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

Zone of Proximal Policy Optimization: Teacher in Prompts, Not Gradients

Knowledge distillation transfers a teacher's competence to a small student but is brittle in the small-student regime: forcing the student to imitate logits from a much larger teacher concentrates it on the teacher's sharpest modes, hurting generalization on benchmark families beyond the training corpus. Reinforcement learning (RL) avoids logit imitation by training on the student's own rollouts. However, on questions where every rollout fails-yielding zero advantage and being silently discarded-injecting a stronger teacher's response into the policy gradient breaks the on-policy assumption and induces drift. We introduce Zone of Proximal Policy Optimization (ZPPO), inspired by Vygotsky's zone of proximal development, which keeps the teacher inside the prompt rather than the policy gradient. On hard questions, ZPPO constructs two reformulated prompts: a Binary Candidate-included Question (BCQ) pairs one correct teacher response with one incorrect student response as anonymized candidates the student must discriminate, and a Negative Candidate-included Question (NCQ) aggregates the student's wrong rollouts into a single prompt to surface their shared failure modes. A prompt replay buffer recirculates each hard question until it either graduates-the student's mean rollout accuracy on it reaches half- or is FIFO-evicted under finite capacity, amplifying BCQ and NCQ inside the student's current zone of proximal development. On the Qwen3.5 family at four student scales (0.8B-9B) with a 27B teacher, post-trained as vision-language models and evaluated on a 31-benchmark suite (16 VLM, 10 LLM, 5 Video), ZPPO outperforms off/on-policy distillation and GRPO, with the largest gains at the smallest scale.

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

HSQ-VLM: A Novel Spatially-Constrained Quadrant Segmentation VLM Model for Explainability in Diabetic Retinopathy

Authors:

Diabetic Retinopathy (DR) is an aggressive retinal disease and a leading cause of global blindness, yet its clinical management is currently hindered by the black-box nature of diagnostic AI. While deep learning models achieve high classification accuracy, there is a critical lack of explainability methods capable of detailing the exact anatomical landmarks and lesion distributions that lead to a clinical decision for DR. Therefore, we propose HSQ-VLM, a novel quadrant segmentation pipeline on fundus images that utilizes a Landmark-Anchored Cartesian Cross-Attention mechanism to unify visual feature extraction with structured clinical reasoning. Unlike traditional methods that rely on arbitrary image partitioning, our pipeline implements 4-quadrant Topological Latent Partitioning (TLP) to dynamically align retinal features with a fovea-centered coordinate system. This allows the Vision-Language Model to generate natural language reports that quantify pathology with anatomical precision. On a dataset of 3,500 high-resolution fundus images, this innovative methodology achieved a lesion detection sensitivity of 99.6% for hemorrhages and 96.4% for microaneurysms, while demonstrating a significant reduction in boundary-ambiguity errors compared to standard segmentation baselines.

03.
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.

04.
arXiv (math.PR) 2026-06-15

Universality for Products of Random Matrices with i.i.d. Entries and the Fuss–Catalan Number

arXiv:2606.14450v1 Announce Type: cross Abstract: Let \((w_{ij})_{i,j\ge1}\) be a single infinite array of independent identically distributed real- or complex-valued entries of mean zero, variance \(\sigma^2\), and finite fourth moment. Set \(W_n=(w_{ij})_{1\le i,j\le n}\) and \(X_n=n^{-1/2}W_n\). For every fixed \(k\ge1\), we identify the almost sure limiting operator norm of several fixed products built from this family. Define the \(k\)-th freeness coefficient by \[ \gamma_k:=\sqrt{\frac{(k+1)^{k+1}}{k^k}}. \] Then we prove \[ \|X_n^k\|\to\sigma^k\gamma_k \qquad almost surely. \] The same limit holds for products sampled with replacement from any fixed finite pool of independent copies of \(X_n\); in particular, it holds for the product of \(k\) independent copies. Thus, the freeness coefficient captures the non-commuting characteristic between large random matrices %powers and independent or fixed-pool sampled products under the finite fourth moment assumption. The improvement of the classical Bai–Yin-type power estimate from the scale \(\sigma^k(k{+}1)\) to \(\sigma^k \sqrt{k{+}1}\) is a direct corollary of our result. The main technical challenge is to prove the upper bound using a high-moment expansion of %the upper bound is proved by a high-moment expansion of \(\E\Tr((X_n^kX_n^{*k})^m)\). The leading zero-defect trace words are tree-like and are counted by the Fuss–Catalan number \[ F_{k,m}= \frac1{km+1}\binom{(k+1)m}{m}. \] The combinatorial tool helps to devise a defect-sensitive global enumeration: if \(L=km\) and \[ r=(L+1-v)+(L-q), \] then the number of admissible word classes with defect \(r\) is at most \(F_{k,m}(Cm)^{Dr}\). This polynomial-in-\(m\) loss, with degree proportional to the defect, is summable in the logarithmic moment range.

