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

Graph Reduction in Multirelational Networks: A Spreading-Oriented Reduction Benchmark

arXiv:2606.12581v1 Announce Type: cross Abstract: Real-world networks are inherently incomplete, noisy, and dynamically evolving, making it difficult to capture all actors and their relationships. Their scale often renders direct analysis computationally demanding. While influence maximisation (IM) has been widely studied, the role of graph reduction as a preprocessing step, and its impact on IM accuracy, remains underexplored. In this work, we introduce the Spreading-Oriented Reduction Benchmark (SORB), an open-source, standardised framework for systematically evaluating IM models across diverse task settings. SORB provides an extensible pipeline operating on a representative collection of real-world networks, including single- and multilayer structures, and accounts for graph reduction directly into the evaluation process. This design shifts the focus from analysing IM algorithms in isolation to quantifying how graph reduction alters predictive performance. Using SORB, we study the effects of sparsification and coarsening across multiple IM scenarios. Our results show that the impact of reduction is strongly dependent on both the network type (single-layer vs. multirelational) and the downstream task ($Gain@k$ vs. $\mathrm{AUC}_{\mathrm{cutoff}}$): sparsification preserves seed set quality on single-layer networks, whereas flattened multilayer networks exhibit systematic ranking degradation regardless of reduction strategy. These findings highlight the importance of reduction-aware, multi-task evaluation when studying spreading processes in complex networks.

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

Beyond English: Uncovering the Multilingual Gap in Vision-Language-Action Models

Vision-Language-Action models have recently demonstrated promising capabilities in learning generalist robot policies from large-scale multimodal data. However, most existing VLA systems are trained and evaluated primarily with English instructions, leaving their ability to understand and execute instructions in other languages largely unexplored. While the underlying large language models often possess multilingual capabilities, it remains unclear whether these multilingual capabilities transfer to VLAs during training. In this work, we present the first systematic study of multilingual instruction following in VLA models. We first construct multilingual instructions by extending existing benchmarks with translations of their instructions. Using these instructions, we evaluate several representative VLA models across a range of tasks in simulation settings. Our experiments reveal a significant multilingual gap: models trained primarily on English instructions exhibit substantial performance degradation when evaluated on other languages, even when the underlying language backbone is multilingual. We provide several findings and analyses to understand the multilingual gap. Cross-lingual transfer behavior analysis shows that performance drops correlate with both instruction understanding and action execution. Representation analyses suggest that multilingual instruction-caused representation shifts may contribute to the multilingual gap. Motivated by these findings, we further explore strategies to improve multilingual performance in VLAs. We propose a simple yet effective multilingual fine-tuning approach, Multilingual Principal Component Alignment, which leverages Principal Component Analysis to get the principal component subspace and align projected multilingual representations, effectively reducing the multilingual performance gap.

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

XPASS-Vis: A Dataset for Cross-Domain Personalized Image Aesthetic Assessment

Personalized image aesthetic assessment (PIAA) seeks to model, at the individual level, the subjective nature of aesthetic judgments toward artworks and photographs. Aesthetic preference is known to be both deeply personal and partially consistent across visual domains. Yet existing PIAA datasets and methods are largely confined to a single domain, or provide too few samples per annotator within each domain to enable personalization across domains. Consequently, the cross-domain generalization of personalized aesthetic preferences remains largely unexplored. To address this gap, we introduce XPASS-Vis, the first dataset explicitly designed for cross-domain PIAA. XPASS-Vis comprises 6,526 stimuli from three visual domains – art, fashion, and landscape – rated by 129 annotators, yielding 87,836 user-stimulus interactions, each annotated with an overall aesthetic score and nine aesthetic-emotion ratings. Notably, each annotator rated more than 200 stimuli per domain, providing sufficient per-domain coverage to support personalization both within and across domains. Moreover, we establish baseline models for cross-domain PIAA under unsupervised domain adaptation (UDA), where a model trained on a labeled source domain is transferred to an unlabeled target domain. A systematic evaluation of representative UDA approaches shows that the best-performing method recovers approximately 60\% (Spearman's $\rho$ = .28) of the supervised upper bound under a fully unsupervised setting. This provides encouraging evidence that personalized aesthetic preferences are, to a meaningful extent, transferable across visual domains. At the same time, a substantial gap remains, highlighting the need for PIAA-specific adaptation strategies. XPASS-Vis and the accompanying baselines provide a foundation for future research on cross-domain PIAA. All datasets and code will be made publicly available upon acceptance.

