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01.
arXiv (CS.AI) 2026-06-19

Wisdom of Committee: Diverse Distillation from Large Foundation Models and Domain Experts

arXiv:2402.14035v4 Announce Type: replace-cross Abstract: Knowledge distillation from foundation models to compact domain models is challenging due to substantial gaps in capacity, architecture, and modality. For example, in our experiments, distilling from a 76M-parameter language model to a 2M-parameter recommender closes less than 40% of the performance gap between the undistilled student and the teacher. We show that introducing domain-specific experts – which share the student's architectural characteristics – alongside the foundation model as a diverse teacher committee significantly improves transfer. However, standard multi-teacher methods fail to exploit this diversity: naively combining heterogeneous teachers can degrade performance below single-teacher distillation. To address this, we propose DiverseDistill, an interactive distillation framework that employs a learnable Question-Answer mechanism to generate teacher-conditioned queries and align heterogeneous teacher outputs into the student's representation space. Unlike methods requiring gradient-based co-optimization or architectural modification of teachers, DiverseDistill operates with frozen teachers using only forward-pass inference through their intermediate layers: no parameter updates, no co-training, and no architectural surgery. A dynamic teacher importance mechanism further reduces training cost by filtering low-relevance teachers per sample (e.g., ~30% fewer forward passes with no quality loss for recommendation tasks), while the entire Distillation Module is discarded after training, adding zero inference overhead. Evaluations on recommendation (38x compression) and vision (3.6x compression) tasks demonstrate that DiverseDistill recovers 73-114% of the teacher-student performance gap, consistently outperforming all single- and multi-teacher baselines.

02.
arXiv (CS.CL) 2026-06-15

Be My Tutor: On-Policy Co-Distillation for Mutual LLM Improvement via Peer Feedback

We study multi-domain LLM training in which two models, each stronger in a different domain, co-evolve by tutoring each other through on-policy feedback. Unlike one-way distillation or single-model fine-tuning, our goal is mutual Pareto improvement: each model improves across domains without losing its original strength. To this end, we propose On-Policy Co-Distillation (OPCoD), where each student's self-distillation is conditioned on its own correct rollout and feedback from its peer. To make feedback exchange effective, OPCoD uses cognizance-based gating to decide when to give feedback and feedback anchoring to ground feedback in the problem. On Science Q\&A tasks, OPCoD consistently outperforms baselines and achieves Pareto improvement across all evaluated domain pairs and students.

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

Learning Patterns and Abstractions from Perceptual Sequences

Authors:

arXiv:2503.10973v2 Announce Type: replace Abstract: Cognition swiftly breaks high-dimensional sensory streams into familiar parts and uncovers their relations. Why do structures emerge, and how do they enable learning, generalization, and prediction? What computational principles underlie this core aspect of perception and intelligence? A sensory stream, simplified, is a one-dimensional sequence. In learning such sequences, we naturally segment them into parts – a process known as chunking. In the first project, I investigated factors influencing chunking in a serial reaction time task and showed that humans adapt to underlying chunks while balancing speed and accuracy. Building on this, I developed models that learn chunks and parse sequences chunk by chunk. Normatively, I proposed chunking as a rational strategy for discovering recurring patterns and nested hierarchies, enabling efficient sequence factorization. Learned chunks serve as reusable primitives for transfer, composition, and mental simulation – letting the model compose the new from the known. I demonstrated this model's ability to learn hierarchies in single and multi-dimensional sequences and highlighted its utility for unsupervised pattern discovery. The second part moves from concrete to abstract sequences. I taxonomized abstract motifs and examined their role in sequence memory. Behavioral evidence suggests that humans exploit pattern redundancies for compression and transfer. I proposed a non-parametric hierarchical variable model that learns both chunks and abstract variables, uncovering invariant symbolic patterns. I showed its similarity to human learning and compared it to large language models. Taken together, this thesis suggests that chunking and abstraction as simple computational principles enable structured knowledge acquisition in hierarchically organized sequences, from simple to complex, concrete to abstract.

