aware correction designed to counteract the loss increase induced by quantization. CAGE is derived from a multi-objective view of QAT that balances loss minimization with the quantization constraints, yielding a principled correction term that depends on local curvature information. On the theoretical side, we introduce the notion of Pareto-optimal solutions for quantized optimization, and establish that CAGE yields strong convergence guarantees in the smooth non-convex setting. In terms of implementation, our approach is optimizer-agnostic, but we provide a highly-efficient implementation that leverages Adam statistics. CAGE significantly improves upon the prior state-of-the-art methods in terms of accuracy, for similar computational cost: for QAT fine-tuning, it halves the compression accuracy loss relative to the prior best method, while for QAT pre-training of Llama models, its accuracy for 3-bit weights-and-activations (W3A3) matches the accuracy achieved at 4-bits (W4A4) with the prior best method. The official implementation can be found over https://github.com/IST-DASLab/CAGE .

08.
arXiv (quant-ph) 2026-06-11

Shadow Engineering of Quantum Processes

arXiv:2606.12035v1 Announce Type: new Abstract: Characterizing quantum processes is essential for hardware benchmarking, error diagnosis, and algorithm verification. While recent work [PRX QUANTUM 4, 040337 (2023)] extended classical shadows from quantum state to quantum process, enabling efficient single-channel $\mathcal{E}$ property prediction, its applicability to composite processes $f(\mathcal{E}_1, \mathcal{E}_2,\cdots, \mathcal{E}_k)$ remains unexplored. We introduce shadow engineering, a framework encoding the classical shadows of processes into sparse transfer matrices to predict $f(\mathcal{E}_1, \mathcal{E}_2,\cdots, \mathcal{E}_k)$ properties with proven polynomial sample complexity, matching single-channel efficiency while exponentially lower than quantum process tomography. Crucially, this approach repurposes existing $\mathcal{E}_m$-shadow data without physical execution of $f(\mathcal{E}_1, \mathcal{E}_2,\cdots, \mathcal{E}_k)$, enabling flexible quantum process characterization with minimal hardware overhead. We demonstrate the framework's effectiveness and practicality on a superconducting quantum processor for typical applications such as error mitigation and Hamiltonian dynamical simulation. This framework unlocks new capabilities for predicting complex quantum behaviors without physical re-execution, with immediate applications in near-term device calibration and quantum simulation.

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

Hierarchical Probabilistic Conformal Prediction for Distributed Energy Resources Adoption

arXiv:2411.12193v4 Announce Type: replace-cross Abstract: The rapid growth of distributed energy resources (DERs) presents both opportunities and operational challenges for electric grid management. Accurately predicting DER adoption is critical for proactive infrastructure planning, but the inherent uncertainty and spatial disparity of DER growth complicate traditional forecasting approaches. Moreover, the hierarchical structure of distribution grids demands that predictions satisfy statistical guarantees at both the circuit and substation levels, a non-trivial requirement for reliable decision-making. In this paper, we propose a novel uncertainty quantification framework for DER adoption predictions that ensures validity across hierarchical grid structures. Leveraging a multivariate Hawkes process to model DER adoption dynamics and a tailored split conformal prediction algorithm, we introduce a new nonconformity score that preserves statistical guarantees under aggregation while maintaining prediction efficiency. We establish theoretical validity under mild conditions and demonstrate through empirical evaluation on customer-level solar panel installation data from Indianapolis, Indiana that our method consistently outperforms existing baselines in both predictive accuracy and uncertainty calibration.

