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

Constrained hybrid modelling to predict microbial dynamics and organic matter turnover in soil systems

arXiv:2606.20329v1 Announce Type: new Abstract: Soil microorganisms control organic matter cycling and largely determine how soil systems can cope with and mitigate climate change and environmental threats. Representing microbial dynamics in process-based soil models is therefore critical to predict carbon cycling in soils, albeit highly challenging to inform from data. One promising approach to improve their parametrisation is the integration of genomic data, yet modelling the complex and unknown relationship between genomes and the processes the microbes are driving is an unsolved problem. In this work, we present the first hybrid modeling framework for deriving biokinetic parameter values of a process-based soil organic matter turnover model from metagenome-inferred functional traits based on DNA sequencing data. Our model predicts biokinetic parameters of the process-based model from genomic trait data with a neural network and integrates constraints from ecological theory and literature to ensure realistic behavior, even of non-observed state variables. We evaluate our method on synthetic genomic trait datasets of varying complexity and on real data, showing that our approach improves performance over multiple baselines and learns the dynamics of unmeasurable components of the process-based model effectively, even for small training datasets.

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

Mind-Studio: Executable World Models with Lookahead Evaluation for Partially Observable Games

arXiv:2606.16070v1 Announce Type: new Abstract: World-model synthesis aims to turn interaction experience into an internal model of environment dynamics. Existing symbolic approaches often fit observed transitions or mixtures of local rules, but they do not produce a complete executable program that can run independently of the real environment. We present Mind-Studio, a framework that synthesizes executable pygame-style world models from state-action-next-state trajectories using large language models. Mind-Studio combines entropy-selected traces with a lightweight game skill file containing object, action, and static scene information extracted from screenshots. We evaluate synthesis quality with a K-step lookahead fidelity protocol that compares generated world-model rollouts against Real-ALE rollouts from the same state. On Montezuma's Revenge, Mind-Studio improves chosen-action next-state prediction from 0.3% for PoE-World to 48.7% while verifying 5 of 8 subgoals; across Alien, Assault, and Skiing, it achieves stronger branch-level fidelity than prior learned lookahead sources.

03.
arXiv (CS.AI) 2026-06-16

MA-SBI: Misspecification-Aware Simulation-Based Inference via Side-Channel Guidance

arXiv:2606.16923v1 Announce Type: new Abstract: Simulation-based inference (SBI) of latent parameters is often hindered by simulator misspecification, the mismatch between simulated and real-world observations caused by inherent modeling simplifications. RoPE, the recent state-of-the-art for robust SBI, addresses this through optimal transport between learned representations of real and simulated observations, but requires ground-truth parameter calibration pairs that are typically unavailable in the very settings where SBI is needed. What practitioners do have is unstructured side-information such as regime labels, instruction text, and policy bulletins. We propose Misspecification-Aware Simulation-Based Inference (MA-SBI), a calibration-free framework that turns this side-channel into a posterior correction. A learned corrector maps side-channel text to an observation-space shift applied before any pre-trained amortized posterior, requiring no retraining and no parameter ground-truth. Our main theorem bounds achievable bias reduction by the mutual information between misspecification and side-channel, with a non-vacuous constant that extends to all sub-Gaussian noise via Donsker-Varadhan. On hide-the-calibration benchmarks, MA-SBI with text alone matches the oracle posterior across 10 seeds and two backbones (TOST equivalence), while RoPE given more data does not. The two approaches are complementary: where misspecification is structural and recoverable from parameter pairs, RoPE dominates, as the theory predicts. A stochastic variant improves posterior-predictive log-likelihood on real COVID and OxCGRT epidemiological data, and correctly leaves the posterior unchanged on a well-specified cognitive-science corpus.

