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01.
Nature (Science) 2026-06-10

Gen Z scepticism towards AI is a wake-up call — universities must take it seriously

作者:

The challenge for universities is not adopting artificial intelligence, but doing so in ways that the current generation of students can trust. The challenge for universities is not adopting artificial intelligence, but doing so in ways that the current generation of students can trust.

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

High-Dimensional Random Projection for Activation Steering in Language Models

arXiv:2606.15092v1 Announce Type: new Abstract: Activation steering has emerged as a key methodology for controlling the behavior of large language models (LLMs). Existing difference-in-means based methods, however, are fundamentally limited: they capture only mean differences between class activations and fail to recover discriminative signals that naturally exist in the nonlinear feature subspace under the superposition hypothesis. Motivated by that, we propose High-Dimensional Random-projection for Activation Steering (HiDRA), a training-free approach that integrates seamlessly with existing activation steering methods. By performing activation addition in the projected high-dimensional space, HiDRA can provably capture a better discriminative structure beyond the reach of linear methods. Experiments across diverse LLM families and benchmarks demonstrate that HiDRA consistently outperforms baseline counterparts, achieving stronger behavioral control without significant computational overhead.

03.
arXiv (CS.AI) 2026-06-19

PiDR: Physics-Informed Inertial Dead Reckoning for Autonomous Platforms

arXiv:2601.03040v2 Announce Type: replace-cross Abstract: A fundamental requirement for full autonomy is the ability to sustain accurate navigation in the absence of external data, such as GNSS signals or visual information. In these challenging environments, the platform must rely exclusively on inertial sensors, leading to pure inertial navigation. However, the inherent noise and other error terms of the inertial sensors in such real-world scenarios will cause the navigation solution to drift over time. Although conventional deep-learning models have emerged as a possible approach to inertial navigation, they are inherently black-box in nature. Furthermore, they struggle to learn effectively with limited supervised sensor data and often fail to preserve physical principles. To address these limitations, we propose PiDR, a physics-informed inertial dead-reckoning framework for autonomous platforms in situations of pure inertial navigation. PiDR offers transparency by explicitly integrating inertial navigation principles into the network training process through the physics-informed residual component. PiDR plays a crucial role in mitigating abrupt trajectory deviations even under limited or sparse supervision. We evaluated PiDR on real-world datasets collected by a mobile robot and an autonomous underwater vehicle. We obtained more than 29% positioning improvement in both datasets, demonstrating the ability of PiDR to generalize different platforms operating in various environments and dynamics. Thus, PiDR offers a robust, lightweight, yet effective architecture and can be deployed on resource-constrained platforms, enabling real-time pure inertial navigation in adverse scenarios.

04.
arXiv (CS.AI) 2026-06-16

Autonomous End-to-End SOH Prediction Services for Battery Systems via Temporal-Contrastive Representation Learning

arXiv:2606.16434v1 Announce Type: cross Abstract: Accurate state of health (SOH) estimation is a critical diagnostic service for lithium-ion battery management. However, reliance on labor-intensive manual feature engineering and opaque black-box models hinders scalable industrial deployment. To address this, we introduce TC-SOH: a modular, plug-and-play service architecture for autonomous, end-to-end SOH prediction. TC-SOH employs a temporal-contrastive mechanism and a cross-window prediction pretext task to extract degradation-relevant representations directly from raw operational data. To improve transparency, we connect model efficacy with representation diagnostics: visualization, sensitivity analysis, redundancy analysis, bidirectional probing, future-SOH probing, and temporal shuffling show that learned features overlap with selected expert descriptors while retaining additional SOH-relevant variation, and that ordered temporal context improves subsequent-SOH prediction. Across four public datasets, TC-SOH outperforms the considered physics-informed and data-driven baselines, reducing MAPE by 1.91 times and RMSE by 2.13 times.

