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01.
medRxiv (Medicine) 2026-06-18

Distinct Neuronal, Proliferative, and Secretory Pathways are Perturbed in Cancer Survivors with Depressive Symptoms

Introduction Depression is highly prevalent among cancer survivors and may be biologically distinct, although clinical studies investigating these mechanisms remain limited. Thus, the aims of this study were to (1) identify perturbed biological pathways associated with depressive symptom severity in cancer survivors, and (2) investigate whether these pathways are common or distinct to those perturbed in an age-matched non-cancer cohort. Methods We analyzed cross-sectional self-reported and transcriptomic data from the Multi-Ethnic Study of Atherosclerosis (PHD #39341). Cancer survivors and an age-matched non-cancer cohort (target ratio 1:2) were identified. The 20-item Center for Epidemiologic Studies Depression Scale (CES-D) was used to split participants into low (CES-D

02.
arXiv (CS.CV) 2026-06-11

RankVR: Low-Rank Structure Perception and Value Recalibration for Robust Composed Image Retrieval

Composed Image Retrieval (CIR) constitutes a pivotal paradigm requiring models to perform joint reasoning on reference images and modification texts. However, the prevalence of Noisy Triplet Correspondence (NTC) in large-scale datasets severely constrains model performance. Existing denoising methods either target binary mismatches or rely on scalar-based point-wise estimation, neglecting rich global structural correlations among sample populations and dynamic value variations during training, thereby yielding suboptimal results. This paper identifies two critical unresolved challenges: Global Structural Inconsistency of Semantic Correlations and Hard Sample Discrimination Uncertainty. To address these, we propose RankVR, a framework designed to construct a robust CIR model via global structure consistency and dynamic value perception. Specifically, we introduce the Global Structure Consistency Perception (GSCP) module, which utilizes the Effective Rank of the Correlation Matrix to decouple clean samples from structural noise. By measuring rank difference, GSCP identifies samples disrupting macroscopic semantic symmetry. Furthermore, we develop the Adaptive Semantic Value Calibration (ASVC) module to distinguish high-value hard clean samples. By integrating training potential and reliability, it dynamically quantifies the semantic value of each triplet, ensuring effective utilization of hard samples while suppressing noise characterized by logical conflicts. Extensive experiments on the FashionIQ and CIRR benchmark datasets demonstrate that RankVR significantly outperforms existing state-of-the-art methods, validating its superior robustness in noisy environments.

03.
bioRxiv (Bioinfo) 2026-06-12

Computational Design of Optimal Sequences for Targeted Hypermutagenesis Using Recombination-Coupled Diversity-Generating Retroelements

Diversity-generating retroelements (DGRs) are natural systems that accelerate evolution via targeted hypermutation at adenines. We previously developed DGRec, a system combining DGRs and recombineering for programmable mutagenesis in Escherichia coli. We here address two important issues with DGRec: the dependence of mutagenesis efficiency on the dgrRNA secondary structure and the variability of the reverse-transcription biases with sequence context and position. First, we introduce and validate a method to recode non-functional templates, i.e. with low mutagenesis efficiency, into highly functional ones through synonymous mutations. Second, we develop a Long Short-Term Memory (LSTM) model to predict DGRec mutational profiles for any given template sequence. By integrating this LSTM model with our recoding method, we establish a comprehensive workflow for customized directed evolution, enabling researchers to precisely fine-tune DGRec in vivo mutagenesis to their engineering needs.

04.
arXiv (quant-ph) 2026-06-24

Improved State Readout in NV Centers using Regression Models and Rabi Driving

arXiv:2606.23454v2 Announce Type: replace Abstract: Readout of state populations in nitrogen-vacancy centers from fluorescence measurements at room-temperature is routinely achieved via contrast-based calibration. The fidelities achieved by this conventional approach are limited by reducing the dynamical fluorescence behaviour of the NV center to a scalar value, and calculating the population of each possible state independently. To address these limitations, we use regression models trained on experimental data to map the fluorescence signals onto ideal simulated populations. Additionally, we enhance the informational content of the fluorescence signals by performing measurements during induced Rabi oscillations. Our results demonstrate that including these dynamical signals significantly reduces state readout errors across multiple tested models. Notably, linear ridge regression performs nearly on par with a non-linear kernel-based model, showing that simple models already capture the relevant mapping between the enhanced fluorescence signals and the underlying state populations. This data-driven approach provides a robust alternative that achieves higher fidelities than conventional calibration in our setting, paving the way for high-fidelity state readout in solid-state quantum registers.