05.
arXiv (CS.LG) 2026-06-19

Adversarial Dependence Minimization

arXiv:2502.03227v2 Announce Type: replace Abstract: Minimally redundant representations are typically learned by minimizing feature covariance. However, covariance-based methods fail to eliminate all dependencies/redundancies, as linearly uncorrelated variables can still exhibit nonlinear relationships. To address this, we introduce ADM, a differentiable algorithm that minimizes statistical dependence between feature dimensions through an adversarial game: auxiliary networks identify dependencies, while the encoder removes them. We prove that mutual independence is achieved at the global optimum, empirically verify convergence, and study three potential applications: extending PCA to nonlinear decorrelation, improving generalization in image classification, and preventing dimensional collapse in self-supervised learning. By promoting statistically independent representations, ADM paves the way for learning more robust, compressed, and generalizable representations across diverse applications.

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

Using AI in engineering education: a balancing act, driven by clear purpose

Authors:

arXiv:2606.16626v1 Announce Type: cross Abstract: Based on a questionnaire of 100 higher-education students, predominantly from engineering-related fields, and a critical review of recent literature, this chapter examines how students use and perceive Large Language Models (LLMs) in engineering education. Students primarily value LLMs for writing support, conceptual clarification, coding assistance, and brainstorming, while simultaneously expressing concerns about inaccuracies, bias, overreliance, academic integrity, and the burden of verification. Through an analysis of two dominant metaphors, namely LLMs as an "oracle" and as a "tutor," the chapter shows how these systems cultivate expectations of authority, expertise, and personalized learning that often exceed their actual capabilities. The chapter further argues that students' attachment to the promises of efficiency and personalized support reflects a form of "cruel optimism," where the perceived benefits of LLMs often depend on the very skills, vigilance, and expertise that students are still developing. Overall, the chapter argues for a purpose-driven and context-sensitive approach to AI integration in engineering education, emphasizing critical AI literacy, reflective assessment design, pedagogical caution, and consideration of broader ethical and environmental impacts.

07.
arXiv (quant-ph) 2026-06-11

Coupled integrated photonic quantum memristors using a single photon source made of a colour center

arXiv:2602.14736v2 Announce Type: replace Abstract: Photonic quantum memristors provide a measurement-induced route to nonlinear and history-dependent quantum dynamics. Experimental demonstrations have so far focused on isolated devices or simple cascaded devices configurations. Here, we experimentally realize and characterize a network of two coupled photonic quantum memristors with crossed feedback, implemented on a silicon nitride photonic integrated circuit and fed by a room-temperature single-photon source based on a silicon-vacancy color center SiV$^-$ in a nanodiamond. Each memristor consists of an integrated Mach-Zehnder interferometer whose transfer function is adaptively updated by photon detection events on another memristor, thus generating novel non-Markovian input-output dynamics with an enhanced memristive behaviour compared to single devices. In particular, we report inter-memristor input-output hysteresis curves exhibiting larger form factors and displaying self-intersecting loops, respectively revealing marked bistability and self-intersecting hysteresis geometry. Furthermore, numerical simulations show how these features emerge from the interplay between memory depth and relative input phase, for both intra- and inter-memristor input-output relations. We experimentally test the performance of our system in the NARMA task. Our results establish coupled integrated photonic quantum memristors as scalable nonlinear building blocks and highlight their potential for implementing compact quantum neuromorphic and reservoir computing architectures.