10.
arXiv (quant-ph) 2026-06-16

Rigorous extension of semilocal collinear functionals to noncollinear DFT using $SU(2)$ rotations

arXiv:2605.31203v2 Announce Type: replace-cross Abstract: In the presence of spin-orbit coupling and in geometrically frustrated materials, a noncollinear treatment the magnetization density is essential. However, in density functional theory most exchange–correlation functional approximations were originally developed for locally collinear magnetization. Many practical approaches to noncollinear DFT have emerged over the past decade. However, a first-principles connection between widely used semilocal collinear functionals and their noncollinear generalizations remains lacking. In this work, a locally exact relation between collinear and noncollinear exchange–correlation functionals is derived at the level of gradient expansions within a $u(2)$ matrix representation of the energy functional. Within this framework, collinear semilocal variables naturally acquire distinct dependencies on transverse and longitudinal magnetization gradient components. The widely used Scalmani–Frisch scheme emerges as a first-order approximation. The transformation of collinear functional derivatives to noncollinear space is implemented through numerically robust $SU(2)$ rotations. A consistent description of local magnetic torques is demonstrated for the prototypical spin-frustrated Cr$_3$ cluster. The approach further extends to fully nonlocal functionals and provides a direct route towards numerically stable relativistic response calculations. The influence on magnetic properties in presence of spin-orbit coupling is illustrated through calculations of hyperfine couplings in the high-spin ground states of uranium and the uranium ion.

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

Why Sampling Is Not Choosing: Intentionality, Agency, and Moral Responsibility in Large Language Models

Authors:

Recent advances in large language models (LLMs) have prompted claims that such systems exhibit agency or qualify as moral agents. This paper argues that these attributions are misguided. We maintain that moral responsibility requires commitment-bearing agency grounded in intrinsic intentionality and self-attributed action, and that such agency constitutes the form of free will relevant to responsibility. Although LLMs generate coherent and normatively evaluable outputs, their operation is fully characterized by probabilistic input-output mappings learned from data. Their apparent intentionality is derived rather than intrinsic, and their outputs are neither owned as commitments nor guided by reasons. Variability introduced by stochastic sampling does not amount to choice or authorship. We address objections from the intentional stance, functionalism, compatibilism, and the presence of moral reasoning in model outputs, arguing that none suffice to establish genuine agency.

12.
arXiv (CS.CL) 2026-06-19

TerraMARS: A Domain-Adapted Small-Language-Model Pipeline for Mars Terraforming Literature

Researchers are interested in learning about Mars so that it may eventually become habitable for humans. To achieve this, there is a need for comprehensive knowledge of the planet's atmosphere, hydrology, surface chemistry, radiation environment, and spatial features through the scientific literature. These contain valuable information and meaningful quantitative constraints that can be used in other models and studies, such as habitability assessment and future terraforming studies. We present TerraMARS, an end-to-end information extraction pipeline that combines a domain-adapted Small Language Model to answer Mars terraforming-related questions and convert unstructured Mars science text into machine-readable structured outputs in JavaScript Object Notation (JSON) format. A corpus of open-access papers is collected and processed using a multistage retrieval and chunking framework. Google Gemma 3 1B was adapted to the domain using Quantized Low-Rank Adaptation (QLoRA) fine-tuning on Mars-specific question-answering and information extraction datasets. The resulting pipeline generates both types of output and provides a foundation for integrating knowledge from scientific literature into downstream applications like digital twins and habitability modeling for Mars. The output from this pipeline looks promising, but further improvements are needed to increase extraction accuracy and factual consistency.

13.
arXiv (CS.CV) 2026-06-19

SurgVista: Long-Horizon Surgical World Modeling with Plausible Instrument-Tissue Dynamics

Scaling robot policy learning for autonomous surgery is challenging, as expert demonstrations are expensive and in vivo exploration poses substantial safety risks. Surgical world models address this by generating realistic, action-conditioned future frames from an initial observation, but existing methods exhibit two persistent failure modes: spatial interaction incoherence, where visible instrument contact fails to induce spatially consistent tissue deformation, and temporal fidelity collapse, where prediction errors compound across autoregressive rollouts and progressively corrupt visual quality. We present SurgVista, a surgical world model that mitigates both failures through two training recipes. Deformation Consistency Regularization extracts scene-point trajectories from training videos and enforces cross-frame coherence through latent contrastive learning, strengthening physically consistent instrument-tissue dynamics. Drift Adaptation Training mitigates long-horizon drift by perturbing conditioning frames with online prediction residuals and photometric augmentations calibrated to long-horizon drift statistics, sustaining visual fidelity over extended rollouts. To enable rigorous evaluation, we further introduce SurgWorld-Bench, featuring diverse procedure types, long-range rollouts, and decoupled metrics for instrument-motion accuracy and tissue-response fidelity. Extensive experiments show that SurgVista consistently outperforms state-of-the-art methods across visual quality, temporal consistency, and interaction fidelity, with gains widening as the prediction horizon grows.

