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01.
Science (Express) 2026-04-16

Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) are widespread bacterial anti-phage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6 Å resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.

02.
medRxiv (Medicine) 2026-06-17

Preserved Medial Temporal Lobe Flexibility Predicts Memory Generalization Only in the Context of Good Sleep Quality among Older African Americans

Objectives: Poor sleep quality is a risk factor for Alzheimer's disease (AD). Older African Americans experience disproportionately high rates of sleep disturbance and AD. Medial temporal lobe (MTL) flexibility reflects dynamic neural reorganization and may be a marker of generalization performance. This study examined whether sleep quality moderates the association between MTL flexibility and memory generalization. Methods: Fifty older African Americans (MeanAge=69.7{+/-}6.21 years; 80% women) underwent rs-fMRI to quantify MTL flexibility, Rutgers Acquired Equivalence Task for memory generalization, and Pittsburgh Sleep Quality Index for sleep quality. Results: Greater MTL flexibility was associated with better generalization (r=0.367, p=.017). Good sleepers showed higher MTL flexibility (F(1,44)=8.11, p2=.156, p=.007) and superior generalization (F(1,46)= 12.33, p2=.211, p=.001). Sleep quality significantly moderated the MTL flexibility and generalization relationship ({beta}=-1.519, p=.012). Conclusions: Preserved MTL flexibility may confer generalization only in good sleepers, suggesting that sleep disturbance may disrupt the MTL neural resilience among older African Americans.

03.
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.

04.
Nature (Science) 2026-06-09

Daily briefing: Trial to ‘de-age’ cells treats first person

作者:

The gene-therapy trial aims to treat glaucoma by rejuvenating cells in the optic nerve. Plus, the mystery of how things freeze and encouragement to go out into the sunlight. The gene-therapy trial aims to treat glaucoma by rejuvenating cells in the optic nerve. Plus, the mystery of how things freeze and encouragement to go out into the sunlight.

05.
arXiv (CS.CL) 2026-06-16

It's About Time: Temporal References in Emergent Communication

Emergent communication enables agents to develop bespoke languages that improve communication efficiency. Despite the known importance of temporal structure in natural language, there is no existing evidence of temporal references in emergent communication. This paper addresses this gap, by exploring how agents communicate about temporal relationships. We analyse three potential factors for the emergence of temporal references: environmental, external, and architectural. Our experiments demonstrate that altering the loss function is insufficient for temporal references to emerge; rather, architectural changes are necessary. A minimal change in agent architecture, using a different batching method, allows the emergence of temporal references. This modified design is compared with the standard architecture in a temporal referential games environment, which emphasises temporal relationships. The analysis shows that over 95% of the agents with the modified batching method develop temporal references, without changes to their loss function. We consider temporal referencing necessary for future improvements to the agents' communication efficiency, enabling future agents to use a closer to optimal coding as compared to purely compositional languages. These insights provide the basis for incorporation of temporal references into other emergent communication settings, and investigation of other aspects of language.

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

Latent World Recovery for Multimodal Learning with Missing Modalities

arXiv:2606.12362v1 Announce Type: cross Abstract: We study multimodal learning under missing modalities, with particular motivation from bioscience applications in which heterogeneous modalities are often only partially available when decisions need to be made. We propose Latent World Recovery (LWR), a framework built on two key ideas: (i) modality-specific embeddings from different modalities are aligned in a shared latent space, and (ii) a unified representation is constructed by fusing only the embeddings of the modalities that are actually available at both training and inference time. Rather than imputing missing modalities or requiring a fixed modality set, LWR treats each modality as a partial perception of an underlying latent state and performs availability-aware representation learning directly from the observed modalities. This combination of neighbor-based latent alignment and availability-aware modality fusion enables robust multimodal prediction under partial observation, while avoiding error propagation from explicit reconstruction of missing modalities. We evaluate the proposed framework on real-world incomplete multi-omics benchmarks and demonstrate that it provides an effective approach to downstream tasks such as cancer phenotype classification and survival prediction.