04.
arXiv (CS.CV) 2026-06-16

Near–Real-Time Conflict-Related Fire Detection in Sudan Using Unsupervised Deep Learning

Ongoing armed conflict in Sudan highlights the need for rapid monitoring of conflict-related fire-affected areas. Recent advances in deep learning and high-frequency satellite imagery enable near–real-time assessment of active fires and burn scars in war zones. This study presents a near–real-time monitoring approach using a lightweight Variational Auto-Encoder (VAE)–based model integrated with 4-band Planet Labs imagery at 3 m spatial resolution. We demonstrate that these impacted regions can be detected within approximately 24 to 30 hours under favorable observational conditions using accessible, commercially available satellite data. To achieve this, we adapt a VAE–based model, originally designed for 10-band imagery, to operate effectively on high-resolution 4-band inputs. The model is trained in an unsupervised manner to learn compact latent representations of nominal land-surface conditions and identify burn signatures by quantifying changes between temporally paired latent embeddings. Performance is evaluated across five case studies in Sudan and compared against cosine distance, CVA, and IR-MAD using precision, recall, F1-score, and the area under the precision-recall curve (AUPRC) computed between temporally paired image tiles. Results show that the proposed approach consistently outperforms the other methods, achieving higher recall and F1-scores while maintaining viable precision in highly imbalanced fire-detection scenarios. Experiments with 8-band imagery and temporal image sequences yield only marginal performance gains over single 4-band inputs, underscoring the effectiveness of the proposed lightweight approach for scalable, near–real-time conflict monitoring.

05.
arXiv (CS.CV) 2026-06-11

Exploring Adaptive Masked Reconstruction for Self-Supervised Skeleton-Based Action Recognition

Recently, masked skeleton reconstruction models have emerged as strong action representation learners, driving significant progress in self-supervised skeleton-based action recognition. However, existing state-of-the-art methods must predict an exceedingly large number of spatiotemporal patches, significantly prolonging training time. Besides, by treating all spatiotemporal regions equally during reconstruction, these models are distracted from learning the critical motion patterns that underlie action semantics. To address these challenges, we propose Adaptive Masked Reconstruction (AMR), a faster and stronger pre-training framework. We first decouple the decoder from the encoder, enabling flexible prediction of larger spatiotemporal patches and dramatically reducing reconstruction complexity. Given that larger patches contain more complex information, which is challenging to predict and consequently degrades performance, we accordingly introduce an adaptive guidance module. This module identifies regions of high motion informativeness, guiding the model to focus on the most discriminative parts of each patch and alleviating reconstruction difficulty. Experiments on NTU RGB+D 60, NTU RGB+D 120, and PKU-MMD datasets demonstrate that AMR not only accelerates pre-training substantially but also improves downstream recognition accuracy, surpassing current state-of-the-art approaches.

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

MoSE: Mixture of Slimmable Experts for Efficient and Adaptive Language Models

Mixture-of-Experts (MoE) models scale large language models efficiently by sparsely activating experts, but once an expert is selected, it is executed fully. Hence, the trade-off between accuracy and computation in an MoE model typically exhibits large discontinuities. We propose Mixture of Slimmable Experts (MoSE), an MoE architecture in which each expert has a nested, slimmable structure that can be executed at variable widths. This enables conditional computation not only over which experts are activated but also over how much of each expert is utilized. Consequently, a single pretrained MoSE model can support a more continuous spectrum of accuracy-compute trade-offs at inference time. We present a simple and stable training recipe for slimmable experts under sparse routing, combining multi-width training with standard MoE objectives. During inference, we explore strategies for runtime width determination, including a lightweight test-time training mechanism that learns how to map router confidence/probabilities to expert widths under a fixed budget. Experiments on GPT-style models, various routing regimes, zero-shot downstream reasoning benchmarks, and continual pre-training adaptation of DeepSeek model show that MoSE matches or improves standard MoE at full width and consistently shifts the compute-quality frontier toward lower inference FLOPs. The code can be found at: https://github.com/tnurbek/mose.