08.
medRxiv (Medicine) 2026-06-17

Postoperative Cognitive Decline in Older Patients with Cardiovascular Disease and Preoperative Mild Cognitive Impairment

Objective. Older adults undergoing cardiac surgery may be vulnerable to postoperative cognitive decline. However, no studies have examined postoperative cognitive outcomes in older patients with cardiovascular disease (CVD) according to preoperative mild cognitive impairment (MCI). This study examined 12-month postoperative cognitive outcomes in older CVD patients according to preoperative MCI diagnosis and explored predictors of postoperative cognitive decline. Method. Twenty-two older CVD patients ([≥]65 years) and twenty-five controls were included. Neuropsychological assessment was conducted at baseline in both groups and repeated 12 months after surgery in the CVD group. MCI was diagnosed using current clinical criteria. Postoperative cognitive change was examined across preoperative MCI groups. Results. Fifty percent of patients met criteria for postoperative MCI, showing high diagnostic stability relative to preoperative frequency (45.5%). The preoperative CVD-MCI group showed a decline in working memory, executive functions, visual memory, and naming, whereas CVD-nMCI group declined only in verbal memory. Furthermore, CVD-MCI showed more heterogeneous postoperative cognitive trajectories of change than CVD-nMCI, who showed stability. Estimated IQ, APACHE-II score, and postoperative frailty were important variables in predicting the postoperative pattern. Conclusions. MCI frequency remained high and stable in older CVD patients across the preoperative and one-year postoperative period. However, this apparent diagnostic stability masks subclinical cognitive decline, particularly among patients with preoperative MCI, who showed greater susceptibility to further impairment. Estimated IQ, APACHE-II score, and postoperative frailty may be considered relevant predictors of outcome. These results highlight the value of preoperative neuropsychological assessment for characterizing postoperative cognitive risk in older CVD patients.

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

RAMEN: Resolution-Adjustable Multimodal Encoder for Earth Observation

Earth observation (EO) data spans a wide range of spatial, spectral, and temporal resolutions, from high-resolution optical imagery to low resolution multispectral products or radar time series. While recent foundation models have improved multimodal integration for learning meaningful representations, they often expect fixed input resolutions or are based on sensor-specific encoders limiting generalization across heterogeneous EO modalities. To overcome these limitations we introduce RAMEN, a resolution-adjustable multimodal encoder that learns a shared visual representation across EO data in a fully sensor-agnostic manner. RAMEN treats the modality and spatial and temporal resolutions as key input data features, enabling coherent analysis across modalities within a unified latent space. Its main methodological contribution is to define spatial resolution as a controllable output parameter, giving users direct control over the desired level of detail at inference and allowing explicit trade-offs between spatial precision and computational cost. We train a single, unified transformer encoder reconstructing masked multimodal EO data drawn from diverse sources, ensuring generalization across sensors and resolutions. Once pretrained, RAMEN transfers effectively to both known and unseen sensor configurations and outperforms larger state-of-the-art models on the community-standard PANGAEA benchmark, containing various multi-sensor and multi-resolution downstream tasks. Our code and pretrained model are available at https://github.com/nicolashoudre/RAMEN.

