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01.
arXiv (CS.LG) 2026-06-15

Diffusion Policy Optimization without Drifting Apart

arXiv:2606.13795v1 Announce Type: new Abstract: RL post-training has become increasingly pivotal for improving diffusion policies, but existing diffusion policy-gradient methods are often unstable and cannot achieve reliable policy improvement. We identify the cause as the double-drift phenomenon: optimizing a variational surrogate can let the ELBO separate from the true log-likelihood, which then makes the resulting proxy policy gradient misaligned with the true policy gradient of expected return. We propose DiPOD, a diffusion policy optimization framework that maintains tight-bound behavior throughout training by interleaving self-distillation with policy-improving gradient updates. This leads to a simple and practical algorithm: augmenting each diffusion policy-gradient update with an on-policy ELBO regularizer. Across diffusion language model post-training and continuous-control diffusion policies, DiPOD substantially stabilizes training and reaches higher rewards than previous methods.

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

Position: The Systemic Lack of Agency in Visual Reasoning

This paper argues that a systemic lack of Agency constrains the implicit reasoning capabilities of current Vision-Language Models (VLMs). Implicit reasoning refers to the ability to autonomously discover and utilize hidden visual evidence to bridge information gaps, rather than merely relying on explicitly specified targets. This capacity underlies human visual understanding and everyday reasoning. We argue that this limitation arises from a tendency to approach visual reasoning primarily as passive semantic retrieval, rather than as active, situated reasoning that depends on autonomous visual exploration. As a result, most existing benchmarks primarily assess Passive Capacity, leaving this aspect of reasoning largely unmeasured. To address this gap, we introduce the Visual Implicit Reasoning Diagnosing Benchmark (V-IRD), which targets this missing quadrant by requiring models to derive answers strictly through autonomous visual analysis. Our results show that, despite strong retrieval abilities, prominent VLMs struggle to utilize reference objects and to attend to visual evidence that requires self-directed inquiry. Simply put, strong semantic recognition does not equate to active visual exploration, revealing a critical gap in current VLMs. More information can be found at https://haoychen.github.io/Implicit-Reasoning/

03.
PLOS Computational Biology 2026-06-09

Evolution of phenocopying in a dynamical model of developmental trajectories

by Yuuki Matsushita, Archishman Raju Developmental trajectories are known to be canalized, or robust to both environmental and genetic perturbations. However, even when these trajectories are decanalized by an environmental perturbation outside the range of conditions to which they are robust, they often produce phenotypes similar to known mutants, called phenocopies. This correspondence between the effects of environmental and genetic perturbations has received little theoretical attention. Here, we study an abstract regulatory model that is evolved to follow a specific trajectory. We then study the effects of small and large perturbations to the trajectory, both by changing parameters and by perturbing the state at specific times. We find that the phenomenon of phenocopying emerges in evolved trajectories and is not present in a null model of randomly sampled trajectories. Our results suggest that, in this class of dynamic models, evolution can allow high-dimensional phenotypic landscapes to simultaneously exhibit robustness and phenocopying.

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

Adaptive Kernel Density Estimation with Pre-training

arXiv:2605.13092v2 Announce Type: replace-cross Abstract: Density estimation in high-dimensional settings is an important and challenging statistical problem.Traditional methods based on kernel smoothing are inefficient in high dimensions due to the difficulties in specifying appropriate location-adaptive kernels. In this work, we introduce pre-training, a key idea behind many cutting-edge AI technologies, to the context of non-parametric density estimation. By establishing a pre-trained neural network that can recommend an appropriate location-adaptive kernel for each sample point, efficient density estimation with adaptive kernels is achieved in high dimensions. A wide range of numerical experiments show that this strategy is highly effective for improving density-estimation accuracy, when the target distribution is close to the distribution family for pre-training. When the target distribution is substantially different from the pre-training distribution family, the benefit from the proposed pre-training strategy may be diluted, but can be reactivated by an additional fine-tuning procedure.