05.
arXiv (CS.CV) 2026-06-15

UniversalRAG: Retrieval-Augmented Generation over Corpora of Diverse Modalities and Granularities

Retrieval-Augmented Generation (RAG) has shown substantial promise in improving factual accuracy by grounding model responses with external knowledge relevant to queries. However, most existing approaches are limited to a text-only corpus, and while recent efforts have extended RAG to other modalities such as images and videos, they typically operate over a single modality-specific corpus. In contrast, real-world queries vary widely in the type of knowledge they require, which a single type of knowledge source cannot address. To address this, we introduce UniversalRAG, an any-to-any RAG framework designed to retrieve and integrate knowledge from heterogeneous sources with diverse modalities and granularities. Specifically, motivated by the observation that forcing all modalities into a unified representation space derived from a single aggregated corpus causes a modality gap, where the retrieval tends to favor items from the same modality as the query, we propose modality-aware routing, which dynamically identifies the most appropriate modality-specific corpus and performs targeted retrieval within it, and further justify its effectiveness with a theoretical analysis. Moreover, beyond modality, we organize each modality into multiple granularity levels, enabling fine-tuned retrieval tailored to the complexity and scope of the query. We validate UniversalRAG on 10 benchmarks of multiple modalities, showing its superiority over various modality-specific and unified baselines.

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

3D-RFT: Reinforcement Fine-Tuning for Video-based 3D Scene Understanding

Reinforcement Learning with Verifiable Rewards ( RLVR ) has emerged as a transformative paradigm for enhancing the reasoning capabilities of Large Language Models ( LLMs), yet its potential in 3D scene understanding remains under-explored. Existing approaches largely rely on Supervised Fine-Tuning ( SFT), where the token-level cross-entropy loss acts as an indirect proxy for optimization, leading to a misalignment between training objectives and task performances. To bridge this gap, we present Reinforcement Fine-Tuning for Video-based 3D Scene Understanding (3D-RFT ), the first framework to extend RLVR to video-based 3D perception and reasoning. 3D-RFT shifts the paradigm by directly optimizing the model towards evaluation metrics. 3D-RFT first activates 3D-aware Multi-modal Large Language Models ( MLLM s) via SFT, followed by reinforcement fine-tuning using Group Relative Policy Optimization ( GRPO) with strictly verifiable reward functions. We design task-specific reward functions directly from metrics like 3D IoU and F1-Score to provide more effective signals to guide model training. Extensive experiments demonstrate that 3D-RFT-4B achieves state-of-the-art performance on various video-based 3D scene understanding tasks. Notably, 3D-RFT-4B significantly outperforms larger models (e.g., VG LLM-8B) on 3D video detection, 3D visual grounding, and spatial reasoning benchmarks. We further reveal good properties of 3D-RFT such as robust efficacy, and valuable insights into training strategies and data impact. We hope 3D-RFT can serve as a robust and promising paradigm for future development of 3D scene understanding.

07.
arXiv (CS.CL) 2026-06-16

Understanding Scam Trends and Rail Paths from Reddit Self-Disclosure Narratives

Online scam behavior is inherently multi-stage, and the lifecycle includes temporally ordered rails and events rather than isolated signals. Existing works analyze characteristics of scam types and rails, but they do not track scam trends across years. Moreover, the work on the relations between rails is hampered due to the lack of open-source datasets with annotations and coverage of different scam types. To address these gaps, we build a dataset to analyze the yearly trend of scam characteristics and rail paths using Reddit self-disclosure narratives from 2023 to 2025. We collect 21,304 posts from scam-related subreddits with at least one rail among identity, communication, platform, and payment for trend analysis by heuristic annotation. Then, we label 1,800 posts containing explicit or recoverable scam chains by an LLM-assisted method for scam path analysis. The method is evaluated with human annotation. Lastly, we run a topic model on the comments of the posts to analyze the community support behavior. The results reveal that scam processes are predominantly multi-rail. Across years, different scam types and rail components dominate. Different scam types vary systematically in path complexity. Reddit support behaviors have become more detailed over time. This work supports synthetic scam chain data simulation and AI-related scam risk assessment, though findings may not generalise to other platforms.