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

Spatial-Aware Reduction Framework: Towards Efficient and Faithful Visual State Space Models

arXiv:2606.19932v1 Announce Type: cross Abstract: Mamba demonstrates strong efficiency in modeling long visual sequences. However, when token reduction is applied to structurally enhanced Mamba variants, these models exhibit a severe performance collapse. We attribute this degradation to the spatially agnostic nature of existing reduction methods, which violate the two-dimensional structural premise required by the selective scanning mechanism. In this work, we propose STORM, a spatial-aware token reduction framework designed to maintain structural integrity throughout the compression process. STORM reformulates reduction into a structured operation on spatial units, enforcing localized constraints to maintain both grid topology and neighborhood coherence. As a plug-and-play module, STORM equips existing reduction pipelines with explicit spatial awareness without any training. Empirical results demonstrate that STORM achieves state-of-the-art pruning accuracy across diverse vision Mamba backbones under training-free settings. Notably, STORM delivers a substantial accuracy recovery on VMamba, outperforming prior methods by up to 63.3\% in top-1 accuracy. Meanwhile, STORM incurs only a 1.0\% accuracy drop on PlainMamba, achieving performance comparable to ViT.

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

Benchmarking Vision Foundation Models for Domain-Generalizable Face Anti-Spoofing

Face Anti-Spoofing (FAS) remains challenging due to the requirement for robust domain generalization across unseen environments. While recent trends leverage Vision-Language Models (VLMs) for semantic supervision, these multimodal approaches often demand prohibitive computational resources and exhibit high inference latency. Furthermore, their efficacy is inherently limited by the quality of the underlying visual features. This paper revisits the potential of vision-only foundation models to establish a highly efficient and robust baseline for FAS. We conduct a systematic benchmarking of 15 pre-trained models, such as supervised CNNs, supervised ViTs, and self-supervised ViTs, under severe cross-domain scenarios including the MICO and Limited Source Domains (LSD) protocols. Our comprehensive analysis reveals that self-supervised vision models, particularly DINOv2 with Registers, significantly suppress attention artifacts and capture critical, fine-grained spoofing cues. Combined with Face Anti-Spoofing Data Augmentation (FAS-Aug), Patch-wise Data Augmentation (PDA) and Attention-weighted Patch Loss (APL), our proposed vision-only baseline achieves state-of-the-art performance in the MICO protocol. This baseline outperforms existing methods under the data-constrained LSD protocol while maintaining superior computational efficiency. This work provides a definitive vision-only baseline for FAS, demonstrating that optimized self-supervised vision transformers can serve as a backbone for both vision-only and future multimodal FAS systems. The project page is available at: https://gsisaoki.github.io/FAS-VFMbenchmark-CVPRW2026/ .

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

Hierarchical Advantage Weighting for Online RL Fine-Tuning of VLAs from Sparse Episode Outcomes

arXiv:2606.17043v1 Announce Type: cross Abstract: When pretrained VLA policies are fine-tuned through online RL, each rollout episode produces only a single binary outcome (success or failure), yet the actor update requires per-transition supervision. Existing approaches commonly reduce this sparse outcome to a single scalar reward or advantage signal, which conflates distinct forms of transition-level feedback and provides limited guidance once basic task success becomes achievable. First, a single scalar signal conflates the two objectives of viability and efficiency; once basic success is achieved, the binary label provides no gradient to distinguish efficient completions from slow ones. Second, real-world rollouts mix autonomous and intervention segments; naively assigning episode outcomes across these boundaries introduces incorrect credit assignment. To address these issues, we propose Hierarchical Advantage-Weighted Behavior Cloning (HABC), which trains separate critic heads for these two objectives on different data subsets and combines their outputs with a state-adaptive balance. A state-adaptive gate $g_t$ merges their one-step advantages, prioritizing viability when success is uncertain and shifting to efficiency only when viability is high, and converts the result into per-transition weights on the actor loss. Intervention-aware credit assignment further restricts outcome labels to segments executed by the current policy, preventing supervision from leaking across intervention boundaries. In real-robot experiments on three contact-rich bimanual tasks, HABC raises success from supervised fine-tuning (SFT) baselines of 36%, 44%, and 12% to 92%, 88%, and 38%.

