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01.
arXiv (quant-ph) 2026-06-19

Quantum Computing Applications for Flight Trajectory Optimization

arXiv:2304.14445v2 Announce Type: replace Abstract: Major players in the global aerospace industry are shifting their focus toward achieving net carbon-neutral operations by 2050. A considerable portion of the overall carbon emission reduction is expected to come from new aircraft technologies, such as flight path optimization. In pursuing these sustainability objectives, we delve into the capacity of quantum computing to tackle computational challenges associated with flight path optimization, an essential operation within the aerospace engineering domain with important ecological and economic considerations. In recent years, the quantum computing field has made significant strides, paving the way for improved performance over classical algorithms. In order to effectively apply quantum algorithms in real-world scenarios, it is crucial to thoroughly examine and tackle the intrinsic overheads and constraints that exist in the present implementations of these algorithms. Our study delves into the application of quantum computers in flight path optimization problems and introduces a customizable modular framework designed to accommodate specific simulation requirements. We examine the running time of a hybrid quantum-classical algorithm across various quantum architectures and their simulations on CPUs and GPUs. A temporal comparison between the conventional classical algorithm and its quantum-improved counterpart indicates that achieving the theoretical speedup in practice may necessitate further innovation. We present our results from running the quantum algorithms on IBM hardware and discuss potential approaches to accelerate the incorporation of quantum algorithms within the problem domain.

02.
arXiv (CS.CV) 2026-06-17

MagicSim: A Unified Infrastructure for Executable Embodied Interaction

Robot learning and embodied agents now require simulation to serve as a shared execution substrate linking control, skills, and planning, not only as a renderer, controller testbed, or fixed task environment. Existing pipelines split these layers with "magic" actions, disconnected training environments, or forward-only renders that cannot reproduce, evaluate, and annotate the same episode. We present MagicSim, an embodied interaction infrastructure built around one deterministic batched runtime and a shared Markov decision process (MDP). From YAML-first specifications that decouple contents, placement, behavior, and agent exposure, MagicSim constructs diverse executable worlds spanning task families, interaction regimes, physics, layouts, sensors, avatars, and robot embodiments in one reset-and-step loop. A common execution interface grounds high-level commands through controllers, atomicskills, planner primitives, and asynchronous planning, realizing them as robot actions rather than simulator-side state edits. One task definition supports three capabilities: benchmark and RL evaluation, an autocollect interface that automatically turns commands into grounded trajectories, and agent/VLM-facing interaction. For automatic execution, commands flow through a Command->Skill->Planner->Robot->Record pipeline, while per-environment command, skill, planning, retry, annotation, and episode states advance independently above the shared physics tick. Successful rollouts are saved as structured multimodal trajectories aligning language supervision, action representations, visual/geometric representations, and task-level status with the executed episode. MagicSim thus unifies diverse world construction, embodied execution, task evaluation, automatic rollout generation, and interactive agent interfaces in one planner-in-the-loop runtime.

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

ST-DiffEye: Diffusion-based Continuous Gaze Generation via Joint Scanpath-Trajectory Modeling

We study the problem of human gaze modeling, which aims to generate the gaze patterns a viewer produces while observing a visual stimulus. Gaze is primarily captured through two modalities: continuous eye-tracking trajectories, which describe fine-grained motion dynamics, and discrete scanpaths, which describe high-level fixation structure. Because gaze varies substantially across viewers and trials, we treat this variability as a defining property rather than noise and model gaze as a stochastic generative process. Existing generative gaze models supervise on only one of these two representations in isolation. We hypothesize that trajectories and scanpaths describe gaze at complementary scales and are jointly informative during training, and test this hypothesis through ST-DiffEye, a joint trajectory-scanpath diffusion framework that couples both modalities by concatenating them as an additional raw input channel, requiring no architectural overhead beyond an input and output channel expansion. We further introduce a principled evaluation framework based on the Continuous Ranked Probability Score (CRPS), which generalizes any existing sequence similarity metric into a proper scoring rule that jointly assesses the accuracy and diversity of generated gaze. Experiments on task-driven visual search, covering both target-present and target-absent scenarios, and on free-viewing benchmarks demonstrate state-of-the-art performance. These results, along with detailed ablations, confirm the benefit of joint modeling and the value of distribution-aware evaluation in capturing the intrinsic variability of human gaze. Project webpage: https://st-diffeye.github.io/

