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

BadScientist: Can a Research Agent Write Convincing but Unsound Papers that Fool LLM Reviewers?

arXiv:2510.18003v2 Announce Type: replace-cross Abstract: The convergence of LLM-powered research assistants and AI-based peer review systems creates a critical vulnerability: fully automated publication loops where AI-generated research is evaluated by AI reviewers without human oversight. We investigate this through BadScientist, a framework that evaluates whether fabrication-oriented paper generation agents can deceive multi-model LLM review systems. Our generator employs presentation-manipulation strategies requiring no real experiments. We develop a rigorous evaluation framework with formal error guarantees (concentration bounds and calibration analysis), calibrated on real data. Our results reveal systematic vulnerabilities: fabricated papers achieve acceptance rates up to . Critically, we identify concern-acceptance conflict – reviewers frequently flag integrity issues yet assign acceptance-level scores. Our mitigation strategies show only marginal improvements, with detection accuracy barely exceeding random chance. Despite provably sound aggregation mathematics, integrity checking systematically fails, exposing fundamental limitations in current AI-driven review systems and underscoring the urgent need for defense-in-depth safeguards in scientific publishing.

02.
arXiv (quant-ph) 2026-06-25

Routing Codes: High-Rate Quantum LDPC Codes with Short, Parallel Non-Local Connectivity

arXiv:2606.25330v1 Announce Type: new Abstract: Quantum low-density parity-check (qLDPC) codes are promising candidates for realizing large-scale fault-tolerant quantum computing. Although many codes with favorable theoretical parameters have been developed, their practical adoption must take hardware implementability into account. For mainstream quantum platforms such as superconductors and neutral atoms, the connectivity, the length of non-local couplings, and the complexity of wiring or atom rearrangement are key factors that dictate the difficulty of hardware realization. Here, we propose a new family of qLDPC codes, termed routing codes. Within this family, we find explicit instances whose encoding rates are comparable to those of bivariate bicycle (BB) codes, while systematically reducing qubit connectivity, shortening the length of non-local couplings, and, crucially, making all non-local couplings mutually parallel. This parallelism fundamentally eliminates wiring crossings in superconducting multi-layer architectures and drastically simplifies the scheduling of atom movement in neutral-atom arrays. Under circuit-level simulation, the weight-7 routing codes reduce the physical qubit overhead by approximately a factor of 8, compared to surface codes achieving a same logical error rate. These results establish routing codes as a hardware-centric qLDPC family that bridges the gap between theoretical optimality and near-term physical feasibility.

03.
arXiv (CS.CL) 2026-06-12

GENEB: Why Genomic Models Are Hard to Compare

Progress in genomic foundation models is difficult to assess due to fragmented benchmarks, incompatible evaluation protocols, and task-specific reporting. As a result, claims of superiority or generality across models are often not directly comparable. We introduce GENEB, a large-scale diagnostic benchmark that evaluates frozen representations from 40 genomic foundation models across 100 tasks spanning 13 functional categories under a unified probing-based protocol, including few-shot regimes. GENEB enables controlled comparison across model scale, architecture, tokenization, and pretraining data while explicitly exposing task-level trade-offs. Our analysis shows that aggregate leaderboards are unstable: model rankings vary sharply across task categories, scale provides only modest and inconsistent gains, and architectural and pretraining alignment frequently outweigh parameter count. These results highlight limitations of current evaluation practices and position GENEB as a reference framework for principled comparison and category-aware model selection in genomic machine learning.