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

ShipNet: A Geometric Deep Learning Surrogate for Real-Time Ship Hydrodynamics

arXiv:2606.15356v1 Announce Type: cross Abstract: Accurate prediction of hydrodynamic performance is central to ship design, yet high-fidelity computational fluid dynamics remains prohibitively expensive for large-scale parametric exploration. This motivates the development of data-driven surrogate models that provide rapid approximations to hydrodynamic predictions at substantially reduced cost. We present ShipNet, a geometric deep-learning surrogate that predicts both hull-surface pressure distributions and far-field free-surface wave patterns directly from hull geometry and speed. The network employs a regularized dynamic graph convolutional backbone on hull point clouds, with a multi-head decoder for simultaneous near-body pressure and free-surface elevation outputs. Training data consist of 420 inviscid free-surface simulations generated using a potential-flow panel method for two parent yacht hulls, each parameterized into 70 variants and evaluated at three speeds. ShipNet predicts per-point pressure coefficient and two-dimensional wave elevation map using a composite loss that combines point-wise regression and image-structure terms. On a geometry-held-out test set, ShipNet achieves R^2=0.98 for hull pressure and R^2=0.91 for wave fields. Inference requires approximately 0.15s per case, yielding over a 550x speedup relative to the potential-flow solver on conventional hardware. Limitations include the restricted geometry and speed ranges and the inviscid training data, while future work will extend the model to high-fidelity viscous simulations with physics-informed regularization.

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

SPATIA: Multimodal Generation and Prediction of Spatial Cell Phenotypes

Understanding how cellular morphology, gene expression, and spatial context jointly shape tissue function is a central challenge in biology. Image-based spatial transcriptomics technologies now provide high-resolution measurements of cell images and gene expression profiles, but existing methods typically analyze these modalities in isolation or at limited resolution. We address the problem by introducing SPATIA, a multi-level generative and predictive model that learns unified, spatially aware representations by fusing morphology, gene expression, and spatial context from the cell to the tissue level. SPATIA also incorporates a spatially conditioned generative framework with confidence-aware OT reweighting and morphology-profile alignment for modeling target-state morphology distributions. Specifically, we propose a confidence-aware flow matching objective that reweights weak optimal-transport pairs based on uncertainty. We further apply morphology-profile alignment to encourage biologically meaningful image generation, enabling the modeling of microenvironment-dependent phenotypic transitions. We assembled a multi-scale dataset consisting of 25.9 million cell-gene pairs across 17 tissues. We benchmark SPATIA against 18 models across 12 tasks, spanning categories such as phenotype generation, annotation, clustering, gene imputation, and cross-modal prediction. SPATIA achieves improved performance over state-of-the-art models, improving generative fidelity by 8% and predictive accuracy by up to 3%.

12.
arXiv (CS.LG) 2026-06-15

Neural Slack Variables for Shape Constraints

arXiv:2606.13803v1 Announce Type: new Abstract: Enforcing functional inequality constraints such as monotonicity and convexity in neural networks is a fundamental challenge in many industrial and scientific applications. Classical one-sided penalty methods, along with primal-dual methods gated by complementary slackness, provide constraint gradients only at violated locations, resulting in fragile satisfaction. Architectures that guarantee feasibility by construction, on the other hand, remain largely limited to elementary cases and impose additional inductive biases. We introduce neural slack variables, a deep learning native primal-side approach that converts constraint enforcement into a regression problem by coupling the primary network with a jointly learned auxiliary network. The auxiliary network serves as a valid target for the primary network's constraint quantities, inducing feasibility and regularity. Neural slack variables achieve zero measured violations on dense-grid monotonicity and convexity test cases, where penalty and primal-dual baselines leave residual violations, and enable arbitrage-free learning of volatility surfaces, an open industrial challenge in quantitative finance.

