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01.
arXiv (CS.AI) 2026-06-18

Quality Perceptions and Intended Engagement in Response to AI-Generated and AI-Assisted News

arXiv:2409.03500v4 Announce Type: replace-cross Abstract: The increasing use of artificial intelligence (AI) in news production raises important questions about how audiences perceive and respond to AI-generated journalism. This preregistered survey experiment (N = 599, German-speaking Switzerland) examines (i) perceptions of article quality (measured as credibility, readability, and expertise) across news excerpts that were human-written, AI-assisted, or fully AI-generated, and (ii) self-reported intentions to engage following disclosure of AI involvement. Participants rated two short news excerpts before learning how they had been produced. Articles across all conditions were evaluated similarly in perceived quality. After disclosure, participants in the AI-assisted and AI-generated conditions reported a higher willingness to continue reading their assigned articles compared to the control group, but future willingness to read AI-generated news did not differ across conditions. Overall, the findings suggest that readers assess AI-generated and human-written news comparably in quality, while disclosure of AI use can momentarily increase curiosity or interest without yet changing longer-term reading intentions.

02.
arXiv (CS.CV) 2026-06-24

Pocket-SLAM: Rendering-Area-Aware Pruning for Memory-Efficient 3DGS-SLAM

3D Gaussian Splatting (3DGS) has garnered significant attention in Simultaneous Localization and Mapping (SLAM) due to its advances in capturing fine-grained geometry features and synthesizing novel views. For SLAM in large-scale scenes, such as autonomous driving, 3DGS-SLAM faces a critical limitation: memory consumption increases continuously over time as Gaussian points accumulate, leading to poor memory efficiency and limiting its applicability. In this work, we propose a rendering-area-aware pruning strategy that selectively removes Gaussians based on their contribution to the effective rendering area, rather than solely relying on Gaussian-level heuristics such as opacity or gradient magnitude. This perspective directly targets the sources of memory redundancy, effectively reducing the peak memory footprint of 3DGS-SLAM during runtime. Evaluations on the EuRoC and KITTI datasets demonstrate that our method consistently outperforms existing pruning approaches in large-scale outdoor scenes, achieving over 60% memory reduction and more than 2 times FPS improvement while preserving localization and mapping accuracy. These results highlight rendering-area-aware pruning as a promising direction for scaling 3DGS-SLAM to real-world autonomous driving scenarios. Our code is publicly available at https://github.com/UMN-ZhaoLab/Pocket-SLAM.git.

03.
PLOS Computational Biology 2026-06-22

Integrative modelling of innate immune response dynamics during virus infection

by Ramya Boddepalli, Harsh Chhajera, Rahul Roya Positive-sense RNA viruses that constitute a large class of human pathogens employ various strategies to suppress and evade host immune defenses. Understanding the dynamic interaction between the viral life cycle and immune signaling is crucial to designing effective antiviral strategies. Although significant progress has been made, quantitative models that can accurately capture the intricate interactions and the intertwined dynamics during viral infection of cells remain missing. In this study, we develop a comprehensive mathematical model that integrates the intracellular viral life cycle with key cellular innate immune pathways, including RIG-I-mediated detection and JAK-STAT signaling. The model provides mechanistic insights into long-standing observations, capturing both virus-specific dynamics and innate immune response, and the key components driving their coupled dynamics. For example, a comparison of viruses shows how the Japanese Encephalitis virus undergoes a dramatic reduction in viral load in cells, due to its rapid replication that robustly activates the RIG-I pathway, in contrast to the poor immune control of Hepatitis C virus. More importantly, our model demonstrates how virus-host interactions exhibit a sharp transition boundary behavior, where minor differences in immune strength or viral suppression capacity can determine whether infections resolve or persist. We propose that ISG mRNA translation and viral replication predominantly dictate these bimodal infection outcomes. Additionally, the model not only recapitulates IFN desensitization but also identifies the molecular players involved. We demonstrate how our model’s ability to capture IFN dynamics allows us to predict optimal timing and dosing strategies for interferon-based prophylactic therapies. Together, our approach reveals fundamental features that govern the delicate balance between the establishment of infection and immune control in RNA virus infections.

