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01.
arXiv (math.PR) 2026-06-11

Additive Noise, Shift Recovery, and Signed Signals in the Cumulative Distribution Transform

arXiv:2606.11432v1 Announce Type: cross Abstract: The cumulative distribution transform (CDT) is a quantile-based transport representation that exactly linearizes one-dimensional translations of positive densities. We study how this structure behaves under additive perturbations and how it can be exploited for shift recovery. Under a local nondegeneracy condition, we derive a first-order expansion showing that additive noise in physical space induces a nonlocal perturbation in CDT space through the primitive of the noise, weighted by the reciprocal density. This yields an explicit description of transform-domain sensitivity and shows, in particular, that perturbations are amplified in low-density regions. When the physical-space perturbation is modeled as a centered Gaussian random field, the induced first-order CDT perturbation is again Gaussian, with an explicit covariance kernel. We then use this structure to study recovery in CDT coordinates. In the known-template setting, the transport shift is obtained by projection onto the constant mode, giving an explicit estimator together with exactness in the noiseless case and a stability bound under perturbations. In the unknown-template setting, multiple observations permit joint recovery of the shifts and a common template up to the natural constant-mode gauge, leading to a simple de-shift–and–average procedure. We also consider a signed-signal analogue based on the signed cumulative distribution transform (SCDT), where shifts are estimated numerically by feature matching and unknown templates are recovered by alternating alignment and averaging. Numerical experiments validate the perturbation analysis and illustrate effective recovery for both density-valued and signed signals.

02.
medRxiv (Medicine) 2026-06-10

Global and local genetic overlap among ME/CFS, irritable bowel syndrome and psychiatric traits: a hypothesis-generating analysis

作者:

Background. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and irritable bowel syndrome (IBS) frequently co-occur following infection, yet shared genetic architecture at the locus level has not been systematically characterised. Aims. To estimate global and local genetic correlations between ME/CFS (including infection-onset subgroup), IBS, major depressive disorder (MDD) and loneliness/isolation, and characterise ME/CFS cell-type heritability enrichment. Method. GWAS summary statistics: DecodeME (15,579 ME/CFS; 9,738 infection-onset), FinnGen R9 (9,296 IBS), PGC MDD Wave 2 (45,396) and UK Biobank loneliness (N=455,364). LDSC for global correlations; LAVA for local correlations across 2,495 loci; MAGMA for cell-type enrichment (Descartes Human atlas); coloc.abf for colocalisation. Results. All pairwise global correlations were significant after Bonferroni correction, including ME/CFS-all-MDD (rg=0.598, 95% CI 0.46-0.74) and ME/CFS-all-IBS (rg=0.573, 0.39-0.75). Of 4,232 local tests, 16 reached FDR

03.
arXiv (CS.LG) 2026-06-12

Aerial Wildfire Suppression Planning with a Hybrid CNN-Cellular Automata Fire Model

arXiv:2606.13633v1 Announce Type: cross Abstract: Aerial wildfire suppression requires not only predicting fire spread, but also designing effective intervention strategies under operational and environmental uncertainty. We present a modeling and optimization framework for aerial wildfire suppression that combines a hybrid neural-cellular automaton wildfire model with gradient-based design of targeted aerial drops. The wildfire model predicts spatially varying spread behavior from terrain, fuel, and wind data, while the intervention module determines binary drop actions with continuous-valued location and orientation parameters mapped to the simulation grid. Water and retardant are represented with distinct suppression effects, corresponding to immediate reduction of active burning and persistent reduction of future spread. To evaluate the robustness of the resulting suppression plans, we quantify both aleatoric uncertainty through Monte Carlo sampling of daily fire-state realizations and epistemic uncertainty through spatially correlated prediction-error perturbations. A case study based on the 2020 Bear Fire shows that the framework can generate coherent aerial suppression schedules for reducing total fire-affected area and can support uncertainty-aware analysis of wildfire intervention strategies.