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

Prediction of Runtime Parameters of Parallel Chemistry Applications via Active and Generative Learning

arXiv:2606.16226v1 Announce Type: new Abstract: In this work, we develop two main Machine Learning based approaches to predict the runtime parameters of highly scalable parallel chemistry computations.These approaches employ active and generative learning together with the empirically determined gradient boosted regression tree models chosen among a rich suite of machine learning models. When evaluated on Coupled-Cluster with Singles and Doubles computations, our models achieve a mean absolute error percentage (MAPE) as low as 0.023 and a coefficient of determination as high as 99.9%. Furthermore, when combined with active learning to mitigate the lack of large amounts of training data, our models score a MAPE about 0.2 with 20-25% of the original dataset.

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

FoundCause: Causal Discovery with Latent Confounders from Observational Data

arXiv:2606.17516v1 Announce Type: cross Abstract: Causal discovery from observational data remains challenging due to the need to recover directed structure and latent confounding without interventions. We propose FoundCause, an amortized causal discovery model trained entirely on synthetic data that maps datasets directly to causal graphs in a single forward pass. By learning from large collections of simulated structural causal models, FoundCause captures transferable statistical patterns that generalize beyond individual datasets. The architecture incorporates several key inductive biases for causal discovery. It uses a permutation-invariant transformer encoder with alternating attention over samples and variables to jointly model cross-variable dependence and per-variable distributions. Pairwise statistical features derived from classical asymmetry measures are injected through statistics-conditioned attention, guiding the model toward known causal signals. A factorized decoder separates edge existence from direction, while a triangular refinement module enables reasoning over higher-order causal motifs such as chains and colliders. In addition, a dedicated confounder module based on learnable latent tokens explicitly models hidden common causes, and the model explicitly handles missing data via its masked input representation. To our knowledge, FoundCause is the first amortized causal discovery approach to explicitly model latent confounding. FoundCause outperforms 11 classical non-amortized methods (e.g., PC, GES, NOTEARS-style optimization) and 4 amortized causal discovery methods on 15 real-world datasets, achieving +9.6% improvement in $F_1$, +1.2% in AUROC, and an 18.9% reduction in structural Hamming distance relative to the strongest non-amortized methods, while performing inference in a single forward pass.

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

Understanding Latent Diffusability via Fisher Geometry

arXiv:2604.02751v2 Announce Type: replace Abstract: Diffusion models often degrade in latent spaces, yet the formal causes remain poorly understood. We quantify latent-space diffusability via the rate of change of the Minimum Mean Squared Error (MMSE) along the diffusion trajectory. Our framework decomposes this MMSE rate into contributions from Fisher Information (FI) and Fisher Information Rate (FIR). We demonstrate that while global isometry ensures FI alignment, FIR is governed by the interplay between encoder and data geometries. Our analysis decouples diffusion degradation into four penalties: dimensional compression, tangential distortion, high-frequency encoder curvature, and intrinsic data curvature. We derive theoretical conditions for FIR preservation to ensure stable diffusability. Experiments across diverse autoencoding architectures demonstrate the implications of our theoretical bounds. We establish FI and FIR as a comprehensive analytical framework for understanding latent diffusability.