04.
arXiv (CS.AI) 2026-06-11

Are Frontier LLMs Ready for Cybersecurity? Evidence for Vertical Foundation Models from Dual-Mode Vulnerability Benchmarks

arXiv:2605.23243v2 Announce Type: replace-cross Abstract: We evaluate whether frontier LLMs are ready for cybersecurity through a dual-mode benchmark: white-box function-level vulnerability detection (VulnLLM-R, across C/Java/Python) and black-box web application security testing (five production-style applications with 118 ground-truth vulnerabilities across 20+ CWE families, which we will open-source). We test six frontier models (GPT-5.4, Codex~5.3, Claude Opus~4.6, Sonnet~4.6, Gemini~3.1~Pro and Gemini~3~Flash) and two domain-specialized models across four testing paradigms. Our findings are sobering: (1)~every frontier model produces 10-50% false positive rates in white-box detection, systematically over-predicting vulnerabilities; (2)~in black-box testing, frontier models achieve only 4-8% ground-truth coverage, improving to just 10-19% even with external security tools (Playwright MCP, Burp Suite MCP); (3)~structured penetration-testing methodology encoded in domain-specialized agents raises per-family detection above 50%, demonstrating that methodology, not scale, is the primary lever; and (4)~a domain-specialized defense model achieves the highest precision (0.904) and lowest false positive rate (9.7%) among all models, on a single GPU. We identify the absence of structured security testing traces end-to-end request/response sequences, failure-heavy data, and multi-step attack chains as the fundamental training data bottleneck, and propose self-play security testing as a data generation strategy. Our results make the case for vertical foundation models purpose-built for cybersecurity.

05.
medRxiv (Medicine) 2026-06-22

T Cell Receptor repertoire analysis reveals antigenic convergence and immunotherapeutic opportunities in Prostate Cancer

Background: The T-cell receptor {beta} (TCR{beta}) repertoire reflects antigen-driven adaptive immune responses and provides insight into tumor-immune interaction. In prostate cancer (PCa), the immunosuppressive tumor microenvironment limits effective T-cell activation, and the antigenic drivers shaping intratumoral TCR repertoires remains poorly defined. This study aimed to characterize matched tumor and peripheral TCR{beta} repertoires from treatment-naive PCa patients and to identify shared clonotypes and antigenic specificities associated with disease severity. Methods: Next-generation sequencing was used to profile TCR{beta} repertoires from matched tumor biopsies and peripheral blood mononuclear cells obtained from treatment-naive PCa patients. Repertoires clonality, diversity, and was assessed using established metrics. Antigenic convergence was evaluated using GLIPH2 to identify shared CDR3{beta} motifs and predicted tumor-associated antigen (TAA) recognition, followed by functional validation using IFN-{gamma} ELISpot and T-cell expansion assays. Results: Tumor-derived TCR{beta} repertoires displayed reduced richness and increased clonality compared with peripheral blood mononuclear cells, consistent with local antigen-driven expansion. High-grade tumors demonstrated greater interpatient clonotype sharing and motif-level convergence, indicative of recognition of common TAAs. GLIPH2 analysis associated expanded clonotypes with epitopes derived from prostate-specific G-protein coupled receptor (PSGR), prostate-specific membrane antigen (PSMA), and prostate-specific antigen (PSA). Functional validation confirmed that peptide pools containing PSGR- and PSMA-derived epitopes induced IFN-{gamma} production and antigen-specific T-cell proliferation in vitro. Conclusions: These findings reveal an oligoclonal, antigen-driven intratumoral TCR{beta} landscape and identify PSGR and PSMA as immunogenic, potentially actionable targets. Integration of TCR profiling with antigen discovery pipelines may support the development of TCR-based biomarkers and precision immunotherapeutic strategies in prostate cancer.

