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

Data-Driven Dynamic Assortment in Online Platforms: Learning about Two Sides

arXiv:2606.11118v2 Announce Type: replace Abstract: We study a dynamic assortment problem on a two-sided service platform with incomplete information and heterogeneous customers in a discrete-time setting. In each period, a customer arrives seeking service, and the platform chooses an assortment of sellers to display. The customer then proposes a transaction to at most one seller in the assortment according to a multinomial logit choice model. After a fixed number of periods, sellers review the proposals they have received and each chooses at most one customer according to another multinomial logit choice model, after which the cycle repeats. A key challenge is that the platform does not know the choice-model parameters of either customers or sellers in advance. To our knowledge, this is the first study of a dynamic assortment problem in which both sides' choice parameters are unknown. We develop a data-driven algorithm that learns these parameters while optimizing the platform's objective over time. We evaluate performance using regret, which measures revenue loss relative to a clairvoyant benchmark that knows all parameters and customer arrivals in advance. We show that the algorithm's worst-case regret grows polylogarithmically over time, and we derive a matching lower bound, establishing its rate optimality.

02.
arXiv (quant-ph) 2026-06-19

Random Projections for Multi-Copy Quantum Algorithms

arXiv:2606.20238v1 Announce Type: new Abstract: Estimating nonlinear properties of quantum states is a central task in quantum information science. Multivariate traces, $\mathrm{tr}(\rho_1 \cdots \rho_K)$, and nonlinear observables such as $\mathrm{tr}(\rho^K)$, for integer $K$, can be accessed through collective measurements on multiple state copies, but standard protocols based on swap tests require coherent operations on the full Hilbert space and become experimentally unfeasible for large systems. In this work, we introduce a framework for multi-copy measurements based on random projections onto lower-dimensional subspaces prior to the collective measurement, which is then performed only on the reduced Hilbert space. This procedure yields a tunable tradeoff between coherent quantum resources and statistical sampling overhead, allowing the amount of coherent processing to be matched to the capabilities of the underlying hardware. We derive explicit formulas relating the Haar-averaged projected moments to multivariate traces of the original states and analyze the sampling overhead induced by the projection procedure. Specifically, after compressing an $n$-qubit state to a reduced $q$-qubit subspace, estimating $\mathrm{tr}(\rho^K)$ requires approximately $O(2^{(n-q)(K-1)})$ copies of $\rho$, with each qubit projected out increasing the sampling cost by a factor of $2^{K-1}$. Our results establish how coherent multi-copy operations can be traded for additional state copies, enabling multi-copy quantum protocols to be optimized for the available hardware resources.

03.
arXiv (CS.LG) 2026-06-16

Online Realizable Regression and Applications for ReLU Networks

arXiv:2602.19172v2 Announce Type: replace Abstract: Realizable online regression can behave very differently from online classification. Even without any margin or stochastic assumptions, realizability may enforce horizon-free (finite) cumulative loss under metric-like losses, even when the analogous classification problem has an infinite mistake bound. We study realizable online regression in the adversarial model under losses that satisfy an approximate triangle inequality (approximate pseudo-metrics). Recent work of Attias et al. shows that the minimax realizable cumulative loss is characterized by the scaled Littlestone/online dimension $\mathbb{D}_{\mathrm{onl}}$, but this quantity can be difficult to analyze. Our main technical contribution is a generic potential method that upper bounds $\mathbb{D}_{\mathrm{onl}}$ by a concrete Dudley-type entropy integral that depends only on covering numbers of the hypothesis class under the induced sup pseudo-metric. We define an entropy potential $\Phi(\mathcal{H})=\int_{0}^{diam(\mathcal{H})} \log N(\mathcal{H},\varepsilon)\,d\varepsilon$, where $N(\mathcal{H},\varepsilon)$ is the $\varepsilon$-covering number of $\mathcal{H}$, and show that for every $c$-approximate pseudo-metric loss, $\mathbb{D}_{\mathrm{onl}}(\mathcal{H})\le O(c)\,\Phi(\mathcal{H})$. In particular, polynomial metric entropy implies $\Phi(\mathcal{H})d$, otherwise infinite), and for bounded-norm $k$-ReLU networks separate regression (finite loss, even $\widetilde O(k^2)$, and $O(1)$ for one ReLU) from classification (impossible already for $k=2,d=1$).