16.
arXiv (CS.CL) 2026-06-19

Leverage Is Not Reach: A Control-Window Law for Single-Neuron Steering in Language Models

Aligned language models gate behaviors such as refusal and language routing through sparse feed forward neurons, yet no theory predicts when a single neuron intervention controls a behavior coherently rather than collapsing the output. We develop a budget normalized control window framework for single neuron steering. A dose along one write direction reduces to one control coordinate: the alignment between the residual stream and the write, driven along a universal saturation curve in units of a coherence budget set by the residual norm divided by the write norm. Coherent control exists when a behavior trigger lies below the collapse ceiling. The same coordinate governs benign mode switches and refusal; the ceiling follows from weights and one generic forward pass, while triggers are measured at rollout. On fifteen held out neurons, the predicted ceiling has mean absolute error 0.14, about 0.07 in bulk layers, and the committed open or closed verdict holds on eleven against a ten of fifteen majority baseline. Closed cases expose three failure modes rather than violations: collapse before trigger, too little depth to propagate, or a normalization that caps how far one neuron can push. The law explains why local gradient attribution anti predicts control: true controllers write off the readout axis and carry a near zero first order gradient. A forward only contrastive screen made precise by the window recovers controllers that attribution misses. On refusal, the hardest case, intervention success is typed, not scalar: coherent bypass and strict actionable reach separate, so a neuron can flip refusal in fluent, on task text with no actionable content, and genuine actionable reach appears only for three of six audited Llama pivots and only at later rollout horizons. Single neuron steering is therefore a budgeted, typed audit of controllability rather than a fixed dose anecdote.

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

From Uncertain Judgments to Calibrated Rankings: Conformal Elo Estimation for LLM Evaluation

arXiv:2606.13221v1 Announce Type: new Abstract: Evaluating new large language models typically requires costly human annotation campaigns at scale. LLM-as-a-judge offers a cheaper alternative, but judge scores carry systematic errors - such as position bias, self-preference, or intransitivity - that can strongly miscalibrate the resulting rankings. We quantify the resulting judge-human disagreement at two complementary levels. At the local level, we estimate per-battle uncertainty from the judge's own score differences by propagating calibrated win probabilities rather than hard labels into the Bradley-Terry procedure. This alone provides a drastic improvement to Elo estimation accuracy, bringing LLM-derived ratings within 17.9 Elo MAE of human-derived ones when averaged over 55 held-out models on LMArena. At the global level, we apply split conformal prediction to the residual gap between LLM-derived and human-derived Elo ratings across held-out models, producing prediction intervals with distribution-free marginal coverage guarantees that account for irreducible LLM-human disagreement. Together, these two layers yield a low-cost evaluation tool that provides developers with calibrated Elo estimates and honest uncertainty bounds, without access to large-scale human annotations.To facilitate reproducibility, we release our code at https://github.com/kargibora/SoftElo .

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

Protein Design with Agent Rosetta: A Case Study for Specialized Scientific Agents

arXiv:2603.15952v2 Announce Type: replace Abstract: Large language models (LLMs) are capable of emulating reasoning and using tools, creating opportunities for autonomous agents that execute complex scientific tasks. Protein design provides a natural testbed: although machine learning (ML) methods achieve strong results, these are largely restricted to canonical amino acids and narrow objectives, leaving unfilled need for a generalist tool for broad design pipelines. We introduce Agent Rosetta, an LLM agent paired with a structured environment for operating Rosetta, the leading physics-based heteropolymer design software, capable of modeling non-canonical building blocks and geometries. Agent Rosetta iteratively refines designs to achieve user-defined objectives, combining LLM reasoning with Rosetta's generality. We evaluate Agent Rosetta on design with canonical amino acids, matching specialized models and expert baselines, and with non-canonical residues – where ML approaches fail – achieving comparable performance. Critically, prompt engineering alone often fails to generate Rosetta actions, demonstrating that environment design is essential for integrating LLM agents with specialized software. Our results show that properly designed environments enable LLM agents to make scientific software accessible while matching specialized tools and human experts.