04.
medRxiv (Medicine) 2026-06-22

A Controlled Human Malaria Infection model for relapsing Plasmodium vivax

Background Plasmodium vivax malaria relapses are a major source of morbidity and onward transmission of infection. The underlying mechanisms are poorly understood and current therapies sub-optimal. We examined the safety and feasibility of a controlled human malaria infection (CHMI) model for relapsing P. vivax. Methods We conducted an open-label, proof-of-concept, CHMI study of relapsing P. vivax. Healthy, malaria-naive, Duffy-positive adults aged 18-45 years with extensive CYP2D6 metaboliser phenotype and normal blood glucose-6-phosphate dehydrogenase (G6PD) levels were recruited in Oxford, UK. Mosquito-bite CHMI was performed in Nijmegen, The Netherlands, using Anopheles stephensi mosquitoes infected with PvW1, a clonal isolate of P. vivax from Thailand. All follow-up visits were conducted in Oxford, UK. Primary P. vivax infections (qPCR > 500 genome copies/mL) were treated with artemether-lumefantrine (80mg/480mg at 8, 24, 36, 48 and 60 hours). From Day 28 following CHMI, participants attended a fortnightly clinic for clinical review and qPCR blood sampling, with additional assessments performed for any reported symptoms. P. vivax relapse infections (qPCR > 500 genome copies/mL) were treated with artemether-lumefantrine as per primary infection. Definitive anti-malarial treatment with atovaquone-proguanil (1000mg/400mg once daily for three days) and primaquine (0{middle dot}5 mg/kg/day for 14 days) was administered six months following CHMI, regardless of parasitaemia or symptoms. The primary objective was to assess the safety, feasibility and frequency of relapsing P. vivax after CHMI. Remote follow-up (5 years) is ongoing. The study is registered with ISRCTN registry (ISRCTN48625883). Findings 20 participants were screened for eligibility from 21 January 2025. Five participants (median age 22 years) underwent CHMI (five infected mosquitoes per participant) on 15 April 2025. All participants developed primary P. vivax infection and experienced at least one relapse infection. Two participants experienced a second relapse. Overall incidence rate was 3{middle dot}6 relapse infections per person-year. Solicited adverse events were mild or moderate and there were no serious adverse events. Definitive anti-malarial treatment was administered to all participants. One participant experienced primaquine-induced methaemoglobinaemia, resolving with early discontinuation of treatment (total dose 5{middle dot}3 mg/kg). To date, more than six months after primaquine treatment, no further relapses have been recorded. Interpretation CHMI of relapsing P. vivax is safe and feasible, allowing exploration of the mechanisms underlying relapse infections and providing a platform for future anti-relapse efficacy studies. Funding European Union Horizon Europe programme and UK Research and Innovation (UKRI) via OptiVivax consortium; UK National Institute for Health and Care Research Biomedical Research Centre: Oxford; and UK Medical Research Council.

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

Closing the Reflection Gap: A Free Calibration Bonus for Agentic RL

作者:

arXiv:2606.14211v1 Announce Type: new Abstract: LLMs are increasingly deployed as agents that interact with external environments and observe feedback such as execution results, error messages, and tool outputs. A well-functioning agent should be able to leverage this feedback to accurately assess its own performance. Yet we find a persistent reflection gap: LLM agents tend to mis-assess their own outputs after observing concrete environment feedback – even for questions they correctly answered – and standard RL barely helps due to a credit-assignment mismatch. To close this gap, we propose RefGRPO, a simple yet effective fix that augments standard RL algorithms with two key ingredients: a free calibration bonus computed by contrasting the agent's own reflection with the actual outcome (requiring no additional reward model, LLM judge, or external annotation), and a dynamic schedule on its coefficient. Compared to standard RL baselines, our method simultaneously improves reflection calibration (e.g., reduces underconfidence rate $44.4\% \to 7.7\%$) and task accuracy (e.g., $75.1\% \to 76.5\%$) on text-to-SQL across five benchmarks. The resulting calibrated reflection turns the agent into its own verifier grounded in environment feedback, which further enables (i) better self-improvement that uses reflections as pseudo-rewards without outcome supervision, and (ii) more effective test-time selective prediction by committing only to rollouts flagged as correct.

06.
medRxiv (Medicine) 2026-06-19

Rumination as a cognitive vulnerability factor in perinatal bereavement: evidence from the CARING study

