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01.
arXiv (CS.LG) 2026-06-12

Reliability of Probabilistic Emulation of Physical Systems

arXiv:2606.12997v1 Announce Type: new Abstract: Two dominant approaches have emerged for generating probabilistic forecasts of physical systems: generative models, such as diffusion or flow matching; and ensembles of deterministic models with stochasticity injected, trained using the continuous ranked probability score (CRPS) loss. While both approaches have demonstrated strong predictive accuracy, the reliability of their uncertainties has not been systematically assessed. We address this gap by developing a framework to evaluate both approaches across diverse 2D spatiotemporal physical systems, under matched model size and computational budget. We assess the reliability of probabilistic emulation by inspecting the empirical coverage of predictive intervals, while also considering accuracy and computational efficiency metrics. CRPS-trained ensembles typically achieve more reliable uncertainties on both single-step prediction and autoregressive rollouts, demonstrating better coverage than the standard alternative of training generative models in a latent space. Moreover, the CRPS approach offers significantly faster inference. When generative models are trained in ambient rather than a compressed latent space, which is often infeasible for high-dimensional problems, they exhibit comparable coverage to CRPS-trained ensembles, though with substantially larger inference latency. In contrast, when CRPS-trained ensembles are trained in latent space they do not show a marked degradation in coverage with respect to ambient space. Both generative models and CRPS-trained ensembles demonstrate good predictive accuracy. To facilitate future research and application, we release AutoCast, a modular framework implementing both generative models and CRPS-trained ensembles, alongside AutoSim, a flexible dataset generation package for rapid prototyping.

02.
arXiv (CS.AI) 2026-06-18

R2BC: Multi-Agent Imitation Learning from Single-Agent Demonstrations

arXiv:2510.18085v2 Announce Type: replace-cross Abstract: Imitation Learning (IL) is a natural way for humans to teach robots, particularly when high-quality demonstrations are easy to obtain. While IL has been widely applied to single-robot settings, relatively few studies have addressed the extension of these methods to multi-agent systems, especially in settings where a single human must provide demonstrations to a team of collaborating robots. In this paper, we introduce and study Round-Robin Behavior Cloning (R2BC), a method that enables a single human operator to effectively train multi-robot systems through sequential, single-agent demonstrations. Our approach allows the human to teleoperate one agent at a time and incrementally teach multi-agent behavior to the entire system, without requiring demonstrations in the joint multi-agent action space. We show that R2BC methods match, and in some cases surpass, the performance of an oracle behavior cloning approach trained on privileged synchronized demonstrations across four multi-agent simulated tasks. Finally, we deploy R2BC on two physical robot tasks trained using real human demonstrations.

03.
arXiv (CS.CV) 2026-06-17

Detail++: Training-Free Detail Enhancer for Text-to-Image Diffusion Models

Recent advances in text-to-image (T2I) generation have led to impressive visual results. However, these models still face significant challenges when handling complex prompt, particularly those involving multiple subjects with distinct attributes. Inspired by the human drawing process, which first outlines the composition and then incrementally adds details, we propose Detail++, a training-free framework that introduces a novel Progressive Detail Injection (PDI) strategy to address this limitation. Specifically, we decompose a complex prompt into a sequence of simplified sub-prompts, guiding the generation process in stages. This staged generation leverages the inherent layout-controlling capacity of self-attention to first ensure global composition, followed by precise refinement. To achieve accurate binding between attributes and corresponding subjects, we exploit cross-attention mechanisms and further introduce a Centroid Alignment Loss at test time to reduce binding noise and enhance attribute consistency. Extensive experiments on T2I-CompBench and a newly constructed style composition benchmark demonstrate that Detail++ significantly outperforms existing methods, particularly in scenarios involving multiple objects and complex stylistic conditions.