07.
arXiv (CS.CV) 2026-06-17

NTIRE 2025 Challenge on Image Super-Resolution (x4): Methods and Results

This paper presents the NTIRE 2025 image super-resolution ($\times$4) challenge, one of the associated competitions of the 10th NTIRE Workshop at CVPR 2025. The challenge aims to recover high-resolution (HR) images from low-resolution (LR) counterparts generated through bicubic downsampling with a $\times$4 scaling factor. The objective is to develop effective network designs or solutions that achieve state-of-the-art SR performance. To reflect the dual objectives of image SR research, the challenge includes two sub-tracks: (1) a restoration track, emphasizes pixel-wise accuracy and ranks submissions based on PSNR; (2) a perceptual track, focuses on visual realism and ranks results by a perceptual score. A total of 286 participants registered for the competition, with 25 teams submitting valid entries. This report summarizes the challenge design, datasets, evaluation protocol, the main results, and methods of each team. The challenge serves as a benchmark to advance the state of the art and foster progress in image SR.

08.
arXiv (CS.CV) 2026-06-16

GeoStream: Toward Precise Camera Controlled Streaming Video Generation

Accurate interactive camera control is essential for video-based world models, but most existing approaches learn camera motion implicitly, leading to inaccurate control under out-of-distribution trajectories. Explicit geometric conditioning improves controllability, but existing methods are non-autoregressive and rely on a static 3D cache built from an initial frame, which becomes ineffective once the viewpoint moves beyond the original frustum. We propose GeoStream, a framework that enables precise metric-scale camera control in autoregressive streaming video generation. Our method maintains a self-refreshing 3D cache that is periodically updated online from the model's own outputs: we estimate depth from the most recently generated frame, unproject to 3D, and reproject into the target view to produce point reprojections as geometric conditioning for subsequent synthesis. By the same principle, the conditioning seen during training is also rendered from the student's own generated frames, yielding a fully on-policy distillation that naturally aligns the train and inference conditioning distributions. Unlike prior work that uses off-policy condition noising, our approach trains the model against the exact error distribution it encounters at inference, mitigating both standard autoregressive drift and the second-order geometric feedback loop that arises when the cache itself is derived from generated outputs. Quantitative and qualitative results show that our approach substantially improves camera controllability.

09.
arXiv (CS.LG) 2026-06-19

Calibrating Generative Models to Feature Distributions with MMD Finetuning

arXiv:2606.19496v1 Announce Type: new Abstract: Generative models can produce individually plausible samples while deviating substantially from a target set in the distribution of key features. For example, a model pretrained on broad drug-like chemical space may generate molecules whose molecular features differ from those of a therapeutic class of interest, such as known antibiotics. Correcting such distributional miscalibration is challenging: direct finetuning on the target set can overfit and does not control which features are matched. To fill this gap, we introduce kernel Calibrating Generative Models (kCGM). kCGM minimizes a maximum mean discrepancy (MMD) between generated and target feature distributions using an unbiased score-function estimator, with KL regularization to remain close to the pretrained model. On a target set of 174 antibiotics, direct finetuning sacrifices chemical validity for feature-distribution matching, whereas kCGM improves target feature matching while increasing validity. We further demonstrate kCGM in protein and DNA generation tasks, showing it can adapt autoregressive, continuous-space diffusion, and discrete diffusion models using only feature-level supervision. Code is available at https://github.com/smithhenryd/cgm.

