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01.
arXiv (quant-ph) 2026-06-19

Exploiting More Than Symmetry in Variational Quantum Machine Learning

arXiv:2606.20316v1 Announce Type: new Abstract: The success of variational quantum learning models crucially depends on choosing parametrizations that reflect the structure of the problem at hand. Symmetries provide one of the clearest such structures: whenever transformations of the input leave the desired outcome unchanged, this invariance should be built into the model rather than discovered during training. However, imposing a symmetry does not by itself determine a useful ansatz. Even within the symmetry-preserving space, one must decide where the trainable degrees of freedom should be placed. In this work, we study this remaining design freedom in equivariant variational quantum circuits. Building on symmetry-based parameter sharing, we disentangle two architectural choices: how much symmetry should be enforced, and which symmetry-respecting interactions should be trainable. Using Tic-Tac-Toe as a fully enumerable and structurally transparent test case, we find that suitable subgroups preserve most of the generalization benefit. By contrast, the dominant gains arise from gates acting directly on decisive task motifs. Thus, symmetry defines the admissible design space, while effective ansatze require an additional task-informed choice of trainable interactions.

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

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

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

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

Kolmogorov-Arnold Reservoir Computing

arXiv:2606.19984v1 Announce Type: new Abstract: Reservoir computing offers a lightweight framework for forecasting dynamical systems but may struggle to capture long-range dependencies due to limited representational capacity. Conventional reservoir computing recurrently uses trainable reservoirs with hyperparameter sensitivity, while the next-generation reservoir computing removes recurrence at the cost of rapidly growing feature dimensions. Here, we develop Kolmogorov-Arnold Reservoir Computing (KARC), which replaces reservoirs with explicit basis-function expansions inspired by the Kolmogorov-Arnold representation theorem. We rigorously show that KARC is a lightweight design of Kolmogorov-Arnold networks (KANs), preserving the potential expressive capacity of KANs while admitting efficient closed-form training of reservoir computing. At comparable cost, KARC outperforms existing reservoir computing methods on challenging benchmarks including partial differential equations. It can also be integrated with generative diffusion models for text-to-image generation. This work thus establishes a principled bridge between reservoir computing and KANs, enabling efficient and high-fidelity dynamical system forecasting.

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

Enhancing quantum-classical configuration interaction methods using a neural-network classifier

arXiv:2606.24332v1 Announce Type: cross Abstract: Selected configuration interaction methods achieve near-exact electronic structure calculations by iteratively constructing compact variational spaces, but their efficiency depends critically on the heuristics used to identify important determinants. Here, we introduce a data-driven selection framework that recasts determinant importance as a binary classification task and integrates a neural-network classifier into the iterative CI workflow through an active-learning loop. At each iteration, a random subset of candidate determinants is labelled via temporary diagonalisation, and the trained classifier guides selection of the remaining configurations. We demonstrate the utility of this framework for both classical and quantum CI methods by calculating the ground-state energy of a diatomic molecule. Our method achieves result parity with traditional configuration interaction methods at substantially lower computational cost: roughly a $\times 5$ reduction in memory and per-iteration cost for the classical cHCI variant, and convergence in markedly fewer iterations for the quantum-classical cSQD variant. These results establish classifier-assisted determinant selection as a lightweight, method-agnostic tool for compressing variational spaces and accelerating both classical and hybrid quantum-classical configuration interaction algorithms.

05.
arXiv (CS.CL) 2026-06-24

Progressive Alignment Objectives for Aligner-Encoder based ASR

Aligner-Encoders are recently proposed seq2seq end-to-end ASR models that replace decoder attention by predicting the uth token directly from the u-th encoder position, so the encoder must learn the alignment internally without cross-attention or a transducer lattice. In practice, this alignment often forms abruptly in the upper layers, making training sensitive and brittle on long utterances. We propose InterAligner, which adds an intermediate Aligner objective so alignment can form progressively across depth, together with an intermediate CTC loss (InterCTC) to stabilize optimization. On LibriSpeech with a 17-layer Conformer, a final-only Aligner reaches 5.0/7.8 WER (test-clean/other). InterCTC improves to 3.4/6.0, and InterAligner further reduces WER to 3.1/5.6 with the largest gains on long utterances.