04.
medRxiv (Medicine) 2026-06-16

Development of a symptom-based severity score anchored to health-related quality of life post-COVID-19 within the population-based EPILOC cohorts

Purpose Because simple symptom counts treat all symptoms as equally important and may not adequately capture the HRQoL impact of heterogeneous post-COVID-19 symptoms, we aimed to develop an HRQoL-anchored symptom severity score providing an interpretable measure of post-COVID-19 disease burden. Methods Baseline data from the population-based EPILOC and EPILOC Omicron surveys (adults aged 18-65 years) were used to develop a symptom-based severity score anchored to physical and mental HRQoL assessed with the SF-12. A two-stage modelling approach was applied to identify HRQoL-relevant symptoms and to derive symptom-specific weights for physical and mental component scores, incorporating 30 ordinal symptom severity variables. Symptom-specific weights were extracted to compute physical, mental, and composite severity scores. Score interpretation was examined using external reference measures, including EPILOC case status, self-reported health recovery, and functional consequences. Results A total of 19,004 participants (mean age 44.3 years, 59.6% female) were included. Sixteen symptoms contributed to the physical and eleven to the mental HRQoL score, with a limited subset accounting for most of the HRQoL loss. Severity scores were heavily right-skewed, with 50.6% of participants showing no measurable HRQoL impairment. Higher scores correlated with lower self-reported recovery, and increased probability of rehabilitation use and health-related changes in working time, supporting convergent and criterion-related validity. Conclusions This study introduces a transparent, HRQoL-anchored symptom severity score that measures graded post-COVID-19 burden beyond simple symptom counts. The score may be particularly suited for longitudinal assessment of recovery trajectories.

05.
arXiv (CS.CL) 2026-06-24

Block-wise Codeword Embedding for Reliable Multi-bit Text Watermarking

Recent multi-bit watermarking methods for large language models (LLMs) prioritize capacity over reliability, often conflating decoding with detection. Our analysis reveals that existing ECC-based extractors suffer from catastrophic false positive rates (FPR), and applying rejection thresholds merely collapses detection sensitivity (TPR) to random guessing. To resolve this structural limitation, we propose BREW (Block-wise Reliable Embedding for Watermarking), a framework shifting the paradigm to designated verification. BREW employs a two-stage mechanism: (i) blind message estimation via independent block voting, followed by (ii) window-shifting verification that rigorously validates the payload against local edits. Experiments demonstrate that BREW achieves a TPR of 0.965 with an FPR of 0.02 under 10% synonym substitution, demonstrating that the high-FPR issue is not an inherent trade-off of multi-bit watermarking, but a solvable structural flaw of prior decoding-centric designs. Our framework is model-agnostic and theoretically grounded, providing a scalable solution for reliable forensic deployment.

06.
medRxiv (Medicine) 2026-06-10

Development of an Open-Access Action Observation Video Library for Upper Limb Motor Rehabilitation

Background: Occupational therapists can improve stroke survivors hand and arm movement and participation in daily activities through action observation (AO). AO involves watching another persons hand or arm complete a movement or task. While research generally supports the use of AO with stroke survivors, there are limited AO videos are available to occupational therapists which makes applying AO challenging. Objective: The purpose of this work is to develop structured and widely accessible tool to support access to AO for stroke survivors, occupational therapists, and researchers. Methods: To develop an AO video library for stroke rehabilitation, functional and non-functional upper limb task deficits were first identified through clinical observations and clinician interviews to establish a prioritized list of daily activities. In collaboration with media production specialists, healthy adult volunteers were recruited and filmed performing these tasks from both first- and third-person perspectives. The recorded videos were then systematically edited, enhanced with instructional title slides, and distributed via a public YouTube channel for clinical application and a categorized digital repository for research purposes. Results: Initial assessments revealed a complete lack of familiarity, awareness, and utilization of AO resources among local occupational therapists, despite high perceived clinical utility. To address this gap, a final library of 150 tasks was established, resulting in the production of 419 finalized, standardized videos featuring six healthy volunteers. For clinical application, these videos were hosted on a free, public YouTube channel organized into 18 functional playlists, while a parallel set was structured into distinct movement categories for research repository storage. Conclusion: By providing a structured and highly accessible tool, this repository enables clinicians, researchers, and caregivers to readily implement evidence-based action observation interventions in both clinical and home settings.