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

Repeated Bilateral Trade: The Quest for Fairness

arXiv:2606.15369v1 Announce Type: new Abstract: We study repeated bilateral trade from a fairness perspective. At each round, a fresh seller-buyer pair arrives, and the platform posts a price before observing the traders' valuations. Trade occurs only if both agents accept the price. Rather than maximizing only the gain from trade, we consider platforms that seek balanced divisions of the generated surplus. We show that natural fairness desiderata lead to a one-parameter Rawls-to-Nash family of fair-gain objectives, obtained by aggregating the seller's and buyer's net gains through nonpositive Hölder means. Unlike the standard gain-from-trade objective and the Rawlsian fair-gain objective studied in prior work, our proposed objectives induce a new statistical structure in which expected rewards are recovered from threshold feedback through a two-dimensional singular-kernel integral identity. This leads to a nonstandard pure-exploration problem whose natural estimators are rectangular double sums with row-column dependence and singular weights. Assuming independent i.i.d. seller and buyer valuation sequences with arbitrary unknown marginals, we characterize the optimal learning rates for the whole Rawls-to-Nash family of fair-gain objectives, giving matching fixed-confidence sample-complexity and regret bounds up to polylogarithmic factors.

11.
arXiv (CS.AI) 2026-06-16

QoS-Aware Token Scheduling and Private Data Valuation for Multi-Modal Agentic Networks

arXiv:2606.15573v1 Announce Type: new Abstract: In agentic systems, human-generated data records anchor the value of AI services. Yet cloud compute pipelines centralize processing on remote servers. Data centralization reduces personal data sovereignty and may potentially degrade the quality of service (QoS). Meanwhile, user contributions are diverse in quantity and quality: decentralized records can be biased, noisy, and heterogeneously distributed. To address the data challenge, we study fair token allocation and private data valuation for decentralized and resource-constrained agentic systems. Our approach embeds multi-modal representations in a shared semantic space and releases differentially private (DP) prototypes to preserve utility while reducing semantic leakage. With the DP guarantee, we design a fair token allocation scheme that rewards effective contributions and remains robust to data heterogeneity and AI resource scarcity. Extensive simulations demonstrate improved contribution-based fairness and QoS compared to standard benchmarks. The improved resistance to image reconstruction attacks indicates enhanced privacy for multi-modal personal data.

12.
Nature (Science) 2026-06-17

Spatial distribution of the proteome in the human body and in cancers

Authors:

A detailed, spatially resolved quantitative map of the human proteome is essential for a deeper understanding of human biology and disease1–4. Here we present a comprehensive human proteomic landscape, generated by profiling more than 13,000 proteins across 2,856 samples using data-independent acquisition mass spectrometry. The dataset spans 58 major tissue types, 251 specific tissue subtypes and 25 distinct carcinomas. This resource enables the depiction of spatially resolved proteome trajectories across tissue types and physiological states, including fetal, tumour, adjacent non-tumour and healthy adult tissue, thereby providing insight into both developmental processes and oncogenic progression. Furthermore, quantitative proteomics comparisons across diverse tissue types and states facilitate the indication of organ-specific toxicity, the identification of repurposable anticancer drug candidates and the prioritization of therapeutic targets for cancers. This study establishes a quantitative resource for navigating the proteome in the human body and in common cancers. A spatially resolved map of the human proteome across a variety of healthy tissues and cancers provides wide-ranging insights in developmental biology and oncology, and could aid the identification of therapeutic targets and development of treatments for cancer.

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

Demystifying Variance in Circuit Discovery of LLMs

arXiv:2606.16920v1 Announce Type: cross Abstract: Circuit discovery is a key technique in mechanistic interpretability to pinpoint the model components that are crucial for performing a given task. Although the current state-of-the-art method (EAP-IG) performs well on the metric of (un)faithfulness, it suffers from substantial variability. This includes resampling variance, where the circuit changes when we probe with a new batch of data from the same distribution; rephrasing variance, where the discovered circuit shifts when the prompts are rephrased; and sample-wise variance, where a circuit with low population unfaithfulness exhibits large fluctuations in unfaithfulness across individual samples. This paper studies the roots of these variances. We demonstrate that CEAP, our new circuit discovery method that improves upon EAP-IG with a theoretical guarantee, can substantially lessen resampling variance. We further show that rephrasing variance arises because prompts with different templates tend to activate different circuits in the model. This leads us to argue that it may be challenging to find a comprehensive circuit that explains and controls the model's behavior on a task, which can be expressed in countless templates, suggesting that LLMs may be inherently hard to steer. We show that sparsity, which has been claimed to form more compact and interpretable task circuits, fails to solve this problem. Regarding sample-wise variance, we argue that it is largely benign: extremely poor unfaithfulness scores often stem from how unfaithfulness is defined, rather than from defects in the measured circuits. We show that the magnitude of unfaithfulness is affected by selective contribution scaling, a neural mechanism that accounts for the extremely poor scores sometimes observed.