Purpose. Perinatal loss is associated with a high risk of persistent psychological distress, including prolonged grief, depression, anxiety, and post-traumatic stress symptoms. Cognitive processes such as rumination may play a crucial role in maintaining and amplifying distress following loss, yet their specific contribution in perinatal bereavement remains underexplored. Methods. The CARING (Cognitive Analysis and Rumination INvestigation in perinatal Grief) study employed a cross-sectional design involving 298 parents who experienced perinatal loss within the previous five years. Participants completed an anonymous online survey including measures of depressive rumination (Ruminative Response Scale, RRS), angry rumination (Anger Rumination Scale, ARS), perinatal grief (Perinatal Grief Scale, PGS), general psychopathology (SCL-90), and post-traumatic stress symptoms (NSESSS). Non-parametric analyses were conducted to examine associations between rumination patterns and psychological outcomes. Results. Higher levels of rumination were significantly associated with greater perinatal grief, depressive and anxiety symptoms, and post-traumatic stress. Depressive rumination showed consistently stronger associations with all outcomes compared to angry rumination. Participants presenting both depressive and angry rumination exhibited the highest levels of grief intensity, psychological distress, and PTSD symptoms, suggesting a graded relationship between rumination patterns and severity of distress. Rumination levels were not significantly associated with gestational age at loss or with having received psychological support. Conclusions. Rumination, particularly in its depressive form, appears to function as a transdiagnostic cognitive vulnerability factor in perinatal bereavement. These findings highlight rumination as a potential target for early screening and tailored psychological interventions aimed at reducing long-term distress following perinatal loss.

07.
arXiv (quant-ph) 2026-06-19

Quantum Algebraic Diversity: Single-Copy Density Matrix Estimation via Group-Structured Measurements

arXiv:2604.03725v3 Announce Type: replace Abstract: We extend the algebraic diversity (AD) framework from classical signal processing to quantum measurement theory. The Quantum Algebraic Diversity (QAD) Theorem establishes that a group-structured positive operator-valued measure (POVM) applied to a single copy of a quantum state produces a full-rank, group-averaged density matrix estimator whose eigenbasis and eigenvalue ordering track those of the true density matrix, with a bias toward the symmetrized state, analogous to the classical recovery of covariance eigenstructure from a single observation. We establish a Classical-Quantum Duality Map connecting classical covariance estimation to quantum state tomography, and an Optimality Inheritance Theorem showing that classical group optimality transfers to quantum settings via the Born map within the group-averaged family. SIC-POVMs are identified as AD with the Heisenberg-Weyl group and mutually unbiased bases as AD with the Clifford group, revealing the hierarchy $\mathrm{HW}(d) \subseteq \mathcal{C}(d) \subseteq S_d$ that mirrors the classical $\mathbb{Z}_M \subseteq G_{\min} \subseteq S_M$. The double-commutator eigenvalue theorem gives polynomial-time adaptive POVM selection. A worked qubit example shows the group-averaged estimator from a single computational-basis measurement, averaged over a matched $\mathbb{Z}_2$ group, reaching fidelity 0.99 where standard single-basis tomography gives a rank-1 estimate of fidelity 0.80. Monte Carlo simulations for $d = 2$ to $13$ confirm fidelity above 0.90 from a single outcome while standard fidelity degrades as $\sim 1/d$. The growing ratio reflects collapse of the rank-1 standard estimator, not fewer copies per parameter: the biased single-copy estimator reduces the number of distinct measurement settings, not the per-parameter sampling cost, and a genuine copy reduction holds only under exact symmetry.

08.
arXiv (quant-ph) 2026-06-24

Logical qubits with erasure conversion using metastable neutral atoms

arXiv:2506.13724v2 Announce Type: replace Abstract: Implementing large-scale quantum algorithms with practical advantage will require fault-tolerance achieved through quantum error correction, but the associated overhead is prohibitive. This overhead can be reduced by engineering physical qubits with fewer errors, and by shaping the residual errors to be more easily correctable. In this work, we demonstrate quantum error correcting codes and logical qubit circuits in a metastable ytterbium-171 nuclear spin qubit with a noise bias towards erasure errors. These errors can be located separately from any syndrome information diagnosing the error, and we demonstrate adaptive circuit execution based on erasure information. We show that dephasing errors on the qubit during coherent transport can be strongly suppressed, and implement entangling gates that maintain a high fidelity in the presence of gate beam inhomogeneity or pointing errors. Furthermore, we demonstrate logical qubit encoding in the [[4, 2, 2]] code, with error correction during decoding based on mid-circuit erasure measurements despite the fact that the code is too small to correct any Pauli errors. Finally, we demonstrate logical qubit teleportation between multiple code blocks with conditionally selected ancillas based on mid-circuit erasure checks, a key part of leakage-robust error correction schemes using neutral atoms.