04.
arXiv (CS.AI) 2026-06-15

CisTransCell: Single-Cell Perturbation Prediction via Gene Function, Regulatory Control, and Cellular Context

arXiv:2606.13713v1 Announce Type: cross Abstract: Predicting cellular transcriptional responses to genetic perturbations is a central problem in single-cell biology, especially in the zero-shot setting where the perturbed gene or gene combination is unseen during training. A major difficulty is that perturbation effects are not determined by expression state alone: they depend on how the perturbed gene product influences other genes and proteins, how those downstream factors act on cis-regulatory elements, and which regulatory programs are active in the current cell state. To better capture this biological complexity, we propose CisTransCell, a cell-conditioned multi-modal framework for single-cell perturbation prediction that augments each gene with two complementary priors: a regulatory-sequence prior that captures how the gene is controlled, and a coding-sequence prior that captures what the gene product does. By integrating these priors with cellular expression state, CisTransCell models perturbation response as a cascade from gene function to regulatory control to downstream transcriptional change. Experiments on benchmark single-cell perturbation datasets show that CisTransCell achieves strong performance in zero-shot perturbation prediction.

05.
arXiv (CS.CV) 2026-06-17

Flash-GRPO: Efficient Alignment for Video Diffusion via One-Step Policy Optimization

Group Relative Policy Optimization has emerged as essential for aligning video diffusion models with human preferences, but faces a critical computational bottleneck: training a 14B parametered model typically demands hundreds of GPU days per experiment. Existing efficiency methods reduce costs through sliding window subsampling training timesteps, but fundamentally compromise optimization, exhibiting severe instability and failing to reach full trajectory performance. We present Flash-GRPO, a single-step training framework that outperforms full trajectory training in alignment quality under low computational budgets while substantially improving training efficiency. Flash-GRPO addresses two critical challenges: iso-temporal grouping eliminates timestep-confounded variance by enforcing prompt-wise temporal consistency, decoupling policy performance from timestep difficulty; temporal gradient rectification neutralizes the time-dependent scaling factor that causes vastly inconsistent gradient magnitudes across timesteps. Experiments on 1.3B to 14B parameter models validate Flash-GRPO's effectiveness, demonstrating substantial training acceleration with consistent stability and state-of-the-art alignment quality.

07.
medRxiv (Medicine) 2026-06-11

Long-term Penetrance of Disease Variants in Genes Prioritized for Genomic Newborn Screening: Evidence from Adult Biobanks

Importance: Genomic newborn screening (gNBS) is a potential public health intervention, but its positive predictive value (PPV) remains uncertain. Estimating the prevalence and penetrance of pathogenic and likely pathogenic (P/LP) variants in genes prioritized for screening may clarify the long-term PPV and clinical utility of gNBS. Objective: To compare ICD-based ascertainment, electronic medical record (EMR) review, and clinical assessment of genetic disorders in adults with P/LP variants in 54 genes prioritized for gNBS. Design: Two-cohort observational study with EMR review and clinical assessment in the hospital-based cohort. Setting: The U.K. Biobank (UKB) and Mass General Brigham Biobank (MGBB). Participants: 451,877 adults from the UKB and 53,371 from the MGBB, all with exome sequencing data. Exposures: P/LP variants in 54 genes prioritized through expert consensus for gNBS, in genotypes consistent with each gene's inheritance pattern. Main outcomes and measures: The primary outcome was the absolute difference in the proportion of MGBB participants identified as affected by ICD versus EMR ascertainment. Secondary outcomes included findings from clinical assessments of undiagnosed MGBB participants, corrected UKB penetrance estimates, and extrapolation to U.S.. annual birth cohorts and living adults. Results: P/LP variants were identified in 665 UKB participants (0.15%) and 82 MGBB participants (0.15%), approximately 1 in 650. In MGBB, EMR review revealed that 58/82 individuals (70.7%) were undiagnosed, although 25 of 58 (43.1%) had documented symptoms. Disease-associated ICD codes were found in 39.0% (32/82) of participants, whereas EMR review identified symptoms in 59.8% (49/82, McNemar P