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

Ensembling Sparse Autoencoders

arXiv:2505.16077v2 Announce Type: replace Abstract: Sparse autoencoders (SAEs) are used to decompose neural network activations into human-interpretable features. Typically, features learned by a single SAE are used for downstream applications. However, it has recently been shown that a single SAE captures only a limited subset of features that can be extracted from the activation space. Motivated by this limitation, we introduce and formalize SAE ensembles. Furthermore, we propose to ensemble multiple SAEs through naive bagging and boosting. In naive bagging, SAEs trained with different weight initializations are ensembled, whereas in boosting SAEs sequentially trained to minimize the residual error are ensembled. Theoretically, naive bagging and boosting are justified as approaches to reduce reconstruction error. Empirically, we evaluate our ensemble approaches with three settings of language models and SAE architectures. Our empirical results demonstrate that, compared to an expanded SAE that matches the number of features in the ensemble, ensembling SAEs improves the reconstruction of language model activations along with SAE stability. Additionally, on downstream tasks such as concept detection and spurious correlation removal, SAE ensembles achieve better performance, showing improved practical utility.

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

Scratched Lenses, Shifted Depth: Passive Camera-Side Optical Attacks

Physical adversarial attacks on vision systems are typically studied through scene manipulation, such as adversarial patches or projections, where the adversary controls what the camera observes. Camera-side attacks using stickers or auxiliary optics have also been explored, but they treat attacks as image-space perturbations from designed patterns. This misses how physical imperfections interact with scene-dependent lighting and optics. We identify a threat: passive lens-side damage that is persistent yet trigger-conditioned, producing optical artifacts that bias geometric inference under particular visual conditions. We instantiate this threat through Scratch-induced Lens Adversarial Streak Hijacking SLASH, a physical-world attack caused by small scratches on a camera lens or protective cover. Scratches interact with bright light sources and specular reflections to create structured streak artifacts that distort depth cues. Since the perturbation is fixed in the optical path but triggered by the scene, it is both persistent and selective. We formulate the attack in optical space, model the scratch pattern as a trigger-conditioned optical channel, and optimize one fixed configuration across diverse viewing conditions. We evaluate SLASH on monocular depth estimation and monocular 3D object detection in digital and real-world settings. Under the fixed-scratch constraint, directional depth shifts reach up to 32% relative error for monocular depth estimation, with consistent effects on monocular 3D object detection. Physical experiments confirm transfer to real camera recordings, inducing depth shifts above the model's natural prediction baseline. These findings reveal an attack surface where benign-looking hardware imperfections act as latent, scene-triggered adversarial mechanisms, challenging assumptions about physical robustness and motivating defenses for secure vision systems.

12.
arXiv (CS.AI) 2026-06-19

Beyond Entropy: Learning from Token-Level Distributional Deviations for LLM Reasoning

arXiv:2606.19771v1 Announce Type: new Abstract: Reinforcement Learning with Verifiable Rewards (RLVR) has significantly advanced Large Language Model (LLM) reasoning; however, it faces a fundamental optimization instability: uniform token updates precipitate entropy collapse, leading to premature convergence to suboptimal strategies, whereas excessive Shannon Entropy maximization can cause entropy explosion, driving blind exploration toward incoherent reasoning chains. To resolve this dichotomy, we introduce the Independent Combinatorial Tokens (ICT) framework, which shifts the optimization focus from scalar uncertainty to the distributional properties of token logits. By leveraging the Jensen-Shannon (JS) divergence between token logits distributions, ICT identifies tokens with distinctive distributional patterns as critical branching points for guiding effective exploration in LLM reasoning. Our theoretical analysis, grounded in both Shannon and second-order Rényi entropy, proves that selectively updating on these tokens regulates policy concentration: it reduces the overall distribution uncertainty measured by Shannon entropy, while controlling probability concentration captured by second-order Rényi entropy. This dual effect prevents over-concentrated token generation from weakening exploration and effectively stabilizes the training landscape. Empirical results demonstrate that updating only the top 10% of unique tokens on Qwen2.5 (0.5B/1.5B/7B) models yields an average pass@4 improvement of 4.58%, with a maximum gain of 14.9%, over GRPO, 20-Entropy, and STAPO baselines across seven benchmarks spanning math, commonsense, and Olympiad-level problems.