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

Learning New Tasks via Reusable Skills: Skill-Compositional Experts for Embodied Continual Learning

Embodied Continual Learning (ECL) aims to enable robots to continually acquire new manipulation tasks while retaining previously learned behaviors under closed-loop control. Compared with conventional continual learning, ECL suffers from more severe catastrophic forgetting. Feature drift accumulated under closed-loop control progressively propagates through sequential decision-making, leading to degradation of previously learned behaviors. A key challenge in ECL lies in structured skill reuse across continually evolving tasks, since existing methods primarily focus on skill learning without explicitly organizing them for coherent task execution. To address this issue, we propose SCE, a Skill-Compositional Experts framework for ECL. SCE builds a skill base via Compositional Skill Grounding (CSG), which decomposes task demonstrations into reusable skills. Based on this, Dual Execution-and-Transition Experts (DETE) enable new task learning through skill composition, where one branch ensures skill execution and the other supports transitions between skills for coherent behavior. Experiments on LIBERO benchmarks and real-world manipulation tasks demonstrate that SCE consistently improves retention and overall task performance. Further feature drift analyses and ablation studies verify the effectiveness of our method. Project website: https://eqcy.github.io/sce/.

07.
arXiv (CS.LG) 2026-06-19

Semantic-Anchored Evidential Fusion for Domain-Robust Whole-Slide Survival Analysis

arXiv:2606.19966v1 Announce Type: cross Abstract: Whole-slide images (WSIs) are widely used for computational cancer prognosis. However, most existing methods primarily focus on in-domain performance and fail to generalize across clinical centers. This limitation stems from their reliance on pixel-derived representations that are highly susceptible to domain-specific artifacts caused by staining protocols and scanner hardware. We hypothesize that high-level pathology semantics, such as tumor grade and micro-environmental architecture, provide a domain-invariant semantic representation that mirrors the robust diagnostic logic of human pathologists. Therefore, we propose a Semantic-Anchored Evidential Fusion Survival (SAEFS) framework, where SAEFS derives semantic anchors from WSIs via Visual Question Answering (VQA), employs a dual-stream WSI evidence extraction architecture, uses Dirichlet-based Subjective Logic to model uncertainty, and fuses semantic and visual evidence through a cautious conjunction rule to avoid overconfident fusion from correlated sources. Trained exclusively on one source domain and evaluated zero-shot across four unseen domains, SAEFS consistently outperforms state-of-the-art models both in prediction accuracy and reliability, improving the average C-index by 10.2%. Quantitative analyses further show that VQA-derived semantic features exhibit significantly lower cross-center divergence than pixel-derived features, highlighting their robustness for cross-center clinical applications.

08.
arXiv (CS.CL) 2026-06-19

Group-Sparse Matrix Factorization for Transfer Learning of Word Embeddings

Unstructured text provides decision-makers with a rich data source in many domains, ranging from product reviews in retail to nursing notes in healthcare. To leverage this information, words are typically translated into word embeddings – vectors that encode the semantic relationships between words – through unsupervised learning algorithms such as matrix factorization. However, learning word embeddings from new domains with limited training data can be challenging, because the meaning/usage may be different in the new domain, e.g., the word ``positive'' typically has positive sentiment, but often has negative sentiment in medical notes since it may imply that a patient tested positive for a disease. In practice, we expect that only a small number of domain-specific words may have new meanings. We propose an intuitive two-stage estimator that exploits this structure via a group-sparse penalty to efficiently transfer learn domain-specific word embeddings by combining large-scale text corpora (such as Wikipedia) with limited domain-specific text data. We bound the generalization error of our transfer learning estimator, proving that it can achieve high accuracy with substantially less domain-specific data when only a small number of embeddings are altered between domains. Furthermore, we prove that all local minima identified by our nonconvex objective function are statistically indistinguishable from the global minimum under standard regularization conditions, implying that our estimator can be computed efficiently. Our results provide the first bounds on group-sparse matrix factorization, which may be of independent interest. We empirically evaluate our approach compared to state-of-the-art fine-tuning heuristics from natural language processing.