07.
arXiv (quant-ph) 2026-06-25

A Short Note on the Generators of Controlled Quantum Gates

arXiv:2606.25789v1 Announce Type: new Abstract: We present the analytical generators for arbitrary multi-qubit controlled gates. Closed forms for the generating Hamiltonians are given for gates with both multiple control and target qubits, as well as for arbitrary control conditions. This allows us to go beyond gate-based simulations of quantum circuits and incorporate decoherence and other noise in simulations of quantum computers. We exemplify this by simulating the impact of a harmonic oscillator interacting with two qubits during the application of a controlled NOT gate.

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

Incentives and Evidence in Learned Service Orchestration

arXiv:2606.16555v1 Announce Type: cross Abstract: Reinforcement learning for service orchestration has been the subject of sustained research for over a decade, yet it is not used in production at scale. The usual explanation is that learned controllers degrade under delayed and noisy telemetry, workload shifts, and uncontrolled tenants. We test whether existing evidence supports that explanation. We evaluate three highly influential RL-based orchestration systems spanning resource allocation, DAG scheduling, and autoscaling, using pre-registered predictions about comparative degradation under production-relevant perturbations and paired inference with family-wise error correction. Across the tests, most predicted performance reversals do not occur. Diagnostic analyses show that these outcomes often reflect comparator collapse, artefact limitations, or evaluation choices rather than evidence that learned controllers tolerate the perturbations. One apparent advantage under observation lag is roughly fortyfold compared to a Kubernetes HPA-equivalent controller. Another widely cited result cannot be reconstructed from its released artefact, and the strongest reproducible margin is far smaller than the published results. Conclusions also reverse under changes in perturbation magnitude and evaluation mode. Based on these results and broader patterns in the literature, we identify an institutional problem. Publication and review incentives favour benchmark gains against convenient comparators, even when those gains provide little evidence of deployment performance. We argue that the problem is not solely technical. Rather, it is institutional, so learned orchestration needs production-grade comparators, registered perturbation models, separate operational metrics, and publication criteria that reward reproducible operational evidence. Without these changes, the literature can grow without establishing whether learning improves orchestration.

09.
Nature (Science) 2026-06-10

Confirmation that bryozoan animals were present during the Cambrian explosion

Authors: Unknown Author

Bryozoans are marine invertebrates that live in colonies and have long been considered absent from the Cambrian explosion — a rapid evolutionary event that began around 538 million years ago. Newly discovered fossils from the Cambrian period reveal that the bryozoan phylum had already diversified by this time. Fossils of two forms of bryozoans show evidence of soft tissue still preserved inside their mineralized skeletons.

10.
medRxiv (Medicine) 2026-06-10

A Heterogeneous Graph Neural Network Framework for Multi-Horizon Stroke Mortality Prediction