04.
arXiv (CS.LG) 2026-06-12

GenAutoML: An Agentic Framework for Dynamic Architecture Generation and Optimization in Time-Series Analysis

arXiv:2606.05860v2 Announce Type: replace Abstract: Designing neural architectures for time-series forecasting and anomaly detection remains a resource-intensive task that often requires substantial domain expertise. Traditional Automated Machine Learning (AutoML) systems typically rely on static, predefined search spaces, limiting their ability to adapt to diverse data characteristics. We present GenAutoML, an agentic framework that leverages Large Language Models (LLMs) as neural architects to bridge natural-language requirements and executable PyTorch implementations. The framework incorporates a Sandboxed Reflection Loop for autonomous code refinement and a Signature-Aware Runtime that enforces architectural consistency and execution safety. To improve robustness under non-stationary conditions, we further introduce a Dynamic Reversible Instance Normalization (Dyn-RevIN) wrapper. Experiments on the ETTh1, ETTm1, and Weather benchmarks demonstrate that GenAutoML can dynamically generate task-specific neural architectures tailored to dataset characteristics. Among the generated models, WaveInterferenceNet achieves inference latency below 0.01 ms per sample while maintaining competitive predictive performance. By emphasizing computational efficiency, architectural adaptability, and stable optimization behavior, GenAutoML enables the creation of ultra-lightweight neural networks suitable for resource-constrained and latency-sensitive Edge AI deployments.

05.
arXiv (CS.CL) 2026-06-25

Natural Ungrokking: Asymmetric Control of Which Rules Survive Pretraining

Midway through an ordinary pretraining run, a small language model learns the pronoun-gender rule: cued with a girl's name ("Sue cried because"), it resolves the next pronoun to she, generalizing to held-out probes (0.94 by step 925). By step 3,500 the same model scores near zero on the same probes, although the rule's evidence is still in the training data. We call this within-run reversal natural ungrokking: the corpus decides, with no trace in the loss curve, which learned rules a model keeps. Which rules survive is predictable from one corpus statistic: how often the training stream shows the rule winning. Across un-intervened runs (two corpora, three budgets, three seeds), support frequency decides a rule's fate; the data-to-parameter ratio only modulates how deeply a doomed rule falls. The same emerge-then-collapse dynamics appear in public Pythia checkpoints, collapse depth ordered by model scale as predicted. The forgetting is a displacement: a competing surface pattern out-competes the rule, and the log-probability margin between them crosses zero within 100 training steps of the behavioral collapse. Control over this fate is asymmetric: the same edit that destroys a rule on demand cannot restore it. Flipping support to counter-evidence in place kills the rule with monotone dose-response in two unrelated rules; but injecting support back, even to 450 times the level that naturally sustains it, buys no recovery. Every confirmatory threshold and prediction was pre-registered before the data it governed was read.

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

Unraveling Syntax: Language Modeling and the Substructure of Grammars

While language models achieve impressive results, their learning dynamics are far from understood. Many domains of interest – such as natural language syntax, coding languages, arithmetic – are captured by context-free grammars (CFGs). In this work, we extend prior work on neural language modeling of CFGs in a novel direction: how language modeling behaves with respect to CFG substructure, namely subgrammars. We define subgrammars, and prove a set of fundamental theorems connecting language modeling and subgrammars. We show that language modeling loss recurses linearly over its top-level subgrammars; applied recursively, the loss decomposes into losses for "irreducible" subgrammars. Under additional assumptions, and empirically, parametrized models learn subgrammars in parallel, unlike children who first master simple substructures. We find that subgrammar pretraining can improve final performance, but only for tiny models relative to the grammar, while alignment analyses show that pretraining consistently leads to internal representations that better reflect the grammar's substructure.

