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01.
arXiv (math.PR) 2026-06-24

Typical geometry of self-repelling polymers in a constant force field

arXiv:2606.24352v1 Announce Type: cross Abstract: We study a general class of self-repelling polymers on $\mathbb Z^2$, including the simple random walk, the self-avoiding walk and the repulsive Domb-Joyce model, in the presence of a constant force field acting on each monomer. Conditioning the polymer to have fixed length and fixed endpoints, we identify the limiting free energy and prove that typical trajectories concentrate exponentially near a deterministic macroscopic shape. This shape is characterized as the unique minimizer of a variational problem and can be interpreted as a geodesic of a height-dependent Finsler metric. We also analyze two limiting regimes with universal features: for small field strength, in the symmetric case, the geodesic is close to a classical catenary, while for large field strength it converges to a universal polygonal shape governed by the nearest-neighbor lattice constraint.

02.
arXiv (quant-ph) 2026-06-15

Quantum Simulation of Spin-Dependent Electron Transfer in a Synthetic Chiral Lattice with a Trapped Ion

arXiv:2606.13930v1 Announce Type: new Abstract: Electron transfer through chiral structures can exhibit spin asymmetry, known as the chiral-induced spin selectivity effect, whose microscopic origin remains an open question. While path-interference within the chiral moiety has been proposed as a key mechanism, its experimental validation requires precise and versatile tunability of system parameters. Here we implement a programmable quantum simulation of spin-dependent electron transfer in a donor–chiral-bridge–acceptor model using a trapped ion. The bridge is encoded in internal states of the ion with tunable nearest- and next-nearest-neighbor couplings, while donor and acceptor states are coupled via a spectator bosonic motional mode. We observe spin-dependent interference within the bridge, and further reveal spin-dependence in donor-to-acceptor transfer dynamics, controlled by amplitude and phase of the coupling parameter. Our results identify interference among spin-dependent pathways as a microscopic origin of spin-dependent transfer, and open a route toward quantum simulations of complex chiral lattices with multi-level and bosonic degrees of freedom.

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

AsFT: Anchoring Safety During LLM Fine-Tuning Within Narrow Safety Basin

arXiv:2506.08473v4 Announce Type: replace Abstract: Fine-tuning large language models (LLMs) improves performance but introduces critical safety vulnerabilities: even minimal harmful data can severely compromise safety measures. We observe that perturbations orthogonal to the alignment direction - defined by weight differences between aligned (safe) and unaligned models - rapidly compromise model safety. In contrast, updates along the alignment direction largely preserve it, revealing the parameter space as a "narrow safety basin". To address this, we propose AsFT (Anchoring Safety in Fine-Tuning) to maintain safety by explicitly constraining update directions during fine-tuning. By penalizing updates orthogonal to the alignment direction, AsFT effectively constrains the model within the "narrow safety basin," thus preserving its inherent safety. Extensive experiments on multiple datasets and models show that AsFT reduces harmful behaviors by up to 7.60%, improves task performance by 3.44%, and consistently outperforms existing methods across multiple tasks.

04.
arXiv (quant-ph) 2026-06-11

Honest-binding quantum bit commitment from separable operations

arXiv:2501.07351v3 Announce Type: replace Abstract: Bit commitment is a fundamental cryptographic primitive and a cornerstone for numerous two-party cryptographic protocols, including zero-knowledge proofs. However, it has been proven that unconditionally secure bit commitment, both classical and quantum, is impossible. In this work, we demonstrate that imposing a restriction on the committing party to perform only separable operations enables secure quantum bit commitment schemes. Specifically, we prove that in any perfectly hiding bit commitment protocol, an honestly-committing party limited to separable operations will be detected with high probability if they attempt to alter their commitment. To illustrate our findings, we present an example protocol.

