Toward mechanistic virtual immune cells
This Comment outlines molecular and technical considerations for developing mechanistically grounded virtual immune cell models.
Academic Intelligence · Curated Daily
AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。
This Comment outlines molecular and technical considerations for developing mechanistically grounded virtual immune cell models.
arXiv:2605.10967v2 Announce Type: replace Abstract: We develop a theoretical framework for describing superposed coherent states in graphene quantum systems using the concept of catability as a phase-sensitive metric functional measure. In this case, the formalism quantifies interference stability and coherence structure via phase-dependent contributions of quantum superposition states. Catability is defined as a functional measure sensitive to relative phase variations within coherent state combinations, serving as a diagnostic tool for quantum interference effects in graphene-based systems. Also, the formulation is extended using Lie algebra techniques, where the underlying symmetry structure of graphene quantum states is represented through operator algebras governing state transformations in quantum space. In this context, to describe nonlocal propagation and phase-resolved dynamics, a Green function approach is incorporated, enabling systematic treatment of quantum correlations in a spatially extended structures framework. A unified framework is constructed by combining Lie algebraic symmetry analysis with Green function propagation theory, yielding a consistent description of phase-sensitive catability in complex graphene quantum configurations within the framework approach. Results provide a structured route for testing coherence, interference stability, and quantum state control in low-dimensional quantum materials systems.
arXiv:2606.13295v1 Announce Type: cross Abstract: In the era of Explainable Artificial Intelligence, there is a renewed focus on single trees for their ease of interpretation. This paper introduces Simultaneous Latent Budget Trees, a probabilistic machine learning framework for classification trees in the presence of a stratification factor such as a temporal, spatial, or demographic variable, acting as a control variable or potential confounder. Standard tree growth procedures are not designed to optimize a conditional split rule. A model-based split rule is proposed in which child nodes are interpreted as latent components of a simultaneous mixture model, such as the Simultaneous Latent Budget Model and its constrained versions, fitted to the parent node. Mixing parameters drive the observations, differently for each group, to the child nodes whereas latent budgets parameters update the response classes profile of each level of the control variable. Parameters are estimated by least squares considering a neural network perspective of the model. An informative tree structure can be interactively visualized with interpretation aids on the node and the paths, including visual pruning and decision tree selection procedure. Suitable measures are proposed to handle an unbalanced response class distribution. The proposed methodology is applied to investigate gender-related differences in disease progression of Amyotrophic Lateral Sclerosis. The SLBT library with the various tree-based algorithms is available in the linked GitHub repository.
arXiv:2503.22846v2 Announce Type: replace Abstract: We theoretically investigate the stochastic dynamics of two qubits subject to one- and two-site correlated continuous weak measurements. When measurements dominate over the local unitary evolution, the system's dynamics is constrained and part of the physical Hilbert space becomes inaccessible: a typical signature of the Quantum Zeno (QZ) effect. In this work, we show how the competition between these two measurement processes give rise to two distinct QZ regimes, we dubbed standard and correlated, characterised by a different topology of the allowed region of the physical Hilbert space being a simply and non-simply connected domain, respectively. We develop a theory based on a stochastic Gutzwiller ansatz for the wavefunction that is able to capture the structure of the phase diagram. Finally we show how the two QZ regimes are intimately connected to the topology of the flow of the underlying non-Hermitian Hamiltonian governing the no-click evolution.
arXiv:2606.24953v1 Announce Type: new Abstract: Machine learning (ML) algorithms are known to be opaque. We do not know the reasons for their predictions. The learning process leading to the prediction function is also opaque. We do not fully understand the time evolution of the weight values of neural nets (NN) and related dynamical phenomena. While prediction opacity is widely studied, learning opacity remains largely underexplored. This article studies learning opacity trough the lens of complex dynamical systems. We argue that NN learning is essentially a complex system and that learning opacity is due to dynamical complexity and the epistemological challenges that arise from it. We identify three key properties of training complexity – sensitivity to weight initialization, feedback in gradient based optimization, and sensitivity to the training data – and show how each contributes to learning opacity. As these properties are fundamental to the learning process damping or eliminating them would fundamentally alter how ML systems learn. Some sources of opacity in ML may hence be irreducible.