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

Proactive Conversational Assistant for a Procedural Manual Task based on Audio and IMU

Real-time conversational assistants for procedural manual tasks often depend on video input, which can be computationally expensive and compromise user privacy. For the first time, we propose a real-time conversational assistant that provides comprehensive guidance for procedural manual tasks using only lightweight privacy-preserving modalities such as audio and IMU inputs from a user's wearable device to understand the context. Using a furniture assembly task and a cooking task, we show how this assistant proactively communicates step-by-step instructions to a user performing a procedural task, and answers user questions. We illustrate the data generation method and the system design to achieve such an assistant. On observing that an off-the-shelf language model is a talkative assistant but is not always able to answer questions correctly, we demonstrate how finetuning the model improves its ability to limit unnecessary dialogues with a 50% increase in the precision, while also improving its ability to answer questions correctly, measured by a 150% increase in the recall of answers. We further describe how such an assistant is implemented on an edge device with no dependence on the cloud.

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

Multi-HMR 2: Multi-Person Camera-Centric Human Detection, Mesh Recovery and Tracking

Most advances in human mesh recovery (HMR) have focused on pelvis-centered recovery, overlooking metric 3D localization and detection accuracy in the camera coordinate system - two key factors for real-world applications such as human-robot interaction and social scene understanding. Current evaluation protocols often ignore these aspects, emphasizing per-person, root-centered recovery rather than camera-space perception. As a result, existing approaches rely on fixed camera assumptions or handcrafted post-processing, limiting their robustness and practical deployment. We introduce Multi-HMR 2, a simple yet robust DETR-based framework for Multi-person Camera-centric Human detection, mesh Recovery, and tracking. Multi-HMR 2 predicts a scene-consistent camera together with human meshes, enabling metric 3D localization without ground-truth intrinsics. Moreover, by distilling image-based memory features from SAM2, Multi-HMR 2 extends to tracking, achieving consistent identity association without video supervision. Despite its conceptual simplicity - no handcrafted components, no video input, and no ground-truth cameras - Multi-HMR 2 achieves state-of-the-art pelvis-centered performance while substantially improving detection accuracy and metric 3D localization.

07.
arXiv (CS.CV) 2026-06-11

Cross-Domain Multi-Person Human Activity Recognition via Near-Field Wi-Fi Sensing

Wi-Fi-based human activity recognition (HAR) provides substantial convenience and has emerged as a thriving research field, yet the coarse spatial resolution inherent to Wi-Fi significantly hinders its ability to distinguish multiple subjects. By exploiting the near-field domination effect, establishing a dedicated sensing link for each subject through their personal Wi-Fi device offers a promising solution for multi-person HAR under native traffic. However, due to the subject-specific characteristics and irregular patterns of near-field signals, HAR neural network models require fine-tuning (FT) for cross-domain adaptation, which becomes particularly challenging with certain categories unavailable. In this paper, we propose WiAnchor, a novel training framework for efficient cross-domain adaptation in the presence of incomplete activity categories. This framework processes Wi-Fi signals embedded with irregular time information in three steps: during pre-training, we enlarge inter-class feature margins to enhance the separability of activities; in the FT stage, we innovate an anchor matching mechanism for cross-domain adaptation, filtering subject-specific interference informed by incomplete activity categories, rather than attempting to extract complete features from them; finally, the recognition of input samples is further improved based on their feature-level similarity with anchors. We construct a comprehensive dataset to thoroughly evaluate WiAnchor, achieving over 90% cross-domain accuracy with absent activity categories.

08.
arXiv (CS.CL) 2026-06-17

TACOMORE: Exploring a replicable prompting protocol for LLM-assisted corpus analysis

As corpus linguistics continues to scale, researchers are facing a growing methodological bottleneck: while computational tools can easily count billions of words, the qualitative interpretation of these data remains a slow and labor-intensive human task. Large Language Models (LLMs) offer a promising way to automate this process, yet their integration into the field is often hindered by concerns over black-box unpredictability and a lack of replicability. This study introduces TACOMORE, a structured prompting framework designed to transform ad-hoc AI interactions into a standardized linguistic protocol. Built upon four foundational principles (Task, Context, Model, and Replicability), the framework guides LLMs to move beyond generic probability prediction to anchoring their reasoning in the specific co-occurrence patterns of a target corpus. We applied this framework to three core corpus tasks, i.e., the analysis of keywords, collocates, and concordances, using an open corpus of COVID-19 research abstracts. After testing three LLMs, we found that while structured prompting improves accuracy and replicability, inherent limitations regarding hallucination persist. This research offers a critical lens into the role of LLMs in corpus linguistics, highlighting their potential as complementary tools while emphasizing the irreplaceable role of human validation.