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

Can Agents Distinguish Visually Hard-to-Separate Diseases in a Zero-Shot Setting? A Pilot Study

The rapid progress of multimodal large language models (MLLMs) has led to increasing interest in agent-based systems. While most prior work in medical imaging concentrates on automating routine clinical workflows, we study an underexplored yet clinically significant setting: distinguishing visually hard-to-separate diseases in a zero-shot setting. We benchmark representative agents on two imaging-only proxy diagnostic tasks, (1) melanoma vs. atypical nevus and (2) pulmonary edema vs. pneumonia, where visual features are highly confounded despite substantial differences in clinical management. We introduce a multi-agent framework based on contrastive adjudication. Experimental results show improved diagnostic performance (an 11-percentage-point gain in accuracy on dermoscopy data) and reduced unsupported claims on qualitative samples, although overall performance remains insufficient for clinical deployment. We acknowledge the inherent uncertainty in human annotations and the absence of clinical context, which further limit the translation to real-world settings. Within this controlled setting, this pilot study provides preliminary insights into zero-shot agent performance in visually confounded scenarios.

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

Conditional Multi-Event Temporal Grounding in Long-Form Video

Multimodal large language models have made rapid progress in video temporal grounding, yet real-world applications routinely require localizing every event that satisfies compositional temporal and spatial conditions. Existing benchmarks fall short: they localize only a single moment per query, count without temporal conditions, or treat grounding and counting as disjoint tasks. We introduce CoMET-Bench for Conditional Multi-Event Temporal Grounding in long-form video, comprising 2789 queries over 600 videos averaging 33.8 minutes across five real-world domains, with each query composed from 4 temporal conditions, 3 spatial conditions, and a dedicated negative-query subset. We further propose a unified evaluation protocol jointly measuring counting, grounding, and negative-query recognition, including a new Rejection-F1 metric that prevents trivial gaming by lazy "always-empty" models. Benchmarking a broad suite of MLLMs, agent-based, and grounding-specialized methods reveals that existing approaches remain far from solving this task. Building on these findings, we propose CoMET-Agent, a training-free agentic framework that reformulates the task as structured search-and-aggregate, improving F1@0.5 by 6.1% over GPT-5 purely through structural reasoning. Failure analysis further surfaces three open directions: fine-grained entity tracking, position-uniform retrieval, and causal event pairing.

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

Emergency hub placement with a neutral-atom quantum computer

arXiv:2606.19589v1 Announce Type: new Abstract: We study the problem of emergency operation center placement in disaster response, where a minimal number of hubs must be selected to ensure timely coverage of all affected locations. This task can be formulated as a minimum dominating set problem on a graph encoding reachability within a target response time. We propose a hybrid quantum-classical approximation framework that leverages neutral-atom quantum computers as independent set samplers. Candidate dominating sets are constructed from both small maximal independent sets and complements of large independent sets, and are subsequently refined via a lightweight classical procedure. We benchmark the approach on synthetic instances and realistic case studies, and implement it on the Fresnel quantum processor by Pasqal, solving instances of up to 100 nodes. Our results show that quantum-generated samples, despite hardware noise, enable near-optimal solutions of the placement problem. Overall, our results demonstrate that neutral-atom devices operating in analog mode can already be used to tackle graph optimization problems for real-world applications.

08.
arXiv (CS.LG) 2026-06-25

Swarm-Inspired Generation of Collective Behaviors in Graph Dynamical Systems

arXiv:2606.24958v1 Announce Type: new Abstract: Collective behavior arises when locally interacting units produce coordinated global organization, from synchronization in dynamical systems to task-relevant information flow on graphs. The central challenge is not only to explain how collective behavior emerges, but to design local interaction rules that can produce desired global organization and generalize across graphs, dynamics and tasks.To address this challenge, we introduce the Swarm-Inspired Emergent Synchronizer (SIES), a graph-dynamical framework that learns generalizable local-interaction laws for controllable collective organization. Each node is an agent-like dynamical unit with a state and task cue, and signed source-target-conditioned attention acts as an adaptive coupling term inside an explicit evolution model. Therefore, SIES combines an explicit dynamical engine with local agent intelligence, similar to biological swarms. For synchronization control, SIES learns a generalizable coupling operator that produces prescribed synchronization patterns for CDSs across untrained network scales, target phase relations, and intrinsic node dynamics without retraining. The learned operator also reaches gait-related modes faster than three oscillator baselines and generalizes synchronization-driven locomotion to simulated multi-legged robots of different scales and a physical hexapod after leg disablement. For graph representation learning, SIES applies the same signed interaction principle to message passing and achieves the highest performance among the compared methods on heterophilous node-classification benchmarks. Together, these results position SIES as a generalizable and learnable graph-dynamical interaction framework with promise for synchronization control, adaptive robot coordination, and heterophilous graph representation learning.