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

FM-Agent: Scaling Formal Methods to Large Systems via LLM-Based Hoare-Style Reasoning

arXiv:2604.11556v2 Announce Type: replace-cross Abstract: LLM-assisted software development has become increasingly prevalent, and can generate large-scale systems, such as compilers. It becomes crucial to strengthen the correctness of the generated code. However, automated reasoning for large-scale systems remains challenging due to code complexity. Hoare logic offers an approach to decomposing a large system into smaller components and reasoning about them separately (i.e., compositional reasoning). However, existing works still struggle to scale, because Hoare logic requires writing formal specifications for each function, imposing a heavy human burden. The problem is exacerbated when code is generated by LLMs, as developers lack a deep understanding of each function's expected behavior. This paper presents FM-Agent, the first framework that realizes automated compositional reasoning for large-scale systems. Leveraging LLMs, FM-Agent introduces a top-down paradigm to automatically generate function-level specifications. Specifically, FM-Agent derives the specification of a function from how its callers expect the function to behave, so the generated specifications can reflect the developer's intent of a function even if the implementation is buggy. Developers' intent is usually expressed in natural language, while existing verifiers only support formulas. Therefore, FM-Agent generalizes Hoare-style inference to reason about functions against natural-language specifications. Finally, to confirm bug existence and explain bug causes, FM-Agent automatically generates test cases to trigger potential bugs. In our evaluation, FM-Agent successfully reasons about large-scale systems within 2 days, each of which has up to 143k LoC. These systems have already been tested by their developers, but FM-Agent still finds 522 newly discovered bugs. These bugs can cause serious consequences, including system crashes and incorrect execution results.

15.
arXiv (quant-ph) 2026-06-11

Bound State Solutions of the Relativistic Finite-difference Equation for the Ring-shaped Quesne Oscillator Potential

arXiv:2606.12082v1 Announce Type: new Abstract: We solve exactly the relativistic finite-difference equation for the quantum three-dimensional ring-shaped Quesne oscillator potential. Our investigation is based on a finite-difference version of relativistic quantum mechanics. So-called relativistic configurational r-space is a key concept here. We show that the radial wavefunctions and angular wavefunctions are expressed through the continuous dual Hahn polynomials and Jacobi polynomials, respectively. A discrete energy spectrum has been found. The radial wave functions and energy spectrum have the correct nonrelativistic limit. We also build a dynamical symmetry group SU (1, 1) for the radial part of the equation of motion, which allows us to find the energy spectrum purely algebraically.

16.
arXiv (CS.AI) 2026-06-17

Surrogate Assisted Pedestrian Protection Design via a Foundation Model Orchestrated Workflow

arXiv:2606.17577v1 Announce Type: new Abstract: AI-driven engineering workflows face particular challenges in crash safety design: unlike aerodynamics, crash events involve highly nonlinear contact dynamics, material nonlinearity, and discrete state transitions that are difficult to capture with data-driven surrogate models. To the best of our knowledge, we present the first foundation model–orchestrated workflow for crash safety design that enables surrogate-assisted exploration for pedestrian protection, reducing evaluation time from hours per CAE simulation to seconds. The workflow integrates four components: (1) a surrogate trained on CAE crash simulations to predict pedestrian leg injury metrics from design parameters, achieving an average $R^2=0.87$ and providing distribution-free conformal prediction intervals; (2) multiobjective evolutionary search (NSGA-II) to discover diverse feasible parameter sets under user-specified constraints; (3) a morphing-based geometry generator that maps parameters to topology-preserving 3D shapes; and (4) a natural-language interface in which an LLM orchestrates the workflow and a vision–language model supports semantic comparison of generated designs. In an automotive front-bumper case study, the workflow produces 35 distinct safety-compliant alternatives from a single exploration, a process that would require weeks with conventional CAE iteration. These results suggest that foundation models can serve as integration layers between ML surrogates and physics-based simulation, helping bring AI capabilities to safety-critical engineering domains.