05.
medRxiv (Medicine) 2026-06-22

UKBAnalytica: an integrated R package for scalable phenotyping and reproducible epidemiological analysis within the UK Biobank Research Analysis Platform

作者:

UK Biobank provides longitudinal health-related data for approximately 500,000 participants, and its Research Analysis Platform (RAP) has shifted large-scale analyses toward secure cloud-based computation. However, many existing tools address only specific steps of the analytical workflow, leaving a need for an integrated framework that connects multi-source disease phenotyping, survival-ready cohort construction, and downstream analysis on the RAP. Here, we present UKBAnalytica, an extensible R package for scalable phenotyping and integrated analysis of UK Biobank data within the RAP environment. It currently includes 52 predefined baseline variables and a built-in library of 331 curated disease definitions. These definitions are based on multiple UK Biobank data sources, including ICD-10, ICD-9, self-reported conditions, death registry records, algorithmically defined outcomes, and OPCS-4 procedure codes. UKBAnalytica distinguishes prevalent and incident cases, constructs follow-up time, generates analysis-ready survival datasets, and summarizes participant flow. Beyond phenotype construction, UKBAnalytica provides integrated modules for epidemiological analysis, omics analysis, and machine-learning-based modeling and interpretation. By linking endpoint definition with downstream modeling under a consistent data structure, UKBAnalytica reduces repetitive scripting and improves analytical transparency. Furthermore, we demonstrate the package's practical utility through a case study on chronic obstructive pulmonary disease (COPD) proteomics. The findings align closely with previously reported conclusions, underscoring the robustness and reliability of our analytical framework. This phenotype-centered framework complements existing UK Biobank tools and facilitates reproducible RAP-based biomedical research. UKBAnalytica is freely available at https://github.com/Hinna0818/UKBAnalytica.

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

Surpassing Scale by Efficiency: A Compact 135M Parameter Foundational LLM Natively Adapted for the Bangla Language

While the NLP landscape is dominated by multi-billion parameter architectures, their deployment in low-resource, non-Latin scripts remains computationally prohibitive for edge configurations, mobile systems, and decentralized local hardware. This paper presents bangla-smollm-135m, a highly compact 135-million parameter decoder-only foundational model engineered explicitly for high-efficiency language modeling in the Bangla script. By leveraging a deterministic intersect-and-append token merging strategy between TituLLMs and SmolLM2-135M, the model overcomes subword script fragmentation without destabilizing early pretrained parameter states. In zero-shot multi-task benchmark evaluations (PIQA_bn, OpenBookQA_bn, CommonsenseQA_bn, and Bangla_MMLU), bangla-smollm-135m matches or outperforms models twice its size (Gemma-3-270m) and achieves parity with models in the 1B parameter tier. The model is available at rnnandi/bangla-smollm-135m

07.
arXiv (CS.AI) 2026-06-11

Sparsified Kolmogorov-Arnold Networks for Interpretable Quantum State Tomography

arXiv:2606.11814v1 Announce Type: cross Abstract: Machine-learning approaches to quantum state tomography can achieve high reconstruction fidelity, but the physical structure used by the trained model often remains implicit. Here we ask whether a sparsified Kolmogorov-Arnold Network (KAN) can be used not only as a regressor, but also as an inspectable reconstruction rule whose internal organization can be checked against known Pauli structure. We study a controlled three-qubit GHZ-family benchmark in which all 63 non-identity Pauli expectation values are used to reconstruct three GHZ-subspace variables: the population imbalance $z$, the real off-diagonal component $c$, and the imaginary off-diagonal component $s$. Under finite-shot sampling and depolarizing noise, external ablation identifies the extended 12-channel GHZ-relevant Pauli set from the 63 measurements, with exact top-12 recovery across the tested shot counts and depolarizing-noise strengths. These support patterns remain stable across multi-seed random-initialization and noise-level analyses, and collapse under random-label controls. The dominant pruned input-hidden-output pathways organize Z-type population observables and X/Y off-diagonal observables in a pattern consistent with the analytic GHZ Pauli grouping, and sparse formula recovery recovers the canonical signed Pauli relations. The contribution of the KAN is therefore pathway-level structural interpretability within a neural reconstruction model, rather than superior sparse regression. Together with negative controls, these probes provide a consistency chain for auditing learned reconstruction rules against known physical structure.