08.
arXiv (CS.LG) 2026-06-11

JGRA: Jacobian Geometry Robustness Assessment in NISQ Noise-Aware Quantum Neural Networks

arXiv:2606.09964v2 Announce Type: replace-cross Abstract: The NISQ era places stringent constraints on quantum computation, where noise and decoherence fundamentally limit performance. In classical deep learning, model robustness and resilience to perturbations are well studied: deep neural networks (DNNs) maintain high performance despite pruning, noise injection, and structural perturbations due to inherent redundancy in their representations. A central challenge in quantum machine learning is to transfer this notion of robustness to quantum neural networks (QNNs) under realistic NISQ noise. While classical deep learning exhibits robustness through structural redundancy, analogous principles for QNNs remain underdeveloped. We propose JGRA: a framework for assessing robustness in noise-aware QNNs via Jacobian geometry, capturing model sensitivity to parameter perturbations induced by noise. Our method includes entropy-matched noise calibration, noise-aware training, and noise-conditioned Jacobian extraction, yielding geometric descriptors that link clean-regime structure to noisy inference behaviour. We also empirically demonstrate that these descriptors encode predictive information about robustness under unseen noise.

09.
arXiv (CS.LG) 2026-06-17

When the Next Step Is Not One Step: Distribution-Aware Execution Modeling for Concurrent Go Programs

arXiv:2606.17508v1 Announce Type: new Abstract: Training a model to predict the next step in a concurrent program is harder than it looks: two runs of the same program from the same trace prefix can produce different next events, both valid, because the scheduler is nondeterministic. A model trained against a single label is learning to guess one outcome of a random process. We turn this around and use the nondeterminism as a training signal. We run each program many times, aggregate the observed next events into an empirical distribution, and fine-tune a 7B model to match that distribution with a KL objective. On 798 held-out predictions drawn from real production Go bugs (CockroachDB, Kubernetes, gRPC, etcd), fine-tuning on fewer than a thousand traces reaches 36.2% accuracy, ahead of Gemini 3.5 Flash used zero-shot (34.8%) and the same model without fine-tuning (28.6%). Distribution training matches cross-entropy on accuracy (35.8% vs. 36.2%) while reducing Expected Calibration Error from 0.205 to 0.169. We also derive a formal goroutine-leak signature for a class of select-blocked goroutines where P(GoUnblock)=0 holds by scheduler semantics, not by learning. We release the dataset, trained adapters, and all tooling.

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

Rethinking the Trust Region in LLM Reinforcement Learning

Reinforcement learning (RL) has become a cornerstone for fine-tuning Large Language Models (LLMs), with Proximal Policy Optimization (PPO) serving as the de facto standard algorithm. Despite its ubiquity, we argue that the core ratio clipping mechanism in PPO is structurally ill-suited for the large vocabularies inherent to LLMs. PPO constrains policy updates based on the probability ratio of sampled tokens, which serves as a noisy single-sample Monte Carlo estimate of the true policy divergence. This creates a sub-optimal learning dynamic: updates to low-probability tokens are aggressively over-penalized, while potentially catastrophic shifts in high-probability tokens are under-constrained, leading to training inefficiency and instability. To address this, we propose Divergence Proximal Policy Optimization (DPPO), which substitutes heuristic clipping with a more principled constraint based on a direct estimate of policy divergence (e.g., Total Variation or KL). To avoid huge memory footprint, we introduce the efficient Binary and Top-K approximations to capture the essential divergence with negligible overhead. Extensive empirical evaluations demonstrate that DPPO achieves superior training stability and efficiency compared to existing methods, offering a more robust foundation for RL-based LLM fine-tuning. Our code is available at https://github.com/sail-sg/Stable-RL.

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

Notes2Skills: From Lab Notebooks to Certainty-Aware Scientific Agent Skills

Scientific discovery workflows usually contain and rely heavily on lab notes, where researchers record observations, interpret uncertain results, and plan follow-up experiments. Such informative lab notes preserve evolving scientific reasoning and author uncertainty, rather than polished final results exhibited in publications, providing a valuable opportunity for AI to engage in scientific exploration at a more comprehensive and deeper level. However, most prior work on scientific text focuses on papers, protocols, or structured databases, leaving informal laboratory notes underexplored as inputs to AI agents for science. This gap matters because lab notes often intermingle validated observations, tentative judgments, and possible experimental next steps within the same passage. If these signals are conflated, an AI agent may mistake uncertain scientific judgments for confirmed conclusions or executable actions. To this end, we present Notes2Skills, a two-stage framework for turning lab notebooks into verifiable skills for scientific AI agents while preserving the author's certainty. Across seven conditions and three wet-lab sessions, Notes2Skills is the only configuration that neither mistakes uncertain notes for firm instructions nor discards firm ones. We show that certainty preservation is the missing piece between lab notebooks and reliable agent skills, opening a path toward safer AI co-scientist systems.