09.
arXiv (quant-ph) 2026-06-17

Frequency-Division Multiplexed CV-QKD System

arXiv:2603.20718v2 Announce Type: replace Abstract: We propose a frequency-division multiplexed (FDM) continuous-variable quantum key distribution (CV-QKD) system with enhanced spectral efficiency through optimized channel spacing of low-symbol-rate signals. A four-channel 10-Mbaud FDM-CV-QKD system was experimentally demonstrated using Gaussian modulation, a transmitted local oscillator, and homodyne detection. Despite the inter-channel interference, under a finite-size scenario (m=1.25x10^6), the system achieved a 3.6-fold back-to-back secret key rate gain and outperformed the single-channel frequency-upconverted signal up to 26.8 km.

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

SARA: Unlocking Multilingual Knowledge in Mixture-of-Experts via Semantically Anchored Routing Alignment

Sparse Mixture-of-Experts (MoE) architectures have emerged as an increasingly influential paradigm as they offer a strategic balance between parameter scalability and computational efficiency. However, low-resource languages, which suffer from a scarcity of high-quality training data, often have their tokens routed to different experts than those predominantly activated by high-resource inputs, which limits cross-lingual expert sharing. This cross-lingual routing divergence consequently hinders their efficacy in multilingual contexts. To address this issue, we propose SARA (Semantically Anchored Routing Alignment), a framework designed to transfer specialized capabilities from high-resource languages as anchors to low-resource languages. SARA explicitly aligns the routing distribution of multilingual inputs with high-resource semantic anchors using a symmetric Jensen-Shannon (JS) divergence constraint. Unlike traditional distillation methods that operate on output logits, SARA directly aligns the internal routing distributions of MoE layers, encouraging mechanistic consistency in expert selection across languages. We conduct experiments on 2 LLMs across 5 low-resource languages and 3 benchmarks. Experiment results demonstrate that SARA outperforms standard instruction tuning, e.g., +0.8% on Qwen3-30B-A3B and +1.2% on Phi-3.5-MoE-instruct on Global-MMLU. Further analyses show that SARA effectively addresses performance bottlenecks in low-resource languages, providing a scalable pathway to enhance multilingual capabilities in sparse architectures.

11.
arXiv (CS.LG) 2026-06-15

Generalizing GNNs with Tokenized Mixture of Experts

arXiv:2602.09258v2 Announce Type: replace Abstract: Deployed graph neural networks (GNNs) are frozen at deployment yet must fit clean data, generalize under distribution shifts, and remain stable to perturbations. We show that static inference induces a fundamental tradeoff: improving stability requires reducing reliance on shift-sensitive features, leaving an irreducible worst-case generalization floor. Instance-conditional routing can break this ceiling, but is fragile because shifts can mislead routing and perturbations can make routing fluctuate. We capture these effects via two decompositions separating coverage vs selection, and base sensitivity vs fluctuation amplification. Based on these insights, we propose STEM-GNN, a pretrain-then-finetune framework with a mixture-of-experts encoder for diverse computation paths, a vector-quantized token interface to stabilize encoder-to-head signals, and a Lipschitz-regularized head to bound output amplification. Across nine node, link, and graph benchmarks, STEM-GNN achieves a stronger three-way balance, improving robustness to degree/homophily shifts and to feature/edge corruptions while remaining competitive on clean graphs.

12.
arXiv (CS.AI) 2026-06-18

AI-Driven Assessment of Human Tutors: Linking Training Performance to Real-Life Practice