09.
arXiv (quant-ph) 2026-06-11

Rolling Stock Planning Using the Quantum Approximate Optimization Algorithm

arXiv:2606.11383v1 Announce Type: new Abstract: Rolling stock planning is a complex optimization problem in railway management that involves assigning physical trains to scheduled trips while minimizing operational costs. In this work, we address a specific instance of this problem featuring 190 trips over two days, subject to constraints such as mandatory maintenance stops. We reformulate the problem as a Maximum-Weight Independent Set (MWIS) problem on a graph where nodes represent feasible train cycles. To handle the computational complexity of the large search space, we propose a hybrid divide-and-conquer algorithm. This approach iteratively selects subgraphs and solves the MWIS problem using various solvers, including exact classical methods and the Quantum Approximate Optimization Algorithm (QAOA). We evaluate the algorithm's performance by comparing these methods and analyzing the scaling with respect to subgraph size, with QAOA assessed through both classical simulation and execution on a quantum device (IQM Emerald). Our results indicate that increasing the subgraph size generally improves solution quality, demonstrating that the hybrid framework can effectively bridge the gap between polynomial-time approximate solvers and exponential-time exact methods.

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

Scalar-pathway fidelity improves physical accuracy in short-range equivariant interatomic potentials

arXiv:2606.15892v1 Announce Type: new Abstract: Accurate interatomic potentials enable molecular dynamics of materials, molecules, and interfaces beyond density-functional-theory length and time scales. Equivariant neural network potentials have improved the representation of local geometry. However, their deployable energy surfaces ultimately manifest through invariant scalar channels, whose aggregation and spectral resolution remain comparatively underexamined. Here we use Physics-Aware Neighborhood (PAN) pooling and Physics-Guided Spectral (PGS) mixers as controlled scalar-pathway probes: lightweight, symmetry-preserving modifications that act only on \(\ell=0\) channels while leaving the equivariant tensor backbone unchanged. Using MACE as a high-body-order mechanistic scaffold, PAN adds coordination-sensitive amplitude modulation, whereas PGS augments edge and readout scalar features with radial and tapered spectral bases. Across metallic Ag, covalent Si, a short-range ionic LiF/Li–F subset, and MD17/rMD17 molecules, this scalar-pathway correction reduces MACE force errors by 22–27\% and energy errors by 19–22\%; on systems with stress labels, stress errors decrease by 27–28\%, at approximately 5\% additional inference-FLOPs cost. Directionally consistent gains in Allegro and NequIP further indicate that the correction is portable across distinct short-range equivariant backbones, although effect sizes remain architecture-dependent. These results identify scalar-pathway fidelity as a practical design dimension for short-range equivariant interatomic potentials.

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

LLM Consumer Behavior Theory: Foundations of a Novel Research Field

arXiv:2606.18005v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly deployed as autonomous agents that make consumption decisions on behalf of users. This shift raises fundamental questions for consumer theory, which has traditionally modeled humans as the primary decision-makers. In this paper, we introduce LLM Consumer Behavior Theory, a new field of study concerned with analyzing consumer behavior in agentic markets. Drawing on classical and behavioral economics alongside recent advances in Natural Language Processing, we formalize how human preferences are reflected and acted upon by LLM-based agents, and how agent-level decisions aggregate into market demand. We unify previously fragmented literature on LLM decision-making, human behavior simulation, and preference elicitation under a common economic lens, highlighting where assumptions, such as rationality and heterogeneity, may fail in agentic markets. Rather than providing empirical validation, this paper outlines the scope of LLM consumer behavior and identifies open research questions related to alignment, preference representation, and market dynamics.