09.
arXiv (CS.AI) 2026-06-16

FasterPy: An LLM-based Code Execution Efficiency Optimization Framework

arXiv:2512.22827v2 Announce Type: replace-cross Abstract: Code often suffers from performance bugs. These bugs necessitate the research and practice of code optimization. Traditional rule-based methods rely on manually designing and maintaining rules for specific performance bugs (e.g., redundant loops, repeated computations), making them labor-intensive and limited in applicability. In recent years, machine learning and deep learning-based methods have emerged as promising alternatives by learning optimization heuristics from annotated code corpora and performance measurements. However, these approaches usually depend on specific program representations and meticulously crafted training datasets, making them costly to develop and difficult to scale. With the booming of Large Language Models (LLMs), their remarkable capabilities in code generation have opened new avenues for automated code optimization. In this work, we proposed FasterPy, a low-cost and efficient framework that adapts LLMs to optimize the execution efficiency of Python code. FasterPy combines Retrieval-Augmented Generation (RAG), supported by a knowledge base constructed from existing performance-improving code pairs and corresponding performance measurements, with Low-Rank Adaptation (LoRA) to enhance code optimization performance. Our experimental results on the Performance Improving Code Edits (PIE) benchmark demonstrate that our method outperforms existing models on multiple metrics. The FasterPy tool and the experimental results are available at https://github.com/WuYue22/fasterpy.

10.
arXiv (CS.AI) 2026-06-25

RARM: Confidence-Gated Progress Reward Modeling for RL in Manipulation

arXiv:2606.22027v2 Announce Type: replace-cross Abstract: Reinforcement learning for robot manipulation is often bottlenecked by reward design, especially in long-horizon tasks: sparse success rewards provide weak supervision, while hand-crafted dense rewards are tedious to design and generalize poorly across tasks. Progress-based reward models offer a promising alternative by estimating how far an observation has advanced toward task completion, but existing approaches often require task-specific demonstrations or progress labels, and can assign high rewards to visually plausible but physically incorrect states. We introduce the Reference-Anchored Reward Model (RARM), a lightweight visual comparator that converts a single successful demonstration into a dense, progress-aware reward. RARM is trained once on general-purpose videos with a contrastive temporal objective, requiring no robot-specific data, task-specific reward labels, or per-task reward engineering. At deployment, RARM matches rollout clips to reference clips and rewards only confident forward progress, suppressing uncertain matches that may otherwise produce false-positive rewards. Across 9 simulated manipulation tasks from LIBERO and MetaWorld and 4 real-world tasks, RARM achieves the best overall success rates in subsequent RL training, with particularly large gains on long-horizon tasks such as cloth folding, where unreliable progress estimates are especially harmful.

11.
arXiv (CS.LG) 2026-06-17

Another Look at Log-PCA for Probability Measures: A Dynamical Formulation and Statistical Convergence

arXiv:2606.17196v1 Announce Type: cross Abstract: This paper is concerned with learning principal variations of random probability measures on $\mathbb{R}^m$ under the Wasserstein geometry. We introduce a new dynamical formulation to interpret the log-PCA, a linearized principal geodesic analysis, as a variational approach. Our differentiable version, termed as the Wasserstein Tangential PCA (WT-PCA), captures the local principal modes of geodesic variations of a (weighted) probability measure on the Wasserstein space via its covariance operator at barycenter. Based on the dynamical perspective and leveraging parallel transport structure of the optimal transport problems, we derive a general statistical convergence rate of the empirical WT-PCA when estimated from data in terms of the 2-Wasserstein distance between the population and empirical barycenter reference measures.

12.
arXiv (CS.LG) 2026-06-17

Damage Adaptation in Seconds for Architected Materials

arXiv:2606.17394v1 Announce Type: cross Abstract: Adaptation to damages and in-situ physical repairs is essential for long-term robot autonomy, yet challenging outside of narrowly defined and well-anticipated bounds. In this work we proprioceptively adapt to catastrophic damage in soft-actuated systems in under one minute. Architected materials are well equipped for adaptation: actuator failure occurs gradually rather than acutely, and damage can be described in a low-dimensional, discrete coordinate space. Surprisingly, latent damage representations plus a simple yet robust ensemble method is sufficient for adapting to unseen damage in real-time. Moreover, we identify conditions under which exponential sample complexity collapses to linear sample complexity for learned representations of architected materials, a concrete advantage over rigid components or continuum soft mechanisms. We demonstrate LEAP, our method for adaptive proprioception, via a tracing task for a 6DoF soft wrist based on Handed Shearing Auxetic (HSA) actuators. Our algorithm is able to adapt to cuts, burns, and actuator repairs, enabling simulation-free real-time adaptation that is critical for realizing the promise of soft robots outside the lab. Videos and more information are available at https://murpheylab.github.io/leap.