The integration of spatial transcriptomics (ST) data across species is essential for cross-species and translational studies, but remains challenging due to molecular divergence and anatomical differences between organisms. We present STACAME, a graph attention autoencoder-based framework to decipher shared and divergent tissue architectures from cross-species ST data by explicitly modeling both orthologous and species-specific genes. STACAME aligns ST slices in a spatially aware manner, identifies homologous and species-specific domains, and enables a suite of downstream comparative analyses. We demonstrate its utility by integrating ST datasets from diverse tissues, including hippocampus, isocortex, embryo, breast, liver, and cerebellum, across multiple species such as human, macaque, marmoset, mouse, and zebrafish. STACAME supports cross-species spatial domain alignment, the detection of shared and divergent spatially variable genes, development alignment and comparison, and the 3D integration of tissue architecture. This flexible approach facilitates the translation of findings from model organisms to humans, providing a unified computational platform for cross-species spatial transcriptomics.
arXiv:2602.10896v2 Announce Type: replace-cross Abstract: Quantum Electrodynamics predicts that the vacuum must behave as a nonlinear optical medium: the vacuum optical index should increase when it is stressed by intense electromagnetic fields. The DeLLight (Deflection of Light by Light) project aims to measure it by using intense and ultra-short laser pulses. The experiment uses a Sagnac interferometer to amplify the tiny deflection signal of a low-intensity probe pulse crossing the vacuum refractive-index gradient produced by an external high-intensity pump pulse. The measurement of the amplified signal by a CCD camera requires a high spatial resolution, which is limited by the ultimate quantum noise of the CCD. However, interferometric phase noise induced by the mechanical vibrations of the interferometer is also amplified and degrades spatial resolution. To overcome this, we propose a new method named High-Frequency Phase Noise Suppression (HFPNS), based on the addition of a delayed replica (5 ns) of the probe pulse. The delayed pulse, which is not affected by the pump but is subject to the same vibration noise, enables offline subtraction of correlated phase noise. In this work, we present an experimental proof-of-concept on a prototype interferometer operating with a limited amplification factor ($\mathcal{A}\simeq25$), about 10 times smaller than the required value of the final experiment. We have succeeded in reducing phase noise by a factor of 40, resulting in a residual noise level 2.3 times higher than the expected quantum noise. The residual noise is linked to delay-line instabilities and incident beam pointing fluctuations present during these tests. This result validates HFPNS as a robust method for future quantum-noise-limited interferometric measurements of vacuum optical nonlinearity, though additional stabilization and higher interferometric amplification are still needed.
Vision-Language Models (VLMs) are typically pre-trained on large-scale image-text datasets to capture semantic correspondences between visual content and natural language. However, they remain surprisingly brittle to negation: models often rely on shallow word co-occurrence and are easily distracted by misleading or irrelevant textual cues, even when their overall retrieval or classification performance is strong. Moreover, directly finetuning on negation data can interfere with previously acquired knowledge, causing noticeable degradation on standard vision-language benchmarks. To tackle these issues, this work introduces HANCLIP (Hyperbolic + Angular + Negation), a family of VLMs that explicitly restructures the embedding space to encode "what an image is not" alongside "what it is." HANCLIP is trained on a compact set of 20,000 image-text quadruplets and combines a hyperbolic formulation, which models hierarchical semantic relations and asymmetries, with an angular triplet objective that drives systematic separation between negated descriptions and their corresponding positives. This geometry-aware design strengthens negation sensitivity while preserving the global structure of pretrained representations, rather than overwriting them. Extensive experiments across multiple vision-language tasks show that HANCLIP delivers consistent gains on the negation-focused NegBench benchmark, while maintaining competitive or improved performance on standard classification and image-text retrieval benchmarks. The framework is model-agnostic and can be plugged into CLIP, LongCLIP, SmartCLIP, and HiMo-CLIP without large-scale retraining, demonstrating that a carefully designed geometric objective can substantially extend the reasoning capabilities of existing VLMs using only modest additional data.