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

Estimating Tail Risks in Language Model Output Distributions

arXiv:2604.22167v2 Announce Type: replace-cross Abstract: Language models are increasingly capable and are being rapidly deployed on a population-level scale. As a result, the safety of these models is increasingly high-stakes. Fortunately, advances in alignment have significantly reduced the likelihood of harmful model outputs. However, when models are queried billions of times in a day, even rare worst-case behaviors will occur. Current safety evaluations focus on capturing the distribution of inputs that yield harmful outputs. These evaluations disregard the probabilistic nature of models and their tail output behavior. To measure this tail risk, we propose a method to efficiently estimate the probability of harmful outputs for any input query. Instead of naive brute-force sampling from the target model, where harmful outputs could be rare, we operationalize importance sampling by creating unsafe versions of the target model. These unsafe versions enable sample-efficient estimation by making harmful outputs more probable. On benchmarks measuring misuse and misalignment, these estimates match brute-force Monte Carlo estimates using 10-20x fewer samples. For example, we can estimate probability of harmful outputs on the order of 10^-4 with just 500 samples. Additionally, we find that these harmfulness estimates can reveal the sensitivity of models to perturbations in model input and predict deployment risks. Our work demonstrates that accurate rare-event estimation is both critical and feasible for safety evaluations. Code is available at https://github.com/rangell/LMTailRisk

13.
arXiv (CS.LG) 2026-06-24

Constrained Variable Projection for Structured Problems

arXiv:2606.23939v1 Announce Type: cross Abstract: Variable projection is a classical technique for separable nonlinear least-squares problems, in which variables that enter linearly are eliminated exactly, yielding a reduced nonlinear problem. By expressing this framework as a particular instance of a broader class of bilevel optimization problems, we develop a constrained variable-projection framework for data-science models, where the remaining variables are subject to convex constraints and the eliminated variables arise from a lower-level least-squares problem. In particular, by interpreting variable projection as a collapsed bilevel optimization problem, we derive exact reduced-gradient formulas compatible with automatic differentiation and propose a conditional-gradient algorithm for the resulting constrained reduced problem. We establish convergence guarantees under standard smoothness and compactness assumptions, and discuss extensions to structured lower-level variables. Numerical experiments on sparse autoencoding, dictionary learning, blind deconvolution, and few-shot learning suggest that the method can improve wall-clock efficiency and data efficiency relative to natural joint-optimization baselines.

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

Learning to Prompt: Improving Student Engagement with Adaptive LLM-based High-School Tutoring

LLMs can personalize education, although current static-prompt tutoring systems struggle to adapt to diverse academic disciplines. We develop and test a system with subject-aware prompting, based on 14 pedagogical features (e.g., tutor scaffolding, student understanding) extracted from raw transcripts. We first train a prompt routing model in a simulation environment, and then deploy it for online adaptation with actual high-school students. The simulation benchmark shows the router outperforming two static baselines ($0.694$ vs. $0.647$ and $0.64$, $p

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

Knowledge Graph Enhanced Memory-Augmented Retrieval for Long Context Modeling

Long-context language modeling requires not only extending context windows but maintaining coherent understanding of entity states and relationships across thousands of tokens – a challenge that semantic similarity alone cannot address. KGERMAR addresses this by constructing dynamic, context-specific knowledge graphs from input text during inference, enabling domain-adaptive retrieval that leverages both semantic similarity and explicit entity relationships. The framework performs real-time entity and relation extraction to build contextual knowledge graphs, then integrates graph-structural embeddings with textual semantics through a multi-component memory architecture. Three memory banks – contextual, semantic, and structural – are maintained with retrieval signals fused via learned weights to capture both surface-level semantics and deeper relational patterns. Evaluated on SlimPajama (84.7K training examples), WikiText-103 (4,358 examples), PG-19 (100 examples), and Proof-pile (46.3K examples), KGERMAR achieves up to 8.5\% lower perplexity and 2–2.5x better memory efficiency than memory-augmented baselines across context lengths from 1K to 32K tokens, with superior in-context learning performance across five NLU tasks. The dynamic knowledge graph construction approach advances memory-augmented language modeling by enabling domain-specific knowledge representation that adapts to input contexts rather than relying on fixed knowledge bases.