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

Equity with Efficiency: An Empirical Study of Tokenizers for Multilingual Large Language Models

Multilingual large language models (LLMs) depend on subword tokenization to bridge discrete text and continuous neural representation. State-of-the-art multilingual LLMs often use Byte-level Byte-Pair Encoding (BPE) tokenizers that structurally favor high-resource languages and Latin scripts. For speakers of underrepresented languages, particularly those across Southeast Asia, this bias inflates inference costs and widens cross-lingual capability gaps. We present the first systematic comparison of equitable tokenizers on a unified benchmark spanning 11 Southeast Asian languages. Beyond tokenizer-level analysis of compression efficiency and cross-lingual equity, we assess downstream task performance through controlled 1.5B-parameter language model training using the same training data. Our results show that Parity-aware BPE lies on the Pareto frontier of the efficiency-equity trade-off, achieving strong compression parity at competitive cost. Morphology-Driven Byte Encoding delivers the best semantic reasoning performance through morphologically richer representations, albeit at a higher computational expense. Byte Latent Transformer underperforms on downstream tasks, possibly because its architectural assumptions misalign with the constraints of limited low-resource training data. Together, our findings demonstrate that cross-lingual fairness and tokenization efficiency are not fundamentally at odds, and offer practical guidance for designing equitable multilingual models.

10.
arXiv (CS.CL) 2026-06-15

Efficient Rationale-based Retrieval: On-policy Distillation from Generative Rerankers based on JEPA

Unlike traditional fact-based retrieval, rationale-based retrieval typically necessitates cross-encoding of query-document pairs using large language models, incurring substantial computational costs. To address this limitation, we propose Rabtriever, which independently encodes queries and documents, while providing comparable cross query-document comprehension capabilities to rerankers. We start from training a LLM-based generative reranker, which puts the document prior to the query and prompts the LLM to generate the relevance score by log probabilities. We then employ it as the teacher of an on-policy distillation framework, with Rabtriever as the student to reconstruct the teacher's contextual-aware query embedding. To achieve this effect, Rabtriever is first initialized from the teacher, with parameters frozen. The Joint-Embedding Predictive Architecture (JEPA) paradigm is then adopted, which integrates a lightweight, trainable predictor between LLM layers and heads, projecting the query embedding into a new hidden space, with the document embedding as the latent vector. JEPA then minimizes the distribution difference between this projected embedding and the teacher embedding. To strengthen the sampling efficiency of on-policy distillation, we also add an auxiliary loss on the reverse KL of LLM logits, to reshape the student's logit distribution. Rabtriever optimizes the teacher's quadratic complexity on the document length to linear, verified both theoretically and empirically. Experiments show that Rabtriever outperforms different retriever baselines across diverse rationale-based tasks, including empathetic conversations and robotic manipulations, with minor accuracy degradation from the reranker. Rabtriever also generalizes well on traditional retrieval benchmarks such as MS MARCO and BEIR, with comparable performance to the best retriever baseline.

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

Environment-Grounded Automated Prompt Optimization for LLM Game Agents

LLM agents in interactive environments are highly sensitive to their prompts, yet prompt engineering remains a manual, task-specific process. We introduce an automated prompt optimization framework for LLM agents that decomposes the observation-to-action pipeline into a goal-conditioned descriptor agent and an action selection agent, and iteratively refines each module's prompt through an LLM-driven evolutionary loop guided by environment returns. We propose a behavior analyzer to attribute episode outcomes to specific prompt components, and a mutator to propose targeted revisions to the prompt, before validating them through environment rollouts. We evaluate on all five BabyAI tasks in the BALROG benchmark, comparing our pipeline against BALROG's RobustCoTAgent under both plain and guided prompt initializations. Optimization improves performance consistently across tasks and conditions, without requiring updates to the model weights. On PutNext, a multi-step coordination task where the RobustCoTAgent achieves 0% success, our framework reaches up to 72.5% success rate using the same underlying LLM with optimized prompts. These results suggest that a multi-agent framework, combined with automatic prompt optimization, enhances LLMs without the need for fine-tuning or extensive human supervision.