08.
arXiv (quant-ph) 2026-06-16

Scheme for Transport-based Global Entanglement Distribution using Quantum Processors

arXiv:2606.15421v1 Announce Type: new Abstract: We propose a scheme for distributing entanglement over global distances in a heralded manner by using satellites to physically transport entangled processor nodes with rare-earth-ion qubits. A full analysis of channel losses, errors and background light is performed to determine the fidelity and number of entangled pairs that can be distributed between two ground stations. We show that the scheme works already with a single satellite and can distribute close to the theoretical maximum number of entangled pairs that can be generated in a satellite overpass. In addition, we argue that in theory transportation-based schemes outperform other satellite-based schemes and can be scaled up to a constellation without additional channel losses. Daytime operation seems feasible as long as the sky is clear, with an EPR pair fidelity ranging from 99.3% at shorter network lengths to 93.9% with global coverage and can be further improved by active error correction or entanglement purification.

09.
arXiv (CS.LG) 2026-06-12

Generative Modeling of Bach-Style Symbolic Music: A Comparative Study of Autoregressive, Latent-Variable, and Adversarial Approaches

arXiv:2606.13626v1 Announce Type: cross Abstract: We study generative modeling of Bach-style symbolic piano music using a shared MIDI corpus and three model families: autoregressive LSTMs with attention, latent-variable models including recurrent VAEs and vector-quantized VAEs, and generative adversarial networks. We compare their ability to model polyphonic note sequences, learn useful latent representations, and generate stylistically coherent compositions. Our experiments show that the autoregressive LSTM with attention produces the most musically coherent samples, while vector quantization helps mitigate posterior collapse and yields more structured outputs than conventional recurrent VAEs. The adversarial approach captures local pitch patterns but remains difficult to train and generalizes less reliably to Bach's style. These results highlight the relative strengths and failure modes of autoregressive, latent-variable, and adversarial approaches for symbolic music generation.

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

Light Forcing: Accelerating Autoregressive Video Diffusion via Sparse Attention

Advanced autoregressive (AR) video generation models have improved visual fidelity and interactivity, but the quadratic complexity of attention remains a primary bottleneck for efficient deployment. While existing sparse attention solutions have shown promise on bidirectional models, we identify that applying these solutions to AR models leads to considerable performance degradation for two reasons: isolated consideration of chunk generation and insufficient utilization of past informative context. Motivated by these observations, we propose \textsc{Light Forcing}, the first sparse attention solution tailored for AR video generation models. It incorporates a Chunk-Aware Growth mechanism to quantitatively estimate the contribution of each chunk, which determines their sparsity allocation. This progressive sparsity increase strategy enables the current chunk to inherit prior knowledge in earlier chunks during generation. Additionally, we introduce a Hierarchical Sparse Attention to capture informative historical and local context in a coarse-to-fine manner. Such two-level mask selection strategy (i.e., frame and block level) can adaptively handle diverse attention patterns. Extensive experiments demonstrate that our method outperforms existing sparse attention in quality (e.g., 84.5 on VBench) and efficiency (e.g., $1.2{\sim}1.3\times$ end-to-end speedup). Combined with other efficient solutions, \textsc{Light Forcing} further achieves a $2.0{\sim}3.0\times$ end-to-end speedup across diverse GPUs (e.g., 27.4\,FPS on RTX 5090 and 33.9\,FPS on H100). Code is released via this \href{https://github.com/chengtao-lv/LightForcing}{link}.

11.
arXiv (math.PR) 2026-06-19

An alternative approach to well-posedness of McKean-Vlasov equations arising in Consensus-Based Optimization

arXiv:2512.19446v4 Announce Type: replace-cross Abstract: In this work we study the mean-field description of Consensus-Based Optimization (CBO), a derivative-free particle optimization method. Such a description is provided by a non-local SDE of McKean-Vlasov type, whose fields lack of global Lipschitz continuity. We propose a novel approach to prove the well-posedness of the mean-field CBO equation based on a truncation argument. The latter is performed through the introduction of a cut-off function, defined on the space of probability measures, acting on the fields. This procedure allows us to study the well-posedness problem in the classical framework of Sznitman. Through this argument, we recover the established result on the existence of strong solutions, and we extend the class of solutions for which pathwise uniqueness holds.