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

Iterating Toward Better Search: A Two-Agent Simulation Framework for Evaluating Agentic Search Architectures in E-Commerce

arXiv:2606.12924v1 Announce Type: new Abstract: We present a modular two-agent simulation framework for evaluating conversational shopping assistant architectures. An independent buyer agent, configured with personas, missions, and patience levels, is paired with an interchangeable responder that integrates with a real e-commerce search API. Holding the buyer constant across experiments enables controlled comparison of responder designs on identical scenarios. Using 2011 conversations across 14 persona buckets, we establish four empirical findings. First, rolling-window memory outperforms intent-extraction memory on all quality metrics while being 35% faster per query. Second, illustrating rapid evidence-driven iteration, a systematic failure analysis of a responder version enables targeted fixes that reduce failure and near-failure rates by 62% across the full dataset. Third, swapping the responder LLM backbone from Gemini~2.5 to Llama~3.3~70B costs 0.16–0.45 points despite identical architecture. Finally, we document systematic philosophical disagreement between frontier LLM judges: Gemini rewards process correctness while Claude demands concrete outcomes, despite using the same evaluation prompt.

18.
bioRxiv (Bioinfo) 2026-06-15

Maternal BMI and Placental Transcriptomic Changes: A Meta-Analysis of Gene Expression at the Maternal-Fetal Interface

Objective: Maternal body mass index (BMI) is often used as a measure of metabolic status and increased or decreased maternal BMI is associated with a heightened risk of cardiometabolic diseases across generations. The placenta mediates these maternal metabolic cues; however, its genome wide transcriptional adaptations in response to maternal BMI remain incompletely defined. Methods: To delineate placental genes, pathways, and interaction clusters whose transcript abundance varies with maternal prepregnancy BMI through a genome wide meta analysis of human placental RNA sequencing datasets. Placental RNA seq reads from four publicly available cohorts (n=146) were mapped to the GRCh38 reference genome and differentially expressed genes were identified. An independent microarray cohort (n=19) was reanalysed separately to facilitate cross platform comparison. Functional enrichment employed GO, KEGG, and STRING protein interaction resources. Results: Meta-analysis of 146 RNA seq samples identified eight genes with genome-wide significance in placentae from underweight pregnancies including inflammatory signaling gene MAP4K1 and metabolic enzyme PSPH, while overweight and obese categories revealed nominally significant differential expression. KEGG analysis demonstrated significant downregulation of oxidative phosphorylation with increasing maternal BMI, and protein-protein interaction networks revealed inflammatory mediators as central nodes in overweight and obese groups. Independent microarray validation corroborated key findings, including consistent downregulation of oxidative phosphorylation in obesity. Conclusion: Maternal BMI is associated with placental transcriptomic signatures involving inflammatory, metabolic, and hormonal pathways, with consistent downregulation of oxidative phosphorylation across platforms. This genome-wide meta-analysis provides a reproducible catalogue of BMI-responsive placental transcripts that may contribute to developmental programming of offspring health.

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

MaineCoon: Pursuing A Real-Time Audio-Visual Social World Model

As an increasing majority of global video content is consumed on social platforms for interactive social purposes, video generation models built for social worlds are important but largely overlooked by previous studies. In this work, we define the position of social world models and build a prototype model as the first step towards this goal. While previous world models successfully simulate physical environments or gaming world exploration, they remain fundamentally detached from human-centric social dynamics. To bridge this gap as the first step to social world models, we present MaineCoon, the first real-time audio-visual autoregressive model that has 22B parameters and is capable of real-time streaming generation and sub-second interaction, with a record-breaking frame rate of up to 47.5 FPS, on a single GPU. To the best of our knowledge, MaineCoon is also the first real-time audio-visual generation model specifically optimized for social-interactive applications. To enable efficient and stable training, we introduce several novel techniques into MaineCoon, including self-resampling, cross-modal representation alignment, domain-aware preference optimization, and reinforced online-policy distillation (ROPD). We also design the first agentic streaming inference framework that supports thousand-second-scale or even longer generation while mitigating drift with agentic cache management and prompt planing. These innovations significantly accelerate training while optimizing real-time inference performance. We believe this work not only sets a new state-of-the-art (SOTA) performance benchmark for high-quality, low-latency, and long-horizon audio-visual autoregressive models, but also points out the paradigm shift desired for next-generation AI-native social platforms.