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

Nous: An Attempt to Extract and Inject the Cognition Behind Prediction-Market Behavior

作者:

arXiv:2606.13038v1 Announce Type: new Abstract: As LLM agents proliferate in prediction markets and collective decision-making, they risk a cognitive monoculture: agents built on shared foundation models produce correlated forecasts, and recent measurement finds frontier-model errors correlated at r ~ 0.77. We ask whether human cognitive diversity can be recovered from behavior and transferred to LLM agents. Nous extracts a structured eight-dimension behavioral profile from real Polymarket trading activity and injects it into agents through prompts. Our central finding is a dissociation between the two halves of that pipeline. Extraction works, partially: across 100 wallets, 8 of 14 parameters are temporally stable (split-half ICC >= 0.5, bootstrap CI lower bound > 0.3; contrarian score reaches ICC ~ 0.9); wallets are identifiable from their profiles well above chance (top-1 retrieval 17-22% vs. 1% chance); and two of four pre-specified dimensions rank-correlate with future realized profit out-of-sample, though the correlations do not survive behavioral-confound controls. Prompt-level injection does not measurably transmit it: on a semantic embedding metric, structured injection shows no significant advantage over a length-matched control on any model, and the diversity it induces neither reduces ensemble error correlation nor improves Brier score – a null that persists across exploratory checks on sampling temperature, profile diversity, and question difficulty. Measuring the prompts themselves locates the compression before the model: the structure-to-narrative translator emits near-uniform prompts whose spread does not track profile spread. We position Nous as measuring the cognitive-monoculture problem and the limits of a prompt-level remedy, motivating deeper, below-the-prompt injection (fine-tuning, activation steering). Code, frozen profiles, prompts, and model outputs: https://github.com/WillChienT/nous-paper

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

FPGA-Based Neural Network Accelerators for Space Applications: A Survey

arXiv:2504.16173v3 Announce Type: replace-cross Abstract: Space missions are becoming increasingly ambitious, necessitating high-performance onboard spacecraft computing systems. In response, field-programmable gate arrays (FPGAs) have garnered significant interest due to their flexibility, cost-effectiveness, and radiation tolerance potential. Concurrently, neural networks (NNs) are being recognized for their capability to execute space mission tasks such as autonomous operations, sensor data analysis, and data compression. This survey serves as a valuable resource for researchers aiming to implement FPGA-based NN accelerators in space applications. By analyzing existing literature, identifying trends and gaps, and proposing future research directions, this work highlights the potential of these accelerators to enhance onboard computing systems.

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

Coherent Dark State Formation of a Lead-Vacancy Spin Qubit in Diamond

arXiv:2605.27841v2 Announce Type: replace Abstract: A lead-vacancy (PbV) center in diamond exhibits coherent emission above the liquid helium temperature, making it highly attractive for quantum network applications. Here, we report the magneto-optical and spin properties of PbV centers in diamond. We record a spin lifetime of 12 ms at 7.5 K under large off-axis magnetic field. Furthermore, we observe formation of the coherent dark state by coherent population trapping and estimate a spin dephasing time of 177 ns at 6.5 K. This work demonstrates the outstanding thermal robustness of the PbV spin compared to other group-IV centers above 4 K.

07.
arXiv (CS.AI) 2026-06-18

Caring Without Feeling: Affective Dynamics as the Control Layer of Human-AI Agent Collaboration

arXiv:2606.18259v1 Announce Type: cross Abstract: AI agents that plan, retain memory across sessions, invoke external tools and act with partial autonomy are transforming human–AI collaboration. Research on affective computing, simulated empathy in large language models, trust in automation and AI safety has illuminated important design principles, yet these literatures remain fragmented. No integrated account explains how affective cues operate within agentic collaboration – settings in which humans delegate, monitor and correct consequential tasks. This Review synthesises computational and interactional mechanisms of affective dynamics: the processes through which affective cues, emotion-like behaviour and perceived agent affect shape trust calibration, delegation decisions, error correction, dependence and governance. We trace how model-generated affective signals enter interaction loops that govern reliance, repair and oversight, and propose a framework that treats affect not as an internal property of AI but as a coordination layer through which humans and agents negotiate capability, uncertainty and responsibility. The framework provides a foundation for calibrated measurement, purposeful design and informed governance.