arXiv:2606.16607v1 Announce Type: cross Abstract: This paper considers neural channel state information (CSI) compression for time-varying massive multiple-input multiple-output (MIMO) channels in frequency division duplex (FDD) systems with limited feedback resources. The main challenge lies in obtaining a compact and efficient representation of the CSI given that it exhibits strong temporal correlation across successive snapshots. Existing memoryless compression models do not exploit this property, while simple temporal extensions often incorporate multiple observations without explicitly modeling the latent dynamics. We propose a context-aware compression framework based on a k-memory Markov variational autoencoder (k-MMVAE), which uses a finite temporal window to capture the evolution of CSI in the latent space. The model introduces Markov-structured latent dynamics with finite memory, enabling efficient use of temporal dependencies for compression. Simulation results show that the proposed approach improves target CSI reconstruction performance compared to memoryless and weakly sequential baselines, particularly at low and moderate compression rates. These results suggest that explicit latent temporal modeling can provide an effective mechanism for CSI compression under limited feedback constraints.
arXiv:2606.15057v1 Announce Type: cross Abstract: Indirect prompt injection (IPI) is a major security threat to LLM-powered agents. Thus, a growing body of work have proposed a variety of defensive approaches against IPI. These can be grouped into three broad categories: 1) prompt-based (using prompting as a way to prevent agents from following malicious instructions), 2) detection-based (identifying and filtering malicious instructions), and 3) system-level (using systems insights, such as control and data isolation, for defense). However, commonly used benchmarks for evaluating defense, such as AgentDojo, are inherently static, generating a fixed distribution of IPI attacks. Consequently, static benchmarks do not usefully evaluate defense robustness to adaptive threats. We address this issue by developing AutoDojo, an adaptive extension of AgentDojo that optimizes IPI against a given defense. Using AutoDojo against state-of-the-art IPI defenses across three task suites and five target models, we make two key observations. First, many defenses offer only limited protection: a cheap, black-box adaptive attack using a frontier LLM to iteratively optimize the injection raises attack success rate (ASR) well above the level achieved by static injections against nearly all evaluated defenses. Against a filter that reduces static ASR to 0\%, AutoDojo recovers 28\% overall and 64\% on action-open tasks. Second, for prompt-level and filter-based defenses, ASR is substantially higher on action-open tasks – where the user's request delegates the action itself to attacker-controlled content – than on precisely specified tasks. This is a structural limit: on such tasks the injection can pose as ordinary data rather than an explicit instruction, bypassing defenses that rely on detecting instruction-like text. AutoDojo is publicly available at https://github.com/xhOwenMa/AutoDojo.
Pansharpening aims to generate high-resolution multispectral (HRMS) images by fusing low-resolution multispectral (LRMS) and panchromatic (PAN) observations. Most existing deep learning methods treat pansharpening as fixed-grid prediction, which limits scale adaptation. To address this, we propose GSPan, a framework that introduces 2D Gaussian Splatting (GS) into pansharpening. Instead of directly predicting pixels, GSPan represents band-wise residual details as continuous and learnable 2D Gaussian primitives. We design a Dual-Stream Hierarchical Interaction (DSHI) architecture with a Spatial-Spectral Interactive Attention (SSIA) module to estimate these primitives from complementary PAN and MS observations. The predicted primitives are rendered as a residual detail field and injected into the upsampled MS image. This continuous representation allows GSPan to render fused images on arbitrary target sampling grids without scale-specific retraining. It further enables a Scale-Decoupled Asymmetric Inference (SDAI) strategy, which estimates primitives at a reduced resolution and renders the fused image at the target resolution for efficient large-scene pansharpening. Experiments on QuickBird, GaoFen-2, WorldView-3, and WorldView-3-4K datasets show that GSPan delivers state-of-the-art fusion performance. Moreover, SDAI markedly accelerates inference, achieving a favorable trade-off between computational efficiency and fusion quality. Our results demonstrate the potential of continuous Gaussian residual representations as a flexible and scale-decoupled alternative to fixed-grid prediction.