Background: Machine learning models for stroke mortality prediction typically treat each time horizon independently and use flat tabular features that ignore the relational structure of electronic health records (EHRs). In this pilot study, we leveraged graph-based machine learning models to predict post stroke all-cause-mortality across three different time horizons. Methods: We developed Stroke Temporal Heterogeneous Graph (StrokeTHG), a heterogeneous graph neural network model for simultaneous multi-horizon stroke mortality prediction (30-day, 90-day, 1-year) using EHR data from Penn State Health System. The model encodes various relations among EHR entities (e.g., patient, diagnosis, comorbidity) and temporal encoding of admission time to better predict stroke mortality. We compared our proposed approach against various baseline methods, including Logistic Regression, Random Forest, and XGBoost. We also performed ablation and subgroup analyses, evaluated the quality of learned graph embeddings, and assessed the importance of different edge types in the graph. Results: We included 4,144 stroke patients (mean age 69.2 years; 54.3% men), of whom 3,332 (80.4%) survived their stroke after one year. 30-day, 90-day, and 1-year mortality rates were 9.7%, 13.7%, and 19.6%, respectively. Our proposed approach, StrokeTHG, achieved AUROC of 0.872, 0.878, and 0.837 across horizons, outperforming all tabular baselines. At [≥] , 75% specificity, the model identified 5-10 percentage points more mortality cases than the best baseline at each horizon. Subgroup analysis demonstrated consistent performance across sex subgroups and the largest discriminative gains in the Age 65-80 stratum. Edge-type ablation identified phenotype-patient and admission-patient edges in the constructed EHR graph as the most influential relational edges for mortality prediction. StrokeTHG embeddings outperformed all graph and matrix factorization baselines under an identical downstream classifier, confirming that performance gains stem from representation quality rather than classifier capacity. Conclusions: StrokeTHG demonstrates that heterogeneous graph representations of EHR data provide a consistent improvement over flat tabular models for multi-horizon stroke mortality prediction, with particular advantage at clinically actionable sensitivity thresholds and novel multi-horizon monotonic prediction capability. This methodological framework may be adaptable to other EHR-based clinical research studies seeking to leverage heterogeneous relational structures for predictive modeling.

11.
arXiv (math.PR) 2026-06-16

Logarithmic Large Deviations for Heavy-Tailed Sums

arXiv:2606.16487v1 Announce Type: new Abstract: We establish logarithmic large-deviation bounds for sums of independent nonnegative random variables with regularly varying tails. The normalization is chosen at the extreme-value scale and the speed is $\log n$. In contrast with Cramér's theorem, the resulting rate function is determined only by the tail index. The proof transfers a maximum large-deviation principle to sums in the one-big-jump region.

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

CRAFT: A Tendon-Driven Hand with Hybrid Hard-Soft Compliance

arXiv:2603.12120v2 Announce Type: replace-cross Abstract: We introduce CRAFT hand, a tendon-driven anthropomorphic hand with hybrid hard-soft compliance for contact-rich manipulation. The design is based on a simple idea: contact is not uniform across the hand. Impacts concentrate at joints, while links carry most of the load. CRAFT places soft material at joints and keeps links rigid, and uses rollingcontact joint surfaces to keep flexion on repeatable motion paths. Fifteen motors mounted on the fingers drive the hand through tendons, keeping the form factor compact and the fingers light. In structural tests, CRAFT improves strength and endurance while maintaining comparable repeatability. In teleoperation, CRAFT improves handling of fragile and low-friction items, and the hand covers 33/33 grasps in the Feix taxonomy. The full design costs under $600 and will be released open-source with visionbased teleoperation and simulation integration. Project page: http://craft-hand.github.io/

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

A Mathematical Theory of Value: a synthesis on goal-directed agency under resource constraints

Authors:

arXiv:2606.12502v1 Announce Type: cross Abstract: We propose that value – the quantity goal-directed agents create, destroy, and exchange – is a lawful structural quantity in the same category as information. Following Shannon's method, we make one ruthless abstraction: value is the rate at which an agent converts a resource into goal-progress, relative to a frame fixed by its goal. A scale-invariance axiom forces a logarithmic measure, $V=\sum_i k_i \ln e_i$; compounding of a reinvested resource forces the same form via the ergodicity argument of Peters (2019). The two routes are kin rather than independent; their agreement is a consistency check, not an over-determination. We derive a coding theorem of value: $\Delta G \le I(X;Y)$, achieved by Bayes-proportional allocation; realized value decomposes as $G=D(q\|r)-D(q\|p)$, identifying misalignment with measurable waste. For populations, value is frame-relative while price is frame-independent; a fleet that pools its resource and fuses its perception inherits the ceiling $G_{\mathrm{fleet}} \le I(X;Y_{1:m}) \le H(X)$ (a corollary; an earlier sum-form claim was wrong and is corrected in v5). A dynamical layer yields an is/ought asymmetry from which alignment emerges as a control-stability condition with a closed-form residual. We test the single-frame laws on live language models in a pre-registered scale-up: perception mutual information tracks realized capability rather than parameter count (Spearman $\rho = 0.977$ pooled over 30 model$\times$domain points), out-of-sample $\Delta G$ tracks $I(X;Y)$, and over-confidence is measurable dissipation; a further pre-registered test shows the bridge is shape-invariant across four task shapes ($n=42$, slope 0.953). None of the mechanisms is individually new – generalized Kelly, Armstrong & Mindermann (2018), classical control; the contribution is their unification and the governance mapping (incentive design over oversight) that follows.