08.
arXiv (CS.AI) 2026-06-18

Analysing drivers and interdependencies in European electricity markets using XAI

arXiv:2606.19118v1 Announce Type: new Abstract: Electricity markets are inherently complex systems characterised by strong nonlinearities, high-dimensional interactions, and increasing interdependence across regions. While deep neural networks (DNNs) have demonstrated strong predictive capabilities for electricity prices, their lack of interpretability limits their usefulness for understanding the underlying drivers of price formation. This paper addresses this gap by combining DNN models with explainable artificial intelligence (XAI) techniques to analyse the determinants of electricity prices across 39 European bidding zones. We employ SHAP (SHapley Additive exPlanations) to quantify feature contributions and apply and extend SSHAP, an aggregation framework to improve interpretability in high-dimensional settings. The analysis identifies that renewable energy sources, particularly solar, play a disproportionately important role in price formation despite their lower share in total power generation. Gas prices remain a dominant and consistent driver across electricity markets, while interconnections significantly shape price dynamics, highlighting the strong interdependence of European electricity systems. In addition, a synthetic EU-wide electricity market is constructed to explore the counterfactual scenario of a fully integrated market with a single price.

09.
medRxiv (Medicine) 2026-06-11

A Global Health Quality Improvement Project: Enhancing Cervical Cancer Awareness and screening in Nigeria

Background Cervical cancer remains a significant global public health challenge, ranking as the fourth most common cancer among women worldwide. According to The World Health Organization (WHO) 604,000 women were diagnosed with cervical cancer globally in 2020, with over 342,000 deaths amongst this group [1]. Despite its high mortality, cervical cancer is largely preventable through early detection and vaccination against human papillomavirus (HPV), which causes nearly all cases of cervical cancer [1,2] In Nigeria, it is the second most common cancer among women in Nigeria and a leading cause of cancer-related deaths, with low screening rates exacerbating late diagnoses and poor outcomes [1]. Despite global commitments to elimination with Pap smear screening and HPV vaccination, less than 10% of women in Nigeria have undergone screening due to misconceptions, stigma, and limited awareness. Educational interventions may improve awareness and promote screening behaviors. This global health quality improvement (QI) project aimed to enhance cervical cancer awareness and increase Pap smear uptake at the Central Bank of Nigeria (CBN) Clinic in Abuja, Nigeria. Methods In November 2024, we conducted a health education intervention at the Central Bank of Nigeria (CBN) through a structured educational session for male and female CBN staff members. The session focused on cervical cancer prevention, risk factors, and screening guidelines. Additionally, cervical cancer awareness was raised via email, social media, and electronic bulletin board. Participants completed pre and post-interventions surveys assessing cervical cancer knowledge across 10 key items and demographic characteristics. Pap smear uptake was assessed using the CBN clinic records for three months before and after the intervention. Institutional approval was obtained from CBN and external institutional review board approval was not required. Results 188 participants attended the health education session with 124 survey responses (70 pre-event, 54 post-event). Participants were mostly women aged 30-39. Post-intervention, eight of ten survey questions showed improved knowledge, with five demonstrating statistically significant gains: understanding Pap smear frequency (p

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

ForceForget: Reinforcement Concept Removal for Enhancing Safety in Text-to-Image Models