05.
arXiv (CS.AI) 2026-06-12

Hallucination in Medical Imaging AI: A Cross-Modality Analytical Framework for Taxonomy, Detection, and Mitigation under Regulatory Constraints

arXiv:2606.13211v1 Announce Type: new Abstract: AI systems are being deployed across medical imaging faster than their failure modes are understood. At this point in time, the failure of greatest clinical concern is hallucination: clinically plausible but factually incorrect outputs, including fabricated anatomical structures, missed findings, incorrect laterality, and invented measurements in generated reports, with direct consequences, for example, for biopsy decisions, staging, and treatment planning. This structured narrative synthesizes peer-reviewed studies, benchmark datasets, and FDA regulatory guidance across five imaging modalities to produce a cross-modality analysis of hallucination taxonomy, etiology, detection, and mitigation. Specifically, we address three questions in this study: (1) how can existing taxonomies be unified across modalities?, (2) how do medical-specialized foundation models hallucinate less than general-purpose ones?, and (3) which mitigation strategies are effective and compatible with FDA lifecycle oversight? We note that three taxonomic frameworks together cover the imaging pipeline in a way no single framework does alone. We also highlight that general-purpose foundation models outperform medical-specialized models on hallucination-specific benchmarks, indicating that narrow domain fine-tuning can introduce overfitting-induced confabulation. At the same time, the oversight of radiologists remains essential; for instance, a very high percentage of of AI-generated flags required expert correction before clinical use. Physics-informed architectural constraints, Chain-of-Thought prompting, and human-in-the-loop safeguards each address different failure modes and is effective when combined. All findings are mapped to the FDA's Total Product Lifecycle and Predetermined Change Control Plan frameworks, which treat hallucination management as a lifecycle obligation rather than a pre-deployment checklist.

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

EHRNote-ChatQA: A Benchmark for Evidence-Grounded Multi-Turn Clinical Question Answering over Longitudinal Discharge Summaries

Discharge summaries are crucial clinical documents containing the context of a patient's overall hospital stay, and are routinely reviewed by medical experts for patient readmission, ongoing care, and diagnostic decision-making. When reviewing them, medical experts often must iteratively synthesize information across multiple summaries while verifying the evidence supporting each answer. Although large language models (LLMs) are increasingly explored for clinical question answering, existing benchmarks do not sufficiently reflect this setting: they often evaluate exam-style medical knowledge or focus on single-turn question answering with limited evidence-grounding evaluation. We introduce EHRNote-ChatQA, the first benchmark for evidence-grounded multi-turn clinical question answering over patients' multiple discharge summaries. Built from de-identified MIMIC-IV discharge summaries, EHRNote-ChatQA contains 967 patient-level multi-turn samples spanning one to five notes and 16,072 medical-expert-verified QA pairs (8,036 content questions, each paired with an evidence-grounding question) across eight clinical categories. The benchmark is constructed through an expert-informed pipeline combining discharge-summary structuring schema, expert-curated multi-turn QA templates, and LLM-based generation, followed by review and revision of every single QA sample by 11 medical experts. Benchmarking 22 open- and closed-source LLMs reveals several challenges, including that LLMs struggle more with evidence grounding than content answering, multi-turn errors compound across turns, and single-turn clinical QA performance does not reliably transfer to this setting. These findings establish EHRNote-ChatQA as a rigorous and practical benchmark for evaluating clinical QA systems. The dataset will be made publicly available through PhysioNet credentialed access.

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

LoRDO: Distributed Low-Rank Optimization with Infrequent Communication

arXiv:2602.04396v2 Announce Type: replace-cross Abstract: Distributed training of foundation models via $\texttt{DDP}$ is limited by interconnect bandwidth. While infrequent communication strategies reduce synchronization frequency, they remain bottlenecked by the memory and communication requirements of optimizer states. Low-rank optimizers can alleviate these constraints; however, in the local-update regime, workers lack access to the full-batch gradients required to compute low-rank projections, which degrades performance. We propose $\texttt{LoRDO}$, a principled framework unifying low-rank optimization with infrequent synchronization. We first demonstrate that, while global projections based on pseudo-gradients are theoretically superior, they permanently restrict the optimization trajectory to a low-rank subspace. To restore subspace exploration, we introduce a full-rank quasi-hyperbolic update. $\texttt{LoRDO}$ achieves near-parity with low-rank $\texttt{DDP}$ in language modeling and downstream tasks at model scales of $125$M–$720$M, while reducing communication by $\approx 10 \times$. Finally, we show that $\texttt{LoRDO}$ improves performance even more in very low-memory settings with small rank/batch size.