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

Squeeze-Release: Iterative Pruning with Exact Structural Minimization

arXiv:2606.14346v1 Announce Type: cross Abstract: Unstructured pruning produces sparse weight tensors, but the standard implementation keeps tensor shapes unchanged so the deployed model is no smaller than before pruning. We present an exact structural rewrite, which we call minimization, that converts a masked network into a smaller dense network with the same forward function up to floating-point rounding. The Squeeze-Release cycle iterates pruning and minimization with an intermediate release step that re-enables the exact-zero positions inside the compacted tensors as small calibrated noise, turning otherwise wasted capacity back into trainable parameters. Successive cycles use that capacity to find structural redundancy a single pass cannot reach. We additionally introduce CompensatedLayerNorm, a function-preserving replacement for LayerNorm that extends minimization to channel reduction across LayerNorm-equipped residual streams. Squeeze-Release compresses the deployable network to 39x smaller than the unpruned model on a fully-connected model network and 14.8x smaller on modern CNN (ConvNeXt-Tiny), at comparable accuracy. In addition we prove that the rewrite can be extended to transformer architectures.

05.
arXiv (quant-ph) 2026-06-12

From 2D Yang-Mills to Calogero-Sutherland via a colored particle

arXiv:2606.13388v1 Announce Type: cross Abstract: We study Yang-Mills theory coupled to a particle on a cylinder, where gauge invariance and compactness reduce the dynamics to a finite dimensional quantum system. In the Abelian case, this yields a model equivalent to the Landau problem on a torus, with a degenerate ground state structure. We generalize this construction to non-Abelian gauge groups and show that, for SU(N), the system reduces to a one dimensional quantum many body problem with a singular Calogero-Sutherland-type interaction.

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

Exploring How Agent Voice Accents Shape Human-AI Collaboration in K-12 Group Learning

arXiv:2606.12805v1 Announce Type: cross Abstract: Collaboration is widely recognized as a cornerstone of 21st-century education, yet teachers still encounter persistent challenges in fostering productive peer interaction. LLM conversational peer agents introduce new possibilities for mediating in-person group work, raising questions about how persona design, particularly their voice characteristics, shapes learners' perceptions, trust, and interactional dynamics. While prior work has examined agent accent effects in one-to-one settings, little is known about how these effects manifest in groups. We conducted a between-subjects mixed-methods study with 33 teachers examining how a GenAI voice agent with different accents (British, Indian, and African American) influenced collaboration and agent perception. Across surveys, group interaction analyses, and artifacts, we find that accent shaped participants' mental models and the roles the agent assumed in group interaction. The British-accented agent was largely treated as a tool and engaged in detached, utility-based ways, whereas Indian- and African American-accented agents were more readily anthropomorphized and integrated as peers. These role expectations influenced trust, engagement, and reliance over time. This work advances understanding of how GenAI's sociolinguistic design features shape group dynamics in CSCL, with implications for designing culturally inclusive AI partners in group learning.