arXiv:2606.18617v1 Announce Type: cross Abstract: There exist numerous tutor training platforms. However, few provide AI-driven training and evaluation for human tutors based on real-life performance. We present an AI-driven system that assesses both open responses during training and authentic real-life tutoring. Unlike platforms that only assess learning through online training or simulations, our system utilizes Generative AI (Gemini-2.5-pro) to analyze transcriptions of authentic tutoring, measuring the transfer of tutor skills to real-life application. Human tutors instructing students remotely in math (N=86) completed six scenario-based lessons, averaging a significant 7.4% learning gain. Using mixed-effects models across 405 session-to-lesson pairs, we found that training performance significantly predicted real-life transcript scores with an effect size of 0.25 SD. Model comparison (AIC/BIC) indicated averaging open response and multiple choice performance during training predicted real-life tutor performance best, although open responses were comparatively more predictive. Exploratory analysis showed that after training, tutors were significantly more likely to encounter pedagogical opportunities to apply their skills (61.1% to 68.9%) and demonstrated higher execution quality within those opportunities (65.5% to 68.1%). Interrupted time series analysis suggested that these tutor improvements were part of a gradual trend over time rather than an immediate intervention effect of training. We illustrate an AI-driven method to link tutor training with real-life assessment. In doing so, we contribute open datasets, AI prompts, and scoring rubrics to support transparency and reproducibility.

14.
arXiv (CS.LG) 2026-06-16

Agent trajectories as programs: fingerprinting and programming coding-agent behavior

arXiv:2606.16988v1 Announce Type: cross Abstract: Benchmark scores tell you what an agent got right; they do not tell you how it got there. In this work, we introduce methods for comparing agents procedurally in different contexts, where the model, tasks, and approaches vary. We compare ten agents and find that they are identifiable by their behavioral habits, which we define as fingerprints: a probe over these procedural signatures attributes an unseen trajectory to the correct agent at 85.7% accuracy, controlling for leakage across tasks. We develop procedural representations for agent problem-solving procedures with an emergent vocabulary induction technique that is meant to be maximally compressive to avoid surface-level variation while being expressive enough to unveil the quirks of the models' patterns. We apply our framework to the software engineering evaluation dataset SWE-Bench to study the structural distinctness of agent trajectories and find that behavior is most similar between models from similar release periods and those that are distilled from one another (e.g., a distilled student model and its teacher have a Jensen-Shannon divergence of 0.25, about half the distance between other model pairs). As more models saturate evaluations, we believe that it will be important to probe model behavior along more holistic dimensions than success rates alone. We introduce ProcGrep, a library for auditing and evaluating agents for how they approach tasks at a procedural level given their traces in a top-down fashion. We believe this work has a range of applications to help developers work with and program coding agents, such as task-aware model routing, agent monitoring, and finer-grained cost analysis.

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

Hidden Ghost Hand: Unveiling Backdoor Vulnerabilities in MLLM-Powered Mobile GUI Agents

Graphical user interface (GUI) agents powered by multimodal large language models (MLLMs) have shown greater promise for human-interaction. However, due to the high fine-tuning cost, users often rely on open-source GUI agents or APIs offered by AI providers, which introduces a critical but underexplored supply chain threat: backdoor attacks. In this work, we first unveil that MLLM-powered GUI agents naturally expose multiple interaction-level triggers, such as historical steps, environment states, and task progress. Based on this observation, we introduce AgentGhost, an effective and stealthy framework for red-teaming backdoor attacks. Specifically, we first construct composite triggers by combining goal and interaction levels, allowing GUI agents to unintentionally activate backdoors while ensuring task utility. Then, we formulate backdoor injection as a Min-Max optimization problem that uses supervised contrastive learning to maximize the feature difference across sample classes at the representation space, improving flexibility of the backdoor. Meanwhile, it adopts supervised fine-tuning to minimize the discrepancy between backdoor and clean behavior generation, enhancing effectiveness and utility. Extensive evaluations of various agent models in two established mobile benchmarks show that AgentGhost is effective and generic, with attack accuracy that reaches 99.7\% on three attack objectives, and shows stealthiness with only 1\% utility degradation. Furthermore, we tailor a defense method against AgentGhost that reduces the attack accuracy to 22.1\%. Our code is available at \texttt{anonymous}.

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

Perceptual compensation for tonal context in self-supervised speech models

This study examines the extent to which the wav2vec2.0 architecture exhibits evidence of compensation for phonological context. We conducted a pseudo-replication of a perceptional compensation experiment on Mandarin Chinese tones, and compared the embedding similarities and probing classifier outputs between a purely self-supervised pre-trained model and a model fine-tuned for Mandarin ASR. No evidence of compensation was found in the embedding similarities of the purely pre-trained model. Probing classifiers showed some evidence of compensation in addition to the expected layer-wise improvements in categorization, but failed to replicate human performance on isolated test syllables. Our findings contrast with previous reports of sensitivity to phonological structure emerging through pre-training alone, and suggest that supervised objectives may be necessary to encourage the abstraction of at least some types of phonological regularities.