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

Seeing Roads Through Words: A Language-Guided Framework for RGB-T Driving Scene Segmentation

Robust semantic segmentation of road scenes under adverse illumination, lighting, and shadow conditions remain a core challenge for autonomous driving applications. RGB-Thermal fusion is a standard approach, yet existing methods apply static fusion strategies uniformly across all conditions, allowing modality-specific noise to propagate throughout the network. Hence, we propose CLARITY that dynamically adapts its fusion strategy to the detected scene condition. Guided by vision-language model (VLM) priors, the network learns to modulate each modality's contribution based on the illumination state while leveraging object embeddings for segmentation, rather than applying a fixed fusion policy. We further introduce two mechanisms - one which preserves valid dark-object semantics that prior noise-suppression methods incorrectly discard, and a hierarchical decoder that enforces structural consistency across scales to sharpen boundaries on thin objects. Experiments on the MFNet dataset demonstrate that CLARITY establishes a new state-of-the-art (SOTA), achieving 62.3% mIoU and 77.5% mAcc.

09.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

10.
Nature (Science) 2026-06-23

Silicon Valley’s vision for global AI is flawed: each country needs its own blueprint

From energy grids to language performance, emerging economies are exposing the limits of today’s artificial-intelligence strategy as it expands globally. From energy grids to language performance, emerging economies are exposing the limits of today’s artificial-intelligence strategy as it expands globally.

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

When Do Data-Driven Systems Exhibit the Capability to Infer?

arXiv:2606.11769v1 Announce Type: new Abstract: The European AI Act is the first comprehensive regulation of artificial intelligence (AI), setting out extensive obligations, particularly for so-called high-risk and general-purpose AI systems. A key distinguishing feature of AI systems under the AI Act is the capability to infer. Since the AI Act does not clearly define what inference is, there is a gray area for certain data-driven systems. A specific example is credit scoring systems, which are listed by Annex III of the AI Act. At the same time, however, these are often implemented using statistical models for which it is unclear whether they have the capability to infer and thus fall under the AI definition of the AI Act at all. Motivated by statistical learning theory, this work develops a framework for grading different levels of the capability to infer. Based on the AI Act and the Commission Guidelines on the definition of an artificial intelligence system, we analyze which levels constitute sufficient capability to infer within the meaning of the AI Act and where further regulatory clarity is needed. We illustrate the framework by creating two realistic credit scoring workflows and show whether and where inference occurs in them. Our analysis illustrates that not only individual models but the entire data processing workflow must be considered. It also shows that the involvement of human experts during development can have significant influence on the capability to infer. Code can be found at https://github.com/fraunhofer-iais/inference-framework-creditscorecards.

12.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Authors:

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.

13.
medRxiv (Medicine) 2026-06-22

Mapping abstraction and metacognition onto distinct transdiagnostic symptom profiles

Transdiagnostic psychiatric research on reward-guided learning has largely focused on simple associative processes, leaving it unclear whether or how higher-level processes are disrupted. Here, we studied how abstraction, the ability to extract relevant features from complex information, and metacognition, the ability to monitor and evaluate one's own mental processes, map onto specific transdiagnostic dimensions. Using an online sample (N = 249), we examined associations between these processes and three cross-culturally robust transdiagnostic dimensions derived from a large existing dataset (N = 19,505): Compulsive hypersensitivity, Social withdrawal, and Addictive behaviours. Computational modelling of an abstract representation learning task with confidence judgments revealed that Compulsive hypersensitivity was negatively associated with both abstraction ability (pboot = 0.003) and metacognitive sensitivity (pboot = 0.005), while Social withdrawal was positively associated with metacognitive sensitivity alone (pboot = 0.002). Moreover, transdiagnostic dimensions revealed more coherent associations with higher-order cognition than symptom-level analyses, highlighting the added value of examining psychopathology at the factor rather than the symptom level. These findings portray a hierarchical view of cognitive dysfunctions in psychopathology and point to representational and metacognitive processes as potential targets for transdiagnostic intervention.