07.
arXiv (quant-ph) 2026-06-15

Quantum Entanglement of Bethe States

arXiv:2606.14140v1 Announce Type: cross Abstract: We investigate the quantum entanglement of Bethe states across a family of integrable spin chains, including the XXX$_{\frac{1}{2}}$ model, its higher-spin generalizations (XXX$_s$), and the non-compact $SL(2,\mathbb{R})$ chain. For on-shell eigenstates, we perform a comprehensive scan of the bipartite entanglement entropy across the entire spectrum of finite chains with periodic boundary conditions, and identify the Bethe solutions that minimize and maximize the entanglement. These extremal solutions follow systematic, spin-dependent patterns in the Bethe quantum numbers. In the XXX$_{\frac{1}{2}}$ spin chain, for the antiferromagnetic chain, the state with minimal entropy always coincides with the lowest-energy state (the ground state) within a given fixed-magnon sector. For the higher-spin XXX$_s$ model, however, the lowest-entropy state is not always identical to the ground state, and can even be the state of highest energy. By contrast, the Bethe roots that maximize entropy exhibit considerably more intricate structure. Our analysis further reveals how special Bethe root configurations, such as singular and strange solutions, affect entanglement, and it uncovers characteristic entanglement features in the non-compact $SL(2,\mathbb{R})$ chain that are absent from compact spin chains. For off-shell Bethe states, we develop an optimization algorithm that extremizes the entanglement entropy over rapidity distributions, enabling us to explore the maximum entanglement achievable by a Bethe state without imposing the Bethe ansatz equations.

08.
arXiv (CS.CV) 2026-06-17

ReAge3D: Re-Aging 3D Faces with View Consistency

We present a novel framework for realistic and controllable 3D face re-aging which produces highly detailed, identity-preserving results. Existing 3D editing methods, while effective for coarse semantic changes, are not well suited for re-aging, as even small inconsistencies across re-aged 2D views can lead to over-smoothing of subtle but perceptually important age-related details. To address this challenge, we first introduce a 2D diffusion-based re-aging model, DiffReaging, trained on synthetically generated image pairs. We further propose a center-out editing propagation strategy that leverages this re-aging model to reconstruct multi-view-consistent re-aged images. Specifically, starting from a re-aged frontal pivot view, we reconstruct the remaining views through warping and our proposed Masked-DiffReaging process. By injecting existing content at every step of the diffusion process, Masked-DiffReaging ensures that the reconstructed regions remain coherent with existing pixels. The resulting consistent set of re-aged views supervises the optimization of the re-aged 3D representation. Our method outperforms existing 3D editing techniques both visually and quantitatively, enabling smooth, fine-grained control over age transformations in 3D face models.

09.
arXiv (CS.CV) 2026-06-15

Avatar V: Scaling Video-Reference Avatar Video Generation

Generating avatar videos that are not merely visually similar to a target individual but behaviorally recognizable, faithfully reproducing their talking rhythm, gestural tendencies, and expression dynamics, remains an open challenge. Existing methods predominantly condition on single static images, which provide insufficient identity information and cannot capture dynamic motion traits, while standard pixel-level objectives underserve the perceptually critical facial regions that determine avatar fidelity. We present Avatar V, a production-scale framework that addresses these limitations through video-reference-conditioned identity modeling. Rather than compressing identity into fixed-size embeddings, the model conditions directly on the full token sequence of a reference video, learning to reproduce both static identity attributes (facial geometry, skin texture) and dynamic behavioral patterns (talking rhythm, micro-expressions) through attention over the reference context. We introduce Sparse Reference Attention, an asymmetric mechanism achieving linear-complexity conditioning on arbitrarily long references; a motion representation stream enabling closed-loop talking style transfer; and an identity-aware super-resolution refiner inheriting the full reference conditioning. These are supported by a data engine curating 100M+ training clips from 50M raw videos, and a five-stage training pipeline with flow matching pre-training, personality fine-tuning, two-phase distillation (>10x acceleration), and RLHF alignment, deployed across thousands of GPUs. Avatar V generates 1080p videos of unlimited duration, achieving state-of-the-art identity preservation, lip synchronization, and generation quality on our cross-scene benchmark, consistently outperforming leading systems including Seedance 2.0, Kling O3 Pro, Veo 3.1, and OmniHuman 1.5 in both automated metrics and human evaluation.

10.
arXiv (CS.AI) 2026-06-16

Proximal Policy Optimization for Amortized Discrete Sampling

arXiv:2606.15793v1 Announce Type: cross Abstract: This paper explores policy gradient algorithms for training stochastic policies to sample from structured discrete probability distributions under the Generative Flow Network (GFlowNet) framework. Building on extensive theoretical connections between GFlowNets and entropy-regularized reinforcement learning, we derive equivalents of standard policy gradient algorithms for training GFlowNets, as well as experimentally explore their various methodological aspects, including baseline training and advantage estimation. Most importantly, our work is the first to derive and successfully apply proximal policy optimization to GFlowNets, showing its improved convergence speed and data efficiency compared to standard GFlowNet training objectives on benchmarks ranging from synthetic energies to molecular graph generation.