08.
arXiv (CS.LG) 2026-06-15

Hybrid Uncertainty Sensitivity Analysis Based on the HSIC for High-Dimensional Responses with Aleatory–Epistemic Separation

arXiv:2606.14053v1 Announce Type: cross Abstract: Quantifying the influence of hybrid aleatory and epistemic uncertainties on high-dimensional system responses remains a major challenge in global sensitivity analysis (GSA). Existing Hilbert–Schmidt Independence Criterion (HSIC)-based approaches are primarily restricted to single-output settings and lack a rigorous decomposition of heterogeneous uncertainty sources and their interactions. To address this limitation, a novel double-space tensor-product RKHS framework is proposed for sensitivity analysis under hybrid uncertainty. By constructing factorized kernels over both the latent input space and the multidimensional output space, a concurrent double Möbius inversion is derived to orthogonally decompose the global dependence measure into pure aleatory effects, pure epistemic effects, and their interaction contributions. The resulting dimension-wise sensitivity indices preserve the uncertainty attribution structure across all output dimensions. To satisfy the independence assumptions required by the decomposition, an auxiliary-variable representation based on the inverse probability integral transform is introduced, enabling the treatment of hierarchical uncertainties and Copula-induced correlations within a unified latent space. A fully vectorized single-loop implementation is further developed to avoid the computational burden of nested Monte Carlo simulation. Statistical significance and estimation uncertainty are quantified through permutation testing and Bootstrap confidence intervals. Numerical studies on a modified multi-output Ishigami function and an aerodynamic pressure-field problem demonstrate the accuracy, scalability, and practical applicability of the proposed framework.

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

DiffCoord: Differentiable Coordination for Distributed Multi-Agent Trajectory Optimization

arXiv:2509.01630v3 Announce Type: replace Abstract: Integrating the Alternating Direction Method of Multipliers (ADMM) with Differential Dynamic Programming (DDP) provides a scalable framework for distributed multi-agent trajectory optimization. In practice, ADMM is typically truncated for computational efficiency, tightly coupling parameters that would otherwise separately govern coordination quality and task performance. In this paper, we propose Differentiable Coordination (DiffCoord), a unified framework that jointly meta-learns these coupled parameters for the truncated ADMM-DDP pipeline. These parameters are generated by agent-wise neural networks for task adaptation, and the same networks are shared among isomorphic agents to enable scalability to varying agent counts. We achieve efficient meta-learning by differentiating the ADMM-DDP pipeline end-to-end. Notably, this yields an auxiliary ADMM-LQR distributed gradient solver that computes and coordinates meta-gradients with respect to these parameters. This solver inherits the computational structure of the pipeline, enabling reuse of key computation results and efficient parallelization over agents and along trajectory horizons. We validate DiffCoord through numerical and physical experiments on a cooperative aerial transport system, where it reconfigures quadrotor formations for safe 6-DoF load manipulation in tight spaces. It adapts robustly to varying team sizes and load dynamics, while reducing per-agent gradient computation time by up to 70% compared with state-of-the-art trajectory-gradient methods.