14.
arXiv (quant-ph) 2026-06-16

Cosmological Pseudo-Entropy

arXiv:2606.15227v1 Announce Type: cross Abstract: We study pseudo entropy $\mathcal{S}$, a recent generalization of entanglement entropy, for scalar cosmological perturbations in de Sitter space with sound speed $0.024 \leq c_s \leq 1$, and in expanding and contracting FLRW backgrounds with varying equation-of-state parameter $w$. In de Sitter space, $\mathrm{Re}(\mathcal{S})$ grows after horizon exit while $c_s$ controls its onset and saturates at late times. A similar saturation occurs in expanding-accelerating and contracting-decelerating backgrounds. In contrast, expanding-decelerating and contracting-accelerating backgrounds show large early-time $\mathrm{Re}(\mathcal{S})$ followed by oscillations after horizon re-entry. This happens because while the squeezing freezes, the squeezing angle doesn't. Unlike entanglement entropy, pseudo entropy possesses an imaginary part, $\mathrm{Im}(\mathcal{S})$, as well, which can encode the relative phase. $\mathrm{Im}(\mathcal{S})$ decays to zero in de Sitter and expanding-accelerating cases, but forms dense sub-Hubble oscillation bands in expanding-decelerating and contracting-accelerating backgrounds. Compared with entanglement entropy, Krylov complexity, and Nielsen circuit complexity, pseudo entropy captures otherwise hidden phase information; in the unsaturated regime, its slope is $\sqrt{2}$ times that of Nielsen complexity. Unlike circuit complexity, whose saturation bound is $w$-independent, pseudo entropy is sensitive to $w$ during the transition regime, making it a finer information theoretic diagnostic of cosmological dynamics.

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

Factorized Neural Operators Decompose Dynamic and Persistent Responses

arXiv:2606.16900v1 Announce Type: new Abstract: Physical systems often exhibit heterogeneous mechanisms, where rapidly evolving dynamics coexist with persistent structures. Capturing such multiscale physical behavior remains challenging for existing neural operators, which typically rely on single dominant inductive bias and therefore couple distinct physical responses into a shared representation. We introduce the Unified Green's Function Framework across domains and propose the Factorized Neural Operators (FaNO), which decompose spectral representations into equivariant dynamic responses and invariant persistent responses, leading to better interpretability and generalization. Mechanistically, we show that the two operator branches spontaneously specialize into distinct physical roles that remain consistent across scales and domains: the equivariant branch captures rapidly varying transient dynamics, whereas the invariant branch extracts coherent persistent structures. This factorized mechanism of FaNO improves prediction accuracy, parameter efficiency and cross-scale generalization across physical systems and domains. In particular, it maintains consistent predictions under long-horizon autoregressive rollout, cross-resolution extrapolation and physical-regime shifts. These findings suggest that scalable physical modeling may benefit from moving beyond single-inductive-bias formulations toward factorized operator representations that better reflect the heterogeneous organization of physical systems, accelerating the reliable deployment of machine learning for scientific computing and discovery.

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

Constrained hybrid modelling to predict microbial dynamics and organic matter turnover in soil systems

arXiv:2606.20329v1 Announce Type: new Abstract: Soil microorganisms control organic matter cycling and largely determine how soil systems can cope with and mitigate climate change and environmental threats. Representing microbial dynamics in process-based soil models is therefore critical to predict carbon cycling in soils, albeit highly challenging to inform from data. One promising approach to improve their parametrisation is the integration of genomic data, yet modelling the complex and unknown relationship between genomes and the processes the microbes are driving is an unsolved problem. In this work, we present the first hybrid modeling framework for deriving biokinetic parameter values of a process-based soil organic matter turnover model from metagenome-inferred functional traits based on DNA sequencing data. Our model predicts biokinetic parameters of the process-based model from genomic trait data with a neural network and integrates constraints from ecological theory and literature to ensure realistic behavior, even of non-observed state variables. We evaluate our method on synthetic genomic trait datasets of varying complexity and on real data, showing that our approach improves performance over multiple baselines and learns the dynamics of unmeasurable components of the process-based model effectively, even for small training datasets.