With the advance of generative AI, the text-to-image (T2I) model has the ability to generate various contents. However, T2I models still can generate unsafe contents. To alleviate this issue, various concept erasing methods are proposed. However, existing methods tend to excessively erase unsafe concepts and suppress benign concepts contained in harmful prompts, which can negatively affect model utility. In this paper, we focus on eliminating unsafe content while maintaining model capability in safe semantic meaning interpretation by optimizing the concept erasing reward (CER) with reinforcement learning. To avoid overly content erasure, we introduce the Safe Adapter to project partial text embedding for efficient concept regulation in cross-attention layers. Extensive experiments conducted on different datasets demonstrate the effectiveness of the proposed method in alleviating unsafe content generation while preserving the high fidelity of benign images compared with existing state-of-the-art (SOTA) concept erasing methods. In terms of robustness, our method outperforms counterparts against red-teaming tools. Moreover, we showcase the proposed approach is more effective in emerging image-to-image (I2I) scenarios compared with others. Lastly, we extend our method to erase general concepts, such as artistic styles and objects. Disclaimer: This paper includes discussions of sexually explicit content that may be offensive to certain readers. All images used in this work are synthesized or from public datasets.

11.
medRxiv (Medicine) 2026-06-23

Multivariate Echocardiographic Phenotyping of Hypertensive Heart Failure Using Unsupervised Machine Learning: A Pilot Study

Background Heart failure in hypertensive patients is heterogeneous and poorly captured by traditional left ventricular ejection fraction (LVEF) based classification. Multivariate echocardiographic data combined with unsupervised machine learning may provide a more precise phenotypic characterization. This pilot study evaluated the feasibility of unsupervised clustering of routine transthoracic echocardiographic data to identify phenotypic subgroups of hypertensive heart failure. Methods This retrospective pilot study analyzed transthoracic echocardiography reports from hypertensive patients with clinical heart failure. After data cleaning and exclusion of incomplete records, 102 patients with 11 echocardiographic variables were included. Variables describing left ventricular geometry, systolic function, and diastolic performance were standardized and subjected to K-means clustering. Optimal cluster number was determined using the elbow method and silhouette analysis. Cluster characteristics were assessed using descriptive statistics and Kruskal Wallis testing. Concordance with LVEF based heart failure categories was evaluated. Results Three distinct echocardiographic phenotypes were identified. Cluster 0 (n = 50) demonstrated preserved LVEF with concentric remodeling, consistent with heart failure with preserved ejection fraction (HFpEF) phenotype. Cluster 1 (n = 37) showed marked ventricular dilation and reduced systolic function, consistent with heart failure with reduced ejection fraction (HFrEF). Cluster 2 (n = 15) exhibited concentric hypertrophy with intermediate LVEF, consistent with heart failure with mildly reduced ejection fraction (HFmrEF) like phenotype. All echocardiographic variables differed significantly across clusters (p < 0.001). While Cluster 0 showed strong concordance with HFpEF (96%), Clusters 1 and 2 demonstrated substantial overlap across LVEF categories, indicating partial discordance between structural phenotypes and LVEF based classification. Conclusion Application of unsupervised machine learning to routine echocardiographic data identifies distinct heart failure phenotypes in hypertensive patients. These phenotypes demonstrate significant structural heterogeneity beyond LVEF based classification, supporting the utility of data-driven approaches for refined cardiac phenotyping. This pilot study provides a foundation for larger prospective studies.

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

PaLMR: Towards Faithful Visual Reasoning via Multimodal Process Alignment

Reinforcement learning has recently improved the reasoning ability of Large Language Models and Multimodal LLMs, yet prevailing reward designs emphasise final-answer correctness and consequently tolerate process hallucinations–cases where models reach the right answer while misperceiving visual evidence. We address this process-level misalignment with PaLMR, a framework that aligns not only outcomes but also the reasoning process itself. PaLMR comprises two complementary components: a perception-aligned data layer that constructs process-aware reasoning data with structured pseudo-ground-truths and verifiable visual facts, and a process-aligned optimisation layer that constructs a hierarchical reward fusion scheme with a process-aware scoring function to encourage visually faithful chains-of-thought and improve training stability. Experiments on Qwen2.5-VL-7B show that our approach substantially reduces reasoning hallucinations and improves visual reasoning fidelity, achieving state-of-the-art results on HallusionBench while maintaining strong performance on MMMU, MathVista, and MathVerse. These findings indicate that PaLMR offers a principled and practical route to process-aligned multimodal reasoning, advancing the reliability and interpretability of MLLMs.