14.
arXiv (quant-ph) 2026-06-12

Quantum-Driven Neuromorphic Computing for Million-Qubit-Scale Workloads

arXiv:2606.12968v1 Announce Type: new Abstract: We introduce Apollo, a 10000 node p-qubit neuromorphic processor fabricated in 16 nm mixed signal CMOS and operating fully at room temperature with a typical analog core power envelope of about 0.5 W. Its fundamental element, the p-qubit, is a bistable stochastic unit whose continuous time state fluctuations are driven by integrated quantum entropy units that inject true quantum derived randomness. This enables ultrafast stochastic transitions at low energy while preserving a classical state representation. Apollo combines these p-qubits with a high degree Hyperion 256 interconnect topology, allowing efficient embedding of dense Ising and QUBO problems with substantially reduced minor embedding overhead compared with sparse annealing platforms. We show that, through the Suzuki Trotter correspondence, the equilibrium statistics and annealing dynamics of the p-qubit network reproduce key properties of transverse field quantum annealing without cryogenic cooling, long lived coherence, or microwave control. Beyond device level validation, Apollo is evaluated on a three dimensional spin glass benchmark previously used to study quantum advantage in superconducting annealers. Across 300 disorder realizations, Apollo reaches substantially lower ground state energies than reported cryogenic quantum annealing hardware, while remaining distinct from classical simulated annealing and simulated quantum annealing. A 350 nm release candidate device experimentally validates the core p-qubit dynamics, thermodynamic sampling correctness, and continuous time annealing behavior. These results establish Apollo as a room temperature, industrially scalable platform for quantum driven energy based optimization, probabilistic inference, generative modeling, and hybrid classical quantum workflows.

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

ReGenHuman: Re-Generating Human Appearances for Realistic Full-Body Video Anonymization

Anonymizing human-centric video data is an understudied problem. Prior anonymization techniques either blur or redact pixels at the cost of realism and downstream utility, or generate frame-by-frame at the cost of temporal coherence. We introduce ReGenHuman, the first full-body video anonymization pipeline that is simultaneously realistic, temporally consistent, and anonymous by construction. Contrary to past approaches which redact or edit the inputs directly, we propose a regenerate, don't edit paradigm. Our approach composites 2D pose, segmentation, and monocular depth into two complementary conditioning streams - StructAll and StructHuman, which are used to fine-tune a video-to-video diffusion backbone on in-the-wild human videos, synthesizing the human regions entirely from identity-free structural cues. We evaluate our model on privacy, quality, and utility, and show that our ReGenHuman achieves the best tradeoff across all three axes against current baselines. We further show that our anonymized videos remain effective for downstream tasks, including video question answering.

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

How fast can you find a good hypothesis?