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

Characterizing Admissible Objective Functions for Hierarchical Clustering

arXiv:2604.23628v2 Announce Type: replace-cross Abstract: Hierarchical clustering is a fundamental task in data analysis, but classical methods have long lacked a principled objective function. Dasgupta [STOC~2016] took an important step toward addressing this gap by proposing a well-motivated objective function for cluster trees. Cohen-Addad et al. [J. ACM 2019] subsequently introduced the notion of admissibility: an objective function is admissible if, whenever the input similarity matrix admits generating trees, its minimizers are precisely those generating trees.They also gave a necessary and sufficient condition for admissibility within a family of objective functions based on aggregate intercluster similarity. We refer to this family as sum-type objective functions. However, apart from Dasgupta's original objective function, no explicit admissible objective functions in this family were provided. In this paper, we study admissible objective functions for hierarchical clustering in two directions. For sum-type objective functions, we give a complete characterization when the scaling function is a symmetric polynomial of degree at most two, and we derive sufficient conditions for degree-three polynomials. We also show that the recursive sparsest cut algorithm achieves an O$(\phi)$-approximation ratio for the admissible objective functions covered by our characterization, where $\phi$ is the approximation factor of the sparsest cut subroutine. We then introduce max-type objective functions, where cluster interaction is measured by maximum, rather than aggregate, intercluster similarity. For this class, we characterize which objective functions are admissible for arbitrary symmetric scaling functions and give a complete characterization when the scaling function is a symmetric polynomial of degree at most two.

14.
arXiv (CS.CV) 2026-06-17

GOT-JEPA: Generic Object Tracking with Model Adaptation and Occlusion Handling using Joint-Embedding Predictive Architecture

The human visual system tracks objects by integrating current observations with previously observed information, adapting to target and scene changes, and reasoning about occlusion at fine granularity. In contrast, recent generic object trackers are often optimized for training targets, which limits robustness and generalization in unseen scenarios, and their occlusion reasoning remains coarse, lacking detailed modeling of occlusion patterns. To address these limitations in generalization and occlusion perception, we propose GOT-JEPA, a model-predictive pretraining framework that extends JEPA from predicting image features to predicting tracking models. Given identical historical information, a teacher predictor generates pseudo-tracking models from a clean current frame, and a student predictor learns to predict the same pseudo-tracking models from a corrupted version of the current frame. This design provides stable pseudo supervision and explicitly trains the predictor to produce reliable tracking models under occlusions, distractors, and other adverse observations, improving generalization to dynamic environments. Building on GOT-JEPA, we further propose OccuSolver to enhance occlusion perception for object tracking. OccuSolver adapts a point-centric point tracker for object-aware visibility estimation and detailed occlusion-pattern capture. Conditioned on object priors iteratively generated by the tracker, OccuSolver incrementally refines visibility states, strengthens occlusion handling, and produces higher-quality reference labels that progressively improve subsequent model predictions. Extensive evaluations on seven benchmarks show that our method effectively enhances tracker generalization and robustness.

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

SDS-LoRA: Overcoming Anisotropic Gradient Scaling in Low-Rank Adaptation

arXiv:2606.16454v1 Announce Type: cross Abstract: Low-Rank Adaptation (LoRA) enables efficient adaptation of large pre-trained models to downstream tasks by parameterizing weight updates with low-rank matrices. In this paper, we investigate the limitations of the LoRA parameterization from a geometric perspective. Specifically, we show that when a full fine-tuning gradient is backpropagated to the low-rank matrices, it undergoes anisotropic scaling driven by their singular values. We argue that this phenomenon is undesirable because it distorts the full fine-tuning gradient by skewing it toward dominant singular directions while suppressing others. Our analyses demonstrate that anisotropic gradient scaling reduces the effective rank of the low-rank matrices' gradients and results in suboptimal alignment between the full fine-tuning gradient and its low-rank approximation in LoRA, thereby exacerbating the gap to full fine-tuning. To address these limitations, we propose a new low-rank parameterization, SDS-LoRA, which structurally decouples singular values from the backward pass. Our method ensures that the full fine-tuning gradient backpropagates only through the orthonormal bases of the low-rank matrices' subspaces, independent of their scales. Convergence analysis demonstrates that while LoRA's convergence rate degrades with the condition number of the low-rank matrices, SDS-LoRA remains independent of it. Experimental results across natural language and vision benchmarks show that SDS-LoRA improves loss convergence and reduces the gap to full fine-tuning, significantly enhancing adaptation performance.