14.
arXiv (quant-ph) 2026-06-11

Global vs. Local Discrimination of Locally Implementable Multipartite Unitaries

arXiv:2509.10430v2 Announce Type: replace Abstract: We study single-shot distinguishability of locally implementable multipartite unitaries under Local Operations and Classical Communication (LOCC) and global operations. As unitary discrimination depends on both the choice of probing states and the measurements on the evolved states, we classify LOCC and global distinguishability into two categories: adaptive strategies, where probing states are chosen based on measurement outcomes from other subsystems, and restricted strategies, where probing states remain fixed. Our findings uncover three surprising features in the bipartite setting and establish new structural limits for unitary discrimination: (i) Certain pairs of unitaries are globally distinguishable with restricted strategies but indistinguishable under LOCC, even with adaptive strategies. (ii) There exist sets of four unitaries that are distinguishable via LOCC, yet remain globally indistinguishable with restricted strategies. (iii) Some sets of unitaries are globally indistinguishable under adaptive strategies, when probed with separable states, but become distinguishable via LOCC.

15.
arXiv (CS.LG) 2026-06-19

Enhancing Graph Neural Networks Using Proximity Graphs for Dust Source Emission Forecasting

arXiv:2606.19825v1 Announce Type: new Abstract: Accurate prediction of dust source emissions is critical for mitigating the significant environmental and health hazards posed by dust storms. Traditional forecasting methods often struggle to capture the complex spatiotemporal dynamics of these phenomena. In this paper, we demonstrate that proximity graphs enable Graph Neural Networks (GNNs) to effectively model the intricate spatial and temporal relationships between data points. Specifically, we use proximity graphs–such as Delaunay triangulation, Gabriel graph, k-Nearest Neighbor graph, and Yao graph–as the input for GNNs (including GraphSAGE, Graph Convolutional Networks, and Graph Attention Networks) to perform message passing. Our approach highlights the effectiveness of integrating proximity graphs with GNNs for robust and accurate dust source forecasting. To emphasize the importance of proximity graph representations, we compare our method against GNNs using random graphs for message passing. The results show that GNNs with proximity graphs significantly outperform those with random graphs and are also far superior to Long Short-Term Memory (LSTM) model in dust source emission forecasting.

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

Kernel of Partition Paths: A Unified Representation for Tree Ensembles

arXiv:2606.18853v1 Announce Type: cross Abstract: A recent line of work has reframed individual decision trees as linear models on engineered features associated with their splits, opening routes for oracle inequalities and feature-importance reinterpretation, but leaving open the question of what unified geometric object a forest induces when one indexes its feature map by nodes rather than by splits. The present paper studies that object. KPP indexes the feature map by the nodes of the forest, weighted by a path metric that turns each coordinate into a component of a squared-Euclidean path-isometric embedding. KPP unifies four pillars under a single non-diagonal Gram that carries a metric: prediction, exact additive attribution, deterministic Lipschitz robust radius in the KPP metric, and uniform Rademacher risk bounds for regression and classification under fixed, honest, or cross-fit conditioning. All probabilistic guarantees are conditional on the representation and are stated under three explicit conditioning regimes; the robust-radius guarantee is deterministic in the KPP metric rather than in a norm on the raw input. Conjectured fast-rate refinements for both regression and classification are stated as open problems and are not claimed as theorems.