10.
arXiv (CS.CV) 2026-06-18

The Market in the Model: Latent Diffusion as Neural Economy

Valuable critique of generative image models within visual culture and the humanities has emphasized the role of datasets in shaping the images they produce. Yet, close studies of the ideological positions embedded into the mechanism of the models have been neglected, leaving them imagined as "black boxes." In a bid to expand, rather than replace, dataset critique, this paper examines the mechanisms of the latent diffusion model in terms of the problems they were brought in to solve on behalf of computer vision engineers, and the decisions each component was tasked with automating. I interpret that ensemble through the histories of its parts and the theory of vision the system inscribes into every generated image. Drawing on Impett and Offert's notion of neural exchange value, I offer this analysis to argue that the model operates as a neural economy: a contained symbolic system that abstracts social communication into commensurable vectors as it transfers the social sphere into parcels for sale. Tracing the training and generation pipelines component by component reveals what each operation displaces, and how it further entrenches the logics of platform and attention economies over social communication. The paper warns that any critique fixated exclusively on copyright and commodity defenses risks reaffirming the very fetishism the model produces, and argues instead for centering social exchange.

11.
arXiv (quant-ph) 2026-06-16

Optimal Toffoli-Depth Multi-Controlled Toffoli Decomposition in 2D Qubit Layout

arXiv:2606.15113v1 Announce Type: new Abstract: The multi-controlled Toffoli (MCT) gate is a key primitive in quantum arithmetic, oracle construction, and quantum cryptanalysis. Although recent work has established optimal Toffoli-depth MCT decompositions under all-to-all qubit connectivity, their realization on near-term quantum hardware with restricted qubit connectivity remains largely unexplored. While general-purpose quantum mappers can route arbitrary circuits, they do not explicitly exploit the repeated interaction patterns inherent in MCT decompositions. In our present paper, we study architecture-aware mappings of optimal Toffoli-depth MCT decompositions onto restricted two-dimensional qubit layouts. We begin with a structured geometric placements that preserve the parallelism of state-of-the-art Toffoli and MCT decompositions with no additional depth overhead. We further introduce a motif-based packing framework in which decomposition layers are represented by interaction motifs derived from basic Toffoli gates. By embedding these motifs vertex-disjointly into hardware graphs, we characterize the minimum-size topologies supporting the required qubit resources and derive explicit bounds on the resulting depth overhead under tight qubit budgets. Finally, we compare these bounds with routing-aware placement heuristics and empirically evaluate the effectiveness of embedding different motifs across a range of hardware topologies.

12.
arXiv (CS.CV) 2026-06-16

X-Tokenizer: A Multimodal Action Tokenizer for Vision-Language-Action Pretraining

Modern Vision-Language-Action (VLA) models must bridge pretrained vision-language reasoning and precise continuous robot control. Existing action tokenizers discretize actions primarily for reconstruction, producing codes that preserve motion geometry but provide only weak semantic supervision to the backbone. We therefore formulate action tokenization not as mere compression, but as semantic interface learning between multimodal reasoning and executable control. To this end, we introduce X-Tokenizer, a lightweight encoder-Semantic Residual Quantization (SRQ)-decoder architecture that provides a shared action interface across diverse robotic arm embodiments. Its key component, SRQ, imposes an asymmetric structure on residual vector quantization: the first level is trained with Masked Action Modeling (MAM) to form a discrete action language that captures coarse motion intent, while deeper levels remain reconstruction-oriented residuals that preserve fine-grained details. To further align action tokens with multimodal semantics, X-Tokenizer is pretrained with contrastive alignment to the representation space of a pretrained foundation model and with next-frame vision-language feature prediction. Pretrained on 2.4M trajectories (2.0B action frames), a single frozen X-Tokenizer plugs into a mixed discrete-continuous VLA as a representation-shaping supervision signal. X-Tokenizer achieves top real-world aggregate and strong RoboTwin 2.0 simulation results. Outperforming FAST in multimodal grounding (+13.5%) and long-horizon tasks (+8.25), it shows that action tokenizers serve as semantic interfaces for VLA pretraining beyond mere action compression.