07.
arXiv (CS.AI) 2026-06-24

World Models in Pieces: Structural Certification for General Agents

arXiv:2606.24842v1 Announce Type: new Abstract: In the big-world regime, agents cannot be universally capable and their ability is inevitably specialized across a world model in pieces. Consequently, standard uniform guarantees fail to distinguish between the understanding of critical bottlenecks and irrelevant failures. We first formalize this limitation by proving that general agents are not universal, rendering standard worst-case analysis uninformative. To overcome this, we introduce structural certification, a transition-local framework that maps bounded goal-conditioned performance to entry-wise guarantees on the agent's internal world model. Our main contribution is constructive. We provide algorithms that filter specific transitions using deep compositional goals and prove that a general agent on these goals has a structural world model with a $\mathcal{O}(1/n) + \mathcal{O}(\delta)$ error bound. Conversely, this bound is tight in the small-$\delta$ regime, whose existence is explicitly guaranteed by our certification. These results enable the certifiable deployment of general agents by localizing the specific transitions where long-horizon planning is reliable.

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

Reason, Then Re-reason: Cross-view Revisiting Improves Spatial Reasoning

Spatial reasoning from egocentric videos is inherently challenging because the observable evidence is constrained by the camera trajectory. Existing methods rely on single-turn inference, forcing models to resolve geometric ambiguity through semantic priors rather than verifiable evidence. We argue that spatial reasoning should be revisitable: conclusions formed under limited evidence should remain open to revision when complementary viewpoints become available. Building on this insight, we propose Reason, then Re-reason (ReRe), a training-free, inference-time framework with two phases: in the Reason Phase, an MLLM forms a spatial hypothesis from the original video; in the Re-reason Phase, it verifies or revises the hypothesis by observing a synthesized novel-view video. To enable effective cross-view revisiting, we design a Geometry-to-Video pipeline that renders strategically complementary novel views from predicted 3D geometry. These views feature an elevated, oblique perspective with scene-spanning coverage, while preserving the MLLM's native video interface without architectural modifications. Extensive evaluations on VSI-Bench and STI-Bench demonstrate that ReRe substantially boosts open-source MLLMs to rival proprietary state-of-the-art performance. Project page: https://zhenjiemao.github.io/ReRe/

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

Provably Efficient Regularized Online RLHF with Generalized Bilinear Preferences

arXiv:2602.23116v3 Announce Type: replace Abstract: We consider the problem of regularized best-response max-regret minimization in online RLHF under general preferences and bandit feedback. While various regularizers are utilized to robustify alignment, known polylogarithmic regret guarantees remain heavily specific to KL. To investigate whether such fast rates extend beyond KL, we adopt the Generalized Bilinear Preference Model (GBPM) – capturing intransitive preferences over $d$-dimensional item-wise features via a rank-$2r$ skew-symmetric matrix – to isolate the impact of generic regularization. Crucially, under GBPM, we prove that the dual gap of any greedy policy is bounded by the squared estimation error, derived using only strong convexity and skew-symmetry. Under a feature coverage assumption, we establish a generic polylogarithmic regret of $\tilde{\mathcal{O}}(\eta d^4 C_{\min}^{-1} (\log T)^2 \wedge d^2 C_{\min}^{-1/2} \sqrt{T})$ with Greedy Sampling, and a dimension-wise improved regret (for well-conditioned arm-sets) of $\tilde{\mathcal{O}}(C_{\min}^{-2} \sqrt{\eta r T} \wedge r^{1/3} C_{\min}^{-4/3} T^{2/3})$ with Explore-Then-Commit, where $\eta^{-1}$ is the regularization coefficient, $T$ is the time horizon, and $C_{\min}$ is an arm-set dependent quantity. This demonstrates that ``fast'' regrets are not KL-specific, but rather a fundamental consequence of generic strongly convex geometry.