12.
Nature (Science) 2026-06-19

Daily briefing: Human detritus remakes geology

作者:

What, exactly, is a rock? Plus, a stem-cell success for a severe autoimmune disease and evidence that ‘AI deskilling’ is real. Researchers have tracked the electrical activity of individual brain cells during conversation in real time. Plus, the history of GPS and a cross-species transplant that could reveal clues about the origin of animals.

13.
arXiv (CS.AI) 2026-06-11

Embodied-R1.5: Evolving Physical Intelligence via Embodied Foundation Models

arXiv:2606.11324v1 Announce Type: cross Abstract: We introduce Embodied-R1.5, a unified Embodied Foundation Model (EFM) that integrates comprehensive embodied reasoning capabilities, spanning embodied cognition, task planning, correction, and pointing, within a single architecture toward general physical intelligence. Leveraging three automated data construction pipelines to significantly expand the data coverage of critical capabilities, we build a large-scale data system of over 15B tokens, and design a multi-task balanced RL recipe to alleviate heterogeneous task conflicts. We further introduce a Planner-Grounder-Corrector (PGC) closed-loop framework that enables a single model to autonomously execute and self-correct over long-horizon tasks. With only 8B parameters, Embodied-R1.5 achieves SOTA on 16 out of 24 embodied VLM benchmarks, surpassing leading models like Gemini-Robotics-ER-1.5 and GPT-5.4. Benefiting from the internalized embodied capabilities, Embodied-R1.5 can be fine-tuned into a VLA with only a small amount of data, outperforming leading VLA models like $\pi_{0.5}$ across 4 popular manipulation benchmark suites. We further conduct extensive zero-shot real-robot experiments, validating performance in instruction following, affordance grounding, articulated object manipulation, and long-horizon complex tasks, demonstrating strong generalization to the physical world. We open-source model weights, datasets, training code, and EmbodiedEvalKit, an evaluation framework tailored for embodied tasks, to facilitate future research in EFMs.

14.
arXiv (CS.AI) 2026-06-12

Counterfactual Explanations for Deep Two-Sample Testing

arXiv:2606.04009v2 Announce Type: replace-cross Abstract: Two-sample testing is a fundamental tool for detecting distributional differences across scientific domains, but classical tests (including kernel-based tests) can be ineffective on high-dimensional structured data such as images. Recent deep two-sample tests improve sensitivity in these settings by learning informative representations, yet they provide limited insight into which data features drive rejection of the null hypothesis $H_0$. To address this issue, we propose a counterfactual explanation framework for deep two-sample testing that generates sample-level edits moving observations from a source group toward a target group while explicitly reducing the discrepancy measured by the test. Our method combines a diffusion autoencoder with a pretrained deep two-sample test model and optimizes a maximum mean discrepancy (MMD) objective in the test model's representation space to produce plausible counterfactuals. We quantify distribution-level effects through changes in the test statistic and the resulting two-sample p-values. We evaluate the method on synthetic 2D shape datasets and two MRI cohorts. Across both settings, the counterfactual transformations consistently increase p-values relative to the original samples, indicating that the edited source set becomes statistically closer to the target distribution under the test. We measure minimality using LPIPS to ensure the counterfactuals remain close to the original samples. The resulting edits provide interpretable evidence of the features associated with the detected group differences. On MRI, the localized changes are consistent with known anatomical differences between cohorts.

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

Learn from Your Mistakes: Tree-like Self-Play for Secure Code LLMs

arXiv:2606.03489v2 Announce Type: replace-cross Abstract: While Large Language Models (LLMs) excel in code generation, they remain prone to replicating subtle yet critical vulnerabilities endemic to their training data. Current alignment techniques, such as Supervised Fine-Tuning (SFT) and Reinforcement Learning (RL), typically apply coarse-grained optimization at the sequence level. This approach often fails to address the localized nature of security flaws, where a single incorrect token choice can compromise an entire program. To bridge this gap, we introduce Tree-like Self-Play (TSP), a framework that reframes secure code generation as a fine-grained sequential decision process. Unlike standard methods that blindly maximize likelihood, TSP constructs a decision tree where the model explores branching trajectories–generating both secure "golden paths" and vulnerable variants. By treating code generation as a self-play game, the model learns to strictly discriminate against its own localized errors. This provides a dense, on-policy learning signal that forces self-correction precisely at the critical decision nodes where vulnerabilities typically emerge. Our experiments demonstrate that TSP fundamentally enhances model reliability. In Python security benchmarks, TSP boosts CodeLlama-7B's pass rate (SPR@1) to 75.8%, significantly outperforming SFT (57.0%) and unstructured self-play baselines. Crucially, TSP induces robust out-of-distribution generalization: the model not only reduces vulnerabilities in unseen categories (CWEs) by 24.5% but also successfully transfers security principles learned from C/C++ to diverse languages, including Python, Go, and JavaScript. This suggests that TSP does not merely memorize patches, but internalizes abstract, language-agnostic security logic.