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

CoVR-R:Reason-Aware Composed Video Retrieval

Composed Video Retrieval (CoVR) aims to find a target video given a reference video and a textual modification. Prior work assumes the modification text fully specifies the visual changes, overlooking after-effects and implicit consequences (e.g., motion, state transitions, viewpoint or duration cues) that emerge from the edit. We argue that successful CoVR requires reasoning about these after-effects. We introduce a reasoning-first, zero-shot approach that leverages large multimodal models to (i) infer causal and temporal consequences implied by the edit, and (ii) align the resulting reasoned queries to candidate videos without task-specific finetuning. To evaluate reasoning in CoVR, we also propose CoVR-Reason, a benchmark that pairs each (reference, edit, target) triplet with structured internal reasoning traces and challenging distractors that require predicting after-effects rather than keyword matching. Experiments show that our zero-shot method outperforms strong retrieval baselines on recall at K and particularly excels on implicit-effect subsets. Our automatic and human analysis confirm higher step consistency and effect factuality in our retrieved results. Our findings show that incorporating reasoning into general-purpose multimodal models enables effective CoVR by explicitly accounting for causal and temporal after-effects. This reduces dependence on task-specific supervision, improves generalization to challenging implicit-effect cases, and enhances interpretability of retrieval outcomes. These results point toward a scalable and principled framework for explainable video search. The model, code, and benchmark are available at https://github.com/mbzuai-oryx/CoVR-R.

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

Agents All the Way Down; A Methodology for Building Custom AI Agents from Substrate to Production

arXiv:2606.11869v1 Announce Type: cross Abstract: Custom AI agents areagents that live inside their own application, talk to their own data and tools, enforce their own security boundaries, and carry their own brand and audit trail. What separates them from the general-purpose tier is fit, not capability: each is built for one job, by the engineer who will maintain it. No published practice sets out how to build one end to end. The pieces are everywhere (function-calling APIs, the Model Context Protocol, code agents to pair with), but the practice that chains them lives in podcasts, blogs, and leaked system prompts. This paper writes that practice down as a methodology, Agents All the Way Down: two preconditions crossed once and kept, then three practices repeated for the agent's life. The preconditions are (P1) Substrate, the LLM as a software component, framed as tools, then system, then messages under prompt-caching; and (P2) Building blocks: function calling, MCP, CLI orchestration, the liteshell pattern, the agent loop, skills, characters, hooks, and scaffolding. The practices are (P3) prototype with a general-purpose agent; (P4) harvest, fold, and ship the result as a CLI, the Turtle pattern; and (P5) agent-tests-agent, in which a general-purpose agent drives it through behavioural scenarios, a complement to classical testing, not a replacement. The working loop is P3 to P4 to P5 and back, and one corollary falls out for free: multi-agent orchestration is just CLI composition. The methodology is framework-free by construction. It was distilled from the AAC, a custom agent for the open-source LAMB platform, built in about ten days by one developer with an AI pair-programmer and in production . We present it as a transferable practice, independent of any language or framework.