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

RefGC-SR$^2$: Reference-guided Generated Content Super-Resolution and Refinement

Reference-guided generation (e.g., object compositing, customization) has progressed rapidly, yet current pipelines share a fundamental limitation: the object-centric high-resolution reference image (HRRI) provided by users is downsampled to a fixed low-resolution (LR) before being fed into the model, so the fine-grained details are discarded before the output is even produced. In addition, the generation step then introduces its own artifacts (e.g., identity distortion) on top of this loss. Existing reference-guided generated content refinement (RefGCR) methods can correct some of these artifacts but still operate in the LR domain; reference-guided super-resolution (RefSR) methods recover resolution but assume natural-image degradations and ignore the artifact distribution of generative pipelines. To address both gaps in a single formulation, we introduce a new task: reference-guided generated content super-resolution-refinement (RefGC-SR$^2$), where the original HRRI is reused at the post-processing stage to recover lost details, refine generative artifacts, and upscale the output simultaneously. We construct the first real-world triplet data generation pipeline for this RefGC-SR$^2$ task, training a diptych-conditioned generator to synthesize paired low-quality anchors that public pretrained models cannot provide. We further present a frequency-aware diffusion transformer model for RefGC-SR$^2$ that selectively injects fine details from the HRRI while removing generative artifacts. Extensive experiments demonstrate that our RefGC-SR$^2$ model successfully (i) refines the object identity faithfully with respect to the reference, and (ii) recovers high-resolution details, so that the final result is significantly higher quality and practically more usable compared to existing RefGCR and RefSR baselines.

18.
medRxiv (Medicine) 2026-06-18

The relationship between serotonin transporter occupancy and extracellular serotonin concentration is hyperbolic, not linear: implications for safely tapering antidepressants

Background: Hyperbolic tapering is an increasingly recognized approach for discontinuing serotonin reuptake inhibitor (SRI) antidepressants that involves non-linear dose reductions with equal stepwise reductions in serotonin transporter (SERT) occupancy to mitigate withdrawal symptoms. Its theoretical basis is the hyperbolic relationship between SRI dose and SERT occupancy reported in radioligand imaging studies. Hyperbolic tapering implicitly assumes that changes in SERT occupancy approximate changes in biologic effect and withdrawal risk. Because SERT occupancy plateaus across the therapeutic dose range of SRIs, this framework predicts relatively small biologic effects and withdrawal risk within this range. However, SERT occupancy influences serotonergic activity only indirectly via its effects on extracellular serotonin concentrations, and the relationship between these two variables is poorly characterized. Methods: We developed a two-pathway clearance model derived from mass-action kinetics to evaluate the steady-state relationship between SERT occupancy and extracellular serotonin concentrations under chronic SRI treatment. Results: Our analysis indicates that serotonin concentrations increase hyperbolically as transporter occupancy increases, suggesting that biologically meaningful differences in serotonergic signaling persist across the therapeutic dose range of SRIs despite plateauing occupancy. Conclusions: Our model predicts a hyperbolic relationship between SERT occupancy and extracellular serotonin concentrations, suggesting that changes in occupancy may not map proportionally onto serotonergic effect. These findings provide a potential mechanistic explanation for dose-dependent clinical effects of SRIs despite plateauing transporter occupancy and generate testable hypotheses regarding antidepressant tapering strategies. Empirical validation is warranted.

19.
arXiv (CS.LG) 2026-06-18

Stochastic Adaptive Gradient Descent Without Descent

arXiv:2509.14969v2 Announce Type: replace Abstract: We introduce a new adaptive step-size strategy for convex optimization with stochastic gradient that exploits the local geometry of the objective function only by means of a first-order stochastic oracle and without any hyper-parameter tuning. The method comes from a theoretically-grounded adaptation of the Adaptive Gradient Descent Without Descent method to the stochastic setting. We prove the convergence of stochastic gradient descent with our step-size under various assumptions, and we show that it empirically competes against tuned baselines.