16.
arXiv (CS.CV) 2026-06-12

DiskChunGS: Large-Scale 3D Gaussian SLAM Through Chunk-Based Memory Management

Recent advances in 3D Gaussian Splatting (3DGS) have demonstrated impressive results for novel view synthesis with real-time rendering capabilities. However, integrating 3DGS with SLAM systems faces a fundamental scalability limitation: methods are constrained by GPU memory capacity, restricting reconstruction to small-scale environments. We present DiskChunGS, a scalable 3DGS SLAM system that overcomes this bottleneck through an out-of-core approach that partitions scenes into spatial chunks and maintains only active regions in GPU memory while storing inactive areas on disk. Our architecture integrates seamlessly with existing SLAM frameworks for pose estimation and loop closure, enabling globally consistent reconstruction at scale. We validate DiskChunGS on indoor scenes (Replica, TUM-RGBD), urban driving scenarios (KITTI), and resource-constrained Nvidia Jetson platforms. Our method uniquely completes all 11 KITTI sequences without memory failures while achieving superior visual quality, demonstrating that algorithmic innovation can overcome the memory constraints that have limited previous 3DGS SLAM methods.

17.
arXiv (CS.AI) 2026-06-18

Towards Multi-Agent-Simulation-Based Community Note Evaluation

arXiv:2606.18268v1 Announce Type: cross Abstract: Community-based fact-checking that relies on cross-consensus is expanding rapidly on social media platforms. However, the delay and low-ratio of cross-consensus community fact-checks rated by human contributors remains a significant challenge. To address this, we first created ComRate, a large-scale dataset comprising 2.5 million community notes and over 209 million ratings sourced from $\mathbb{X}$. We then propose MultiCom, a persona-guided multi-agent rating framework for community note evaluation. MultiCom simulates diverse rater population by clustering contributors in a matrix-factorized rater space and prompting persona agents to generate structured assessments based on the official community notes rating schema. These agents output structured and explainable judgments, such as confidence, agreement signals and reasons. An out-of-fold calibrated aggregation algorithm combines features such as raw votes and diagnostic reason signals for reliable prediction. Extensive evaluations demonstrate that MultiCom outperforms alternative methods, achieving an average accuracy of 84.7% (balanced accuracy 68.3%, macro-F1 60.1%) on the evaluation set.

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

Sustainable Materials Discovery in the Era of Artificial Intelligence

arXiv:2601.21527v3 Announce Type: replace-cross Abstract: Artificial intelligence (AI) has transformed materials discovery, enabling rapid exploration of chemical space through generative models and surrogate screening. Yet current generative AI models for materials discovery, which now drive exploration of vast chemical and structural spaces, optimize candidates exclusively for structural stability and functional properties, with no integration of environmental assessment at any stage of the design loop. Prospective and ex-ante life cycle assessment methods exist and have been applied to emerging technologies, but they operate as standalone downstream analyses, not as active constraints within generative or active-learning pipelines. The result is that environmental feedback, even when produced, arrives after design decisions have been made rather than informing them. The disconnect between atomic-scale design and lifecycle assessment (LCA) reflects fundamental challenges: (i) data scarcity across heterogeneous sources, (ii) scale gaps from atoms to industrial systems, (iii) uncertainty in synthesis pathways, and (iv) the absence of frameworks that co-optimize performance with environmental impact. In this Perspective, we propose integrating upstream ML-assisted materials discovery with downstream LCA into the ML-LCA framework, comprising five components: information extraction for building materials-environment knowledge bases, harmonized databases linking properties to sustainability metrics, multi-scale models bridging atomic properties to lifecycle impacts, ensemble prediction of manufacturing pathways with uncertainty quantification, and uncertainty-aware optimization enabling simultaneous performance-sustainability navigation. Case studies spanning polymers, glass, photoresists, and cement demonstrate both necessity and feasibility while identifying material-specific integration challenges.