14.
arXiv (CS.AI) 2026-06-18

Domain-Shift Aware Neural Networks for Unbalance Characterization in Rotating Systems

arXiv:2606.18882v1 Announce Type: cross Abstract: This work investigates the application of a domain-shift aware neural network for regression tasks aimed at estimating unbalance masses in rotating shafts under varying operating conditions. Experimental data were collected from a test rig in which a primary shaft, equipped with a flange carrying unbalanced masses, was driven at different rotational speeds, while a secondary shaft could be optionally activated to introduce domain discrepancy. The unbalance masses were positioned at a fixed radial distance, and the dynamic response of the system was recorded using triaxial accelerometers. The inverse problem of mass estimation is formulated within a domain adaptation framework, where the network is trained with a maximum mean discrepancy strategy to align feature representations across source and target distributions. The results demonstrate the effectiveness of explicitly addressing domain shift in improving prediction accuracy, especially when the system's physical behavior and sources of domain discrepancy are not fully known and fall outside the training conditions. These findings highlight the potential of domain-shift aware models for regression tasks in Structural Health Monitoring.

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

Mitigating Content Shift and Hallucination in GenAI Image Editing via Structural Refinement

Generative AI (GenAI) image editors, such as Nano Banana, produce visually compelling results for retouching tasks, enabling non-experts to edit images through text prompts alone. However, the generative nature of these models often introduces spatial misalignment, texture distortion, and content hallucination, all of which are detrimental to downstream workflows that require pixel-level fidelity. We identify a problem setting we call "structure-preserving GenAI fusion" for black-box GenAI image retouching: retain the perceptual enhancements of a GenAI output while enforcing structural faithfulness to the original input image. To address this problem, we propose a post-processing framework that fuses an input image with its GenAI-enhanced counterpart by first establishing coarse spatial and photometric correspondences, then performing a fusion stage that transfers desired enhancements while suppressing hallucinated content. In the absence of direct prior work in this setting, we evaluate our framework against representative methods from photorealistic style transfer and image fusion. Our experiments demonstrate that our method better preserves aesthetic quality while maintaining pixel-level structural consistency and the input resolution.

16.
arXiv (CS.CL) 2026-06-11

BioMamba: Domain-Adaptive Biomedical Language Models

Background. Biomedical language models should improve performance on biomedical text while retaining general-language-modeling fluency. For Mamba-based models, this trade-off has not been systematically studied across biomedical literature and clinical text. Methods. We developed BioMamba, a family of biomedical Mamba2 models at five scales obtained by continued pretraining of released public Mamba2 checkpoints on a balanced 80%/10%/10% mixture of PubMed abstracts, the Colossal Clean Crawled Corpus (C4), and Wikipedia. The contribution is the adaptation recipe and the accompanying open-weight checkpoints. Results. Across five scales, BioMamba consistently lowered PubMed perplexity, improved Wikipedia-style held-out perplexity by 1.46-4.72 PPL, and left C4 perplexity essentially unchanged. On six out-of-domain multiple-choice benchmarks, BioMamba stayed within +/-3 percentage points of Mamba2 with no systematic regression. After supervised fine-tuning, BioMamba+SFT matched or exceeded Mamba2+SFT on MIMIC-IV note completion and discharge summary generation at every evaluated scale, and improved PubMedQA at every scale. The strongest model (BioMamba-2.7B) reached a PubMed perplexity of 5.28 and accuracies of 90.24% and 73.00% on BioASQ and PubMedQA, respectively. Conclusions. A balanced domain-adaptive continued pretraining recipe strengthens Mamba2 language models on biomedical literature and clinical text while preserving general-language-modeling fluency.

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

Beyond Independent Genes: Learning Module-Inductive Representations for Single-Cell Gene Perturbation Prediction

arXiv:2602.04901v2 Announce Type: replace-cross Abstract: Predicting transcriptional responses to genetic perturbations is a central problem in functional genomics. In practice, perturbation responses are rarely gene-independent but instead manifest as coordinated, program-level transcriptional changes among functionally related genes. However, most existing methods do not explicitly model such coordination, due to gene-wise modeling paradigms and reliance on static biological priors that cannot capture dynamic program reorganization. To address these limitations, we propose scBIG, a module-inductive perturbation prediction framework that explicitly models coordinated gene programs. scBIG induces coherent gene programs from data via Gene-Relation Clustering, captures inter-program interactions through a Gene-Cluster-Aware Encoder, and preserves modular coordination using structure-aware alignment objectives. These structured representations are then modeled using conditional flow matching to enable flexible and generalizable perturbation prediction. Extensive experiments on multiple single-cell perturbation benchmarks show that scBIG consistently outperforms state-of-the-art methods, particularly on unseen and combinatorial perturbation settings, achieving an average improvement of 6.7% over the strongest baselines. The code is available at https://github.com/ttruan2426-dot/scBIG.