13.
medRxiv (Medicine) 2026-06-17

Differential Determinants of Past Behavior and Future Intention Regarding Voluntary Blood Donation: A Cross-Sectional Study of Knowledge, Attitudes, and Practices in Qingdao, China

Background A persistent gap between motivation and action threatens voluntary blood supply. This study examined the publics knowledge, attitudes, and practices (KAP) regarding blood donation, with a particular focus on identifying the different determinants of past blood donation behavior and future willingness to donate. Methods Convenience sampling was used to conduct a cross-sectional survey among 1,058 eligible people in Qingdao, China, between July and November 2025. Data were collected via a self-designed KAP questionnaire. To find independent characteristics linked to previous behavior and future intention, respectively, multivariable binary logistic regression was used. Results Overall, 37.0% of participants (n=391) had a lifetime donation history, while 39.2% (n=415) intended to donate in the next 12 months. Past behavior was positively associated with older age (36-45 years: OR=6.84; 95% CI: 3.21-14.58), higher education (OR=2.06; 95% CI: 1.33-3.17), and interpersonal interaction channels (OR=1.45; 95% CI: 1.01-2.09) but hindered by safety concerns (OR=0.23; 95% CI: 0.16-0.34). Conversely, future intention was positively correlated with male sex (OR=1.69; 95% CI: 1.24-2.29), prior donation history (OR=2.69; 95% CI: 1.87-3.86), having family members or friends in need of blood (OR=2.75; 95% CI: 1.96-3.85), and traditional media exposure (OR=3.33; 95% CI: 2.18-5.10). Higher education was adversely correlated with future intention (OR=0.55; 95% CI: 0.38-0.79). Conclusion There is a substantial disparity between donation motivation and action. The determinants of past behavior and future intention are asymmetric, suggesting that stage-specific interventions are required, using social mobilization for initiating first-time donations, while employing family reciprocity and authoritative communication to sustain long-term engagement.

14.
arXiv (quant-ph) 2026-06-19

Quantum Batteries as Work Sources for Phase-Locked Parametric Amplification

arXiv:2606.20306v1 Announce Type: new Abstract: Quantum batteries have been proposed as locally precharged work sources for superconducting quantum technologies, suggesting a route to reduce continuously supplied microwave drives. Here we ask whether the pump tone of a quantum-limited parametric amplifier can be replaced, or strongly duty-cycled, by a finite bosonic quantum battery. Quantizing the pump of a nondegenerate parametric amplifier exposes a resource distinction hidden in the classical description: stored pump energy can generate signal-idler photons, but pump phase coherence is required to generate a phase-locked amplifier field. In a closed trilinear model, coherent and phase-randomized coherent pumps with the same photon-number distribution produce comparable pair numbers, yet only the coherent pump produces anomalous two-mode coherence and an EPR-squeezed interference dip. Including leakage, we collect the emitted fields into cascaded temporal modes. At matched collector bandwidth, the coherent pump gives \(I_{\min}^{(f)}=0.553\), whereas the phase-randomized pump gives \(I_{\min}^{(f)}=1.94\) at nearly identical collected energy. Weak amplitude squeezing slightly improves the dip by reducing finite-pump number fluctuations while preserving the coherent displacement. Thus battery-powered parametric amplification requires phase-coherent stored energy, possibly assisted by number-noise reduction, rather than stored energy alone.

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

WeGenBench: A Multidimensional Diagnostic Benchmark towards Text-to-Image Model Optimization