Existing Vision Foundation Model (VFM)-based iterative stereo pipelines under-exploit three information pathways: multi-scale backbone features are collapsed into single-level correlations, geometric priors remain untapped at initialization, and context propagates only locally. These gaps widen under degraded photometric cues, making underwater scenes a stringent generalization test. To address this, we propose LinStereo, built upon Depth Anything V3, whose core is a Position-Aware Linear Attention (PALA) module that replaces local recurrence with global aggregation at linear cost, propagating reliable estimates from well-matched regions into degraded areas while preserving disparity structure. PALA is made effective by two enabling components: Hierarchical Semantic Cost Volumes (HSCV), which supply scale-aligned correlations from the VFM feature hierarchy, and a Depth Prior Initialization (DPI) that converts monocular depth into a metrically calibrated warm start. LinStereo achieves state-of-the-art-level accuracy on standard benchmarks and strong cross-domain generalization, particularly on underwater scene where severe photometric degradation makes stereo matching particularly challenging, attaining the best overall accuracy with consistent gains 28% lower AbsRel on TartanAir-UW, 26% on SQUID, a real-world underwater dataset).
arXiv:2606.01730v2 Announce Type: replace Abstract: Large language models (LLMs) are increasingly used as heuristic advisors for black-box optimization, yet their suggestions and self-reported confidence are not necessarily calibrated to downstream objective values. This issue becomes more pronounced in multi-objective Bayesian optimization, where different objectives may require different expert knowledge and where an LLM expert can be useful for one objective but misleading for another. We study how to use LLM-generated expert priors in discrete multi-objective Bayesian optimization without blindly trusting them. We propose an objective-wise reputation-market mechanism that treats each expert-objective pair as a falsifiable prior source. Expert weights are updated online from observed objective feedback, discounted over time, and gated by market-level trust. We then introduce a decoupled counterfactual gate that can use the LLM prior without confidence, use it with confidence, or abstain from the LLM prior entirely. Across controlled synthetic stress tests and three molecule optimization benchmarks with \qwenflash{}-generated expert priors, we find that dynamic objective-wise calibration improves robustness over fixed LLM priors. However, raw LLM confidence is not reliably beneficial: on ESOL, confidence is positively correlated with prediction error; on FreeSolv, confidence can help; and on Lipophilicity, ignoring confidence remains strongest. Our fixed three-arm counterfactual gate improves over the first counterfactual variant on ESOL and FreeSolv, while an attempted margin portfolio exposes a useful negative result: margin selection should be acquisition-aware rather than based only on one-step prior error.
arXiv:2606.18108v1 Announce Type: cross Abstract: We develop a text-to-SQL (structured query language) system based on large language models (LLMs) using in-context learning and apply it to the Automatic Learning for the Rapid Classification of Events (ALeRCE) astronomical database. ALeRCE is a community broker for the Zwicky Transient Facility and the Vera C. Rubin Observatory. The system enables users to query the database in natural language (NL) and generates executable SQL queries. To develop and evaluate the system, we constructed a dataset of 110 NL/SQL pairs. We propose a step-by-step generation framework comprising four modules: schema linking, query classification, prompt decomposition, and self-correction. The performance of thirteen LLMs is evaluated using in-context learning and prompt engineering techniques. Text-to-SQL performance is assessed using the perfect-match (PM) rate for row identifiers (e.g., object identifiers) and column identifiers (i.e., column names). The proposed step-by-step framework consistently outperforms a direct-inference baseline, while the self-correction module consistently reduces execution errors. For Claude Opus 4.6, PM performance on row (column) identifiers is high for simple queries, reaching 0.97 (0.94), and decreases with query complexity to 0.44 (0.72) for medium queries and 0.59 (0.49) for hard queries. Among the thirteen evaluated models, the best-performing LLMs for the text-to-SQL task are Claude Opus 4.6, Gemini 2.5 Pro, Gemini 3 Flash, and GPT-5.2-Codex.
Reasoning has substantially improved Large Language Models (LLMs) on analytical tasks such as mathematics and code generation, but its value for abstractive summarization remains unclear. To address this gap, we adapt general reasoning strategies to the summarization setting and conduct a large-scale comparative study of 8 reasoning strategies and 3 Large Reasoning Models (LRMs) across 8 diverse datasets, evaluating both summary quality and factual faithfulness. Our results show that reasoning is not a universal solution and its effectiveness depends strongly on the strategy and the summarization setting. In particular, we find a trade-off between summary quality and factual faithfulness. Explicit reasoning strategies often improve reference-based quality, but may weaken factual grounding, whereas implicit reasoning in LRMs shows the opposite tendency. We further find that increasing an LRM's internal reasoning budget does not reliably improve summarization and can even reduce factual consistency. These findings suggest that, for summarization, more reasoning is not always better. Effective reasoning should preserve faithful compression rather than induce over-elaboration. Our source code is publicly available.