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

KEPLA: A Knowledge-Enhanced Deep Learning Framework for Accurate Protein-Ligand Binding Affinity Prediction

arXiv:2506.13196v5 Announce Type: replace Abstract: Accurate prediction of protein-ligand binding affinity is critical for drug discovery. While recent deep learning approaches have demonstrated promising results, they often rely solely on structural features of proteins and ligands, overlooking their valuable biochemical knowledge associated with binding affinity. To address this limitation, we propose KEPLA, a novel deep learning framework that explicitly integrates prior knowledge from Gene Ontology and ligand properties to enhance prediction performance. KEPLA takes protein sequences and ligand molecular graphs as input and optimizes two complementary objectives: (1) aligning global representations with knowledge graph relations to capture domain-specific biochemical insights, and (2) leveraging cross attention between local representations to construct fine-grained joint embeddings for prediction. Experiments on two benchmark datasets across both in-domain and cross-domain scenarios demonstrate that KEPLA consistently outperforms state-of-the-art baselines. Furthermore, interpretability analyses based on knowledge graph relations and cross attention maps provide valuable insights into the underlying predictive mechanisms.

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

Size Doesn't Matter: Cosine-Scored Sparse Autoencoders

arXiv:2606.15054v1 Announce Type: new Abstract: Sparse autoencoders (SAEs) detect features via inner product, so a feature's activation scales with both its directional alignment and the input's norm. Under BatchTopK, high-norm tokens inflate all pre-activations simultaneously, claiming dictionary slots regardless of content alignment. This matters because sublayer normalization has already discarded the magnitude the score measures, so the encoder detects a quantity the model does not read. We replace the score with a learned blend of cosine similarity and input magnitude, letting the optimizer choose how much norm to use; a per-feature extension lets each feature decide independently. In both regimes, training is free to recover inner product but never does, with no feature ever choosing more than half-magnitude dependence. At matched reconstruction, the cosine encoder learns features that align with human-recognizable concepts far more often than standard, filling dictionary slots that inner product wastes on norm detectors. Loss reweighting that equalizes gradients barely closes the gap, confirming forward-pass score geometry as the lever. The advantage is not universal across tasks or depths, but we believe cosine scoring should be the default for dictionary learning on normalized representations.

21.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

22.
arXiv (CS.CL) 2026-06-15

Did You Forget What I Asked? Prospective Memory Failures in Large Language Models

作者:

Large language models often fail to satisfy formatting instructions when they must simultaneously perform demanding tasks. We study this behaviour through a prospective memory inspired lens from cognitive psychology, using a controlled paradigm that combines verifiable formatting constraints with benchmark tasks of increasing complexity. Across three model families and over 8,000 prompts, compliance drops by 2-21% under concurrent task load. Vulnerability is highly type-dependent: terminal constraints (requiring action at the response boundary) degrade most, with drops up to 50%, while avoidance constraints remain comparatively robust. A salience-enhanced format (explicit instruction framing plus a trailing reminder) recovers much of the lost compliance, restoring performance to 90-100% in many settings. Interference is bidirectional: formatting constraints can also reduce task accuracy, with one model's GSM8K accuracy dropping from 93% to 27%. In additional stacking experiments, joint compliance declines sharply as constraints accumulate. All results use deterministic programmatic checkers without an LLM-as-judge component on publicly available datasets.

23.
medRxiv (Medicine) 2026-06-22

GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations

Introduction: GCH1 has been implicated in Parkinson's disease (PD), but its risks variants and associations are not well defined. Objectives: To investigate the clinical relevance and PD risk associated with the GCH1 p.Ser80Asn variant. Methods: We first identified a segregating GCH1 p.Ser80Asn variant in a Malaysian Chinese PD family via whole genome sequencing (WGS). We assessed its risk association using multi-ancestry WGS data from the Global Parkinson's Genetics Program (GP2) (n=22,372PD vs n=8,826Controls) and meta-analysis of East Asian (EAS) cohorts (n=4,712PD vs 38,733Controls). Clinico-demographic details of affected variant carriers were collated. Results: The GCH1 p.Ser80Asn variant was enriched in GP2 EAS PD populations (n=9/2,757; 0.33%) but not detected in other ancestries. Meta-analysis revealed increased PD risk in EAS populations (odds ratio:5.1; 95%CI:2.3-10.7; p=2.89x10-5). Affected carriers (mean age at onset:56.3+-12.5 years) had additional occurrence of dystonia, while dementia was rare. Conclusions: The GCH1 p.Ser80Asn variant is a rare, EAS-enriched risk variant for PD.