Recent text-to-image generation models have demonstrated remarkable capabilities in synthesizing highly realistic images from text inputs alone. Although existing benchmarks can evaluate the generation capabilities of various models to some extent, they struggle to comprehensively and accurately measure performance across multiple dimensions, often failing to reveal the inherent deficiencies of models in specific categories. To address these limitations, we propose WeGenBench, a novel benchmark designed for the comprehensive, multi-perspective evaluation of text-to-image generation capabilities. Our benchmark comprises a total of 4,000 test prompts across two primary categories, meticulously balanced between Chinese and English to evaluate bilingual and cross-cultural generation capabilities. Beyond macroscopic scene classification, we annotate each prompt with multi-dimensional tags tailored to the distinct content and challenges of each language, thereby refining the generation tasks into more specific sub-categories. Through a cross-dimensional evaluation mechanism leveraging both scene classifications and multi-dimensional tags, WeGenBench can precisely pinpoint model shortcomings in specific generation categories. Furthermore, to measure generation quality more accurately, we design and validate several novel evaluation metrics by integrating Vision-Language Models (VLMs), which assess model performance on domain-specific tasks from three core aspects. Crucially, our approach yields both the assessment outcomes and the detailed reasoning trajectories, facilitating a rigorous verification of the accuracy and soundness of the evaluation results. Finally, we conduct systematic benchmarking on current state-of-the-art methods and provide an in-depth analysis of the limitations present in existing models.

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

Model-Free Reinforcement Learning Control for Resilient Cyber-Physical Systems

arXiv:2606.19069v1 Announce Type: cross Abstract: This paper compares the performance of model-free controllers on a nonlinear system under cyberattacks, including false data injection and denial-of-service attacks. Four RL reward types are analyzed for accuracy, cost, and resilience. Results show that the Lyapunov reward offers the best resilience with low tracking error. Exponential mode also provides good trade-offs with acceptable resilience under moderate training conditions. Progressive and linear rewards converge faster but are less robust. RL-MPCs show strong steady-state resilience but require longer training times; RL-PID controllers are faster with significantly less training time. Proximal Policy Optimization outperforms Deep Deterministic Policy Gradient with a significant reduction in KPI variance. This study serves to highlight how well-designed RL rewards can improve performance and resilience against cyber threats.

17.
arXiv (CS.CL) 2026-06-16

ESBMC-PLC: Formal Verification of IEC 61131-3 Ladder Diagram Programs Using SMT-Based Model Checking

PLCs execute safety-critical programs across industrial sectors. The dominant PLC notation, ladder diagram (LD) per IEC 61131-3, remains absent from formal verification: SMT-based model checkers cannot process LD's rung-and-coil graphics. This paper presents ESBMC-PLC, the first open-source formal verifier with native LD support (PLCopen XML format), implemented as a new ESBMC frontend. ESBMC-PLC translates LD rungs to GOTO IR, models the PLC scan cycle as a while(true) loop with nondeterministic inputs, and checks safety properties via SMT-based bounded model checking or k-induction. A five-property YAML language (mutual_exclusion, invariant, absence, response, reachability) avoids temporal logic. A survey of 22 studies (2020-2026) identifies four research gaps; ESBMC-PLC closes two of them. Evaluation on 13 benchmarks (6 domains, 3 sources - including deployed CONTROLLINO PLCs and MathWorks Simulink PLC Coder) shows correct classification across 61 properties: all 9 author-constructed programs (Categories A/B) as expected, all 4 vendor programs (Category C) correctly unlabeled, with 8 bugs found (actionable counterexamples), 7 unbounded k-induction proofs, all runs under 60ms on Apple Silicon. Feature comparison with PLCverif shows that ESBMC-PLC is the only open-source tool that combines native LD, k-induction, and SMT bit-vector semantics.

18.
arXiv (quant-ph) 2026-06-12

Quantum Otto engine powered by an anisotropic Heisenberg XYZ model under independent local magnetic fields

arXiv:2606.12877v1 Announce Type: new Abstract: We study a quantum Otto heat engine whose working substance is an anisotropic two-qubit Heisenberg XYZ model. Independent local magnetic fields are used to control each spin individually. The influence of the longitudinal coupling, anisotropy, transverse coupling, and local fields on the net work output and efficiency is systematically examined. Reducing the longitudinal coupling is found to markedly improve both the maximum work and the peak efficiency. The engine performance reaches an optimum at a particular value of the anisotropy parameter. A local work analysis clarifies how work is produced during the cycle. Because of the asymmetric local fields and the intrinsic spin-spin interaction, the two qubits play markedly different thermodynamic roles; the interaction term itself contributes crucially to the total work. We further analyze the variation of quantum entanglement, quantified by concurrence, along the cycle. The results indicate that a pronounced change in entanglement between the hot and cold isomagnetic strokes is closely correlated with the efficiency enhancement. This work offers new insight into the operating principles and control of quantum Otto heat engines.