19.
medRxiv (Medicine) 2026-06-17

Macrophage-targeted glucocorticoid prodrug resolves acute inflammation while preserving HPA axis function: mechanistic, preclinical, and Phase II/III clinical evidence

Glucocorticoids (GCs) remain the fastest-acting anti-inflammatory agents but are constrained by systemic exposure that suppresses the hypothalamic pituitary adrenal (HPA) axis, silences adaptive immunity, and drives chronic toxicities. Chronic inflammatory diseases are sustained by long-lived CD206+ macrophages containing immune-resistant pathogenic material not cleared physiologically. We developed 101-PGC-005 ('005), a macrophage-targeted type 1a dexamethasone prodrug engineered for low-affinity, recycling-compatible uptake via CD206, with intracellular release triggered by acidic endosomes. We evaluated '005 in mechanistic assays, pathogen-diverse preclinical models, three human pharmacokinetic (PK) studies, and an adaptive-design randomized Phase II/III trial in 309 hospitalized patients with moderate COVID-19. In two completed Phase I human studies, a first-in-human dose-escalation and repeated-dose study and a dedicated single/multiple-dose PK and safety study; '005 circulated as intact prodrug with rapid systemic clearance (Tmax ~0.5 h; terminal half-life ~1.9 h), with no measurable free dexamethasone after single dosing and only low, clinically non-significant free dexamethasone after repeated dosing, and intact prodrug recovered unchanged in urine. Morning cortisol and ACTH were preserved after 30 mg once daily for three consecutive days (1.5 times the intended therapeutic dose). A cerebrospinal fluid PK study is evaluating central-compartment penetration. In the Phase II/III trial, powered for non-inferiority, conducted across six sites in India under GCP with Ministry of Health approval and independent DSMB oversight; '005 (20 mg IV daily for 3 days) was superior to dexamethasone (6 mg IV daily for 3 -10 days) on the primary endpoint of time to > a 2-point improvement on the WHO ordinal scale (HR 2.31; 95% CI 1.83-2.93; p < 0.0001; median 3 vs. 4 days). '005 was also superior on viral clearance (HR 1.47; 95% CI 1.17-1.84; p = 0.0001), hospital discharge rate, SpO2; recovery, and fever resolution. Zero patients in the '005 arm received investigator-initiated corticosteroid supplementation despite protocol allowance. All 309 randomized patients completed the study (ITT = per-protocol). Safety profiles were equivalent (TEAEs 54.8% vs 54.5%; p = 0.958), with no Grade 3+ events, SAEs, deaths, or discontinuations in either arm. Mechanistically, '005 delivered dual benefit: acute debulking of inflammatory macrophages and selective depletion of chronically activated pathology-sustaining macrophages, while preserving CXCL10 antiviral signaling and physiologic HPA control. Critically, HPA preservation is not merely a safety feature, it is a core efficacy mechanism: by clearing the pathogenic macrophage burden that was overriding HPA regulation, '005 restores the conditions for endogenous cortisol to resume its pulsatile, demand-responsive anti-inflammatory role across all GR-expressing cells, lymphocytes, endothelial cells, neurons, and newly differentiated macrophages, that '005 itself cannot reach. These findings support regulatory-grade evidence for macrophage-targeted corticosteroid therapy and provide the foundation for further development across acute inflammatory indications (sepsis, viral pneumonia, cytokine-release syndromes) and chronic macrophage-driven diseases (atherosclerosis, metabolic steatohepatitis, neurodegeneration, tumor-associated macrophages).