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

Early Anomaly-Onset Detection based on Wigner–Ville Distribution Slice Spectra: A Transmission-Grid Test Case

arXiv:2606.15856v1 Announce Type: cross Abstract: Operational disturbance monitoring in power networks requires decisions to be made from waveform windows as they arrive, rather than from completed records after the event. This study evaluates full-vector Wigner–Ville Distribution Slice (WVDS) spectra for sequential anomaly-onset detection in high-voltage grid-voltage waveforms. The approach keeps the bilinear midpoint interaction structure of the Wigner–Ville distribution and represents each 128-sample voltage window by a 128-dimensional slice spectrum, avoiding manually selected fault-frequency markers. WVDS is used with a baseline-normalized deviation (BND) score and is compared against the BND of Fast Fourier Transform (FFT-BND), raw-window autoencoders, FFT autoencoders, and WVDS autoencoders under the same thresholding and three-window persistence rule. A synthetic autoencoder–clustering teacher is used to select RTE fault records that start from an initially normal region and then transition to anomalous behavior. On the filtered test set, FFT-BND achieves the highest sensitivity, whereas WVDS-BND provides the lowest false-alarm operating point, reducing record-level pre-onset false alarms to 0.69%. The autoencoder comparison follows the same selectivity pattern: WVDS reconstruction decreases false alarms relative to FFT reconstruction but misses more examples. The results indicate that preserved WVD cross-term information can form a selective representation for online grid-waveform anomaly monitoring when false alarms are costly.

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

Focus, Align, and Sustain: Counteracting Gradient Dilution in Incremental Object Detection

Adapting Detection Transformers to Incremental Object Detection (IOD) poses a systemic challenge, as set-based optimization is inherently destabilized by sequential learning. In this work, we identify Gradient Dilution as the root cause of performance degradation, wherein optimization signals required to preserve old knowledge are progressively weakened. This phenomenon manifests as a cascading erosion of preservation gradients in magnitude, direction, and support coverage, driven by three tightly coupled factors: Signal Dispersion, where foreground gradients are overwhelmed by background noise; Assignment Drift, where stochastic query-target matching induces inconsistent gradient trajectories; and Support Attrition, where gradients from retained samples insufficiently cover the old-class feature space, weakening decision boundaries under interference from new classes. To counteract this, we propose FAS, a unified framework that Focuses, Aligns, and Sustains gradient flow throughout incremental learning. Specifically, we introduce prior-injected queries to focus discriminative signals by filtering background interference at the source. We further propose deterministic anchor distillation to align query-target assignments and enforce semantic consistency across stages under unstable matching. Finally, we devise manifold-support replay to sustain distributional support of old classes, counteracting representational erosion induced by continual updates. Extensive experiments show that FAS restores robust optimization dynamics and outperforms state-of-the-art methods, achieving over 5.0 AP improvement in the challenging 40+10x4 incremental setting.

12.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

Authors:

Migratory cells tend to have soft nuclei that deform and penetrate narrow spaces1,2. Extensive nuclear deformation during migration can cause nuclear-envelope rupture and DNA damage in cancer cells, which may contribute to malignant transformation during tumour progression3–6. However, the importance of DNA damage in physiological migration is less well understood. Here we demonstrate that the migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-stranded breaks (DSBs) due to mechanostress during passage through narrow interstitial spaces. In contrast to many other migratory cells, these DSBs occur without detectable nuclear envelope rupture. Confined migration increases topoisomerase-IIβ covalently bound DSBs, and these lesions are repaired through non-homologous end-joining during brain development without causing cell death. Genome sequencing revealed that DSBs tend to occur at transcriptionally inactive regions. The deletion of ligase IV at the onset of neuronal migration leads to persistent DSB accumulation in cerebellar neurons with moderate transcriptional changes in genes related to synaptic function, neuronal development and stress and immune responses. The mutant mouse develops mild motor deficits in later life, suggesting that the DNA damage generated during normal brain development poses a potential disease risk if left unrepaired. The migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-strand breaks due to mechanostress during passage through narrow interstitial spaces.

13.
arXiv (quant-ph) 2026-06-17

Optimal Calibration of Quantum Network Links

arXiv:2606.18167v1 Announce Type: new Abstract: The reliable distribution of entanglement is essential for the effective operation of quantum networks. Due to fundamental differences between quantum and classical communication systems, it is necessary to develop specialised algorithms and protocols that also account for quantum-specific constraints. In this work, we focus on the issue of recalibration. As suggested by recent experimental studies, the process of local entanglement generation in a quantum link degrades over time due to environmental changes that have to be estimated and compensated via a calibration operation, during which the link is not available. Therefore, in such a quantum network, every link alternates between an activation period, during which it operates normally, and a calibration period, during which it cannot participate in the end-to-end entanglement distribution, thereby creating a trade-off between link quality (the fidelity of generated pairs, which decays during activation) and availability (the fraction of time the link is usable, which calibration reduces). We develop analytically a protocol for optimally assigning activation periods to each link in linear quantum repeater chains, subject to any general end-to-end fidelity requirements and local initial fidelity thresholds. Building on this foundation, we extend to general quantum networks, where multiple paths may cross at common links, proposing a heuristic approach evaluated in simulations and compared with a benchmark, numerical approach, and theoretical bounds.