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

$\alpha$-fair heterogeneous agent reinforcement learning

arXiv:2606.13076v1 Announce Type: cross Abstract: Cooperation in multi-agent systems is typically optimized through utilitarian objectives that maximize overall efficiency but fail to account for reward distribution, often resulting in inequitable "leader-follower" dynamics. While fairness-based approaches encourage pro-social behaviors where every agent benefits from cooperation, many current algorithms - including those utilizing reward shaping - break the stationarity of Markov Games or lack rigorous theoretical guarantees. This creates a critical gap between fair objective methods and theoretically safe learning frameworks. We propose a novel framework that bridges $\alpha$-fairness with Heterogeneous-Agent Trust Region Learning (HATRL), ensuring monotonic improvement and convergence toward Nash Equilibria. Our approach leverages a fair advantage function that dynamically weights agent utilities based on their expected returns, allowing the global objective to transition from purely utilitarian efficiency to $\alpha$-fairness welfare based on the parameter $\alpha$. We introduce two practical algorithms, $\alpha$-fair HATRPO and $\alpha$-fair HAPPO, and demonstrate through experiments in sequential social dilemmas like CleanUp and CommonHarvest that they perform better than HATRL's algorithms from a utilitarian point of view while achieving socially higher outcomes.

12.
bioRxiv (Bioinfo) 2026-06-11

Calibrated Uncertainty Quantification for Patient-Level AML Drug Sensitivity Prediction Using Split Conformal Prediction

Accurate prediction of ex vivo drug sensitivity in acute myeloid leukemia (AML) patients from transcriptomic data is a critical challenge for precision oncology. Existing computational approaches have explored uncertainty quantification in cancer drug response prediction primarily using cell line data, while patient-level AML models typically rely on heuristic confidence measures rather than statistically calibrated uncertainty estimates. Here, we present a framework applying split conformal prediction to patient-level AML drug response modeling using the BeatAML 2.0 cohort. We trained Elastic Net and XGBoost regressors on bulk RNA-seq gene expression profiles from 318 AML patients, analyzing 34,764 patient-drug observations across 122 compounds. Baseline models achieved median Pearson R values of 0.291 (Elastic Net) and 0.281 (XGBoost) across 122 drugs. Wrapping these models with split conformal prediction yielded well-calibrated prediction intervals across three confidence levels: empirical coverages of 81.4%, 90.7%, and 95.5% against nominal targets of 80%, 90%, and 95%, respectively. Analysis of prediction interval widths revealed substantial drug-class-specific uncertainty patterns, with HDAC and BCL-2 inhibitors exhibiting markedly higher uncertainty than MDM2 inhibitors, suggesting a potential association between transcriptomic predictability and drug mechanism of action, although several drug classes were represented by only a small number of compounds. Predictive uncertainty was not significantly associated with ELN2017 molecular risk classification (Kruskal-Wallis p=0.395) or NPM1 mutation status (p=0.788). These results demonstrate that statistically valid uncertainty quantification can be achieved for patient-level AML drug response prediction despite substantial biological heterogeneity. to the best of our knowledge, no published study has applied split conformal prediction to patient-level ex vivo drug sensitivity prediction in the BeatAML cohort, providing a principled alternative to heuristic confidence scoring approaches. Keywords: Acute myeloid leukemia (AML); Ex vivo drug sensitivity; Conformal prediction; Uncertainty quantification; Precision oncology; BeatAML; Transcriptomic biomarkers; Machine learning.