20.
bioRxiv (Bioinfo) 2026-06-21

Machine learning evaluation of gene expression-based ALS subtypes across brain and blood tissues

The clinical and molecular heterogeneity observed in amyotrophic lateral sclerosis (ALS) presents a challenge for diagnosis, prognosis, and treatment. RNA sequencing of post-mortem brain samples from ALS patients has identified several subtypes with distinct molecular signatures. We sought to evaluate these subtypes across diverse tissues and datasets and assess the feasibility of supervised machine learning models for sample classification. Unsupervised clustering and pathway analysis were performed to confirm the presence of ALS subtypes in motor cortex samples. Three machine learning strategies were then used to create models based on post-mortem motor cortex expression data of 112 people with ALS from the London Neurodegenerative Diseases Brain Bank. These models were subsequently improved through feature selection and evaluated in independent cohorts from motor cortex (n = 257, NYGC ALS Consortium) and blood (n = 96, Macquarie University Neurodegenerative Disease Biobank) samples. Multi-class linear discriminant analysis (LDA) models were then used for subtype classification. Clustering of ALS post-mortem motor cortex samples confirmed the presence of three subtypes: neuroinflammation (ALS-Neu), extracellular matrix organisation and muscle contraction (ALS-OxA), and synaptic and neuropeptide signalling (ALS-SNs). Among all machine learning strategies, random forests produced the most accurate and stable models for binary classification (~93% accuracy across the three subtypes). After feature selection, random forest models were able to classify samples from an independent post-mortem motor cortex cohort in their respective subtypes (AUC of ~0.98 across the three subtypes). When these models were evaluated in blood using LDA, we found consistent clustering patterns, with samples aligning in the same subtype regions of the post-mortem motor cortex samples, with ALS-SNs being the subtype in which samples were classified with the highest confidence (LDA class probability ~86%). Moreover, classification for this subtype improved when blood samples were collected closer to death. Our findings support the presence of three gene expression-based ALS subtypes in motor cortex samples and the utility of machine learning strategies for subtype classification. We also observed that the subtypes identified in the brain partially match those in the blood, with samples from the late stages of the disease more likely to be correctly predicted into the ALS-SNs cluster. This suggests a longitudinal effect in subtype identification that requires further investigation.

21.
arXiv (quant-ph) 2026-06-12

Coulomb crystallization of xenon highly charged ions in a laser-cooled Ca+ matrix

arXiv:2512.12266v2 Announce Type: replace-cross Abstract: We report on the sympathetic cooling and Coulomb crystallization of xenon highly charged ions (HCIs) with laser-cooled Ca$^+$ ions. The HCIs are produced in a compact electron beam ion trap, then charge selected, decelerated, and finally injected into a cryogenic linear Paul trap. There, they are captured into $^{40}$Ca$^+$ Coulomb crystals, and co-crystallized within them, causing dark voids in their fluorescence images. Fine control over the number of trapped ions and HCIs allows us to realize mixed-species crystals with arbitrary ordering patterns. By investigating Xe$^{q+}$–Ca$^+$ strings, we confirm the HCI charge states, measure their lifetime and characterize the mixed-species motional modes. Our system effectively combines the established quantum control toolbox for Ca$^+$ with the rich set of atomic properties of Xe highly charged ions, providing a resourceful platform for optical frequency metrology, searches for signatures of new physics, and quantum information science.

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

On the spatio-temporal increments of nonlinear parabolic SPDEs and the open KPZ equation

arXiv:2508.05032v3 Announce Type: replace Abstract: We study spatio-temporal increments of the solutions to nonlinear parabolic SPDEs on a bounded interval with Dirichlet, Neumann, or Robin boundary conditions. We identify the exact local and uniform spatio-temporal moduli of continuity for the sample functions of the solutions. These moduli of continuity results imply the existence of random points in space-time at which spatio-temporal oscillations are exceptionally large. We also establish small-ball probability estimates and Chung-type laws of the iterated logarithm for spatio-temporal increments. Our method yields extension of some of these results to the open KPZ equation on the unit interval with inhomogeneous Neumann boundary conditions. Our key ingredients include new strong local non-determinism results for linear stochastic heat equation under various types of boundary conditions, and detailed estimates for the errors in linearization of spatio-temporal increments of the solution to the nonlinear equation.