arXiv:2509.03734v3 Announce Type: replace-cross Abstract: In the hypothesis selection problem, we are given sample and query access to finite set of candidate distributions (hypotheses), $\mathcal{H} = \{H_1, \ldots, H_n\}$, and samples from an unknown distribution $P$, both over a domain $\mathcal{X}$. The goal is to output a distribution $Q$ whose distance to $P$ is comparable to that of the nearest hypothesis in $\mathcal{H}$. Specifically, if the minimum distance is $\mathsf{OPT}$, we aim to output $Q$ such that, with probability at least $1-\delta$, its total variation distance to $P$ is at most $C \cdot \mathsf{OPT} + \varepsilon$. The optimal approximation for proper algorithms (where $Q \in \mathcal{H}$) is $C=3$ using $\Theta(\log(n/\delta)/\varepsilon^2)$ samples from $P$ and for improper algorithms (where $Q$ is not necessarily in $\mathcal{H}$) is $C=2$ using $\tilde{\Theta}(\log(n/\delta)/\varepsilon^2)$ samples from $P$. In the improper setting, the algorithm achieving $C=2$ [Bousquet, Braverman, Kol, Efremenko, Moran, FOCS 2021] runs in time which grows polynomially with $|\mathcal{X}|$ – it does not run in finite time for real-valued distributions. A promising path towards improved runtime is to consider improper algorithms which output a mixture $Q$ of the hypotheses as such a distribution can be represented in $n$ words of memory. We show (1) a lower bound that no algorithm which outputs a mixture can achieve approximation better than $C = 3-2/n$ unless the number of samples is polynomial in $|\mathcal{X}|$, as well as (2) an algorithm which runs in time $poly(n)$ and achieves the same approximation guarantee. In the proper setting, [Aliakbarpour, Bun, Smith, NeurIPS 2024] provided an algorithm with $C=3$ running in $\tilde{O}(n/(\delta^3\varepsilon^3))$ time. We improve this time complexity to $\tilde{O}(n/(\delta \varepsilon^2))$, significantly reducing the dependence on the confidence and error parameters.

17.
arXiv (CS.CV) 2026-06-15

UniversalRAG: Retrieval-Augmented Generation over Corpora of Diverse Modalities and Granularities

Retrieval-Augmented Generation (RAG) has shown substantial promise in improving factual accuracy by grounding model responses with external knowledge relevant to queries. However, most existing approaches are limited to a text-only corpus, and while recent efforts have extended RAG to other modalities such as images and videos, they typically operate over a single modality-specific corpus. In contrast, real-world queries vary widely in the type of knowledge they require, which a single type of knowledge source cannot address. To address this, we introduce UniversalRAG, an any-to-any RAG framework designed to retrieve and integrate knowledge from heterogeneous sources with diverse modalities and granularities. Specifically, motivated by the observation that forcing all modalities into a unified representation space derived from a single aggregated corpus causes a modality gap, where the retrieval tends to favor items from the same modality as the query, we propose modality-aware routing, which dynamically identifies the most appropriate modality-specific corpus and performs targeted retrieval within it, and further justify its effectiveness with a theoretical analysis. Moreover, beyond modality, we organize each modality into multiple granularity levels, enabling fine-tuned retrieval tailored to the complexity and scope of the query. We validate UniversalRAG on 10 benchmarks of multiple modalities, showing its superiority over various modality-specific and unified baselines.

18.
arXiv (CS.CV) 2026-06-11

AGE-MIL: Anchor-Guided Evidence Learning for Patient-Level Prediction

Existing computational pathology methods predominantly operate within whole-slide image (WSI)-level multiple instance learning (MIL) paradigms, while patient-level modeling remains underexplored. In routine pathological practice, however, pathologists derive diagnostic and prognostic conclusions by integrating evidence across multiple WSIs rather than relying on any single slide. This discrepancy creates a fundamental misalignment when patient-level supervision is directly imposed on conventional MIL frameworks, often leading to unstable optimization and degraded predictive reliability. To address this issue, we propose Anchor-Guided Evidence MIL (AGE-MIL), a weakly supervised framework for patient-level prediction. AGE-MIL constructs a patient-level anchor from slide representations to capture global pathological context and guide the retrieval and integration of diagnostically relevant local patches, enabling robust patient-level modeling. Patient-level risk is further modeled as an evidence accumulation process, promoting stable optimization under weak supervision. AGE-MIL is evaluated on six clinically relevant patient-level prediction tasks from two independent cohorts. Experimental results show that the proposed framework consistently outperforms eight state-of-the-art MIL methods. Code is available at https://github.com/wodeniua/AGE-MIL.