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

A Unifying Lens on Reward Uncertainty in RLHF

Reinforcement learning from human feedback (RLHF) is bottlenecked by reward hacking, where the policy exploits errors in a proxy reward model (RM) and produces high RM scores without genuine quality gains. A natural mitigation is pessimism: lowering rewards in regions where the RM is uncertain. However, standard scalar RMs provide no principled notion of uncertainty. We argue that the right object is a distributional reward model $p(r\mid x,y)$. Under either a Bayesian inference or a KL-distributionally robust optimization (KL-DRO) lens, the KL-regularized RLHF objective admits a closed-form effective reward $\tilde r(x,y) = \pm\beta\log\mathbb{E}_p[e^{\pm r/\beta}]$. The pessimistic branch unifies the prior heuristics for RM ensemble aggregation: mean aggregation, worst-case optimization (WCO), and uncertainty-weighted optimization (UWO) all emerge as limits or truncations of this single expression. This also clarifies the implicit assumptions of each existing rule.

14.
arXiv (math.PR) 2026-06-12

Exact Fourier dimensions of dyadic Mandelbrot cascades under minimal integrability

arXiv:2606.08683v2 Announce Type: replace Abstract: We determine the Fourier dimension of dyadic Mandelbrot cascades under the minimal Kahane-Peyriere integrability condition. The interval theorem is proved in a vector-valued dyadic cascade model in which sibling weights may have arbitrary dependence. For every balanced energy-admissible vector law, almost surely on non-extinction, dim_F(mu)=dim_E(mu)=dim_2(mu)=D_E(X). In the canonical scalar case, under W>=0, E W=1, E[W log_2^+ W]

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

Hybrid Open-Ended Tri-Evolution Makes Better Deep Researcher

arXiv:2606.13710v1 Announce Type: new Abstract: Deep research and agent evolution serve as de-facto tasks for AI agents in real-world applications toward artificial general intelligence. The former enables autonomous retrieval and integration of information in open-ended environments to tackle open-ended research tasks, yet it is constrained by the static parametric deep research capabilities of agent systems. The latter allows agents to autonomously interact with the environment to gain experiences that evolve model capabilities. However, its effectiveness has been widely validated only on verifiable tasks with standard answers, leaving a gap with open-ended research tasks. To bridge these two critical tasks, we propose the Hybrid Open-Ended Tri-Evolution (HOTE) framework, which leverages hybrid-mode reinforcement learning to facilitate the collaborative evolution of a proposer, solver and judge based on web-scale knowledge, moving toward autonomous evolving agents in open-ended tasks and environments. Extensive experiments on three long-form deep research benchmarks demonstrate that the 8B model trained via HOTE surpasses the strongest static open 8-32B models as well as those trained by state-of-the-art deep research training methods with less time overhead, and further verify that the evolution of all three modules in HOTE is indispensable.

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

Neuron Level Analysis of Large Language Model in Legal Domain Reasoning

We presented a neuron-level analysis of legal-domain reasoning in LLMs, comparing it with other applied domain tasks across seven open-weight models. Using neuron attribution scores to rank and suppress influential neurons, we confirmed that suppressing the identified neurons collapses accuracy on the target task, whereas suppressing the same number of random neurons does not. We further found a small subset of neurons influential across all seven tasks; once these are removed, suppressing the remaining neurons degrades only the task they were identified from, revealing genuinely task-specific neurons in every model studied. Within the legal domain, the three benchmarks exhibit relatively high neuron overlap and tend to be affected jointly, suggesting of legal components neurons that span jurisdictions. The distribution of identified neurons in our experiments suggests that the hypothesis that influential neurons are concentrated in middle MLP layers may depend on the input format and content, rather than being a universal phenomenon.