Digital Subtraction Angiography (DSA) is one of the gold standards for vascular disease diagnosis. With the help of a contrast agent, time-resolved 2D DSA images deliver comprehensive blood flow information and can be utilized to reconstruct 3D vessel structures for medical assessment. Current commercial DSA systems typically require hundreds of scanning views to perform reconstruction, resulting in substantial radiation exposure. In this study, we propose a neural rendering-based optimization framework tailored for high-quality sparse-view DSA reconstruction to reduce radiation dosage. Our approach, termed vessel probability guided attenuation learning, represents DSA imaging as a complementary weighted combination of static and dynamic attenuation fields, with the weights derived from the time-independent vessel probability field. Functioning as a foreground mask, vessel probability provides proper gradients for both static and dynamic fields adaptive to different scene types. This mechanism enables self-supervised decomposition between static backgrounds and dynamic contrast agent flow, and significantly improves reconstruction quality. Our model is trained by minimizing the discrepancy between synthesized projections and real captured DSA images. We further employ two training strategies to improve reconstruction quality: (1) coarse-to-fine progressive training for better geometry and (2) temporal perturbed rendering loss for temporal consistency. Experimental results have demonstrated high-quality 3D vessel reconstruction and 2D DSA image synthesis.
Public bulk RNA-seq repositories contain hundreds of thousands of samples, creating opportunities for large-scale representation learning, but integration across studies remains challenging because of heterogeneous annotations, experimental protocols, and technical variation. While pre-trained foundation models are now widely available for single-cell RNA-seq, comparable resources for bulk RNA-seq remain scarce, motivating a model that learns a unified, tissue-aware representation directly from bulk data. We trained a supervised variational autoencoder (VAE) on a compendium of 118,263 bulk RNA-seq samples that we assembled from TCGA, GTEx, and ARCHS4 and mapped to 42 tissue categories. The model classifies tissue of origin at 94.9% balanced accuracy (weighted F1 96.2%) and compresses 16,115 genes into a 121-dimensional latent space. Tissue identity is the primary organizing axis of the latent space, while source effects remain secondary. To assess the impact of data volume, we constructed training sets at three different scales (38K, 75K, and 118K samples). Our results demonstrated that reconstruction fidelity improved incrementally with each expansion of the dataset, but with diminishing returns. We validated the model on an independent cohort of 734 paediatric tumour samples from TARGET, achieving 84.6% agreement with the expected tissue of origin. The trained model and code are available at GitHub (https://github.com/BIMSBbioinfo/flexynesis_tissue_vae_manuscript) with an interactive web application.
Decoding visual experience from brain activity has advanced substantially, but current brain-to-text systems largely recover semantic content while discarding affect. Additionally, language models can generate emotional text when prompted with categorical labels, but such labels collapse rich inter-subject variability into coarse discrete bins. We present EmoMind, the first end-to-end pipeline for decoding affective captions directly from fMRI signals. EmoMind first retrieves a semantically grounded neutral scene description from brain-decoded visual features, then rewrites it using a continuous 34-dimensional emotion vector decoded from the same fMRI recording. To control the balance between content preservation and affective expression, we train the rewriter with classifier-free guidance against an identity-preserving null branch, enabling smooth interpolation between semantic fidelity and affective expressivity. We evaluate affective caption generation with a three-axis validation framework spanning subject-specificity, structural geometry, and causal control. We further augment this framework with a synthetic-brain substitution test that probes robustness to the measurement apparatus, and we benchmark each axis against GPT-4 prompted with brain-decoded top-5 emotion labels as a strong discrete baseline. Across two independent emotion fMRI datasets, EmoMind significantly outperforms label-prompted GPT-4 on all three axes, with the largest gains on metrics that require person-specific affective structure rather than population-level emotion aggregation. These results establish continuous brain-decoded affect as a viable control signal for individualized affective caption generation and open new directions for studying individual affective brain organisation.