18.
PLOS Computational Biology 2026-06-11

Catecholamine precursor modulation of human exploration: Evidence from a large gender-balanced sample

by Angela Mariele Brands, Kilian Knauth, David Mathar, Tim Roedder, Kerstin Lisner, Jan Peters The catecholamine precursor Tyrosine has been linked to improved cognitive performance, but investigations into decision-making and reinforcement learning processes known to be under catecholamine control are sparse. We examined the impact of a single dose of Tyrosine (2g) on reinforcement learning and exploration in a large (n = 63) gender-balanced sample in a within-subjects preregistered study. Reinforcement learning performance was significantly improved under Tyrosine. Based on previous work, we preregistered the hypotheses that Tyrosine would reduce directed exploration, response times, and physiological arousal. However, neither response times nor physiological arousal revealed the predicted reductions. Computational modelling using an established pre-registered reinforcement learning model revealed that the performance improvement under Tyrosine was due to an increase value-driven exploitation, without affecting directed exploration. Non-preregistered modelling analyses then revealed that accounting for higher-order perseveration substantially improved model fit, and substantiated the observation of increased value-driven exploitation under Tyrosine. Furthermore, it revealed reliable reductions in directed exploration and value-independent perseveration under Tyrosine. Tyrosine thus improved reinforcement learning performance by stabilizing choice patterns in the service of optimizing reward accumulation, modulating several computational mechanisms thought to be under catecholamine control.

19.
medRxiv (Medicine) 2026-06-22

''Circumstantial Determinants'': An Efficient Approach to Reaching People in Need of HIV Prevention?

HIV prevention and testing programmes primarily reach people who self-refer or attend routine health services. Higher-risk individuals are missed if they are healthy, under-estimate their risk of infection or under-report sexual risk-behaviours. We assess a new approach to address limitations in existing programmes by targeting HIV services on ''Circumstantial Determinants'' (CDs) of HIV risk - the social circumstances, settings, and norms associated with behaviours that increase risk of HIV acquisition. Data on potential CDs and sexual behaviour were collected in a population survey in Zimbabwe in 2018/19 (N=9141). HIV-negative individuals reporting [≥] 1 sexual risk-behaviours were defined as the 'priority population' for HIV prevention. For each sex, six circumstantial determinants were associated with being in the priority population (aOR [≥] 1.30; p [≤] 0.01). Reach and efficiency of CDs (and combinations) were calculated; ROC curve algorithms evaluated their ability to identify priority population membership; and HIV prevention condom cascades were compared between CD-defined priority population subgroups. Example findings include that targeting men at bars and beerhalls could reach 48.5% of the priority population and 25.1% of lower-risk men. These percentages increase to 77.1% and 53.7% if men with poor mental health, no religious affiliation, negative social capital, or living on agricultural estates are also targeted. Targeting women with poor mental health could reach 32.0% of the priority population and 21.3% of lower-risk women. Targeting additional circumstantial determinants increases these percentages to 54.1% and 37.5%, respectively. Cascade barriers to condom use differed between CD-defined subgroups. The Circumstantial Determinants approach demonstrates proof-of-concept potential to strengthen HIV prevention services.