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

Hardware-Oriented Inference Complexity of Kolmogorov-Arnold Networks

arXiv:2604.03345v2 Announce Type: replace Abstract: Kolmogorov-Arnold Networks (KANs) have recently emerged as a powerful architecture for various machine learning applications. However, their unique structure raises significant concerns regarding their computational overhead. Existing studies primarily evaluate KAN complexity in terms of Floating-Point Operations (FLOPs) required for GPU-based training and inference. However, in many latency-sensitive and power-constrained deployment scenarios, such as neural network-driven non-linearity mitigation in optical communications or channel state estimation in wireless communications, training is performed offline and dedicated hardware accelerators are preferred over GPUs for inference. Recent hardware implementation studies report KAN complexity using platform-specific resource consumption metrics, such as Look-Up Tables, Flip-Flops, and Block RAMs. However, these metrics require a full hardware design and synthesis stage that limits their utility for early-stage architectural decisions and cross-platform comparisons. To address this, we derive generalized, platform-independent formulae for evaluating the hardware inference complexity of KANs in terms of Real Multiplications (RM), Bit Operations (BOP), and Number of Additions and Bit-Shifts (NABS). We extend our analysis across multiple KAN variants, including B-spline, Gaussian Radial Basis Function (GRBF), Chebyshev, and Fourier KANs. The proposed metrics can be computed directly from the network structure and enable a fair and straightforward inference complexity comparison between KAN and other neural network architectures.

18.
arXiv (quant-ph) 2026-06-16

Ultrastrongly coupled open systems and fine grained time

arXiv:2606.16634v1 Announce Type: new Abstract: We study the dynamics of a d-level quantum system coupled to a bosonic reservoir when the coupling constant is large. It is known that in the limit of infinite coupling strength, the system undergoes an instantaneous nonselective measurement, resulting in the immediate decoherence in the measurement basis, followed by a unitary Zeno dynamics. Here we resolve this dynamical process by introducing a fine grained scaling regime of short times proportional to the inverse coupling. We provide a rigorous derivation of the open system dynamics in this regime of ultrastrong coupling and demonstrate how decoherence unfolds continuously in the new time scale. We show that Markovian dynamics which are not given by semigroups arise naturally, in contrast to what happens in the weak coupling theory.

19.
arXiv (quant-ph) 2026-06-24

Coherence-gated quantum devices via real-time weak measurement

Authors:

arXiv:2604.18662v3 Announce Type: replace Abstract: Single-photon routers in cavity and circuit QED direct photons by the qubit's energy eigenstate – a projective decision that destroys coherence. We propose a different primitive: coherence-gated routing, where the decision depends on the magnitude of the qubit's quantum coherence, estimated in real time from simultaneous weak measurements of $\sigma_x$ and $\sigma_z$. A photon is accepted if the coherence score $S(T) = \sqrt{\langle\sigma_x\rangle_c^2 + \langle\sigma_y\rangle_c^2}$, extracted from the conditional density matrix via the stochastic master equation, exceeds a tunable threshold $S_{\mathrm{th}}$. Certifying coherence at emission enables two applications conventional heralded sources cannot: (i) a quantum random number generator with min-entropy bounded by Bloch-sphere geometry, $H_\infty \geq -\log_2\!\bigl(\frac{1+\sqrt{1-S_{\mathrm{th}}^2}}{2}\bigr)$, and (ii) a phase-tracked photon source whose two-node coherence certification bounds the matter-matter entanglement fidelity after Bell-state measurement. The estimator is itself a security primitive. Benchmarking seven configurations, we find that underestimating detector efficiency ($\eta_{\mathrm{a}} < \eta_{\mathrm{true}}$) both stabilizes the numerics and suppresses overcertification. We trace this via a purity-monotonicity result, identify a geometric loophole amplifying purity undercertification into coherence overcertification by an order of magnitude ($\sim$40$\times$), and prove two complementary tail bounds: an Ornstein-Uhlenbeck comparison giving $4.5\%$ raw overcertification (empirical $3.7\%$ from $10^6$ trajectories) and an exponential supermartingale establishing structural exponential decay.

20.
arXiv (CS.AI) 2026-06-11

From Uniform to Learned Graph Priors: Diffusion for Structure Discovery

arXiv:2606.11831v1 Announce Type: cross Abstract: Neural relational inference (NRI) methods discover interaction graphs from trajectories through variational reasoning on discrete potential edges. However, these methods typically rely on oversimplified, factorized graph priors. Such priors, typically nearing uniform distributions, treat edges as independent entities. This systemic misalignment does not match the real-world systems and yields diffuse and indecisive edge posteriors limiting the reliability of structural discovery. To address this, we propose Diff-prior, a diffusion-parameterized adaptive prior used to calibrate latent graph distribution rather than generate graphs. Our core insight is to reframe prior integration as a learnable denoising-style calibration that organizes scattered, uncertain edge posteriors into a more reliable overall structure which can be trained by the diffusion model. Diff-prior learns an adaptive structure prior that performs structured calibration on the edge posteriors during inference, guiding it towards a distribution closer to the underlying structure. The diff-prior operates before structural sampling and acts as a denoising calibrator directly on the encoder edge distribution, which provides a generic training paradigm over structured variables. Experiments on standard benchmarks validated our framework, and the results indicate that Diff-prior improves the performance of structure inference and generates more decisive edge posteriors across multiple NRI-family architectures. The code is available on https://github.com/Hardy158118/Diffprior.