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

Shapley-Inspired Feature Weighting in $k$-means with No Additional Hyperparameters

arXiv:2508.07952v2 Announce Type: replace Abstract: Clustering algorithms often assume all features contribute equally to the data structure, an assumption that usually fails in high-dimensional or noisy settings. Feature weighting methods can address this, but most require additional parameter tuning. We propose SHARK (Shapley Reweighted $k$-means), a feature-weighted clustering algorithm motivated by the use of Shapley values from cooperative game theory to quantify feature relevance, which requires no additional parameters beyond those in $k$-means. We prove that the $k$-means objective can be decomposed into a sum of per-feature Shapley values, providing an axiomatic foundation for unsupervised feature relevance and reducing Shapley computation from exponential to polynomial time. SHARK iteratively re-weights features by the inverse of their Shapley contribution, emphasising informative dimensions and down-weighting irrelevant ones, and is equivalent to replacing the arithmetic mean of feature dispersions with their harmonic mean. Experiments on synthetic and real-world data sets show that SHARK consistently matches or outperforms existing methods, achieving superior robustness and accuracy, particularly in scenarios where noise may be present. Software: https://github.com/rickfawley/SHARK.

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

Towards Mitigating Hallucinations in Large Vision-Language Models by Refining Textual Embeddings

Hallucinations in Large Vision-Language Models (LVLMs) remain a persistent challenge, often stemming from inadequate integration of visual information during multimodal reasoning. A key cause is the model's over-reliance on textual priors and underutilization of visual cues, leading to outputs that are linguistically fluent but visually inaccurate. For example, given an image of an empty kitchen countertop, an LVLM might hallucinate a "bowl of fruit" or "cup of coffee", relying on language associations rather than visual evidence. Most LVLMs incorporate visual features by appending them to the input stream of a pre-trained LLM and training on large-scale vision-language datasets. Our systematic analysis reveals that this strategy often leads to over-dependence on textual information due to the inherent bias of LLMs towards language-dominant representations. This imbalance skews attention towards the text over visual content, weakening the model's ability to ground outputs in visual inputs. To address this, we propose a simple yet effective visual feature incorporation method that encourages the model to learn visually-informed textual embeddings distinct from those of the base LLM and promotes a more balanced attention distribution. Experimental results across multiple hallucination benchmarks demonstrate that our method significantly reduces hallucinations and fosters more balanced multimodal reasoning. Notably, our approach achieves substantial gains, including +9.33% on MMVP-MLLM, +2.99% on POPE-AOKVQA, up to +3.4% on Merlin, and +3% on the hard-data split of HallusionBench.

17.
arXiv (CS.AI) 2026-06-25

Lightweight PCGAE-Net: Parallel CrossGate Attention and Bottleneck AutoEncoder for Efficient 5G Channel Prediction

arXiv:2606.25401v1 Announce Type: cross Abstract: Accurate channel state information (CSI) prediction is essential for proactive beamforming and resource management in 5G massive MIMO systems, yet the deployment of high-accuracy transformer-based predictors on base-station hardware remains challenging because the most capable models carry upwards of 30\,M parameters. This paper introduces Lightweight PCGAE-Net, which addresses the efficiency problem not by post-hoc compression but by correcting two architectural flaws in the current state of the art. The first is a sequential attention ordering bias: in CS3T-UNet, group-wise temporal attention (GTA) always operates on features that have already been transformed by cross-shaped spatial attention (CSA), distorting what temporal information GTA can capture. We remove this dependency by routing both attention modules to the same layer-normalized input and combining their independent outputs through a learned per-channel sigmoid CrossGate. The second flaw is an uncompressed bottleneck: applying full self-attention at the deepest encoder stage, where channel depth reaches $4C$, is quadratically expensive and carries redundant features. A Bottleneck AutoEncoder (BAE) with $1\times1$ convolutions halves this depth and uses an auxiliary reconstruction loss to prevent information collapse. Wrapping these components inside a shallower encoder-decoder with frequency-domain dimensionality reduction ($N_f\!=\!32$, $C\!=\!48$) produces a model with just 8.54\,M parameters – 58\% fewer than the CS3T-UNet baseline – that outperforms it by up to 3.26\,dB at 5\,km/h and 6.0\,dB at 9\,km/h in single-step prediction on QuaDriGa dataset.