T cell receptor (TCR)-based immunotherapy holds immense potential for treating cancers and infectious diseases, where highly antigen-specific TCR recognition is crucial for adaptive immunity against tumors and pathogens. Engineering or de novo generation of the complementarity-determining region 3 (CDR3) loops of TCRs using artificial intelligence offers a powerful alternative to designing reactive TCRs rather than laborious experimental screening. However, current in silico approaches are constrained by weak conditional guidance, limited flexibility, and a lack of rigorous functional validation. To address these limitations, we introduce TCRDiff, a generative diffusion framework for designing antigen-specific TCRs conditioned on peptide-MHC (pMHC) targets and germline-encoded variable genes. By leveraging pre-trained knowledge from massive T-cell repertoires and TCR-pMHC recognition data, TCRDiff generates CDR3{beta} sequences with state-of-the-art fidelity to native binding TCRs through a denoising diffusion process. Furthermore, incorporating the interface geometry features generated TCR-pMHC complexes with superior structural plausibility. As a proof of concept, we deployed TCRDiff in a systematic pipeline to design candidate TCRs for immunotherapy. In vitro activation assays validated that TCRDiff-generated TCRs specifically recognize the MAGE-A3 epitope with minimized off-target cross-reactivity. Together, TCRDiff establishes a powerful, validated computational paradigm to accelerate the development of TCR-based immunotherapies.
arXiv:2606.15989v1 Announce Type: cross Abstract: Aligning neural activity across subjects offers the promise of discovering shared computational principles and generalizable decoders. However, traditional alignment methods require shared stimuli across subjects, a constraint that limits applicability to naturalistic paradigms with limited or non-overlapping data. We introduce a Multi-Encoder-Decoder Variational Autoencoder (MED-VAE) that achieves cross-subject alignment without shared stimuli by anchoring representations to a common scaffold provided by a pretrained ANN. Using the Natural Scenes Dataset, we show that MED-VAE creates common latent spaces with superior semantic organisation, achieving higher cross-subject alignment than common methods while maintaining robust generalisation to held-out stimuli where traditional methods degrade. Reconstructing from these common spaces back to each subject's original neural space, MED-VAE preserves equal stimulus-driven signal in its cross-subject latent space. Finally, we show that this superior alignment directly enables cross-subject neural prediction, as demonstrated via cross-subject image decoding. In summary, we introduce a framework to identify generalisable common subspaces for cross-subject predictions and downstream tasks, demonstrated here for visual cortex responses to static images.
arXiv:2602.17187v2 Announce Type: replace-cross Abstract: The problem of domain generalization concerns learning predictive models that are robust to distribution shifts when deployed in new, previously unseen environments. Existing methods typically require labeled data from multiple training environments, limiting their applicability when labeled data are scarce. In this work, we study domain generalization in an anti-causal setting, where the outcome causes the observed covariates. Under this structure, environment perturbations that affect the covariates do not propagate to the outcome, which motivates regularizing the model's sensitivity to these perturbations. Crucially, estimating these perturbation directions does not require labels, enabling us to leverage unlabeled data from multiple environments. We propose two methods that penalize the model's sensitivity to variations in the mean and covariance of the covariates across environments, respectively, and prove that these methods have worst-case optimality guarantees under certain classes of environments. Finally, we demonstrate the empirical performance of our approach on a controlled physical system and a physiological signal dataset.
arXiv:2606.24779v1 Announce Type: cross Abstract: Birth defects are a major cause of fetal loss, neonatal morbidity and long-term disability. In the subset with suspected genetic etiologies, exome and genome sequencing have moved many cases from variant detection to post-sequencing interpretation: clinicians must rank patient-specific candidate variants under incomplete fetal or infant phenotypes and heterogeneous evidence from population genetics, variant-effect prediction, gene-disease validity, phenotype ontologies, cellular and pathway context, protein structure and clinical literature. We present DeepBD, a grounded agentic workflow for variant prioritization and diagnostic interpretation of genetic birth defects. DeepBD organizes the workflow into LLM-assisted case structuring, a pretrained evidence engine, specialist evidence modules and a grounded diagnostic review layer. The evidence engine learns patient-specific variant scores from structured rule evidence, sequence and variant-effect representations and phenotype-conditioned biological context, whereas specialist modules and the agentic layer provide tool-based refinement, candidate-pool review and diagnosis-oriented synthesis from ranked candidates. Developed using an in-house fetal and infant cohort comprising 18,622 cases, DeepBD achieved Recall@1/3/5/10 of 0.658/0.882/0.912/0.929 on an internal held-out solved-case benchmark, outperforming standalone Exomiser, DeepRare and prompted LLM reranking baselines evaluated on Exomiser-derived top-20 candidate variants. Ablation and overlap analyses show that rule evidence, mechanistic context, and specialist refinement provide complementary signals. These findings support a grounded agentic workflow that separates evidence integration, tool-based refinement, and LLM-assisted diagnostic review for retrospective variant prioritization in genetic birth defects.