17.
arXiv (math.PR) 2026-06-18

On a class of unbalanced step-reinforced random walks

arXiv:2504.14767v4 Announce Type: replace Abstract: A step-reinforced random walk is a discrete-time stochastic process with long-range dependence. At each step, with a fixed probability $\alpha$, the so-called positively step-reinforced random walk repeats one of its previous steps, chosen randomly and uniformly from its entire history. Alternatively, with probability $1-\alpha$, it makes an independent move. For the so-called negatively step-reinforced random walk, the process is similar, but any repeated step is taken with its direction reversed. These random walks have been introduced respectively by Simon (1955) and Bertoin (2024) and are sometimes refered to the self-confident step-reinforced random walk and the counterbalanced step-reinforced random walk respectively. In this work, we introduce a new class of unbalanced step-reinforced random walks for which we prove the strong law of large numbers and the central limit theorem. In particular, our work provides a unified treatment of the elephant random walk introduced by Schutz and Trimper (2004) and the positively and negatively step-reinforced random walks.

18.
arXiv (CS.CL) 2026-06-18

DSB: Dynamic Sliding Block Scheduling for Diffusion LLMs

Diffusion large language models (dLLMs) have emerged as a promising alternative for text generation, distinguished by their native support for parallel decoding. In practice, block inference is crucial for avoiding order misalignment in global bidirectional decoding and improving output quality. However, the widely-used fixed, predefined block (naive) schedule is agnostic to semantic difficulty, making it a suboptimal strategy for both quality and efficiency: it can force premature commitments to uncertain positions while delaying easy positions near block boundaries. In this work, we analyze the limitations of naive block scheduling and disclose the importance of dynamically adapting the schedule to semantic difficulty for reliable and efficient inference. Motivated by this, we propose Dynamic Sliding Block (DSB), a training-free block scheduling method that uses a sliding block with a dynamic size to overcome the rigidity of the naive block. To further improve efficiency, we introduce DSB Cache, a training-free KV-cache mechanism tailored to DSB. Extensive experiments across multiple models and benchmarks demonstrate that DSB, together with DSB Cache, consistently improves both generation quality and inference efficiency for dLLMs. Code is released at https://github.com/lizhuo-luo/DSB.

19.
Nature Biotechnology 2026-06-11

Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT

Authors:

Spatially resolved CRISPR screening in vivo has been limited to small perturbation panels and subsets of protein-coding RNAs. We present Perturb-DBiT, a method for co-sequencing of spatial total RNA whole transcriptomes and single guide RNAs (sgRNAs) on the same tissue section in situ. In a human cancer metastatic colonization model, we applied large (80,000+) sgRNA panels across tumor colonies in multiple consecutive tissue sections alongside their corresponding total RNA transcriptomes. We linked perturbations affecting long noncoding RNA covariation, microRNA–mRNA interactions and distinct amino acid-specific tRNA alterations to tumor migration and growth. By integrating transcriptional pseudotime trajectories, we further observed the impact of perturbations on clonal dynamics and cooperation. In an immune-competent syngeneic mouse model, investigation of the tumor immune microenvironment indicated distinct, synergistic effects on immune infiltration and suppression. Perturb-DBiT provides a spatially resolved comprehensive view of perturbation responses in complex tissues, including small and large RNA regulation, tumor proliferation, migration, metastasis and immune interactions. In vivo CRISPR genetic perturbations are spatially mapped at scale.