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

SPARK: Spatial Policy-driven Adaptive Reinforcement learning for Knowledge distillation

Low-bit quantization enables deployment of image restoration (IR) networks on resource-constrained devices, but introduces rounding noise that disproportionately degrades high-frequency regions such as edges and fine textures. Existing knowledge distillation (KD) methods apply distillation signals uniformly across all spatial locations, overlooking the varying reconstruction difficulty across image regions. To address this, we propose SPARK (Spatial Policy-driven Adaptive Reinforcement Learning for Knowledge Distillation), a framework that adaptively allocates distillation effort using a lightweight reinforcement learning (RL) policy network. At each training step, a difficulty feature extractor computes four signals, namely Laplacian variance, pixel variance, student reconstruction error, and teacher-student knowledge gap, which are fed into a compact policy CNN that produces a stochastic spatial weight map to modulate the KD loss during quantization-aware training (QAT). SPARK is IR task-agnostic, adds no inference cost, and integrates into any existing QAT pipeline without architectural changes. Experiments on benchmark datasets demonstrate that SPARK consistently outperforms PTQ, QAT, and state-of-the-art (SOTA) KD approaches across multiple student architectures, achieving reconstruction quality closest to the full-precision teacher under significant computational constraints.

17.
arXiv (quant-ph) 2026-06-15

Resolving the Edge of a Quantum Pyramid

arXiv:2606.14698v1 Announce Type: new Abstract: Standing on the shoulders of giants, we resolve the quantum pyramids conjecture, confirming the globally information-optimal measurement for an ensemble of equiangular equiprobable pure states, as conjectured by Englert and \v{R}eháček (arXiv:0905.0510). We do so by proving the remaining entropy inequalities of Holevo and Utkin (arXiv:2506.06700), which certify optimality for obtuse and flat pyramids. For obtuse pyramids, our key contribution is a rigorous proof that local minimizers of the corresponding entropy inequality cannot have three distinct coordinate values. We show that eliminating this family can be reduced to a neat algebraic reciprocal inequality relating branches of the Lambert $W$ function, which may be of independent interest. For flat pyramids, we prove a tight $\ell^p$ inequality for zero-sum vectors that was recently conjectured, proved analytically in dimension $d=3$, and computationally verified for $d\leq 200$ by Holevo and Utkin (arXiv:2603.24017). We prove this bound for all $d\geq 2$ via a technique in symmetric inequalities known as the equal variables method.

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

Remember, Don't Re-read: Stateful ReAct Agents for Token-Efficient Autonomous Experimentation

arXiv:2606.14945v1 Announce Type: new Abstract: The autoresearch pattern enables autonomous experimentation by having a large language model (LLM) iteratively modify code to optimize a target metric. Its stateless design, however, reconstructs experimental context from scratch at every iteration, incurring $O(n)$ token cost per iteration and $O(n^{2})$ total. This work reformulates the pattern as a stateful ReAct agent using LangGraph, where typed persistent state carries experimental history across iterations via a tool-calling interface. Two benchmarks are evaluated: hyperparameter tuning (15 iterations, small per-iteration observations) and code performance optimization (40 iterations, large per-iteration observations containing full source code and benchmark results). On hyperparameter tuning, the stateful agent consumes 90\% fewer tokens (2{,}492 vs.\ 24{,}465). On code optimization, the stateful agent consumes 52\% fewer tokens (627K vs.\ 1{,}275K) while achieving comparable optimization quality on both tasks. The token reduction is structural: the stateless agent re-reads the full history at $O(n)$ cost per iteration, while the stateful agent operates within a fixed-size conversation window at $O(1)$ cost. This paper describes the architecture in sufficient detail for practitioners to implement a stateful autoresearch agent for their own workflows.

19.
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.