12.
medRxiv (Medicine) 2026-06-15

Quality Improvement Based Implementation and Evaluation of a Decision Aid for Patients with Nephrolithiasis

Introduction Patients with nephrolithiasis face challenges in making a high-quality, preference sensitive decision. Our prior work established feasibility and patient acceptance of a software-based decision aid (DA). The objectives for this study were to identify implementation strategies for the DA in routine care and determine whether DA implementation enhances decisional quality for patients. Methods New nephrolithiasis patients were recruited from the institution Medical Center from June 2018 to April 2024 to receive a software-based pre-visit DA that measured care preferences and used decision analysis to rank treatments. The RE-AIM framework and Plan-Do-Study-Act (PDSA) cycles were used to improve implementation outcomes. Patients completed survey instruments evaluating decisional conflict, shared decision-making, care satisfaction, and treatment choice following their provider visit. These metrics were compared in the DA cohort (n=81) to those in a usual care cohort (n=78) with Wilcoxon rank-sum and Chi-square (or Fishers exact) tests. Results Implementation data revealed sustained reach and progressive improvement in fidelity. The DA cohort reported higher decisional quality relative to controls (p=0.003) and reported greater support/advice to make a choice (p=0.005). The DA cohort more often discussed options with their doctor (87.5% vs 69.2%, p=0.005) and were more likely to be promoters of their provider (p

13.
arXiv (quant-ph) 2026-06-24

q-Askey Deformations of Double-Scaled SYK

arXiv:2605.13956v2 Announce Type: replace-cross Abstract: We construct families of deformations of the double-scaled SYK (DSSYK) model and investigate their bulk interpretation. We introduce microscopic deformations of the SYK model which, after ensemble averaging and in the double-scaling limit, are described by a transfer matrix encoding the recurrence relations of basic orthogonal polynomials in the q-Askey scheme. For certain families of deformations in the semiclassical limit at finite temperature, the chord number (encoding Krylov complexity) corresponds to the length of an Einstein-Rosen bridge connecting an End-Of-The-World brane to an anti-de Sitter asymptotic boundary. By increasing one of the deformation parameters, the models eventually exhibit discrete energy levels, signaling a new geometric transition in sine dilaton gravity. Via the SYK-Schur duality, Krylov complexity also admits a representation-theoretic interpretation as the spread of the SU(2) spin in the index of an $\mathcal{N}=2$ SU(2) gauge theory. We study the operator algebras of the deformed theories. The algebras can be type II$_1$ or type I$_\infty$ factors, depending on the operators that are included. The entanglement entropy between the type II$_1$ algebras for a pure state manifests as an extremal surface through the Ryu-Takayanagi formula. We discuss connections between our results and the emergence of baby universes in the bulk.

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

VidCRAFT3: Camera, Object, and Lighting Control for Image-to-Video Generation

Controllable image-to-video (I2V) generation transforms a reference image into a coherent video guided by user-specified control signals. While precise control over camera motion, object motion, and lighting is essential for high-fidelity creation, existing methods often treat these factors independently. This overlooks the physical coupling among viewpoint, geometry, and illumination in dynamic scenes, leading to visual inconsistencies such as mismatched shadows and perspective drift under simultaneous changes. We present VidCRAFT3, a unified and flexible I2V framework that explicitly models cross-factor interactions among geometry, motion, and illumination, enabling both independent and joint control over camera motion, object motion, and lighting direction. Image2Cloud provides explicit 3D geometric priors for accurate camera motion control. ObjMotionNet encodes sparse object trajectories into multi-scale motion features to guide realistic object motion. A Spatial Triple-Attention Transformer integrates lighting direction through lighting cross-attention for consistent relighting. To address the scarcity of jointly annotated data, we construct the VideoLightingDirection (VLD) dataset with accurate per-frame lighting direction annotations, and introduce a three-stage progressive training strategy that enables robust learning without fully joint annotations. Extensive experiments demonstrate that VidCRAFT3 achieves state-of-the-art performance in control precision and visual coherence across diverse scenarios.