18.
arXiv (CS.CL) 2026-06-11

PRInTS: Reward Modeling for Long-Horizon Information Seeking

Information-seeking is a core capability for AI agents, requiring them to gather and reason over tool-generated information across long trajectories. However, such multi-step information-seeking tasks remain challenging for agents backed by language models. While process reward models (PRMs) can guide agents by ranking candidate steps at test-time, existing PRMs - designed for short reasoning with binary judgment - cannot capture richer dimensions of information-seeking steps, such as tool interactions and reasoning over tool outputs, nor handle the rapidly growing context in long-horizon tasks. To address these limitations, we introduce PRInTS, a generative PRM trained with dual capabilities: (1) dense scoring based on the PRM's reasoning across multiple dimensions of step quality (e.g., interpretation of tool outputs, tool call informativeness) and (2) trajectory summarization that compresses the growing context while preserving essential information for step evaluation. Extensive evaluations across FRAMES, GAIA (levels 1-3), and WebWalkerQA (easy-hard) benchmarks on multiple models reveal that best-of-n sampling with PRInTS enhances information-seeking in open-source models as well as specialized agents, matching or surpassing frontier models with a much smaller backbone agent and outperforming other strong reward modeling baselines.

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

Model Collapse Is Not a Bug but a Feature in Machine Unlearning for LLMs

arXiv:2507.04219v5 Announce Type: replace-cross Abstract: Current unlearning methods for LLMs optimize on the private information they seek to remove by incorporating it into their fine-tuning data. We argue this not only risks reinforcing exposure to sensitive data, but also fundamentally contradicts the principle of minimizing its use. As a remedy, we propose a novel unlearning method-Partial Model Collapse (PMC), which does not require unlearning targets in the unlearning objective. Our approach is inspired by recent observations that training generative models on their own generations leads to distribution collapse, effectively removing information from model outputs. Our central insight is that model collapse can be leveraged for machine unlearning by deliberately triggering it for data we aim to remove. We theoretically analyze that our approach converges to the desired outcome, i.e. the model unlearns the data targeted for removal. We empirically demonstrate that PMC overcomes four key limitations of existing unlearning methods that explicitly optimize on unlearning targets, and more effectively removes private information from model outputs while preserving general model utility. Overall, our contributions represent an important step toward more comprehensive unlearning that better aligns with real-world privacy constraints. Code available at https://www.cs.cit.tum.de/daml/partial-model-collapse/.

20.
bioRxiv (Bioinfo) 2026-06-20

Ribosomes are covered by a coat of flexible protein fragments

Ribosomal proteins contain flexible terminal regions that are averaged out during electron density reconstructions, rendering them absent from experimental models derived by X-ray crystallography or cryogenic electron microscopy. These flexible protein fragments (FPFs) collectively form an invisible coat on the ribosome surface whose presence has been systematically overlooked. Here we analysed FPFs from 36 ribosomes spanning bacteria, eukaryotes, and mitochondria. We found that mitoribosomes harbour the most numerous and longest FPFs. Structural predictions confirmed that FPFs are predominantly disordered across all ribosome classes. Comparison of FPF amino acid composition against proteome-wide background frequencies revealed strong and domain-specific compositional biases. The balance between arginine and lysine content tracks the cardiolipin content of the membrane each ribosome class contacts. The arginine enrichment in mitoribosomal FPFs may additionally reflect selection arising from the RNA-rich environment of mitochondrial RNA granules, membraneless condensates where mitoribosomes are assembled. FPFs are uniformly depleted in aromatic residues, arguing against protein-driven liquid–liquid phase separation propensity. Our findings suggest that the flexibly tethered coat is a highly functional intrinsic part of all ribosomes.