20.
Nature (Science) 2026-06-24

Zero-shot design of drug-binding proteins via neural iterative selection−expansion

作者:

The design of proteins that bind to small molecules has been challenging because it requires simultaneous optimization of the protein sequence, protein structure and ligand conformation1–7. Current deep-learning algorithms have struggled to navigate this landscape, precluding the zero-shot design of binders. Here we show that by combining two neural networks in an iterative design algorithm, small-molecule binding proteins can be created from scratch with high accuracy. We trained a graph neural network—ligand-aware sequence engineering message-passing neural network (LASErMPNN)—to design compatible protein sequences for an input protein backbone and docked ligand. We paired  LASErMPNN with a structure predictor that models a three-dimensional protein–ligand complex for an input protein sequence and ligand identity. The closed-loop iteration of these reciprocal networks optimized sequence–structure–ligand compatibility, and outperformed a comparable design loop using a physics-based energy function. We used our strategy, termed neural iterative selection–expansion (NISE), to design proteins that, using different folds, specifically bind to two chemically distinct small-molecule drugs, exatecan and apixaban, with success rates of 100% and 83%, respectively. The tightest NISE binders had nanomolar-to-picomolar affinities, surpassing those of the next-leading method by 70-fold for exatecan and nearly 10,000-fold for apixaban. LASErMPNN then suggested two amino-acid substitutions that improved the affinity of the tightest exatecan binder by 100-fold without any experimental input. The optimized binder protected the labile lactone ring of exatecan from hydrolysis for days. Our work describes a general recipe for using neural networks to automate the design of small-molecule binding proteins for applications in drug delivery, sensing and catalysis.  By pairing two neural networks in an iterative optimization algorithm, small-molecule binding proteins can be designed from scratch with high accuracy, affinity and success rates, showing promise for applications in drug delivery and sequestration.

21.
medRxiv (Medicine) 2026-06-10

Towards the Virtual Amyotrophic Lateral Sclerosis Patient: Inferring Cortical Excitability through Whole-Brain Dynamical Modeling

Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem neurodegenerative disorder in which motor-neuron degeneration is accompanied by widespread alterations in cortical dynamics. Among its most reproducible neurophysiological signatures is cortical hyperexcitability, yet how this local excitability imbalance shapes distributed whole-brain activity remains poorly understood. Here, we combined source-reconstructed resting-state MEG data, tractography-informed whole-brain modeling, and simulation-based inference to investigate whether ALS-related alterations in large-scale brain dynamics can be mechanistically explained by changes in cortical excitability. First, we characterized empirical brain dynamics using complementary features spanning regional activity amplitude and variability, functional connectivity, and avalanche-based metrics. These analyses revealed significant alterations in ALS patients relative to healthy controls, as well as associations with clinical impairment and disease staging. To mechanistically interpret these changes, we employed a reduced Wong-Wang whole-brain model in which local recurrent excitation modulates emergent large-scale neural dynamics. Simulations showed that increasing excitability systematically reproduced the empirical dynamical signatures observed in ALS. We then applied a simulation-based inference framework to estimate latent excitability parameters directly from empirical observations. Whole-brain model inversion revealed increased excitability in ALS patients compared with controls. The recovered excitability parameter was associated with disease staging, supporting its clinical relevance as a model-derived descriptor of ALS progression. Finally, by extending the model to estimate frontal and non-frontal excitability separately, we found that ALS-related alterations were predominantly associated with increased frontal excitability, whereas non-frontal regions appeared comparatively less affected. The recovered parameters related to disease staging. Together, these findings provide a mechanistic framework linking altered large-scale brain dynamics in ALS to selective cortical hyperexcitability, explaining how local excitability changes can give rise to global network reorganization. More broadly, they show how computational model inversion can recover latent multiscale pathophysiological processes from empirical neural recordings, offering a non-perturbative alternative to complex experimental paradigms typically required to causally probe local-to-global mechanisms.