13.
arXiv (CS.AI) 2026-06-12

Mod-Guide: An LLM-based Content Moderation Feedback System to Address Insensitive Speech toward Indigenous Ethnic and Religious Minority Communities

arXiv:2606.13397v1 Announce Type: cross Abstract: Language operates as a mechanism of both marginalization and resistance, especially for minority communities navigating insensitive and harmful speech online. As content moderation increasingly depends on large language models (LLMs), concerns arise about whether these systems can recognize culturally insensitive speech-language that disregards or marginalizes the cultural and religious perspectives of historically underrepresented communities, often through implicit erasure, misrepresentation, or normative framing, rather than overt hostility. Focusing on Bangladesh's Hindu and Chakma communities – the country's largest religious and Indigenous ethnic minorities, respectively – this paper investigates the epistemic limits of LLM-based moderation systems and explores methods for incorporating minority perspectives. We co-created a culturally grounded corpus of insensitive speech with community members and integrated their narratives into moderation pipelines using retrieval augmented generation (RAG). Our tool, Mod-Guide, improves LLM sensitivity to minority viewpoints by leveraging contextual cues derived from lived experience. Through mixed-method evaluations involving both minority and majority participants, we demonstrate that RAG-enhanced moderation responses are more contextually accurate and perceived differently across ethnic lines. This work advances research in human-computer interaction, AI ethics, and social computing by foregrounding restorative justice and hermeneutical inclusion in the design of content moderation systems.

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

CuMA: Aligning LLMs with Sparse Cultural Values via Demographic-Aware Mixture of Adapters

As Large Language Models (LLMs) serve a global audience, alignment must transition from enforcing universal consensus to respecting cultural pluralism. We demonstrate that dense models, when forced to fit conflicting value distributions, suffer from Mean Collapse, converging to a generic average that fails to represent diverse groups. We attribute this to Cultural Sparsity, where gradient interference prevents dense parameters from spanning distinct cultural modes. To resolve this, we propose \textsc{CuMA} (Cultural Mixture of Adapters), a framework that frames alignment as a conditional capacity separation problem. By incorporating demographic-aware routing, \textsc{CuMA} internalizes a Latent Cultural Topology to explicitly disentangle conflicting gradients into specialized expert subspaces. Extensive evaluations on WorldValuesBench, Community Alignment, and PRISM demonstrate that \textsc{CuMA} achieves state-of-the-art performance, significantly outperforming both dense baselines and semantic-only MoEs. Crucially, our analysis confirms that \textsc{CuMA} effectively mitigates mean collapse, preserving cultural diversity. Our code is available at https://github.com/Throll/CuMA.

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

A Self Consistency Based Reranking for Narrative Question Answering

Narrative question answering (NQA) is a challenging task in natural language processing that requires models to understand long textual contexts, capture relationships across events, and generate coherent responses. Despite recent advances in pretrained language models, most existing approaches rely on a single decoding output during inference, making them sensitive to generation variability and often resulting in incomplete or inconsistent answers .To address this limitation, we propose a self-ensemble Self-Consistency-Based reranking framework for narrative question answering. The proposed method generates multiple candidate answers for each story-question pair and selects the final answer based on semantic agreement among the generated responses. This allows the model to explore diverse answer formulations while improving robustness through consensus-based selection without requiring modifications to the underlying architecture .The framework combines pretrained and fine-tuned language generation with multi-answer inference and similarity-based reranking. We evaluate the proposed approach on the NarrativeQA dataset using multiple models, including FLAN-T5 (Base and Small) and Pegasus-Large, under both baseline and fine-tuned settings .Experimental results demonstrate that the proposed method consistently improves performance across all models. In particular, FLAN-T5-Base achieves the best overall performance, improving from 82.32% to 86.66% (+4.34%) when combined with self-ensemble inference. Additionally, the largest improvement is observed with Pegasus-Large, which increases from 72.50% to 87.07% (+14.57%), highlighting the effectiveness of the proposed strategy.