20.
arXiv (CS.AI) 2026-06-18

Sparsity Curse: Understanding RLVR Model Parameter Space from Model Merging

arXiv:2606.18521v1 Announce Type: cross Abstract: Reinforcement Learning with Verifiable Reward (RLVR) has emerged as a powerful post-training paradigm that surpasses Supervised Fine-Tuning (SFT) in eliciting reasoning intelligence and resisting catastrophic forgetting. Recent studies further reveal that RLVR induces highly sparse and off-principal parameter updates compared to SFT. This naturally raises the question: does such sparsity make RLVR models more amenable to model merging? If so, model merging would offer a scalable, training-free path to aggregate diverse reasoning capabilities from independently trained RLVR models. Surprisingly, we find the opposite, uncovering a sparsity curse: the sparse RLVR updates are spread farther apart in parameter space, forming near-orthogonal shortcuts that make aggregation inherently fragile. This is likely rooted in the stochasticity of RL optimization and the diversity of emergent reasoning patterns. Unlike SFT models that converge to shared, flat basins and merge naturally, RLVR models suffer severe degradation under standard merging methods. Through systematic empirical analysis of the update geometry, we characterize the mechanisms behind this failure and propose Sensitivity-aware Resolving Merging (SAR-Merging), a merging recipe tailored for the unique structure of RLVR parameter spaces. SAR-Merging resolves conflicts in overlapping update regions via Fisher Information-based sensitivity arbitration, followed by magnitude-aware sparsification and rescaling to preserve fragile reasoning pathways. Experiments on mathematical and coding benchmarks demonstrate that SAR-Merging substantially outperforms existing merging methods on RLVR models, enabling both single-task enhancement and multi-capability fusion.

21.
arXiv (quant-ph) 2026-06-16

Generative modelling powered by room-temperature polariton condensates

arXiv:2606.15344v1 Announce Type: cross Abstract: Generative modelling requires efficient stochastic nonlinear transformations and physical platforms that can naturally realise them. We experimentally demonstrate that nonlinear optical systems operating in the strong light-matter coupling regime can serve as physical transformation layers for conditional generative modelling. Specifically, we develop a workflow in which room-temperature exciton-polariton condensates formed in organic dye microcavities act as a physical stochastic transform within a generative adversarial network and enable conditional digit-to-image translation. By using the nonlinear many-body dynamics and intrinsic stochasticity of polariton condensates, the workflow outperforms baseline approaches based on digitally injected perturbations. We find that polariton-enabled sampling via generative adversarial network (Polariton GAN) yields improved inception score, digit preservation accuracy and structural similarity compared with both digital sampling and laser-based systems. We further show that spatially correlated output variations can naturally regularise adversarial training and enhance output diversity. Our results establish polariton condensation as a new computational resource for generative modelling, opening a pathway towards physics-enhanced machine learning systems.

22.
medRxiv (Medicine) 2026-06-24

Genetic overlap with schizophrenia and Parkinson's reveals psychomotor basis of physical activity

Background Physical activity levels are altered across neuropsychiatric disorders. While these traits are heritable, the genetic overlap between normal variation in activity levels and neuropsychiatric disorders that involve motor dysfunction such as schizophrenia and Parkinson's disease (PD) remains unexplored. Objectives To investigate the genetic overlap between physical activity, schizophrenia, and PD. Methods Multi-Trait Analysis of genome-wide association studies (GWAS) was used to boost the GWAS power for objectively measured physical activity (n=89,683) by leveraging three GWAS of self-reported activity (n=124,842-377,234). Genetic overlap between the activity, schizophrenia and PD was characterized using linkage disequilibrium score regression, causal mixture modeling, and local genetic correlations. Pleiotropic variants were identified using the conjunctional false discovery rate, annotated to genes, and investigated for enrichment of biological processes, tissue types and association with GWAS-catalog traits. Results Genetic correlations of physical activity with schizophrenia and PD were negligible (rg=-0.02-0.02, p>0.05), but polygenic overlap was substantial, reflecting mixed effect directions. We identified 32 independent variants shared with schizophrenia and 11 with PD, including CRHR1, MAPT and KANSL1 within the 17q21.31 region. Schizophrenia-shared variants mapped to genes differentially expressed in subcortical regions, especially amygdala and basal ganglia. Gene-set analyses revealed enrichment for mental health and cognitive-behavioural traits (schizophrenia-shared genes) versus structural brain phenotypes and neurodegenerative disorders (PD-shared genes). Conclusions Despite negligible genetic correlations, physical activity shares substantial genetic architecture with schizophrenia and PD. Shared genes implicated brain regions and traits spanning motor and cognitive-affective function, consistent with the psychomotor nature of physical activity.