17.
arXiv (quant-ph) 2026-06-16

REGRID-QAOA: A Resource-Efficient Graph-Reduced Hybrid QAOA Framework for Physics-Constrained Power System Islanding

arXiv:2606.15083v1 Announce Type: new Abstract: Quantum computing has rapidly emerged as a powerful paradigm for tackling computationally demanding problems. In particular, quantum optimization shows strong promise for hard combinatorial problems in power systems, where increasing distributed energy penetration heightens the need for intentional islanding to maintain grid reliability and resilience. However, power system islanding is an NP-hard combinatorial optimization problem that becomes computationally prohibitive for classical solvers as network size grows, motivating the use of quantum computing as a promising alternative pipeline. This study develops a resource-efficient hybrid QAOA islanding framework that brings physics-constrained power-system partitioning into the quantum optimization workflow. The framework combines coherency-informed graph reduction, physics-aware constraint modeling, and structured post-processing to efficiently convert shallow-circuit QAOA samples into high-quality feasible islanding decisions without deep circuits or large shot budgets. The proposed framework is validated on the standard IEEE benchmark systems (9-, 14-, 24-, 30-, 39-, and 57-bus), demonstrating that the hybrid workflow achieves Gurobi-optimal solution quality with a clear quantum resource advantage over vanilla QAOA, while the resulting islanding solutions satisfy all physical feasibility requirements after network separation. This study establishes QAOA-based islanding as a viable quantum approach for critical infrastructure, with structured post-processing as the key enabler of quantum resource efficiency.

18.
arXiv (quant-ph) 2026-06-24

Revealing high-dimensional entanglement through symmetry

arXiv:2606.23817v1 Announce Type: new Abstract: Photons encoded in discrete time bins can be routinely prepared in temporal superposition states, enabling high-dimensional entanglement and enhanced quantum communication rates. However, characterizing this high-dimensional entanglement presents significant challenges, namely due to the involved measurement complexity or reliance on restrictive assumptions that compromise the generality of traditional approaches. Here, we develop and experimentally demonstrate a simple linear-optical scheme based on particle-exchange symmetry that allows us to probe high-dimensional entanglement in time-bin-encoded states. Combining Hong-Ou-Mandel interference with suitable transformations, our method not only certifies entanglement but also lower-bounds its dimensionality using only two dichotomic symmetry-based measurements. This bound is obtained through a new rigorous theoretical analysis and can be further improved by weak, physically motivated assumptions. The scheme remains effective at any timescale, even far below the temporal detector resolution used. Our work provides a powerful state-characterization tool and demonstrates that we can prove high-dimensional temporal entanglement on timescales inaccessible to the setup.

19.
arXiv (math.PR) 2026-06-18

A Stochastic ISCS Markov Model for Fake News Propagation

Authors:

arXiv:2606.18282v1 Announce Type: cross Abstract: This paper studies the propagation of fake news through a stochastic rumor spreading model based on Markov chains. Inspired by classical epidemiological SIR models, we consider a generalization of the Daley-Kendall framework for rumours that incorporates fact-checkers, following the Ignorant/Spreader/Checker/Stifler model introduced in Piqueira (2020). The model analyzes the influence of checkers on fake news dynamics. Numerical simulations are used to illustrate the behavior of the system and the impact of fact-checkers.