16.
arXiv (quant-ph) 2026-06-15

Quantum Simulation of Spin-Dependent Electron Transfer in a Synthetic Chiral Lattice with a Trapped Ion

arXiv:2606.13930v1 Announce Type: new Abstract: Electron transfer through chiral structures can exhibit spin asymmetry, known as the chiral-induced spin selectivity effect, whose microscopic origin remains an open question. While path-interference within the chiral moiety has been proposed as a key mechanism, its experimental validation requires precise and versatile tunability of system parameters. Here we implement a programmable quantum simulation of spin-dependent electron transfer in a donor–chiral-bridge–acceptor model using a trapped ion. The bridge is encoded in internal states of the ion with tunable nearest- and next-nearest-neighbor couplings, while donor and acceptor states are coupled via a spectator bosonic motional mode. We observe spin-dependent interference within the bridge, and further reveal spin-dependence in donor-to-acceptor transfer dynamics, controlled by amplitude and phase of the coupling parameter. Our results identify interference among spin-dependent pathways as a microscopic origin of spin-dependent transfer, and open a route toward quantum simulations of complex chiral lattices with multi-level and bosonic degrees of freedom.

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

UPLOTS: A Unified Pretrained Language Model for Constrained Time-series Generation

arXiv:2606.10466v2 Announce Type: replace-cross Abstract: In time-series generation, existing approaches typically handcraft ortrain a separate model for each dataset, which hinders their scalability and fails to leverage shared temporal structures across domains. To address this fragmentation, we propose UPLOTS, a Unified, Prompt-guided Language model framework fOr constrained Time-Series Generation across diverse domains. Instead of building task-specific models, UPLOTS leverages a single pre-trained transformer backbone guided by learned constraint prompts, enabling on-demand generation with precise pattern control. One key innovation is our dynamic multi-dataset loss re-weighting and prompt-to-pattern mapping, which allows UPLOTS to internalize diverse temporal structures during training and conditionally generate them at inference. We evaluate UPLOTS on four real-world benchmarks and multiple constraint settings, including peak-period, calendar, load-level, and volatility patterns. Additional held-out constraint-combination and downstream forecasting experiments further demonstrate that UPLOTS generalizes beyond the original peak-pattern setting and improves data augmentation under scarce real-data regimes. Our code and baselines are available at anonymous github repo: https://anonymous.4open.science/r/UPLOTS-6C36.

18.
medRxiv (Medicine) 2026-06-17

Multi-strain Probiotics Alter Gut Microbiota and Estrobolome Pathways in Primary Dysmenorrhea

Background: Exact cause of primary dysmenorrhoea is unknown but recent evidence uncovers a potential link between gut dysbiosis and benign gynaecological disorder via disruption of estrobolome. Methods: A randomized controlled trial to investigate the effects of multi-strain oral probiotics on primary dysmenorrhoea has been conducted. This is a secondary analysis comparing the stool microbiome in women with primary dysmenorrhoea and those without (control), and the effects of treatment with probiotics versus placebo. Results: Although microbial richness and evenness were comparable between groups (alpha diversity, p > 0.05), gut microbial community composition differed significantly (Bray Curtis PERMANOVA, p = 0.015), characterised by reduced Bifidobacterium adolescentis and Blautia and enrichment of Faecalibacterium in dysmenorrhoea, alongside condition-specific core taxa. Post-intervention analysis revealed significant shifts in microbial community structure between pre- and post-treatment groups (PERMANOVA, F = 2.11, p = 0.005), with probiotic supplementation inducing more consistent and directed microbiome changes than placebo, without altering alpha diversity (p > 0.05). Functional prediction showed no significant difference in overall beta glucuronidase pathway abundance (p > 0.05); however, dysmenorrhoea was associated with higher abundance of beta glucuronidase producing taxa (MaAsLin2, q < 0.05) that were differentially modulated by probiotic treatment. Conclusion: This discovery provides evidence on the microbial disruption in primary dysmenorrhoea as well as the benefit of probiotics to modulate the intestinal microbiota to improve the condition.