23.
bioRxiv (Bioinfo) 2026-06-21

OracleScreen-LILRB4: Machine Learning-Guided Discovery of Myeloid Immune Checkpoint Binders Validated in Patient-Derived Cells

The identification of small molecule modulators of immune checkpoint proteins remains a significant challenge in drug discovery due to the flat, featureless nature of protein-protein interaction interfaces and the characteristically low hit rates observed in conventional high-throughput screening campaigns. Here we report OracleScreen-LILRB4, an ensemble machine learning framework trained on quantitative biophysical screening data from two structurally diverse compound libraries (19,800 compounds total) screened against the myeloid immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4/ILT3). By formulating binding prediction as a regression task targeting continuous {Delta}Fnorm values rather than binary hit classifications, OracleScreen-LILRB4 achieved a mean Spearman R of 0.61 and ROC-AUC of 0.86 under scaffold-aware cross-validation. Prospective virtual screening of a 45,760-member compound library and experimental validation of the top 200 predictions yielded a 28.5% hit rate, representing a 15.0-fold enrichment over baseline, with 16 compounds demonstrating nanomolar-affinity LILRB4 (ILT3) engagement. Lead compounds ORS-22 and ORS-14 restored anti-tumor immune activity across patient-derived colorectal cancer and acute myeloid leukemia co-culture systems, reversing SCG2-mediated immunosuppression and recovering cytotoxic T-cell function. These findings establish OracleScreen-LILRB4 as an effective computational framework for accelerating small molecule discovery against non-enzymatic immune checkpoint targets.

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

DenseControl: Instance-Level Controllable Synthesis of Dense Crowd Image

In this paper, we introduce DenseControl, a novel pipeline for generating dense crowd images. Specifically, DenseControl meticulously positions and sizes each generated instance to align precisely with the predefined coordinates and scales. Based on this, we further allow for control over the background, style, and attributes of instances. The motivation behind DenseControl stems from the observation of two main challenges in synthesizing crowd images: controlling signal embedding and maintaining topological integrity when imparting instance scale guidance. To address these, we first introduce the Isolated Object Embedding (IOE) map, a novel representation that facilitates spatial location control while mitigating the difficulties associated with learning projections for model. Secondly, we propose an Implicit Scale Embedding (ISE) strategy that seamlessly integrates with the IOE map to encode precise scale information. To further enhance the efficacy of combining ISE with the IOE map, we incorporate a Position Shortcut mechanism that enhances cross-attention to alleviate projection challenges. We evaluate DenseControl through two lenses: synthesis quality and applicability in latent applications. Experiments across different control conditions demonstrate DenseControl achieves state-of-the-art results in dense crowd image synthesis. Furthermore, we showcase applications in augmenting crowd analysis under data scarcity, transfer learning, and weather generalization scenes, to highlight the practical utility of DenseControl. The codebase will be released.

25.
arXiv (CS.CV) 2026-06-11

Global Geometry Is Not Enough for Vision Representations

A common assumption in representation learning is that globally well-distributed embeddings support robust and generalizable representations. This focus has shaped both training objectives and evaluation protocols, implicitly treating global geometry as a proxy for representational competence. While global geometry effectively encodes which elements are present, it is often insensitive to how they are composed. We investigate this limitation by testing the ability of geometric metrics to predict compositional binding across a diverse suite of vision encoders. We find that standard geometry-based statistics exhibit near-zero correlation with compositional binding. In contrast, functional sensitivity, as measured by the input–output Jacobian, reliably tracks this capability. We further provide an analytic account showing that this disparity arises from objective design, as existing losses explicitly constrain embedding geometry but leave the local input–output mapping unconstrained. These results suggest that global embedding geometry captures only a partial view of representational competence and establish functional sensitivity as a critical complementary axis for modeling composite structure.