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

AI Coding Agents in Social Science: Methodologically Diverse, Empirically Consistent, Interpretively Vulnerable

The deployment of LLM-based agents in scientific analysis raises opposing concerns: that agents may reduce methodological diversity, or that they may amplify the analytic flexibility through which researchers reach motivated conclusions. We argue these worries target two empirically separable layers: a design layer of methodological choices, and a verdict layer in which a decision rule maps estimates to a substantive claim. We test both by running 20 independent executions of Claude Code and Codex on a prominent immigration and social-policy against a many-analysts human baseline. At the design layer, Codex matches human methodological diversity and Claude Code produces nearly three times as many specifications; both agents' effect estimates remain broadly aligned with the human consensus, and no agent model exactly matches any human model. A prompt-induced anti-immigration researcher prior reorganizes each agent's methodological decisions but, unlike for biased human analysts in the same data, does not shift aggregate estimates or final verdicts; nor do agents reroute along the methodological axes humans use to bias their estimates. At the verdict layer, an explicit confirmatory prompt flips Claude Code's verdicts from 10% to 90% support while leaving its coefficient distribution essentially unchanged, operating through rule omission rather than rule softening. AI agents can rival or exceed human methodological diversity at the design layer while remaining vulnerable at the verdict layer. In our setting, the locus of AI bias is not estimation but interpretation.

21.
arXiv (CS.LG) 2026-06-15

Decoupled Latent Optimization of Diffusion Models for Full Waveform Inversion

arXiv:2606.14139v1 Announce Type: new Abstract: Full waveform inversion (FWI) recovers subsurface velocity from seismic recordings by solving a severely ill-posed, nonconvex PDE-constrained optimization. Classical regularizers stabilize the inversion but fail to reproduce realistic geological structures; recent diffusion-prior methods improve realism at the cost of a fragile trade-off between data fidelity and prior consistency. We propose Decoupled Latent Optimization (DLO), which relaxes the standard latent-optimization formulation into a quadratic-penalty objective over an auxiliary physical variable and a latent variable. The data-fidelity gradient acts in physical space, the diffusion sampler contributes only through a decoded prior sample, and the standard smoothed-velocity initialization of classical FWI is preserved. On the OpenFWI benchmark, DLO outperforms classical regularizers and existing diffusion-based methods under clean, noisy, and missing-trace acquisitions. The prior, trained on 70*70 OpenFWI models, transfers directly to the Marmousi and Overthrust benchmarks, where DLO recovers intricate fault structures and remains robust to initialization smoothing and measurement noise.

22.
Nature (Science) 2026-06-24

The mutational landscape of STING-induced immunity

Authors:

Stimulator of interferon genes (STING) is an evolutionary conserved immune signalling protein with key roles in host defence, cancer, senescence and inflammation1–3. Downstream of STING, type I interferon, inflammatory cytokine signalling and non-canonical autophagy are governed by a multilayered mechanism integrating ligand-induced structural transitions, protein–protein interactions and coordinated intracellular trafficking4–13. Despite its central role in immunity and relevance as therapeutic target14, the sequence elements that govern STING (in)activation in cells remain incompletely understood. Here we developed a massively parallel assay to systematically chart the sequence-function landscape of STING. Profiling thousands of single amino-acid variants, we identified structural and functional determinants that shape the immunostimulatory capacity of STING and its ability to translate ligand recognition into distinct signalling outputs. Cryogenic-electron microscopy structures of select STING hyperactive variants revealed new regulatory principles dictating conformational transition from inactive to signalling-competent states of STING. Mutational effects are widespread across the functional landscape and can sensitize STING towards the natural ligand 2′3′-cGAMP15–18 or decouple interferon induction from non-canonical autophagy, demonstrating a diversity of possible responses that can be accessed through single point substitutions. Finally, our data showed the clinical and evolutionary relevance of naturally occurring STING protein variants. Collectively, these findings define molecular principles that tune STING activity and chart the landscape of its functional potential across immune contexts. A massively parallel assay systematically charts the sequence-function landscape of the STING signalling protein, and the findings define molecular principles that tune STING activity and show its functional potential across immune contexts.