20.
arXiv (CS.AI) 2026-06-16

Embedded Arena: Iterative Optimization via Hardware Feedback

arXiv:2606.16190v1 Announce Type: cross Abstract: Embedded devices from wildlife monitoring stations to clinical wearables require local AI inference due to latency, communication, or privacy constraints. Optimizing models for heterogeneous microcontrollers (MCUs) requires simultaneously satisfying hard physical constraints on memory, power, and temperature while preserving accuracy, a multidimensional optimization that is today performed manually by experts. We ask whether an LLM agent can autonomously navigate this complex, multi-turn pipeline guided by real hardware feedback, and introduce a hardware-in-the-loop agent arena in which the agent iteratively refines both model and firmware – compiling, flashing, and measuring on real hardware – to enable closed-loop optimization. Frontier models, including Claude Opus 4.7 and Gemini 3.1 Pro, fail entirely without hardware feedback (0% deployment success), whereas our hardware-in-the-loop formulation achieves the first successful deployment within three iterations and can surpass human expert results within seven. This agentic co-optimization achieves 250x compression for vision models with

21.
medRxiv (Medicine) 2026-06-17

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

Despite recent advances in next-generation sequencing, genetic diagnostic rates for dilated cardiomyopathy (DCM) remain low. Among paediatric DCM, causes are often heritable, with a greater frequency of de novo, recessive and syndromic causes of disease. Novel diagnostic methods are therefore required to solve monogenic cases. To assess the value of proteomics as a diagnostic tool for paediatric DCM, we obtained left ventricle myocardial samples from paediatric patients undergoing heart transplantation at the Royal Children's Hospital, Melbourne. We performed genome sequencing and proteomics and leveraged this multi-omics dataset to uncover the molecular cause of disease in a gene elusive proband. The proband carried a heterozygous JPH2 frameshift variant identified on clinical exome sequencing. However, proteomic analysis showed a pronounced downregulation of JPH2, suggestive of biallelic loss-of-function. Closer inspection of the genomic data revealed a large inversion (~8.34 Mb) with a breakpoint falling within intron 5 of JPH2 that displaces the 3'UTR from the coding transcript. The two variants were confirmed to be in trans using long read DNA sequencing, consistent with a diagnosis of JPH2 autosomal recessive DCM. Finally, we applied RNA sequencing with total RNA library preparation to show that transcripts containing a 3'UTR were reduced to ~10% relative to controls. As a proof-of-principle, we present the first reported use of proteomics from explanted cardiac tissue to provide a genetic diagnosis. Our methodology has broad relevance to patients with genetically unsolved Mendelian diseases, who might undergo organ transplantation as part of clinical management.

22.
arXiv (math.PR) 2026-06-11

Heat kernel estimates for Markov processes with blowing-up jump kernels

arXiv:2512.24807v2 Announce Type: replace Abstract: In this paper, we establish sharp two-sided heat kernel estimates for a large class of purely discontinuous symmetric Markov processes on closed subsets $F$ of $\mathbb{R}^d$, whose jump kernels blow up on a Borel subset $\Sigma$ of $F$. We assume that $F\setminus \Sigma$ is a $\kappa$-fat set and is dense in $F$. To the best of our knowledge, this is the first work establishing sharp heat kernel estimates for jump processes whose jump kernels blow up on part of the state space. The jump kernels under consideration take the form $J(x,y)=|x-y|^{-d-\alpha}{\mathcal B}(x,y)$, where $\alpha\in (0,2)$ and the function ${\mathcal B}(x,y)$ blows up at a subset $\Sigma$ of $F$. A fundamental obstacle is that the tails of the jump measures are not uniformly bounded, and hence standard techniques in heat kernel analysis do not provide a priori off-diagonal estimates. To overcome this difficulty, we develop a new approach based on weighted integral estimates for the heat kernel that are sensitive to both the blow-up behavior of the jump kernel and the geometry of $F\setminus \Sigma$. Examples of processes falling within our general framework include traces of isotropic $\alpha$-stable processes in $C^{1,\rm Dini}$ sets, processes in Lipschitz sets arising in connection with the nonlocal Neumann problem, and a large class of resurrected self-similar processes in the closed upper half-space.