24.
arXiv (quant-ph) 2026-06-15

Quantum codes and optimal pure quantum $(r,\delta)$-LRCs via the MP construction

arXiv:2606.14253v1 Announce Type: new Abstract: In this paper, we employ MP codes whose defining matrices are $\tau$-optimal defining ($\tau$-OD) matrices to construct new quantum codes and quantum $(r,\delta)$-LRCs. Specifically, we report the following results: We establish a unified $\tau$-monomial decomposition theorem for invertible self-adjoint matrices over finite fields of arbitrary characteristic, which generalizes the result in "Quantum codes using the $\tau$-OD MP construction" where the characteristic was required to be odd. Based on this theorem, we prove the existence of $\tau$-OD matrices over $\mathbb{F}_{q^2}$ for any characteristic and demonstrate that there exist several new infinite families of $\tau$-OD matrices over $\mathbb{F}_{q^2}$ of characteristic $2$. As an application of MP codes involving $\tau$-OD matrices, we construct several infinite families of quantum codes with flexible parameters. Within this framework, we present $222$ record-breaking quantum codes that surpass the best-known records maintained in Grassl's database. We propose two effective schemes for constructing optimal pure quantum $(r,\delta)$-LRCs via MP codes. Accordingly, we construct four new infinite families of optimal pure quantum $(r,\delta)$-LRCs with flexible parameters. Notably, we report an interesting phenomenon by exhibiting $30$ optimal pure quantum $(r,\delta)$-LRCs derived from our framework; that is, there exist quantum codes that are not only optimal pure quantum $(r,\delta)$-LRCs but also, according to Grassl's database, best-known, optimal, or record-breaking quantum codes. To the best of our knowledge, the new discovery that quantum codes are simultaneously optimal pure quantum $(r,\delta)$-LRCs and record-breaking quantum codes has not been previously reported in the literature.

25.
arXiv (CS.AI) 2026-06-19

BrainG3N: A Dual-Purpose Tokenizer for Controllable 3D Brain MRI Generation

arXiv:2606.19651v1 Announce Type: new Abstract: Three-dimensional (3D) brain MRI is central to clinical neurology and neuro-oncology, where generative models could augment under-represented cohorts, simulate disease trajectories, and support privacy-preserving data sharing. Latent diffusion has been the go-to solution for modeling imaging data, but it places two competing demands on the tokenizer: encoder embeddings must retain the clinical information that downstream tasks act on, and the decoder must reconstruct anatomically faithful volumes. Existing reconstruction-driven tokenizers achieve the second at the expense of the first. To address this, we introduce a fully volumetric masked-autoencoder (MAE) based tokenizer for 3D brain MRI latent diffusion, decoupling encoder and decoder: a frozen 3D MAE encoder produces clinically informative embeddings, while a dedicated CNN decoder reconstructs voxels from a linear projection of those embeddings. We pretrain the encoder on 35,309 volumes from 18 public cohorts spanning four modalities, ten disease categories, and 200+ acquisition sites, and demonstrate its dual utility in two settings. First, on a 23-task linear-probing benchmark, the encoder outperforms or matches SOTA models (i.e., BrainIAC, BrainSegFounder, and MedicalNet) on 21 of 23 tasks. Second, a conditional diffusion transformer (DiT) trained on these clinically informative embeddings supports both conditional generation across six variables and patient-specific longitudinal forecasting. Together these results establish a single 3D brain-MRI embedding space capable of both downstream clinical tasks and controllable generation.