15.
arXiv (CS.AI) 2026-06-24

OrbitForge: Text-to-3D Scene Generation via Reconstruction-Anchored Video Synthesis

arXiv:2606.24799v1 Announce Type: cross Abstract: Generic text-to-video models can be used as rich open-world scene priors. Despite the high quality of today's generated videos, they do not directly yield reliable 3D assets: camera motion is difficult to control, view coverage is partial, and frames often contain inconsistencies across time. We introduce OrbitForge, an adapter built from frozen video priors and per-prompt Gaussian Splatting reconstruction optimization that converts a single text-generated video into a canonical closed-orbit 3D Gaussian Splatting scene. We use 3D reconstruction as an anchor to improve the 3D consistency of the generated video. We obtain a preliminary 3D reconstruction from a first generated video via Deformable Gaussian Splatting with a robust MedianGS proxy. We render views from a prescribed orbit to detect missing viewpoints. OrbitForge uses the text-to-video model to complete only the missing views, and reconstructs the completed orbit into a final Gaussian Splatting scene. This design requires no task-specific video or multiview fine-tuning, avoids per-prompt score-distillation optimization, and does not progressively generate views one step at a time. We further argue that this setting demands coverage-aware evaluation: local smoothness alone rewards methods that never attempt a full orbit. On a frozen 300-prompt T3Bench-derived audit, OrbitForge reconstruction attains a 359.0-degree measured median span, raises originally unsupported-bin Q10 ImageReward from 8.07 to 16.36 relative to MedianGS-only reconstruction, while remaining competitive with VideoMV on the coverage-quality.

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

Conflict-Aware Retriever Editing for Knowledge Injection Attacks on LLM-Based RAG Systems

arXiv:2606.18310v1 Announce Type: cross Abstract: Injecting malicious knowledge into retrieval-augmented generation (RAG) systems can manipulate retrieved evidence and mislead downstream generation, posing a serious security threat for AI applications. Existing RAG injection attacks mainly rely on manipulating external knowledge bases, such as crafting malicious corpus. However, the synthetic text crafted by such data-centric methods could be detectable, leading to the failure of attacks. Beyond corpus manipulation, open-source retrievers are increasingly exposing RAG systems to model-centric attacks. In this paper, we propose conflict-aware retriever editing, i.e., CAREATTACK, a model-centric retriever attack framework for malicious knowledge injection in RAG. Specifically, CAREATTACK consists two stages of conflict-aware retriever editing and attack-preserving anchor repair. Conflict-aware retriever editing adapts efficient closed-form parameter editing to the dense retrieval model, promoting malicious knowledge above benign competing passages and resolving potential parameter conflicts through graph-based conflict detection and parameter editing projection. Then, attack-preserving anchor repair performs lightweight calibration on the edited retriever to further eliminate the impact on non-target prompts while preserving the attack effectiveness for target prompts. We instantiate CAREATTACK on Qwen3-Embedding-0.6B and BGE-M3, and conduct evaluation on three benchmark datasets. Experimental results demonstrate our method substantially promote malicious passages into the retrieved knowledge of RAG systems and can perform attacks for batches of target prompts and passages, given the access of retrieval model parameters. Since most RAG systems are built upon open-source retrieval models, this work reveals a practical attack surface in RAG systems. Codes are public accessible at https://anonymous.4open.science/r/CareAttack-3F1C.

17.
medRxiv (Medicine) 2026-06-22

The Protective Role of Belonging and Socioeconomic Status in Dropout Intent Among Minority Ethnic Students: A Mixed Methods Study

Improving minority ethnic student retention is a global higher education priority. This mixed-methods study investigated how institutional belonging and socioeconomic status interact to shape dropout intentions among minority university students in the UK (N = 182). Quantitative results revealed that perceived course difficulty and lower subjective socioeconomic status were the strongest predictors of dropout intent. While the interaction between socioeconomic status and difficulty was non-significant, qualitative accounts showed distinct structural vulnerabilities. Financial strain restricted social integration, turning socioeconomic disparities into campus isolation. Conversely, representative curricula, diverse peer networks, and stable cultural in-groups (e.g., religious affiliations, living in the parental home) functioned as essential psychological buffers against academic exhaustion and alienation. Universities must shift from transactional models to sustained structural equity to protect vulnerable student groups.