19.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

20.
bioRxiv (Bioinfo) 2026-06-21

ReSeT: a taxonomy-aware reference genome selection tool

Motivation: Reference genome composition determines which taxa a profiling pipeline can detect and distinguish, and becomes of critical importance for high-resolution profiling where taxonomic boundaries begin to blur. Existing selection tools optimize within-taxon representativeness but disregard discrimination across taxa, leaving open whether explicitly accounting for inter-taxon discrimination during selection improves profiling. Results: Here we present ReSeT, a facility-location-based reference genome selection tool that operates on arbitrary pairwise distance matrices, extended with a tunable inter-taxon discrimination term and per-genome selection cost, and solved by local search. We benchmark ReSeT against established selection methods on three viral datasets spanning varying degrees of taxonomic ambiguity. On the high-ambiguity SARS-CoV-2 datasets, appropriately tuned ReSeT selections matched or exceeded the strongest alternatives in terms of profiling accuracy, whereas on the low ambiguity IAV dataset VSEARCH remained dominant. Interestingly, we find that the novel inter-taxon discrimination term contributed weakly, indicating that ReSeT's facility-location formulation and selection cost drives ReSeT's performance. We further propose a novel taxonomic ambiguity index, computable from ReSeT's inputs, that summarizes the taxonomic ambiguity of reference genomes and aligns with where ReSeT improves over existing selection methods. Availability and implementation: ReSeT is implemented in Python ([&ge;]3.10) and is freely available under the MIT license. The source code is available on GitHub at https://github.com/JaspervB-tud/ReSeT and ReSeT can also be installed directly from the Python Package Index (PyPI) via pip install reset-bio.

21.
arXiv (math.PR) 2026-06-18

Formation of clusters and coarsening in weakly interacting diffusions

arXiv:2510.17629v3 Announce Type: replace-cross Abstract: This paper studies the clustering behavior of weakly interacting diffusions under the influence of sufficiently localized attractive interaction potentials on the one-dimensional torus. We describe how this clustering behavior is closely related to the presence of discontinuous phase transitions in the mean-field PDE. For local attractive interactions, we employ a new variant of the strict Riesz rearrangement inequality to prove that all global minimizers of the free energy are either uniform or single-cluster states, in the sense that they are symmetrically decreasing. We analyze different timescales for the particle system and the mean-field (McKean-Vlasov) PDE, arguing that while the particle system can exhibit coarsening by both coalescence and diffusive mass exchange between clusters, the clusters in the mean-field PDE are unable to move and coarsening occurs via the mass exchange of clusters. By introducing a new model for this mass exchange, we argue that the PDE exhibits dynamical metastability. We conclude by presenting careful numerical experiments that demonstrate the validity of our model.

22.
arXiv (CS.LG) 2026-06-18

Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot with Thermodynamics-Driven Machine Learning

arXiv:2604.14906v3 Announce Type: replace-cross Abstract: The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through $-$1 programmed ribosomal frameshifting ($-1$ PRF), a mechanism that allows the virus to generate both structural and non-structural proteins from overlapping reading frames. This pseudoknot exhibits both threaded and unthreaded long-lived topologies. The influence of ligand binding on its folding is a process critical for the development of $-$1 PRF small-molecule inhibitors. Understanding this process through unbiased molecular dynamics (MD) simulations can be facilitated by introducing collective variables (CVs) that capture the corresponding slowest dynamical modes. Here, we use spectral map (SM), a thermodynamics-driven machine learning technique, to learn such CVs directly from all-atom MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the $-$1 PRF inhibitor merafloxacin and its two structural analogs in neutral and ionized forms. Free-energy landscapes (FELs) derived from the learned CVs indicate that ligand-induced destabilization is topology-selective. In the threaded pseudoknot, the inhibitors destabilize the S2 stem, while in the unthreaded pseudoknot, destabilization occurs in the S1 and S3 stems. Furthermore, the extent to which each ligand reshapes the FEL matches experimentally reported antiviral potency, whereas the protonation state qualitatively alters dynamics within the same RNA topology. Overall, our results show how pseudoknot topology, ligand type, and protonation state collectively influence the slow conformational dynamics of viral RNA and establish physiological protonation as a critical factor for modeling RNA-targeted drug action.