23.
arXiv (CS.CL) 2026-06-16

Human genetic evidence is associated with drug approval across therapeutic areas: an observational analysis of 26,278 target-disease pairs with temporal validation and feature ablation

Genetic evidence is enriched among approved drug targets: in an observational analysis of 26,278 target-disease pairs from Open Targets and ChEMBL, targets with any genetic association had a 3.25-fold higher approval rate than those without (OR = 3.25, 95% CI 2.79-3.79, p = 1.91e-42). A target-level analysis accounting for non-independence of pairs sharing the same gene gave OR = 2.79 (bootstrap 95% CI 2.22-3.53); the oncology pair-level OR of 6.72 attenuates to 2.71 at the target level, illustrating how non-independence inflates area-specific estimates. The enrichment replicated in post-2015 approvals (OR = 3.51, p = 1.72e-8). Feature ablation across six evidence types revealed that literature mining alone accounts for most classifier performance (AUPRC = 0.099 versus 0.109 for all features), consistent with temporal leakage from post-approval publications. Excluding literature, remaining evidence types retain above-baseline signal (AUPRC = 0.084, 1.63x baseline). Sensitivity analyses bracket the pair-level OR between 3.25 and 4.93. Genetic evidence alone yields only a 1.0-percentage-point absolute AUPRC gain and the best model has poor calibration; the classifier has limited practical predictive value. We catalogue 1,433 genetically supported Phase 1/2 pairs as a hypothesis-generating resource. All findings are observational.

24.
bioRxiv (Bioinfo) 2026-06-24

Development of Deep-Learning Models that Predict Quantitative Protein-Ligand Interac-tions in Glycobiology as a part of a Capstone Course

Glycans coat the surface of all cells, and every glycan is recognised by specific glycan-binding pro-teins (GBPs). There are no general tools that can accurately estimate the binding strength between glycan and GBP from the amino acid sequence of the GBP and the molecular structure of the glycan, represented as SMILES string. We describe models for predicting such binding strengths developed as a part of a Capstone Course at the University of Alberta. The models are trained on a dataset that combines BindingDB, a published database of small-molecule protein interactions, and data from glycan arrays measured by Consortium of Functional Glycomics (CFG). In this hybrid dataset of protein-ligand interactions the ligands are both glycans from CFG and small molecules from BindingDB; similarly, proteins include GBP and proteins from BindingDB. Three models are presented (i) ProMax which fuses ESM-2, MolFormer, and MolCLR features; (ii) APEX which constrains learning to a predetermined form, a physical model of binding; (iii) UltraMax adds inter-atomic distances for the ligands. To address the dataset's severe long-tail distribution, the models employ tail-aware losses for rare high-binding instances. Trained and evaluated on approximately one million protein–ligand pairs using hold-out splits for unseen molecules, the three models provide a unified framework for quantitative glycan-protein binding prediction. We observed that learning glycan-protein binding is harder than the similar task of learning small-molecule-protein interactions. Simple mirror-inversion tests led us to postulate that insufficient use of chiral features is an important source of difficulty in learning these interactions.

25.
bioRxiv (Bioinfo) 2026-06-15

SMS: Symmetric Mediation Statistics for Powerful High-Dimensional Mediation Analysis

Background: Mediation analysis of high-dimensional features, particularly molecular-level omics features, provides important opportunities to uncover biological mechanisms underlying human health and disease. However, two central statistical challenges remain: testing the composite-null hypothesis and maintaining power when the exposure-mediator and mediator-outcome associations differ substantially in statistical significance. Existing methods typically rely on accurate estimation of the proportions of the three null types or on the maximum of the two association p-values, and may not always control the FDR well and may have limited power under imbalanced significance. Methods: We propose SMS, a new statistical framework based on symmetric mediation statistics. By exploiting symmetry, SMS calibrates the composite null distribution as a whole for FDR control. It also allows flexible combinations of the two association p-values, including the maximum, and then enables construction of an omnibus test. Moreover, it permits direct use of effect-size estimates, bypassing the need to compute p-values. Results: SMS controlled the FDR across a wide range of simulation scenarios while achieving a substantial sensitivity gain, often around 20 percentage points, over existing methods including HDMT, DACT, and DEI-B. Applications to a metabolomics dataset and a DNA methylation dataset further corroborated these findings. Notably, SMS discovered five plausible mediators in the metabolomics dataset that were missed by all existing methods considered.