23.
arXiv (CS.AI) 2026-06-16

Multi-Granular Node Pruning for Causal Circuit Discovery

arXiv:2512.10903v2 Announce Type: replace Abstract: Circuit discovery aims to identify minimal subnetworks that are responsible for specific behaviors in large language models (LLMs). Existing approaches primarily rely on iterative edge pruning, which is computationally expensive and limited to coarse-grained units such as attention heads or MLP blocks, overlooking finer structures like individual neurons. We propose a node-level pruning framework for circuit discovery that addresses both scalability and granularity limitations. Our method introduces learnable masks across multiple levels of granularity, from entire blocks to individual neurons, within a unified optimization objective. Granularity-specific sparsity penalties guide the pruning process, allowing a comprehensive compression in a single fine-tuning run. Empirically, our approach identifies circuits that are smaller in nodes than those discovered by prior methods; moreover, we demonstrate that many neurons deemed important by coarse methods are actually irrelevant, while still maintaining task performance. Furthermore, our method has a significantly lower memory footprint, 5-10x, as it does not require keeping intermediate activations in the memory to work.

24.
bioRxiv (Bioinfo) 2026-06-18

Robust Conditional Diffusion with Noisy Templates for Antibody Sequence-Structure Design

Antibodies specifically recognize antigens and play a central role in therapeutic discovery. Designing antibodies for a given antigen remains challenging because antigen-antibody complex data are limited, whereas the sequence and conformational spaces of complementarity-determining regions (CDRs) are large. Retrieved CDR templates from databases or candidate libraries can narrow the design space and improve controllability, but retrieval for novel antigens is often sparse and imperfect; treating retrieved templates as hard conditions can bias the denoising process and cause negative transfer. To address this problem, we propose Robust Conditional Diffusion with Noisy Templates for antibody sequence-structure design (NT-ABDiff), a joint diffusion framework that treats candidate CDR-only templates as optional and potentially unreliable conditions. NT-ABDiff uses reliability-aware template modulation to estimate the context-conditioned usefulness of each candidate and to adaptively reweight and fuse multiple templates during conditioning. We further train the model with mixed-quality and corrupted templates as conditional perturbation regularization, encouraging the denoiser to exploit informative templates while remaining stable when templates are uninformative. Experiments under controlled template shifts and a train-set retrieval evaluation show that NT-ABDiff improves CDR-H3 sequence recovery and structural accuracy over strong baselines, while retaining robustness to missing, mismatched, and corrupted templates. Under a stringent random-template CDR-H3 evaluation, NT-ABDiff improves amino-acid recovery (AAR) from 30.03% to 39.47% and reduces RMSD from 3.160 to 2.915A; with train-set retrieval candidates, it achieves 39.50% AAR and 2.76 {ring} A RMSD. Code, processed splits, {ring} configuration files, and evaluation scripts are available at https://github.com/ShiDeng7rz/NT-ABDiff.

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

Chroma-gated, differentiable OKLCH interpolation: Continuous Oklab fallback for color-cast reduction

OKLCH – the cylindrical (lightness, chroma, hue) form of Ottosson's Oklab color space – is the interpolation space recommended by CSS Color 4 for gradients and color-mix(), and it is now broadly deployed. Its polar parameterization, however, casts color near the neutral axis in two ways: (1) an inter-hue detour between two chromatic endpoints that sweeps through an unintended hue (blue to yellow visibly passing through green), and (2) an off-line bow when one endpoint is achromatic. Existing remedies are uniformly two-valued – a threshold switch that fires only at an achromatic endpoint – so they address only (2); on chromatic pairs every one of them reduces to raw OKLCH, leaving the (1) inter-hue cast untreated. We introduce Continuous Oklab fallback (COFb), a one-parameter, differentiable chroma gate $w(C)=C^n/(C^n+\sigma^n)$ that continuously blends the OKLCH path toward the linear Oklab path as chroma falls. A single gate reduces the (1) cast that the two-valued family leaves untreated and unifies the handling of (1) and (2) without any endpoint test. We characterize a cast-hue trade-off frontier, adopt a default ($n=1$, the rational Michaelis-Menten form; $\sigma\approx0.19$ for a typical sRGB palette, from a normalization-independent cast-half criterion), and verify the gate's properties symbolically. At the default, COFb halves the inter-hue path detour (mean lateral deviation -49.5%, chroma-weighted hue excursion -35.5%). We also state the method's limits: on (2) alone the two-valued switch remains better, and like any Cartesian blend COFb does not preserve chroma. In deployment, COFb runs entirely in plain Oklab (a,b) to sRGB, so it serves as a fallback that delivers the same cast-reduced gradients where modern CSS color interpolation (color-mix(in oklch) and the like) is unavailable – older engines, image and video pipelines, or GPU shaders.