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

Effective and Low-cost Lane-based Map Localization for Vehicle-Centric Route Generation

Driver-centric route representation plays a vital role in intuitive driving guidance systems. This paper presents OLRA, a low-cost, map-localization-based framework that derives driver-view-aligned routes by matching map-based navigation routes with camera-detected lane markings. This alignment process mutually enhances vehicle localization accuracy and visual route consistency. To bridge the evaluation gap across different paradigms, we introduce practical route evaluation metrics and benchmark OLRA against OpenPilot, a representative direct-generation approach. Experimental results on the nuScenes dataset demonstrate that OLRA outperforms OpenPilot in complex road segments and in route estimation at distance beyond 20 meters, achieving lower overall Euclidean error. This study is expected to promote future research in low-cost, maplocalization-based route generation methods.

14.
arXiv (quant-ph) 2026-06-11

Clifford disentanglers for entanglement reduction in molecular electronic structure simulations

arXiv:2606.12056v1 Announce Type: new Abstract: Entanglement is a key bottleneck limiting the efficiency of tensor-network and quantum simulations of molecular electronic structures. Here, we systematically assess and extend Clifford disentanglers as a structure-preserving approach to entanglement reduction: they can modify the entanglement structure of qubit wavefunctions while retaining the Pauli-string form of qubit Hamiltonians. To enable a practical search over Clifford transformations, we classify Clifford operators by their action on the Schmidt spectrum across a bipartition, reducing the two- and four-qubit search spaces to 20 and 91392 representatives, respectively. Embedded in an iterative Clifford-augmented matrix product state framework, these transformations reduce the energy errors at fixed bond dimension for the molecular test cases studied and mitigate the dependence on orbital orderings and fermion-to-qubit mappings. We further show that Clifford disentanglers can also benefit quantum simulations such as the shallow-circuit variational quantum eigensolver calculations. Together, these results establish Clifford disentanglers as a useful structure-preserving entanglement-engineering tool for tensor-network and quantum simulations of molecular electronic structure, while also clarifying their correlation dependence and motivating future developments.

15.
arXiv (math.PR) 2026-06-17

On Injectivity of Phase Retrieval

Authors:

arXiv:2606.17922v1 Announce Type: cross Abstract: In this short note, we prove that if $A \in \mathbb C^{N \times M}$ with $N=4M-5$ has i.i.d.\ standard complex Gaussian entries, then the probability that the phase retrieval map generated by $A$ is not injective is positive. This proves Part (1) of a conjecture of Cynthia Vinzant, which was later restated by Afonso S. Bandeira in [BDL+26]. The main result of this paper was obtained using generative AI, in particular the Rethlas system.

17.
Science (Express) 2026-05-07

Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design | Science

Authors: Unknown Author

A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.

18.
medRxiv (Medicine) 2026-06-18

Avidity of anti-pertussis toxin antibodies is associated with symptomatic Bordetella pertussis infection in a novel controlled human infection model

Background The association between functional antibody responses following Bordetella pertussis infection and symptomatic disease remains unclear. We characterized the maturation of anti-pertussis toxin (PT) IgG avidity after human challenge with B. pertussis and determined its association with symptomatic infection. Methods Healthy adults were intranasally inoculated with live B. pertussis organisms in a controlled human infection model and monitored for development of pertussis symptoms (NCT05136599). Serum samples were collected one day before inoculation and at 14, 28, 56, 180, and 365 days post challenge. Anti PT IgG avidity was tested using a titration of ammonium isothiocyanate (the bond breaking agent) to quantify a wide range of antibody avidities from low to very-high. Associations between covariates and avidity were examined using linear regression models, and high dimensional analyses were used to integrate all data. Findings Anti PT IgG avidity increased in both symptomatic (n=20) and asymptomatic (n=10) participants after the challenge, reached maximum levels at day 56, and then declined through day 365. Symptomatic participants developed significantly higher levels of high- and very high-avidity anti-PT antibodies at 28, 56, 180, and 365 days post-challenge compared with those who remained asymptomatic. In multivariate analyses, symptomatic infection was associated with higher levels of high and very high avidity anti-PT IgG at day180 and365 after challenge. Distinct avidity profiles in symptomatic vs asymptomatic participants emerged at day28 onwards, with the former group having higher levels of antibodies with higher avidities. However, levels of medium-high, high and very high avidity antibodies in symptomatic participants were lower at day 365 after challenge compared to their peak levels. Interpretation Anti-PT IgG avidity was associated with symptomatic B. pertussis infection and thus may serve as a surrogate of clinical disease outcome. These results highlight that antibody avidity provides an additional functional assay besides antibody quantitation to dissect immune responses to pertussis. Further investigation of anti PT IgG avidity should be pursued in natural pertussis outbreaks to determine whether it might be used to differentiate symptomatic from asymptomatic infections for epidemiologic purposes.