23.
arXiv (CS.AI) 2026-06-11

Mathematical perspective on genetic algorithms with optimization guided operators

arXiv:2606.12279v1 Announce Type: cross Abstract: Recent work in ML applies genetic algorithms at inference time to iteratively improve solutions to optimization problems. The basic mutation and recombination operators involved are qualitatively different from those studied classically. Mutations are no longer random; an ML algorithm mutates a solution with the goal of improving an objective. Similarly, recombination is not based on random collages of parent solutions. Instead, it is an ML optimization-based operator whose goal is to synthesize improved solutions from its inputs. Thus, these mutation and recombination operators are more likely to improve the objective, but their computational cost is much higher. We introduce a general model of genetic algorithms and formulating optimization in this model as a query-complexity problem, using the language of reinforcement learning. We then study specialized models. We show that some optimization problems require generation, mutation, and recombination to be solved. We then obtain qualitatively tight algorithms for a family of problems within this framework that captures the nontrivial role of diversity in the solution pool, a key feature of practical ML genetic algorithms.

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

Q-Fold: Query-Aware Focus-Context Spatio-Temporal Folding for Long Video Understanding

Long-video understanding remains challenging for multimodal large language models, because temporally extended videos often contain thousands of frames and are therefore expensive to process exhaustively. Existing methods usually construct compact visual inputs from long videos under a limited visual budget. However, most of them still follow a frame-centric paradigm and apply similar representations to retained content regardless of its importance. This makes it difficult to preserve both high-fidelity visual evidence and broad temporal coverage. To address this issue, we propose Q-Fold, a training-free input construction framework for long-video understanding. Instead of treating isolated frames as the basic modeling unit, Q-Fold operates on contiguous temporal segments and constructs a heterogeneous Focus–Context representation under query guidance. Query-relevant segments are preserved as high-fidelity Focus Frames, while less relevant segments are folded into chronology-preserving contextual layouts. In this way, Q-Fold preserves critical visual evidence and broad temporal coverage, while better maintaining local temporal continuity within short segments. Experiments on four long-video benchmarks with multiple Video-MLLMs show that Q-Fold consistently improves performance without increasing the input budget. Notably, it achieves gains of up to 9.1 percentage points on an ultra-long video benchmark. Code will be made publicly available.

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

Cross-Silo De-Anonymization Under Local Differential Privacy: Threat Model, Phase Transition, and Coordination Necessity

arXiv:2606.16763v1 Announce Type: cross Abstract: When a person's records appear in k independent data silos, each protected by (epsilon, delta)-differential privacy, standard composition yields a valid (k*epsilon, k*delta)-DP guarantee for the joint output. This worst-case bound, however, does not answer the concrete inference question: at what k can an adversary actually identify a target person? This paper develops the information-theoretic framework needed to answer that question. We introduce cross-silo person-level DP (XSP-DP), a Pufferfish-style privacy notion whose adjacency relation captures all records of a single person across all silos simultaneously, and verify that the standard basic composition bound carries over to this adjacency model. Within this framework we prove that de-anonymization undergoes a phase transition at k* = Theta(log n / epsilon^2) (population size n, per-silo RR parameter epsilon): a Fano lower bound shows any estimator fails for k > k*. An explicit XOR + randomized-response construction demonstrates information synergy: each silo's output is individually uninformative about the target, yet the joint mutual information is strictly positive. For non-coordinated binary randomized-response mechanisms, we prove that de-anonymization is inevitable once k exceeds the threshold, establishing that cross-silo coordination is necessary. These results provide a baseline threat model and Theta-level threshold for cross-silo inference attacks under local DP.