19.
arXiv (quant-ph) 2026-06-16

Theory of the correlated quantum Zeno effect in a monitored qubit dimer

arXiv:2503.22846v2 Announce Type: replace Abstract: We theoretically investigate the stochastic dynamics of two qubits subject to one- and two-site correlated continuous weak measurements. When measurements dominate over the local unitary evolution, the system's dynamics is constrained and part of the physical Hilbert space becomes inaccessible: a typical signature of the Quantum Zeno (QZ) effect. In this work, we show how the competition between these two measurement processes give rise to two distinct QZ regimes, we dubbed standard and correlated, characterised by a different topology of the allowed region of the physical Hilbert space being a simply and non-simply connected domain, respectively. We develop a theory based on a stochastic Gutzwiller ansatz for the wavefunction that is able to capture the structure of the phase diagram. Finally we show how the two QZ regimes are intimately connected to the topology of the flow of the underlying non-Hermitian Hamiltonian governing the no-click evolution.

20.
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.

21.
arXiv (quant-ph) 2026-06-11

Honest-binding quantum bit commitment from separable operations

arXiv:2501.07351v3 Announce Type: replace Abstract: Bit commitment is a fundamental cryptographic primitive and a cornerstone for numerous two-party cryptographic protocols, including zero-knowledge proofs. However, it has been proven that unconditionally secure bit commitment, both classical and quantum, is impossible. In this work, we demonstrate that imposing a restriction on the committing party to perform only separable operations enables secure quantum bit commitment schemes. Specifically, we prove that in any perfectly hiding bit commitment protocol, an honestly-committing party limited to separable operations will be detected with high probability if they attempt to alter their commitment. To illustrate our findings, we present an example protocol.

22.
medRxiv (Medicine) 2026-06-19

A soluble bi-specific fusion protein for the improved expansion of human CD8+ CAR-T cells

The success of Chimeric Antigen Receptor (CAR) T cell therapy is heavily dependent on the quality of the final cellular product. Current expansion protocols often rely on reagents that require removal from cell culture media, posing logistical challenges in manufacturing, and can also lead to terminal differentiation. Here, we evaluate the use of a soluble, bead-free T cell activator, T cell expansion protein (T-CEP), as a streamlined alternative for generating potent CAR-T cells. Human T cells were activated with T-CEP or known T cell activators (Dynabeads and TransAct) and transduced with either CD19 or interleukin-13 (IL-13) mutein (tetravariant-13; TV-13)-based CAR lentiviral vectors. Our results demonstrate that T-CEP supports robust CAR-T cell expansion and achieves transduction efficiencies comparable to commercial reagents for both types of CAR-T cells. Notably, T-CEP significantly favored the expansion of CD8+ T cells, yielding an enhanced CD27+ phenotype and a lower CD4:CD8 ratio compared to TransAct. Cytotoxicity assays confirmed that T-CEP-expanded CAR-T cells possess cytolytic function equivalent to commercial reagents for both CARs, while exhibiting lower levels of inflammatory cytokine secretion. In summary, T-CEP represents a competitive alternative to existing expansion agents, as it does not require its removal during CAR-T manufacturing and generates a CD8+ dominant, less-differentiated phenotype without compromising efficacy.