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

A tensor network approach for chaotic time series prediction

arXiv:2505.17740v2 Announce Type: replace Abstract: Making accurate predictions of chaotic time series is a complex challenge. Reservoir computing, a neuromorphic-inspired approach, has emerged as a powerful tool for this task. It exploits the memory and nonlinearity of dynamical systems without requiring extensive parameter tuning. However, selecting and optimizing reservoir architectures remains an open problem. Next-generation reservoir computing simplifies this problem by employing nonlinear vector autoregression based on truncated Volterra series, thereby reducing hyperparameter complexity. Nevertheless, the latter suffers from exponential parameter growth in terms of the maximum monomial degree. Tensor networks offer a promising solution to this issue by decomposing multidimensional arrays into low-dimensional structures, thus mitigating the curse of dimensionality. This paper explores the application of a previously proposed tensor network model for predicting chaotic time series, demonstrating its advantages in terms of accuracy and computational efficiency compared to conventional echo state networks. Using a state-of-the-art tensor network approach enables us to bridge the gap between the tensor network and reservoir computing communities, fostering advances in both fields.

20.
medRxiv (Medicine) 2026-06-22

A Drug-Specific, Half-Life-Adjusted Framework for Classifying CNS-Active Systemic Therapy Exposure During and After Radiotherapy

Clinical oncology datasets often store systemic therapy as a regimen label with a start date and an end date. Those records are clinically recognizable but can be analytically incomplete when the research question concerns whether a patient was exposed to a concurrent CNS-active drug (cCNS-aD) or an adjuvant CNS-active drug (aCNS-aD) around radiotherapy. Contemporary CNS-oncology studies usually define CNS activity by empiric drug lists and define concurrency by fixed calendar windows, although the literature shows substantial heterogeneity across both concepts. This paper proposes a generalizable framework for converting raw systemic therapy records into reproducible cCNS-aD and aCNS-aD variables, useful in subgrouping for clinical studies. The framework uses a transparent CNS scoring model based on three clinical evidence components: intracranial objective response rate, consensus CNS endorsement, and intrathecal route of administration. It then defines a pharmacokinetic exposure proxy as the recorded end date plus five half-lives. Concurrent exposure is classified by overlap with the radiotherapy interval, while post-radiotherapy exposure is classified by overlap with a prespecified post-RT attribution window. The framework separately identifies post-RT pharmacokinetic persistence and post-RT treatment initiation, allowing investigators to distinguish continued exposure from true adjuvant initiation. This is a methodological framework and reference implementation. Implementation audits and endpoint-specific sensitivity analyses remain necessary before use as a definitive exposure classifier

21.
arXiv (math.PR) 2026-06-16

Steady-State Approximation Error of Heterogeneous Mean-Field Models

Authors:

arXiv:2606.09022v2 Announce Type: replace Abstract: This paper studies heterogeneous mean-field models in which agent parameters are sampled from a population distribution. We establish an $O(1/M)$ bound on the steady-state mean-square error between the occupancy measure of the $M$-agent system and the corresponding annealed mean-field equilibrium. The analysis extends Stein's method for homogeneous mean-field models and reveals a fundamental difference between homogeneous and heterogeneous systems. While stability of the mean-field dynamics is sufficient in the homogeneous setting, heterogeneous systems further require uniform robustness of the occupancy dynamics with respect to perturbations of the initial condition. The results are illustrated through a heterogeneous SIS epidemic model.