18.
arXiv (CS.AI) 2026-06-15

Position: Align AI to Our Aspirations, Not Our Flaws

arXiv:2606.13755v1 Announce Type: cross Abstract: We argue that aligning AI to aggregated human preferences is the wrong target. With current technology, one can train AIs to share the values of a Silicon Valley techno-optimist, a degrowth environmentalist, a national-conservative culture warrior, a single-party state cadre, or a devout religious traditionalist. We should not. Human values produce societies that thrive or fail on the merits of those values - from failed states and extreme inequality to declining happiness, political polarization, and government dysfunction in the world's wealthiest democracies. The pluralistic-alignment program correctly diagnoses that there is no single "humanity" to align with, but is dangerous if taken as the main directive. We argue that AI should be trained to a non-negotiable floor of objective alignment goals - competence, bounded by the constraints of factual accuracy, honesty, and lawfulness and that pluralism belongs at the surface (language, register, conventions, missing-context defaults) and across the wide band of legitimate value tradeoffs that respect the floor, but not at the level of values that violate it. We highlight the empirical reality of unfiltered pluralistic values, propose four commitments as a constructive alternative, and engage six credible objections: commercial pressure and practical feasibility, democratic legitimacy, regulatory compliance, over-reliance on institutionalist explanations, the charge that the floor itself is culturally laden, and the limits of Coherent Extrapolated Volition.

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

Anytime-Valid Confirmation of Label-Shift Corrections

arXiv:2606.14028v1 Announce Type: cross Abstract: In small-batch scientific deployments, labeled target outcomes may be too scarce for reliable shift estimation even when unlabeled target inputs are available. We address the complementary setting where the practitioner has a pre-specified label-shift correction from domain knowledge and asks whether incoming labeled outcomes support it. We show that the per-observation likelihood ratio between a label-shift-corrected predictive and the source predictive is a conditional e-value, so its running product is a nonnegative martingale and Ville's inequality yields an anytime-valid confirmation rule. The log martingale equals the cumulative negative log-predictive density (NLPD) gap between the source and the corrected predictive, converting routine model monitoring into a formal sequential test. Rejection means the incoming data support the posited correction relative to the source predictive, but it is not a precise estimate of the degree of shift. Closed forms are available for GP sources with Gaussian label-shift ratios. GP regression simulations validate Type I control, finite-sample power, miscalibration sensitivity, and the small-batch advantage of a reliable prior over label-based re-estimation.

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

Beyond Artifacts: Towards Generalizable Synthetic Song Detection via Music-Intrinsic Features

arXiv:2606.16612v1 Announce Type: cross Abstract: The rapid advancement of AI music generators highlights the urgent need for reliable Synthetic Song Detection (SSD). Existing SSD methods often rely on low-level artifacts or fixed feature assumptions, struggling to capture generator-agnostic cues. To address this, we propose Sofia (Synthetic-song detection framework via music features), a flexible framework that models music-intrinsic attributes via feature-specific experts and an adaptive Mixture-of-Experts (MoE) module. By configuring Sofia with representative Vocal, Audio-effect, Global structure features, and their combinations, we present their individual and complementary contributions. To comprehensively evaluate our framework, we further construct MUSIC8K, a challenging benchmark featuring lastest emerging generators and realistic audio perturbations. Experiments show that Sofia learns generator-agnostic representations from music-intrinsic features, improving the F1 score by 18.5 points over the strongest baseline on MUSIC8K-O while maintaining strong robustness.