20.
arXiv (CS.CV) 2026-06-19

CrossFlow: One-Step Generation Across Latent and Pixel Spaces

Most diffusion and flow-matching generators define the prior, probability path, and prediction target in the same representation space. Latent diffusion improves efficiency by moving this path into an autoencoder latent space, but the final sample is still produced by a separately trained decoder. This separation creates a mismatch: the generator is optimized for latent-space prediction, while final quality depends on how the decoder handles generated latents that may differ from clean encoder outputs. We introduce CrossFlow, a cross-space flow formulation that maps noisy latent inputs directly to pixel-space images. The key technical step is a velocity-free one-step objective: the latent trajectory defines the training path, but the supervised prediction is an image rather than a latent displacement. This lets one model act both as a one-step latent-to-pixel generator and as a decoder replacement for latent diffusion pipelines. On class-conditional ImageNet-1k at $256\times256$, CrossFlow-XL achieves 1.62 FID with one function evaluation. Ablations show that the latent encoder and pixel-space perceptual and adversarial losses are important for fidelity. These results indicate that cross-space flow objectives can combine the efficiency of latent representations with direct pixel-space supervision, without requiring a separate decoder at inference.

21.
PLOS Computational Biology 2026-06-02

Data-driven model reveals increased stability of CAG-expanded <i>huntingtin</i> RNA due to MID1 binding

Authors:

by Yuhong Liu, Annika Reisbitzer, Domagoj Dorešić, Jan Hasenauer, Sybille Krauß, Tatjana Tchumatchenko RNA-binding proteins (RBP) are important regulators of RNA metabolism. In neurodegenerative disorders such as Huntington’s Disease (HD), disrupted RBP-RNA interactions contribute to neuronal dysfunction. One such RBP, Midline 1 (MID1), has been shown to aberrantly associate with mutant huntingtin (Htt) RNA, enhancing its translation, yet the mechanism driving this effect remains unknown. Here, we develop a computational model to understand the role of MID1. Based on previously published data, our model predicts that MID1 increases the stability of the Htt RNA. We experimentally validate this prediction, showing that overexpression of MID1 significantly prolongs the half-life of mutant Htt RNA. Furthermore, we evaluate model refinements, including clustering of MID1-bound RNA, which allow capturing all key observations in the data. Together, we provide a data-driven framework that underlines the importance of RBP-RNA interaction in post-transcriptional regulation. This framework also shows how individual molecular reactions jointly determine RNA stability and protein levels in HD.

22.
arXiv (CS.LG) 2026-06-16

Branching Flows: Discrete, Continuous, and Manifold Flow Matching with Splits and Deletions

arXiv:2511.09465v4 Announce Type: replace-cross Abstract: Diffusion and flow matching approaches to generative modeling have shown promise in domains where the state space is continuous, such as image generation or protein folding & design, and discrete, exemplified by diffusion large language models. They offer a natural fit when the number of elements in a state is fixed in advance (e.g. images), but require ad hoc solutions when, for example, the length of a response from a large language model, or the number of amino acids in a protein chain is not known a priori. Here we propose Branching Flows, a generative modeling framework that, like diffusion and flow matching approaches, transports a simple distribution to the data distribution. But in Branching Flows, the elements in the state evolve over a forest of binary trees, branching and dying stochastically with rates that are learned by the model. This allows the model to control, during generation, the number of elements in the sequence. We also show that Branching Flows can compose with any flow matching base process on discrete sets, continuous Euclidean spaces, smooth manifolds, and `multimodal' product spaces that mix these components. We demonstrate this in three domains: small molecule generation (multimodal), antibody sequence generation (discrete), and protein backbone generation (multimodal), and show that Branching Flows is a capable distribution learner with a stable learning objective, and that it enables new capabilities.

23.
arXiv (CS.CL) 2026-06-15

Small LLMs: Pruning vs. Training from Scratch

Pruning promises a shortcut to strong small language models. In this work, we examine this promise by pruning Llama-3.1-8B at pruning ratios of 0.5–0.8 with six methods spanning depth, width, and sparse granularities, under two controlled token-matched settings. (1) With the same training token budget, pruned initialization consistently outperforms random initialization. This shows that the parent model provides a strong starting point, although the advantage narrows as the training token budget grows and as the pruning ratio rises, nearly vanishing at the highest pruning ratio we study. (2) When training from scratch is instead given the full token budget consumed by the whole pipeline, pruning at finer granularities still retains an advantage, while coarser structured pruning can be matched or surpassed. This suggests that the parent model transfers knowledge that additional training tokens alone cannot fully recover, but only at fine granularity. Taken together, our results yield a clear recommendation: with a large pretrained model in hand and a limited training token budget, pruning is better than training from scratch; when the training budget is not limited, training from scratch can be competitive for coarser pruning, so a large pretrained parent is not always necessary.