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

Charting the Future of Scholarly Knowledge with AI: A Community Perspective

arXiv:2509.02581v2 Announce Type: replace-cross Abstract: Despite the growing availability of tools designed to support scholarly knowledge extraction and organization, many researchers still rely on manual methods, sometimes due to unfamiliarity with existing technologies or limited access to domain-adapted solutions. Meanwhile, the rapid increase in scholarly publications across disciplines has made it increasingly difficult to stay current, further underscoring the need for scalable, AI-enabled approaches to structuring and synthesizing scholarly knowledge. Various research communities have begun addressing this challenge independently, developing tools and frameworks aimed at building reliable, dynamic, and queryable scholarly knowledge bases. However, limited interaction across these communities has hindered the exchange of methods, models, and best practices, slowing progress toward more integrated solutions. This manuscript identifies ways to foster cross-disciplinary dialogue, identify shared challenges, categorize new collaboration and shape future research directions in scholarly knowledge and organization.

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

Interpretation as Linear Transformation: A Cognitive-Geometric Model of Concepts and Meaning

arXiv:2512.09831v2 Announce Type: replace Abstract: This paper develops a geometric framework for modeling concepts, motivation, and influence across cognitively heterogeneous agents. Each agent is represented by a personalized value space, a vector space encoding the internal dimensions through which the agent interprets and evaluates meaning. Evaluative concepts are formalized as structured vectors, abstract beings, whose transmission is mediated by linear interpretation maps. An abstract being survives communication only if it avoids the null spaces of these maps, yielding a structural criterion for intelligibility, miscommunication, and concept death. Within this framework, I show how conceptual distortion, motivational drift, and the limits of mutual understanding arise from purely algebraic constraints. A central result, the No-Null-Space Leadership Condition, characterizes leadership as a property of representational reachability rather than persuasion or authority. More broadly, the model explains how abstract beings can propagate, mutate, or disappear as they traverse diverse cognitive geometries. The account unifies insights from conceptual spaces, social epistemology, and AI value alignment by grounding meaning preservation in structural compatibility rather than shared information or rationality. I argue that this cognitive-geometric perspective clarifies the epistemic boundaries of influence in both human and artificial systems, and offers a general foundation for analyzing conceptual dynamics across heterogeneous agents.

21.
medRxiv (Medicine) 2026-06-19

Within-host pathogen population diversity predicts treatment response in tuberculosis

Background: Tuberculosis (TB) treatment outcomes remain suboptimal, and standard clinical diagnostics cannot reliably identify patients at high risk of treatment failure or relapse at the time of diagnosis. While within-host Mycobacterium tuberculosis genetic diversity is hypothesized to reflect the viable bacterial burden and adaptive capacity of the infection, its clinical prognostic value remains unknown. Methods: We conducted a prospective cohort study of 364 patients with newly diagnosed, rifampicin-susceptible pulmonary TB in South Africa. Patients received standard 6-month therapy and were monitored for up to two years to ascertain composite unfavorable outcomes (treatment failure, death, or relapse). To accurately detect low-frequency (unfixed) genetic variants and eliminate reference bias artifacts, we mapped medium to high depth short-read sequences against matched, patient-specific long-read assemblies. The association between baseline pathogen genetic diversity and clinical outcomes was evaluated using multivariable Cox proportional-hazards models. Results: After bioinformatic filtering, true unfixed variants were relatively rare but significantly enriched in genes mediating pathogen adaptation and drug tolerance, including transporter proteins and two-component regulatory systems. Within-host bacterial genetic diversity (i.e., the total number of unfixed variants) ranged from 0-20, with a median of 1 per patient. In survival analysis adjusting for known clinical risk factors–including HIV status, prior TB, baseline smear positivity, and radiographic lung involvement–baseline within-host genetic diversity emerged as a strong, independent predictor of unfavorable treatment outcomes. For patients with greater than 3 unfixed variants at diagnosis, each increase of 5 unfixed variants was associated with more than double the risk of a composite unfavorable outcome (adjusted Hazard Ratio, 2.36; 95% CI, 1.27 to 4.39; p=0.007). Conclusions: Baseline within-host pathogen genetic diversity is an independent predictor of unfavorable TB treatment outcomes. As sequencing becomes increasingly integrated into routine diagnostics, quantifying unfixed variants is an accessible approach that promises to risk-stratify patients and guide the duration of individualized regimens.