arXiv:2606.19025v1 Announce Type: cross Abstract: Pre-training Large Language Models (LLMs) typically demands large-scale infrastructure with tightly coupled hardware accelerators. While increasing model and dataset scale remains the dominant driver of performance, Mixture-of-Experts (MoEs) architectures have recently achieved state-of-the-art results by decoupling parameter count from computational cost. This efficiency enables training massive models on constrained compute budgets, yet it typically requires the high-speed interconnects of a single datacenter. To overcome these physical limits, recent approaches such as DiLoCo and Photon use low-communication data-parallel methods to enable scaling across geographically distributed, weakly connected data centers. However, these methods suffer from a fundamental inefficiency: they require full model replicas at every site, which imposes prohibitive memory constraints and communication overheads. In this work, we introduce FoMoE, a system that breaks the full-replica paradigm by partitioning expert layers across workers. We demonstrate that FoMoE: (I) reduces communication costs by up to 1.42x over efficient baselines and 45.44x over DDP via partial expert replication in the studied regimes; (II) achieves empirical throughput speedups of up to 1.4x through a novel skip-token mechanism; and (III) shows stable routing in the trained proxy regimes and projects the communication/memory benefits to 100B-scale configurations through system modelling.
arXiv:2606.15912v1 Announce Type: cross Abstract: Multi-turn agents that plan, invoke tools, and interact with environments offer a promising paradigm for solving complex tasks, yet their capabilities typically rely on very large models whose inference cost is prohibitive in practice.On-Policy Distillation (OPD) is a natural recipe for transferring such capabilities to smaller students, but we find that it suffers a characteristic failure mode in this setting: small student errors compound across turns and push the trajectory out of the teacher's familiar state distribution, so the teacher's supervision becomes least reliable precisely where the student needs it most.We propose Guided On-Policy Distillation (Guided-OPD), a simple yet effective algorithm that mixes teacher- and student-generated turns within each rollout and schedules the teacher's intervention probability along a curriculum that decays to zero.Strong guidance keeps early trajectories close to the teacher distribution and is then gradually withdrawn to recover the purely on-policy regime used at inference.On ALFWorld, ScienceWorld, and WebShop, distilling Qwen3 students from a Qwen3-30B-A3B teacher, Guided-OPD improves Score by 21.1\% and Success Rate by 25.5\% over vanilla OPD on average, with larger gains on smaller students.
Autoregressive video diffusion models have emerged as a promising approach for long video generation, achieving strong performance in streaming settings. However, existing methods are restricted to forward temporal generation, whereas practical video creation often requires flexible generation order, e.g., conditioning on future context to extend backward, or on both past and future context for inbetween generation. We bridge this gap by training an autoregressive model that supports generation in arbitrary temporal directions. A key technical challenge arises from the Causal 3D VAE widely used in video diffusion models, which encodes latents strictly conditioned on past context. While suited for forward generation, this causal structure causes inter-block discontinuities when generation proceeds backward. To address this, we introduce blockwise anchor latents, a set of auxiliary latents that restore the missing past context at block boundaries during backward generation. Built on this design, we propose UniTemp, a bidirectional distillation framework that trains a single autoregressive student model for any-direction video generation. At inference time, UniTemp conditions on arbitrary past and/or future frames, improving controllability for both bidirectional and inbetween generation. Experiments show that UniTemp maintains competitive performance on short and long video generation compared to forward-only methods, while enabling diverse workflows such as bidirectional video extension, inbetween generation, looping video generation, scene transition, and visual story generation. Project website: https://lzhangbj.github.io/projects/unitemp/