21.
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.

22.
Science (Express) 2026-04-16

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

Authors: Unknown Author

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.

23.
arXiv (CS.LG) 2026-06-19

Probe-and-Refine Tuning of Repository Guidance for Coding Agents

arXiv:2606.20512v1 Announce Type: cross Abstract: LLM-based coding agents need higher-level operational knowledge about a repository (which files house which subsystems, how to run the test suite, which workflows have historically led to wrong fixes) that does not exist in the code itself. Engineers typically maintain \texttt{AGENTS.md} files to supply this context as instructions for coding agents, but whether they help is contested: recent studies disagree on whether LLM-generated guidance improves or harms agent performance. In this paper we show that how the guidance is produced is the decisive variable, and introduce probe-and-refine tuning: a procedure that uses synthetic bug-fix probes to iteratively diagnose and patch a repository's guidance file through single-shot LLM calls, with no agent loop or tool use during tuning. On SWE-bench Verified across four independent trials with Qwen3.5-35B-A3B at 200 steps, probe-and-refine achieves 33.0\,\% mean resolve rate vs.\ 28.3\,\% for the static knowledge base used to initialize it and 25.5\,\% for an unguided baseline ($p < 0.001$ for both probe-and-refine contrasts). The improvement comes from coverage rather than precision: refined guidance produces evaluable patches for 14.5 percentage points (pp) more instances while per-patch precision remains statistically constant ($\sim$59\,\%, $p = 0.119$), showing that improved guidance helps agents reach the correct file rather than improving the quality of the changes they make. Further, a step-budget experiment shows that guidance is what lets the agent use a larger step budget productively, and a cross-model experiment with NVIDIA-Nemotron-3-Nano-30B-A3B finds that the tuning loop degrades when the model cannot generate sufficiently diagnostic output, though per-patch precision remains constant even then.

24.
arXiv (math.PR) 2026-06-11

On the Wasserstein distance between a hyperuniform point process and its mean

arXiv:2404.09549v3 Announce Type: replace Abstract: We study the existence of bounds on the expected $p$-Wasserstein distance between a random measure and its mean under the assumption that the $p$-th centered moments of the counting statistics are controlled uniformly in space. The average Wasserstein transport cost is shown to be bounded from above and from below by some multiples of the number of points. $D$-dimensional versions of those results are also obtained. As a corollary, we prove that for any value of $p\geq 1$ the Ginibre point process can be seen as a perturbed lattice with identically distributed perturbations with a finite $p$-th moment.

25.
arXiv (CS.AI) 2026-06-24

ScaleToT: Generalizing Structured LLM Reasoning for Billion-Scale Low-Activity User Modeling

arXiv:2606.24605v1 Announce Type: new Abstract: Accurate user modeling often depends on rich interaction histories, which are unavailable for billions of low-activity users. Large Language Models (LLMs) can infer latent user states from static profiles, but this reasoning becomes unreliable when profiles are sparse, and applying an LLM to billions of users is prohibitively expensive. We present ScaleToT, which learns structured reasoning from a small LLM-processed subset and extends it to the broader low-activity user population. To improve reasoning reliability, ScaleToT constructs typed user-state chains with a bounded entropy-guided Tree-of-Thought (ToT) refinement procedure. To make this structured reasoning usable from sparse profiles, the teacher-curated chains are used to train a student model on static profiles through supervised fine-tuning (SFT) and Outcome-Driven Segment-Aware Implicit Reward Policy Optimization (OSIPO). ScaleToT then transfers the student's reasoning representations to a lightweight profile encoder, providing shared reasoning signals for the remaining users without LLM inference. We evaluate ScaleToT on lifetime value (LTV) prediction in a billion-scale advertising deployment. A randomized online A/B test increased LT30 by 6.738\%, while offline reasoning covered only 7.32\% of the potential population, greatly reducing compute cost compared with full-population reasoning.