21.
medRxiv (Medicine) 2026-06-22

Paired plasma and EV-enriched plasma proteomics reveal nonredundant sepsis-associated host-response signatures in critical illness

Background: Plasma proteomics may identify host-response signatures in sepsis, but it is unclear whether extracellular vesicle (EV)-enriched plasma provides distinct or redundant information compared with plasma. We compared paired plasma and EV-enriched plasma proteomes in critically ill patients with sepsis and critically ill non-sepsis controls (CINS). Methods: In this prospective observational study, paired plasma and EV-enriched plasma samples were analyzed from 56 critically ill adults, including 40 patients with sepsis and 16 CINS patients. Protein abundance was quantified using liquid chromatography-tandem mass spectrometry. Analyses compared proteomic depth, protein overlap, global concordance between compartments, and differential protein abundance between CINS and sepsis. Exploratory Gene Ontology enrichment was performed as a supplementary analysis. Results: EV-enriched plasma expanded proteomic detection, identifying 2,476 filtered proteins compared with 506 in plasma. Only 386 proteins were detected in both compartments, while 2,090 were unique to EV-enriched plasma and 120 were unique to plasma. Among shared proteins, plasma and EV-enriched plasma showed modest global concordance across critically ill patients (Spearman coeff = 0.322, p = 9.19 x 10^-11), with similar findings in sepsis alone. Differential abundance analysis identified 11 sepsis-associated proteins in plasma and 22 in EV-enriched plasma. Only SAA1, SAA2, and IGFBP6 were significant in both compartments. Exploratory pathway analysis supported acute-phase and inflammatory enrichment in plasma sepsis-associated proteins, while EV-enriched signals were directionally plausible but did not meet prespecified FDR thresholds. Conclusion: Plasma and EV-enriched plasma proteomics capture related but nonredundant sepsis-associated host-response information in critically ill patients.

22.
arXiv (CS.LG) 2026-06-11

Data-Driven Dynamic Assortment in Online Platforms: Learning about Two Sides

arXiv:2606.11118v2 Announce Type: replace Abstract: We study a dynamic assortment problem on a two-sided service platform with incomplete information and heterogeneous customers in a discrete-time setting. In each period, a customer arrives seeking service, and the platform chooses an assortment of sellers to display. The customer then proposes a transaction to at most one seller in the assortment according to a multinomial logit choice model. After a fixed number of periods, sellers review the proposals they have received and each chooses at most one customer according to another multinomial logit choice model, after which the cycle repeats. A key challenge is that the platform does not know the choice-model parameters of either customers or sellers in advance. To our knowledge, this is the first study of a dynamic assortment problem in which both sides' choice parameters are unknown. We develop a data-driven algorithm that learns these parameters while optimizing the platform's objective over time. We evaluate performance using regret, which measures revenue loss relative to a clairvoyant benchmark that knows all parameters and customer arrivals in advance. We show that the algorithm's worst-case regret grows polylogarithmically over time, and we derive a matching lower bound, establishing its rate optimality.

23.
bioRxiv (Bioinfo) 2026-06-14

Generative design of antigen-specific T-cell receptor sequences with a conditional diffusion model

T cell receptor (TCR)-based immunotherapy holds immense potential for treating cancers and infectious diseases, where highly antigen-specific TCR recognition is crucial for adaptive immunity against tumors and pathogens. Engineering or de novo generation of the complementarity-determining region 3 (CDR3) loops of TCRs using artificial intelligence offers a powerful alternative to designing reactive TCRs rather than laborious experimental screening. However, current in silico approaches are constrained by weak conditional guidance, limited flexibility, and a lack of rigorous functional validation. To address these limitations, we introduce TCRDiff, a generative diffusion framework for designing antigen-specific TCRs conditioned on peptide-MHC (pMHC) targets and germline-encoded variable genes. By leveraging pre-trained knowledge from massive T-cell repertoires and TCR-pMHC recognition data, TCRDiff generates CDR3{beta} sequences with state-of-the-art fidelity to native binding TCRs through a denoising diffusion process. Furthermore, incorporating the interface geometry features generated TCR-pMHC complexes with superior structural plausibility. As a proof of concept, we deployed TCRDiff in a systematic pipeline to design candidate TCRs for immunotherapy. In vitro activation assays validated that TCRDiff-generated TCRs specifically recognize the MAGE-A3 epitope with minimized off-target cross-reactivity. Together, TCRDiff establishes a powerful, validated computational paradigm to accelerate the development of TCR-based immunotherapies.