17.
arXiv (quant-ph) 2026-06-19

Optimized Quantum States for Sensing in the Presence of Loss and Phase Noise

arXiv:2606.19649v1 Announce Type: new Abstract: Squeezed vacuum lets gravitational-wave detectors and other quantum sensors surpass the standard quantum limit, and is optimal in the loss-limited regime; phase noise breaks this optimality. Numerically optimizing the quantum Fisher information across the loss and phase-noise landscape, we identify non-Gaussian states that outperform any Gaussian state. These fall into three classes: Fock-like, cubic-phase-like, and states with discrete rotational symmetry. Limiting the average number of photons in the input state to $\bar{n}=5$, with $1-\eta = 5\%$ photon loss and 200 mrad phase noise, the non-Gaussian advantage reaches up to 2.2 dB. Furthermore, we observe that the non-Gaussian advantage can persist even when the measurement strategy is homodyne detection.

18.
Nature (Science) 2026-06-10

Human migration has surged since 2000 — these maps reveal where people are going

Modelling with artificial-intelligence tools has filled gaps in migration data, revealing detailed global population movements from 1990 to 2023. Modelling with artificial-intelligence tools has filled gaps in migration data, revealing detailed global population movements from 1990 to 2023.

19.
arXiv (CS.AI) 2026-06-11

Subliminal Learning Is Steering Vector Distillation

arXiv:2606.00995v3 Announce Type: replace Abstract: Subliminal learning refers to a student language model acquiring a teacher's traits (e.g. a system-prompted preference for owls) when fine-tuned on the teacher's outputs, despite the outputs being semantically unrelated to those traits. It remains poorly understood how data without semantic meaning can transfer specific semantic traits. In this work, we show that subliminal learning is mediated by a single steering vector, i.e. a vector added to the model's activations. Across two open-source models, we find that the teacher's system prompt is well approximated by a steering vector, and that the student's behavior is driven by learning an aligned vector over fine-tuning. System prompts that are not well approximated by steering vectors are not subliminally learned. This is a special case of steering vector distillation, in which a student trained on the outputs of a steered teacher learns to imitate that steering. We demonstrate steering vector distillation on a range of semantic and random vectors. Adding a semantic vector to a model's activations can have both model-independent and model-specific (i.e. non-semantic) effects on its behavior, so generated data that is non-semantic can transmit a vector with semantic effects, enabling subliminal learning. This also explains why subliminal learning does not transfer between models. We find that adaptive optimizers are necessary for subliminal learning in language models: activation gradients on steered data carry a small but consistent component along the steering direction, and non-adaptive optimizers impede this by allowing outlier gradients to dominate.

20.
arXiv (CS.AI) 2026-06-15

Dense Coordinate-List Fine-Tuning Induces a Controllable Interference Surface in Vision-Language Models

arXiv:2606.14507v1 Announce Type: new Abstract: Fine-tuning vision-language models to emit dense coordinate lists improves visual grounding but also changes how models serialize, repeat, and terminate structured outputs. We study this behavior as a generation and control surface. In Gemma 4 12B, high-capacity q/k/v/o LoRA raises class-aware F1@0.3 from 0.007 to 0.448 while inducing repeated-tail pressure (duplicate rate 0.080, max repeat 23). A q/v rank sweep keeps max repeat at 21-22 across ranks 4-64, showing capacity persistence. The target signal is separable: object-level repeat-stop removes exact repeated records (duplicate rate 0.000, max repeat 1) while preserving F1 (0.494 to 0.490) and stricter F1@0.5 (0.381 to 0.385). Structure-axis probes localize the effect to bbox-coordinate object lists; dense non-bbox and spatial/count JSON remain repeat-clean, including under high-capacity adapters. Qwen3-VL-8B reproduces a clean controlled endpoint (F1@0.3 0.318, duplicate rate 0.000), and COCO 2017 reproduces acquisition plus duplicate pressure. Dense coordinate-list adaptation therefore creates a structure-bound, cross-family interference surface that can be measured and controlled.