22.
arXiv (CS.LG) 2026-06-17

Broadcast Product: Redefining Shape-aligned Element-wise Multiplication and Beyond

arXiv:2409.17502v2 Announce Type: replace Abstract: Broadcast operations are widely used in scientific computing libraries, yet their mathematical formulation is often implicit and inconsistently represented in machine learning literature. This problem frequently leads to invalid equations when element-wise products are written despite mismatched tensor shapes. In this paper, we formalize such operations by introducing the broadcast product $\boxdot$, which explicitly extends the Hadamard product through shape-aligned element duplication. We provide a rigorous definition of the broadcast product, analyze its algebraic properties, and show how it can be expressed using standard linear algebra. Building on this framework, we formulate least-squares problems and sketch a proof-of-concept broadcast decomposition. As a preliminary illustration, we show that the formalism enables a new family of decompositions with distinct structural properties from conventional tensor decompositions. This work establishes a mathematical foundation for broadcast-aware tensor operations, connecting practical implementations with rigorous tensor analysis.

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

CCKS: Consensus-based Communication and Knowledge Sharing

arXiv:2606.12281v1 Announce Type: cross Abstract: In Decentralized Training and Decentralized Execution (DTDE) for cooperative Multi-Agent Reinforcement Learning (MARL), action-advising-based knowledge sharing promotes interpretable and scalable cooperation among agents. However, current action advising approaches often adhere too much to the teacher's guidance without evaluating teacher-student compatibility, which causes excessive advising, suboptimal stability, and degraded performance. To overcome these challenges, this paper presents a Consensus-based Communication and Knowledge Sharing (CCKS) framework, which allows agents to adopt recommendations based on consensus-derived constraints and to follow the teacher's instructions more smartly. This mechanism enables agents to balance exploration and learning from experienced teachers, improving overall performance. The key is the consensus model construction, for which we propose to employ contrastive learning to construct consensus models based on local observations in the agents' training phase. In action selection, agents score and choose actions based on consensus and shared knowledge. Designed as a plug-and-play solution, CCKS integrates seamlessly with existing DTDE algorithms. Experiments conducted in the Google Research Football environment and the complex StarCraft II Multi-Agent Challenge demonstrate that the integration with CCKS significantly improves cooperation efficiency, learning speed, and overall performance compared with current DTDE baselines. The code is available at https://github.com/yuanxpy/CCKS.

25.
arXiv (CS.LG) 2026-06-15

Cluster LOCO: Feature Importance For Interpreting Clusters

arXiv:2606.14592v1 Announce Type: cross Abstract: Clustering is widely used for exploratory analysis and scientific discovery, driving insights from market segmentation to biological data analysis, but its outputs can be difficult to interpret, audit, and reproduce as modern datasets become increasingly large and complex. Reliable use of clustering requires understanding which features drive the discovered structure, yet feature-level explanations for clustering remain scarce compared with methods in supervised learning. Furthermore, existing clustering feature importance scores are often tied to specific algorithms and data assumptions. To address these challenges, we propose Cluster LOCO (Leave-One-Covariate-Out), a family of model-agnostic feature importance scores for clustering. Cluster LOCO is built on feature occlusion and clustering generalizability, defined as whether cluster labels learned on one subset of the data can be accurately predicted on held-out samples. For any chosen clustering algorithm, Cluster LOCO quantifies a feature's importance by measuring how much its removal degrades generalizability. We first introduce Cluster LOCO-Split, which relies on data splitting, and then extend it to Cluster LOCO-MP, a minipatch ensemble-based version designed for large-scale data. Across synthetic simulations and an application to cell-type discovery in single-cell transcriptomics, we show that Cluster LOCO more reliably recovers informative features than existing clustering feature importance methods.