23.
arXiv (CS.CV) 2026-06-16

Enhancing Precision Agriculture with a Hybrid Deep Learning Framework for Multi-Class Plant Disease Classification and Interpretability

This study proposes an overall deep learning architecture for multi-class classification of plant diseases from high-resolution leaf imagery, with a particular interest in investigating the behavior of ResNet-50 and a hybrid ResNet + Vision Transformer (ViT) design. A specially gathered image database with 15,200 training images and 3,800 validation images spanning 38 classes across multiple crops, including tomato, apple, grape etc. were subjected to preprocessing steps such as resizing, normalization, and data augmentation to enhance model robustness. Multiple architectures, including ResNet-50, MobileNetV2, and EfficientNet-B0, were trained and compared with the hybrid ResNet + ViT model. All models were fine-tuned using the AdamW optimizer and cross-entropy loss, with early stopping applied to prevent overfitting and ensure generalization. Furthermore, interpretability techniques such as Grad-CAM and saliency maps were implemented to indicate disease-relevant regions, while segmentation-based analysis was performed to identify the affected parts of a leaf. For every one of the considered architectures, ResNet-50 led to the highest accuracy of 98.74%, whereas the hybrid ResNet + ViT model achieved a competitive accuracy of 98.58%, showing that the hybrid architectures were effective in capturing both local and overall information. The experimental results showcase the promise of transformer-based models to achieve highly accurate, interpretable, and computationally efficient computer-based multi-class multi-disease classification systems, providing helpful assistance for cultivation management practices as well as for precision farming.

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

MODF-SIR: A Multi-agent Omni-modal Distilled Framework for Social Intelligence Reasoning

arXiv:2606.12018v1 Announce Type: new Abstract: We propose a multi-agent collaborative framework built upon a lightweight Multimodal Large Language Model (MLLM), specifically designed for social intelligence reasoning. A key feature of our approach is that both the training and inference phases are augmented via knowledge distillation. Within this architecture, multi-modal data pertinent to social intelligence is precisely localized. Furthermore, relevant long-tail events are identified, extracted, and rendered as formatted, explicit text. This formatting strategy prevents critical long-tail information from being overshadowed by head events and environmental noise during the tokenization process. Specifically, we integrate Test-Time Adaptation (TTA) across the entire reasoning pipeline, encompassing the extraction and representation of long-tail events, Chain-of-Thought (CoT) prompting, and self-reflection. This TTA mechanism is also distillation-enhanced, utilizing Low-Rank Adaptation (LoRA) to fine-tune the foundation model exclusively for instance-level reasoning. Extensive evaluations against various open-source and proprietary AI models across multiple benchmarks demonstrate the effectiveness of the proposed framework. With around 30% of training data from IntentTrain, we achieve state-of-the-art results. Codes are available at https://github.com/eeee-sys/MODF-SIR, demo is available at https://huggingface.co/spaces/Harry-1234/MODF-SIR, LoRA is available at https://huggingface.co/Harry-1234/MODF-SIR and the dataset for training router is available at https://huggingface.co/datasets/Harry-1234/IntentRouterTrain.

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

MIVE: A Minimalist Integer Vector Engine for Softmax LayerNorm and RMSNorm Acceleration

arXiv:2606.17781v1 Announce Type: cross Abstract: The rapid growth of Large Language Models (LLMs) has intensified the need for specialized hardware accelerators that can satisfy stringent inference latency and power constraints. Although matrix multiplications dominate the overall computational workload, non-linear vector normalization operations, such as LayerNorm, RMSNorm and Softmax can become critical hardware bottlenecks. Existing accelerators typically implement these functions using dedicated hardware blocks, leading to duplicated resources and inefficient silicon utilization. To address this limitation, we propose a Minimalist Integer Vector Engine (MIVE), a programmable architecture capable of executing all three operations within a unified datapath. By exploiting common computational patterns across LayerNorm, RMSNorm and Softmax the proposed vector engine maximizes hardware sharing while reducing implementation overhead. Physical ASIC implementation results show that MIVE provides comprehensive multi-function support while achieving higher area and hardware efficiency than most state-of-the-art standalone accelerators.