21.
arXiv (CS.AI) 2026-06-15

Metabolic cost of information processing in Poisson variational autoencoders

arXiv:2602.13421v2 Announce Type: replace-cross Abstract: Computation in biological systems is fundamentally energy-constrained, yet standard theories of computation treat energy as freely available. Here, we argue that variational free energy minimization under a Poisson assumption offers a principled path toward an energy-aware theory of computation. Our key observation is that the Kullback-Leibler (KL) divergence term in the Poisson free energy objective becomes proportional to the prior firing rates of model neurons, yielding an emergent metabolic cost term that penalizes high baseline activity. This structure couples an abstract information-theoretic quantity – the *coding rate* – to a concrete biophysical variable – the *firing rate* – which enables a trade-off between coding fidelity and energy expenditure. Such a coupling arises naturally in the Poisson variational autoencoder (P-VAE) – a brain-inspired generative model that encodes inputs as discrete spike counts and recovers a spiking form of *sparse coding* as a special case – but is absent from standard Gaussian VAEs. To demonstrate that this metabolic cost structure is unique to the Poisson formulation, we compare the P-VAE against Grelu-VAE, a Gaussian VAE with ReLU rectification applied to latent samples, which controls for the non-negativity constraint. Across a systematic sweep of the KL term weighting coefficient $\beta$ and latent dimensionality, we find that increasing $\beta$ monotonically increases sparsity and reduces average spiking activity in the P-VAE. In contrast, Grelu-VAE representations remain unchanged, confirming that the effect is specific to Poisson statistics rather than a byproduct of non-negative representations. These results establish Poisson variational inference as a promising foundation for a resource-constrained theory of computation.

22.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

作者:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

23.
bioRxiv (Bioinfo) 2026-06-22

PanRes: A database of latent and acquired antimicrobial resistance allowing 3D-based protein homology search

Antimicrobial resistance databases are central to genomic surveillance, but resistance determinants remain distributed across resources with different scopes, structures, and annotations. We developed PanRes, a curated resistance database of 11,717 genes integrating acquired and latent determinants of antibiotic, biocide, and metal resistance within a unified ontology. We predicted representative protein structures and clustered them by structural similarity, grouping proteins into 598 structurally conserved clusters coherent despite sequence divergence. Their structure-guided alignments were used to build Hidden Markov Models (HMMs) for remote homology search. In wastewater metagenomes from seven European cities, PanRes 3D-based HMMs expanded detection beyond high-confidence BLAST, with 35.2% of retained hits identified only by the HMMs and generally showing greater divergence from known proteins. For beta-lactamases, several proteins retained beta-lactamase-like folds and catalytic geometry despite weak sequence similarity. PanRes is available through an interactive web platform (https://panres.rambio.dk/), a structure-informed resource for exploring the whole resistome.

24.
arXiv (CS.LG) 2026-06-19

Learning to Emulate Chaos: Adversarial Optimal Transport Regularization

arXiv:2604.21097v2 Announce Type: replace-cross Abstract: Chaos arises in many complex dynamical systems, from weather to power grids, but is difficult to accurately model with data-driven methods such as machine learning emulators. While emulators are promising tools for accelerating simulations and solving inverse problems, they still struggle to learn chaotic dynamics, where sensitivity to initial conditions renders exact long-term forecasts infeasible, especially given noisy data. Recent work instead trains emulators to match the statistical properties of chaotic attractors, but these approaches often rely on handcrafted summary statistics or large, diverse multi-environment datasets. In this work, we propose a family of adversarial optimal transport objectives that can jointly learn high-quality summary statistics and a physically consistent emulator from a single noisy trajectory. We theoretically analyze and experimentally validate a Sinkhorn divergence formulation (2-Wasserstein) and a WGAN-style dual formulation (1-Wasserstein) of our approach. Numerical experiments across a variety of chaotic systems, including ones with high-dimensional spatiotemporal chaos, show that emulators trained using our proposed objectives have significantly improved long-term statistical fidelity.

25.
arXiv (quant-ph) 2026-06-16

Non-Markovianity-based ultrasensitive parameter estimation

arXiv:2211.05142v2 Announce Type: replace Abstract: Accurate parameter estimation is a central task in quantum metrology and sensing, where quantum resources can provide precision beyond classical limits. In realistic settings, however, system-environment interactions lead to decoherence, reducing these strategies to their classical counterparts. Noise is typically classified as Markovian or non-Markovian, with the latter often preserving quantum coherence longer and thus supporting better metrological performance. Still, the absence of noise is generally considered ideal. In this work, we uncover a striking reversal: certain non-Markovian environments not only outperform Markovian ones - including their quantum Cramér-Rao bounds - but can also surpass the entirely noiseless case. We demonstrate these findings numerically for an all-optical setup, which is experimentally feasible and can be extended to other physical platforms. In general, our results open new avenues for noise-assisted quantum metrology beyond conventional limits.