21.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

作者:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue&nbsp;degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

22.
arXiv (CS.LG) 2026-06-16

Generative Molecular Design with Steerable and Granular Synthesizability Control

arXiv:2505.08774v2 Announce Type: replace-cross Abstract: Designing molecules that are both property-optimal and readily synthesizable is a central challenge in drug discovery. Existing works that do consider synthesizability can jointly output predicted synthesis routes for generated molecules. However, there has been minimal attention in addressing the ease of synthesis and with flexibility to incorporate desired reaction constraints. On the other hand, virtual screening searches for commercially available compounds, but imposes challenges when scaling to ultra-large (billion-size and beyond) chemical spaces. Here, we propose a generative design framework that unifies synthesis-constrained molecular design and ultra-large-scale virtual screening through steerable and granular synthesizability control. Generated molecules satisfy arbitrary multi-parameter optimization objectives with predicted synthesis routes satisfying mix-and-match constraints: including or avoiding certain reactions, incorporating specific building blocks, and minimizing synthesis route length. In an end-to-end in-house campaign targeting BRD4, we designed molecules synthesizable with specific selected reactions and building blocks, synthesized all six selected compounds, and identified two micromolar binders. We further demonstrate that reaction control enables efficient navigation of ultra-large make-on-demand chemical spaces to identify property-optimal candidates. By applying our framework to Chemspace's Freedom 4.0 make-on-demand space (142 billion molecules), we generated ~320k molecules (0.00023% of the library) on a single consumer-grade GPU (with only 8 GB GPU memory) and identified a micromolar Wee1 binder amongst 60 synthesized candidates. The single unified framework thus enables generating novel synthesizable molecules and retrieving catalogue-ready candidates, offering a flexible solution to mitigating the synthesizability bottleneck.

23.
Nature Medicine 2026-06-12

Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial

Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith−Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: −4.04, 95% confidence interval: −6.89 to −1.18, P = 0.006, Hedges’ g = 0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 . Pramipexole, in patients with major depressive disorder, dysthymia or bipolar depression, reduced Snaith−Hamilton Pleasure Scale scores significantly compared to placebo.

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

Wavelet Matrix Product States for Quantum Fields

arXiv:2606.23823v1 Announce Type: new Abstract: We introduce a variational method to solve continuum quantum models with discrete tensor network techniques. The method leverages wavelet matrix product states (wMPS): matrix product states built on top of sufficiently regular ($N\geq 6$) Daubechies scaling functions. These states live in the continuum field theory Fock space, have finite energy density, and can be optimized with standard algorithms, without restriction to free theories. Further, exploiting the multi-resolution analysis built into wavelets, and its quantum circuit description, we can iteratively refine wMPS to obtain accurate approximations at arbitrarily fine length-scales. We showcase the efficiency of the method on the Lieb-Liniger model, computing energy density and correlation functions.

25.
arXiv (CS.CV) 2026-06-16

When RAG Hurts: Diagnosing and Mitigating Attention Distraction in Retrieval-Augmented LVLMs

While Retrieval-Augmented Generation (RAG) is one of the dominant paradigms for enhancing Large Vision-Language Models (LVLMs) on knowledge-based VQA tasks, recent work attributes RAG failures to insufficient attention towards the retrieved context, proposing to reduce the attention allocated to image tokens. In this work, we identify a distinct failure mode that previous study overlooked: Attention Distraction (AD). When the retrieved context is sufficient (highly relevant or including the correct answer), the retrieved text suppresses the visual attention globally, and the attention on image tokens shifts away from question-relevant regions. This leads to failures on questions the model could originally answer correctly without the retrieved text. To mitigate this issue, we propose MAD-RAG, a training-free intervention that decouples visual grounding from context integration through a dual-question formulation, combined with attention mixing to preserve image-conditioned evidence. Extensive experiments on OK-VQA, E-VQA, and InfoSeek demonstrate that MAD-RAG consistently outperforms existing baselines across different model families, yielding absolute gains of up to 4.76%, 9.20%, and 6.18% over the vanilla RAG baseline. Notably, MAD-RAG rectifies up to 74.68% of failure cases with negligible computational overhead.