22.
bioRxiv (Bioinfo) 2026-06-12

Computational Design of Optimal Sequences for Targeted Hypermutagenesis Using Recombination-Coupled Diversity-Generating Retroelements

Diversity-generating retroelements (DGRs) are natural systems that accelerate evolution via targeted hypermutation at adenines. We previously developed DGRec, a system combining DGRs and recombineering for programmable mutagenesis in Escherichia coli. We here address two important issues with DGRec: the dependence of mutagenesis efficiency on the dgrRNA secondary structure and the variability of the reverse-transcription biases with sequence context and position. First, we introduce and validate a method to recode non-functional templates, i.e. with low mutagenesis efficiency, into highly functional ones through synonymous mutations. Second, we develop a Long Short-Term Memory (LSTM) model to predict DGRec mutational profiles for any given template sequence. By integrating this LSTM model with our recoding method, we establish a comprehensive workflow for customized directed evolution, enabling researchers to precisely fine-tune DGRec in vivo mutagenesis to their engineering needs.

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

A Decision-Theoretic View of Test-Time Training: When, How Far, and Which Directions to Adapt

arXiv:2606.15569v1 Announce Type: new Abstract: Test-time training (TTT) adapts a pretrained model to each prompt via parameter updates, improving accuracy under pretraining-to-test distribution shifts. Yet, its performance often suffers from instability and sensitivity to hyperparameters such as update steps and subspace. We explain this behavior through a decision-theoretic lens, treating TTT as implicit Bayesian inference in the kernel regime. Under a Gaussian process benchmark, we show that TTT reduces prediction error when updates are spectrally matched to the prompt's signal-to-noise ratio and aligned with query-relevant eigen-directions. This perspective underpins the following results: (1) we show when fixed update steps and subspaces fail under distribution shifts, motivating adaptive strategies; (2) we prove that selecting update steps via prompt evidence admits a PAC-Bayes guarantee against overfitting; and (3) we characterize the Bayes-optimal update subspace under a linear-Gaussian correction model, yielding a scoring rule for selecting Transformer blocks and heads. Our theory helps explain the empirical instability of TTT, taking a step toward principled guidance for when, how far, and which directions to adapt.

25.
bioRxiv (Bioinfo) 2026-06-18

Metrics for Evaluating Biological AI Model Predictive Accuracy at the Data-Substrate Level

Authors:

Reports in the biological literature disagree on whether a given model can predict a biological outcome from a given data sample — one study finding a model capable, another, on the same kind of data, finding it is not. This is particularly a challenge in relation to LLMs–where the models are large and opaque, with weights and training data inaccessible.textbf{ }Such disagreements cannot be settled by directly inspecting the model. To address this challenge, we considertextbf{ }an alternative approach: assessing whether the data sample is adequate to support the prediction asserted. For a given dataset, its substrate — the underlying structure of the data — determines what any model can recover, independent of architecture or capacity. At the same time, predicting the present state of a biological process and predicting the direction of its future change are different tasks; the second is supportable among AI models only where the data encode direction as determinable from the state — a property we call encoding — and is unsupportable where the same observed state precedes change in opposite directions — a property we call non-identifiability, in the informational rather than the statistical sense. We introduce two generic metrics, Predictive Blindness Risk (PBR) and Prediction Indeterminacy Measure (PIM), that evaluate a data substrate for predictive accuracy directly — without access to model weights, architecture, or training data — and locate the regions of a data substrate where a predictive claim can be supported and where it cannot. Using human biological subjects, we employ the Yale Brain Metastases Longitudinal Data (1,430 human subjects; 11,892 MRI studies; four sequences) and show that direction of change was non-identifiable across regions encompassing the majority of transitions; a nonlinear AI model gained essentially nothing over majority-direction prediction there while recovering direction near-perfectly where the state encoded it; and model accuracy tracked data-substrate resolvability continuously (Spearman {rho} = -0.95 to -1.00). The metrics adjudicate, before any model is trusted and from the data alone, where claims of predictive accuracy — of state, or of the law of change — can be supported.