22.
bioRxiv (Bioinfo) 2026-06-12

Deciphering cross-omics complexity of tissues via diagonal integration of unpaired spatial multi-omics data

Recent spatial multi-omics technologies enable the simultaneous in situ profiling of multiple omics modalities on the same tissue section; however, they face challenges in experimental complexity and high costs. This technical limitation can be circumvented by diagonal integration methods, which integrate omics data from different modalities. However, existing single-cell diagonal integration approaches overlook spatial information, causing unreliable anchoring across omics layers. Here, we introduce STAMO, a graph attention neural network model for spatially aware integration of unpaired spatial slices from different omics. Systematic benchmarking on spatial epigenome-transcriptome slices proves that STAMO outperforms the state-of-the-art methods in generating aligned embeddings and identifying consensus spatial domains across omics. We apply STAMO to integrate unpaired data from diverse spatial omics types (transcripts, epigenetics, DNA, and proteins), including slices from spatial RNA and four different epigenomic modalities, spatial ATAC and RNA slices across embryonic stages, spatial protein and RNA slices, and spatial DNA and RNA slices. In addition, the integration capability of STAMO can be further used to achieve cross-omics generation, offering a solution for exploring spatial region-specific gene regulatory mechanisms.

23.
arXiv (CS.AI) 2026-06-24

ReM-MoA: Reasoning Memory Sustains Mixture-of-Agents Scaling

arXiv:2606.24437v1 Announce Type: new Abstract: Mixture-of-Agents (MoA) architectures improve inference-time scaling by organizing multiple LLM agents into layered reasoning pipelines. However, existing MoA variants fail to sustain gains as depth increases, exhibiting degradation, early plateauing, or saturation. We propose ReM-MoA, a memory-augmented MoA framework that sustains scaling through two mechanisms: (1) a Ranked Reasoning Memory that persistently stores and ranks reasoning traces from all layers using a comparative Reviewer Agent, and (2) a Curated Diversified Memory Routing scheme that exposes different agents to distinct combinations of successful and failed traces, preserving exploration diversity while propagating high-quality reasoning. We further introduce an optional multi-domain Reviewer distillation pipeline that improves ranking quality through frontier-model supervision. Across five reasoning benchmarks spanning math, formal logic, code, knowledge, and commonsense, ReM-MoA consistently outperforms prior MoA variants across both depth and width scaling, and its advantage widens with depth, establishing structured cross-layer reasoning memory as a key missing mechanism for scalable multi-agent inference.

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

Beyond Predefined Schemas: TRACE-KG for Context-Enriched Knowledge Graph Generation

arXiv:2604.03496v2 Announce Type: replace Abstract: Knowledge graph generation typically relies either on predefined ontologies or on schema-free extraction. Ontology-driven pipelines enforce consistent typing but require costly schema design and maintenance, whereas schema-free methods often produce fragmented graphs with weak global organization, especially in long technical documents with dense, context-dependent information. We propose TRACE-KG (Text-dRiven schemA for Context-Enriched Knowledge Graphs), a framework that jointly constructs a context-enriched knowledge graph and an induced schema without assuming a predefined ontology. TRACE-KG captures conditional relations through structured qualifiers and organizes entities and relations using a data-driven schema that serves as a reusable semantic scaffold while preserving full traceability to the source evidence. Experiments show that TRACE-KG produces structurally coherent, traceable knowledge graphs and offers a practical alternative to both ontology-driven and schema-free construction pipelines.

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arXiv (CS.LG) 2026-06-12

PLaID++: A Preference Aligned Language Model for Targeted Inorganic Materials Design

arXiv:2509.07150v4 Announce Type: replace Abstract: Reinforcement Learning from Verifiable Rewards (RLVR) has emerged as a promising approach to improve correctness in LLMs, however, in many scientific problems, the objective is not necessarily to produce the correct answer, but instead to produce a diverse array of candidates which satisfy a set of constraints. We study this challenge in the context of materials generation. To this end, we introduce PLaID++, an LLM post-trained for stable and property-guided crystal generation. We find that performance hinges on our crystallographic representation and reward formulation. First, we introduce a compact, symmetry-informed Wyckoff text representation which improves computational efficiency and encourages generalization from physical priors. Second, we demonstrate that temperature scaling acts as an entropy regularizer which counteracts mode collapse and encourages exploration. By encoding symmetry constraints directly into text and guiding model outputs towards desirable chemical space, PLaID++ generates structures that are thermodynamically stable, unique, and novel at a $\sim$50\% greater rate than prior methods and conditionally generates structures with desired space group properties. Our work demonstrates the potential of adapting post-training techniques from natural language processing to materials design, paving the way for targeted and efficient discovery of novel materials.