20.
arXiv (CS.LG) 2026-06-12

Contrastive Geometric Learning Unlocks Unified Structure- and Ligand-Based Drug Design

arXiv:2601.09693v3 Announce Type: replace Abstract: Structure-based and ligand-based computational drug design have traditionally relied on disjoint data sources and modeling assumptions, limiting their joint use at scale. In this work, we introduce Contrastive Geometric Learning for Unified Computational Drug Design (ConGLUDe), a single contrastive geometric model that unifies structure- and ligand-based training. ConGLUDe couples a geometric protein encoder that produces whole-protein representations and implicit embeddings of predicted binding sites with a fast ligand encoder, removing the need for predefined pockets. By aligning ligands with both global protein representations and multiple candidate binding sites through contrastive learning, ConGLUDe supports ligand-conditioned pocket prediction in addition to virtual screening and target fishing, while being trained jointly on protein-ligand complexes and large-scale bioactivity data. Across diverse benchmarks, ConGLUDe achieves competitive zero-shot virtual screening performance, substantially outperforms existing methods on a challenging target fishing task, and demonstrates state-of-the-art ligand-conditioned pocket selection. These results highlight the advantages of unified structure-ligand training and position ConGLUDe as a step toward general-purpose foundation models for drug discovery.

21.
arXiv (CS.AI) 2026-06-19

SleepMaMi: A Universal Sleep Foundation Model for Integrating Macro- and Micro-structures

arXiv:2602.07628v2 Announce Type: replace Abstract: While the shift toward unified foundation models has revolutionized many deep learning domains, sleep medicine remains largely restricted to task-specific models that focus on localized micro-structure features. These approaches often neglect the rich, multi-modal context of Polysomnography (PSG) and fail to capture the global macro-structure of a full night's sleep. To address this, we introduce SleepMaMi , a Sleep Foundation Model engineered to master both hour-long sleep architectures and fine-grained signal morphologies. Our framework utilizes a hierarchical dual-encoder design: a Macro-Encoder to model full-night temporal dependencies and a Micro-Encoder to capture short-term characteristics from biosignals. Macro-Encoder is trained via Demographic-Guided Contrastive Learning, which aligns overnight sleep patterns with objective subject metadata, such as age, sex and BMI to refine global representations. Micro-Encoder is optimized via a hybrid Masked Autoencoder (MAE) and multi-modal contrastive objective. Pre-trained on a massive corpus of $>$20,000 PSG recordings (158K hours),SleepMaMi outperforms or matches state-of-the-art existing foundation models across a diverse suite of downstream tasks, demonstrating superior generalizability and label-efficient adaptation for clinical sleep analysis.

22.
arXiv (CS.LG) 2026-06-11

RePAIR: Predictive Self-Supervised Representation Learning in Chess

arXiv:2606.11860v1 Announce Type: new Abstract: In this paper, we introduce Representation Prediction via Autoencoding using Iterative Refinement (RePAIR) - a novel self-supervised representation learning architecture that synthesizes Masked Autoencoders (MAE), Joint Embedding Predictive Architectures (JEPA), and Bidirectional Encoder Representations from Transformers (BERT). We demonstrate how it can be used to encode objects in sequential data like consecutive chess positions into compact yet meaningful representations. The basic principle of the architecture is to mask large portions of a sequence of latent states, similar to BERT and MAE. Then, we apply a lightweight Predictor to the latent representations that repairs gaps in the sequence in a lower-dimensional embedding space akin to JEPA. Our experiments in the domain of chess show that the Encoder refines the board representations such that meaningful chess concepts emerge clustered in the latent space. Furthermore, reconstructions of the masked board states show that the model is able to reason about the piece movements without relying on costly reinforcement learning methods. Lastly, we find that the resulting representation space allows for quick and intuitive dissections of chess games by observing the game path trajectories in this semantically rich space.