24.
PLOS Medicine 2026-06-23

Prevalence and epidemiological patterns of <i>Neisseria gonorrhoeae</i> infection in sub-Saharan Africa, 1964–2025: Systematic review, meta-analyses, and meta-regressions

Authors:

by Aisha Osman, Hina Akram, Bayan Alemrayat, Sumaya Al-Maraghi, Manale Harfouche, Laith J. Abu-Raddad Background Neisseria gonorrhoeae (NG) infection is a global health concern because of its morbidity and increasing antimicrobial resistance. Sub-Saharan Africa is believed to carry a disproportionately high burden of NG infection, but the epidemiology of NG infection in this region has not been comprehensively synthesized. This study systematically reviewed and analyzed NG prevalence in sub-Saharan Africa to characterize prevalence patterns and identify populations at risk. Methods and findings A systematic review was conducted and reported following PRISMA guidelines. Embase, PubMed, Scopus, and Web of Science were searched from inception to June 4, 2025. Eligible studies reported NG prevalence in sub-Saharan Africa. Random-effects meta-analyses generated pooled prevalence estimates, and random-effects meta-regression analyses identified associations and sources of heterogeneity.Nine hundred fifty publications contributed 1,604 prevalence measures spanning 1964–2025. In the general population, pooled urogenital prevalence was 3.2% (95% confidence interval (CI): 2.9–3.5), with substantial between-study heterogeneity and a wide prediction interval, indicating considerable variation in prevalence across settings. Prevalence was high in key populations: among female sex workers, 11.5% (95% CI: 9.9–13.2) for urogenital and 2.0% (95% CI: 0.4–4.5) for anorectal infection; and among men who have sex with men, 2.8% (95% CI: 2.4–3.3) for urogenital, 8.3% (95% CI: 5.8–11.0) for anorectal, and 5.7% (95% CI: 3.6–8.3) for oropharyngeal infection. Symptomatic men exhibited high urogenital prevalence (51.5%; 95% CI: 47.5–55.5), and symptomatic women showed 9.0% (95% CI: 7.7–10.4). Among women with adverse pregnancy or birth outcomes, urogenital prevalence was 8.6% (95% CI: 5.3–12.6). Meta-regression analyses explained over half of the variability in prevalence, showing a long-term decline of 1% per year, a clear population type gradient, subregional differences, and decreasing prevalence with increasing age, but no variation by sex. These findings may be affected by variability in data availability across countries, anatomical sites, and population groups, as well as heterogeneity across included studies. Conclusions NG prevalence remains markedly high in this region but has declined over time. These findings highlight the need for strengthened surveillance, expanded prevention and diagnostic strategies, and continued monitoring of gonococcal antimicrobial resistance to support effective control efforts in sub-Saharan Africa.

25.
arXiv (CS.CL) 2026-06-12

Agents' Last Exam

Recent AI systems have achieved strong results on a wide range of benchmarks, yet these gains have not translated into economically meaningful deployment across many professional domains. We argue that this gap is largely an evaluation problem: widely used benchmarks lack sustained performance measurement on real and economically valuable workflows. This paper introduces Agents' Last Exam (ALE), a benchmark designed to evaluate AI agents on long horizon, economically valuable, real world tasks with verifiable outcomes. Developed in collaboration with 250+ industry experts, ALE covers non-physical industries defined with reference to O*NET / SOC 2018 (the U.S. federal occupational taxonomy). It is organized around a task taxonomy with 55 sub fields grouped into 13 industry clusters covering 1K+ tasks. Current results show that the hardest tier remains far from saturated: across mainstream harness and backbone configurations, the average full pass rate is below 1%. ALE is designed as a living benchmark: its task pool grows continuously as new workflows and industries are onboarded. More broadly, ALE is intended not merely as another leaderboard, but as an instrument for closing the gap between benchmark success and GDP relevant impact.