24.
arXiv (CS.CL) 2026-06-17

Non-negative Elastic Net Decoding for Information Retrieval

Dense retrieval has become the dominant paradigm in information retrieval, in which each document is scored against a query by the inner product of their vector embeddings, and the top-$k$ documents by score are retrieved for this query. However, since each document's score depends solely on the embedding of the query and itself, the retrieval process is oblivious to the content of the entire corpus. Therefore, dense retrieval cannot avoid selecting semantically similar documents from the corpus, which may result in a non-diverse, redundant set of retrieved documents. To this end, we approach retrieval as a joint decoding problem, in which documents are selected as a set with regard to the context of the rest of the corpus. To achieve this, we propose Non-Negative elastic Net (NNN) decoding, which selects documents whose embeddings jointly reconstruct the query embedding as a sparse non-negative linear combination. Our main theoretical result establishes a strict separation between dense retrieval and NNN decoding. For any corpus, every query correctly handled by dense retrieval is also handled by NNN decoding, while on corpora containing correlated documents, NNN decoding additionally handles queries that dense retrieval cannot. Experimental results indicate that applying NNN decoding to frozen embeddings trained for inner-product scoring yields consistent improvements across several benchmarks. Moreover, we introduce an end-to-end training procedure which optimizes the embeddings for NNN decoding, producing significant performance gains surpassing in all metrics and benchmarks compared to dense retrieval. Our work establishes a new paradigm for leveraging dense embeddings in information retrieval, beyond the standard practice of inner-product scoring.

25.
Nature Medicine 2026-06-08

Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants

Although the beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in heart failure (HF) have been well established, it is unknown whether SGLT2 inhibition confers benefit in carriers of rare variants in cardiomyopathy-associated genes. Here we evaluated whole-exome sequencing data from the randomized DECLARE-TIMI 58 trial, in which adults with type 2 diabetes and increased cardiovascular risk were randomized to dapagliflozin or placebo treatment. Pathogenic or likely pathogenic variants (P/LP) in high-confidence cardiomyopathy genes were identified, and treatment effects on hospitalization for HF (HHF) were compared between carriers of such variants and noncarriers. Among 12,685 patients for whom sequence data were obtained, 121 carried a cardiomyopathy variant (76 dilated cardiomyopathy, 25 hypertrophic cardiomyopathy and 25 arrhythmogenic cardiomyopathy). Over a median follow-up of 4.2 years, dapagliflozin lowered the risk of HHF more strongly in carriers (hazard ratio 0.18, 95% confidence interval 0.04–0.86) than in noncarriers (hazard ratio 0.70, 95% confidence interval 0.57–0.86; P interaction 0.03). Absolute risk reduction was 13.0% in carriers and 1.0% in noncarriers (P interaction 0.03). Most carriers (82%) had no prior HF, and in carriers without prior HF, treatment with dapagliflozin reduced the absolute risk of HHF by 12.8%, compared with a reduction of 0.6% in noncarriers (P interaction 0.01). The findings from this cohort of older and high-risk patients raise the possibility that SGLT2 inhibitor treatment should be started early to prevent HF in individuals who carry P/LP cardiomyopathy variants. These results need to be confirmed in a prospective, dedicated trial of preventive HF treatments in carriers of P/LP cardiomyopathy-associated variants. In a whole-exome sequencing analysis, the beneficial effects of the SGLT2 inhibitor dapagliflozin in reducing the risk of future heart failure hospitalization in individuals with type 2 diabetes were markedly greater in individuals who carried a cardiomyopathy-associated genetic variant compared with noncarriers, suggesting a personalized preventative therapy based on genetic information.