23.
arXiv (CS.LG) 2026-06-19

Beyond Averaging in John Ellipsoid Approximation: High-Accuracy Algorithms in the Leverage-Score Model

arXiv:2606.20082v1 Announce Type: cross Abstract: The John ellipsoid of a symmetric polytope $P=\{\mathbf{x}\in\mathbb{R}^d:\|\mathbf{A}\mathbf{x}\|_\infty\le1\}$, $\mathbf{A}\in\mathbb{R}^{n\times d}$, is computed by a long line of leverage-score algorithms, from Cohen, Cousins, Lee and Yang (COLT 2019) to its successors [WY24, CLS+25], all reaching a $(1+\varepsilon)$-approximation in $\Theta(\varepsilon^{-1}\log(n/d))$ iterations. We separate this complexity into three costs the modern line conflates (certification, identification, and accuracy) and locate the historical $\varepsilon^{-1}$ in the first alone. In the equivalent D-optimal-design form $\min_{\mathbf{p}\in\Delta_n}-\log\det(\sum_i p_i\mathbf{a}_i\mathbf{a}_i^\top)$, the leverage-score oracle is exactly the first-order oracle and the $(1+\varepsilon)$-John guarantee the Frank-Wolfe gap $g(\mathbf{p})\le\varepsilon d$; through this dictionary the costs come apart. The $\varepsilon^{-1}$ is a certification artifact: the uniform average of the iterates, the certificate used throughout the line, has gap exactly $\Theta(1/T)$, however cheap each iteration is made. Pointed instead at the last iterate the same oracle is fast: a warm-started accelerated method reaches the guarantee in $C(\mathbf{A})+O(\sqrt{\kappa}\log(1/\varepsilon))$ queries after an $\varepsilon$-independent setup $C(\mathbf{A})$, and once the optimal face is identified the facial problem is an unconstrained self-concordant minimization whose Hessian the oracle recovers exactly, so damped Newton needs only $O(\log\log(1/\varepsilon))$ steps, for a total of $C(\mathbf{A})+O(d^2\log\log(1/\varepsilon))$ queries. The accuracy dependence is thus doubly logarithmic after an $\varepsilon$-independent, condition-dependent setup; the open problem is the remaining identification cost (a condition-free bound on reaching the optimal face) and lower bounds. Accuracy is not the obstruction.

24.
arXiv (CS.CV) 2026-06-11

Continual Learning with Support Boundary Experience Blending

Continual learning (CL) seeks to mitigate catastrophic forgetting when models are trained with sequential tasks. A common approach, experience replay (ER), stores past exemplars but only sparsely approximates the data distribution, yielding fragile and oversimplified decision boundaries. We address this limitation by introducing Support Boundary Data (SBD), generated via differential-privacy-inspired noise into latent features to create boundary-adjacent representations that implicitly regularize decision boundaries. Building on this idea, we propose Experience Blending (EB), a framework that jointly trains on exemplars and SBD through a dual-model aggregation strategy. EB has two components: (1) latent-space noise injection to generate support boundary data, and (2) end-to-end training that jointly leverages exemplars and SBD. Unlike standard experience replay, SBD enriches the feature space near decision boundaries, leading to more stable and robust continual learning. Extensive experiments on CIFAR-10, CIFAR-100, Tiny ImageNet, and ImageNet1K demonstrate consistent accuracy improvements of 10%, 6%, 13%, 2%, respectively.

25.
arXiv (CS.CL) 2026-06-16

CODA-BENCH: Can Code Agents Handle Data-Intensive Tasks?

Advanced agents are increasingly demonstrating the potential to operate as autonomous engineers, creating a growing demand for evaluation benchmarks that capture the complexity of real-world development. Such environments typically involve both complex code and large-scale data (i.e., file system). However, existing benchmarks usually evaluate code-centric or data-centric capabilities in isolation, leaving a clear gap with real development scenarios. In this paper, we bridge this gap by introducing CODA-BENCH, the first benchmark to jointly evaluate code and data intelligence in a data-intensive environment. We construct a data-intensive Linux sandbox based on the Kaggle ecosystem (containing hundreds of datasets), where agents must actively explore complex file hierarchies to identify relevant resources and generate code for data-driven analytical tasks. CODA-BENCH comprises 1,009 tasks spanning 31 communities, with each task environment containing an average of 980 files, simulating realistic data scale and noise. Evaluations of advanced agents reveal that even top-performing systems struggle to effectively integrate data discovery with code execution, achieving a success rate of only 61.1%. These results highlight a substantial gap in current agentic capabilities for data-intensive tasks and point to promising directions for future research.