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

Influcoder: Distilling Decoders' Gradient Influence Rankings into an Encoder for Data Attribution

With the growth of LLMs' (Large Language Models) capabilities, there has been an increasing push to curate high quality datasets by filtering samples in the training data. In general, Data Attribution (DA) methods aim to estimate how individual samples in a training dataset can precondition a model to generate certain outputs. As an example, one might be interested in which samples in the data could be the source of toxic behavior after training the LLM. Many methods quantify this conditioning through the paradigm of influence functions. While methods of this family are effective in its function, they lack the necessary processing speed and storage compactness to be practically implemented on large datasets. We propose a method, Influcoder, as a quick and cost-effective approach to influence-based Data Attribution at scale.

24.
arXiv (CS.AI) 2026-06-16

Cognitive Debt: AI as Intellectual Leverage and the Dynamics of Systemic Fragility

Authors:

arXiv:2606.15078v1 Announce Type: new Abstract: We develop a formal theory of cognitive debt: the stock of unverified reasoning obligations that accumulates when individuals use AI as a substitute rather than a complement for first-principles cognition. The model features two state variables per agent, cognitive capital and cognitive debt, and a multiplicative production technology in which cognitive capital functions as collateral that determines the return to AI adoption. We establish six propositions. Rational agents incur positive cognitive debt because the costs are deferred, partially external, and masked by short-run productivity gains. Tranquil periods lower subjective risk assessments, raise AI substitution intensity, and compound leverage, generating a cognitive Minsky moment in which subjective risk falls while true systemic fragility rises. Expected crisis losses are convex in aggregate leverage. Post-crisis, output-target pressure can produce a false-correction loop in which agents patch AI failures with more AI. The decentralised equilibrium over-adopts substitutive AI relative to the social optimum because of systemic risk, cognitive public goods, and arms-race externalities. In a two-type heterogeneous-agent economy, high-cognitive-capital agents adopt AI more intensively and may eventually erode their unaided cognitive capital below that of initially lower-skilled agents.

25.
arXiv (CS.LG) 2026-06-18

Modeling Doppler Shifts in Radial-Velocity Data with Deep Learning toward Earth-mass Exoplanet Detection

arXiv:2606.18464v1 Announce Type: cross Abstract: Detecting the tiny Doppler shifts induced by Earth-mass planets in stellar radial-velocity measurements remains extremely challenging due to stellar activity. Many deep-learning methods performing well on simulated data remain difficult to apply reliably on real stellar spectra. The aim of this work is to develop a deep-learning framework that generalizes to real, unseen spectra and improves the detectability of Earth-mass planets in radial-velocity data. We train artificial neural networks on HARPS-N solar spectra with injected planetary signals, using physics-motivated spectral representations based on flux and line-formation temperature, together with their velocity gradients. Two training strategies are explored: hold-out testing and cross-validation. Model robustness is enhanced through genetic-algorithm-based hyperparameter optimization, and predictive uncertainty is quantified using Monte Carlo dropout. Our most precise neural network model reliably retrieves, under the cross-validation strategy, the amplitudes, phases, and orbital periods of planetary signals with amplitudes greater than or equal to 25 cm/s and periods between 10 and 550 days. In addition, in all cases tested here, the successfully recovered signals correspond to the most significant peaks in the periodograms of the Doppler-shift predictions. Temperature-based spectral-shell representations consistently outperform flux-based shells. We also release doppleriann, a Python package implementing the proposed framework. Our results demonstrate that combining physically motivated spectral representations with deep learning provides a promising pathway toward the detection of Earth-mass planets in radial-velocity data from real observations, supported by a modeling framework that is both physically grounded and statistically rigorous, incorporating uncertainty quantification and optimized training strategies.