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

An Introduction to Causal Reinforcement Learning

arXiv:2606.24160v1 Announce Type: new Abstract: Causal inference provides a set of principles and tools that allow one to combine data and knowledge about an environment to reason with questions of counterfactual nature, i.e., what would have happened had reality been different, even when no data of this unrealized reality is currently available. Reinforcement learning provides methods to learn a policy that optimizes a specific measure (e.g., reward, regret) when the agent is deployed in an environment and pursues an exploratory, trial-and-error approach. These two disciplines have evolved independently and with virtually no interaction between them. We note that they operate over different aspects of the same building block, counterfactual relations, which makes them umbilically connected. Based on these observations, novel learning opportunities arise when this connection is explicitly acknowledged and mathematized. To realize this potential, we note that any environment where the RL agent is deployed can be decomposed as a collection of autonomous mechanisms with different causal invariances, parsimoniously modeled as a structural causal model; any standard RL setting implicitly encodes such a model. This formalization allows us to put under a unifying treatment different modes of learning, including online, off-policy, and causal calculus learning, which appear unrelated in the literature. However, these modalities are not exhaustive: we introduce several natural and pervasive classes of learning settings that entail novel dimensions of analysis. Specifically, we introduce and discuss through causal lenses generalized policy learning, where to intervene, imitation learning, and counterfactual learning. These tasks lead to a broader view of counterfactual learning and suggest great potential for studying causal inference and reinforcement learning side by side, which we call causal reinforcement learning (CRL).

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

When Does q-error Predict Plan Regret? Three Regimes of Cardinality-Estimation Error

arXiv:2606.15600v1 Announce Type: cross Abstract: Cardinality-estimation (CE) research ranks estimators by q-error, yet it is well known that q-error is an imperfect proxy for query-plan quality. We give a measurement-driven account of when it is a good proxy and when it is not, and why. Modeling plan selection as an argmin over a piecewise-linear cost landscape, we find that plan regret (the cost of the chosen plan relative to the optimal, under true cardinalities) is governed by plan-cost geometry in a regime-dependent way. (i) For small errors, a true-point condition number kappa predicts regret and out-predicts q-error; its predictive power decays to zero as error grows, as a local linearization must. (ii) For large errors – where deployed learned estimators operate – an estimator-independent average-case sub-optimality measure ACS-infinity predicts which queries are regret-prone (Spearman rho ~ 0.54 on STATS-CEB), while q-error is nearly uninformative at the query level (rho ~ 0.05). (iii) The worst case is Haritsa's maximum sub-optimality (MSO). The three are one cost-ratio spectrum under three weightings. We prove a limit law ACS-infinity = sum_k r_k pi_k with cardinality-independent combinatorial weights, and validate every claim on STATS-CEB and JOB-light with four released estimators under pre-registered decision rules, and confirm on real PostgreSQL runtime that ACS-infinity predicts regret where q-error does not. The contribution is conceptual and empirical – an average-case companion to worst-case robust query optimization, and a characterization of when an accuracy metric tracks plan quality – rather than a new estimator. Code and the full pre-registration are public.

08.
medRxiv (Medicine) 2026-06-23

Uptake of minimal intervention dentistry among Romanian dental professionals and trainees: an exploratory cluster and network analysis

Background Minimal intervention dentistry (MID) is promoted as a prevention-oriented approach to caries management, but its integration into routine practice remains uneven. Existing research often examines MID-related knowledge, attitudes, or practices separately, offering limited insight into how these dimensions co-occur within individuals or are conditionally associated. Methods This exploratory cross-sectional survey examined multidimensional MID uptake among 327 Romanian dental students, residents, and specialists from five university centers. Ten MID-related scores were analyzed, including nine formative composites and one single-item peer-norm indicator. K-means clustering examined uptake profiles, and Gaussian graphical model network analysis with stepwise BIC selection examined conditional associations among constructs. Results A two-cluster solution was highly reproducible but modestly separated (n = 144 vs n = 183; average silhouette width = 0.13; mean Jaccard similarities = 0.92 and 0.94). The profiles reflected broadly lower versus higher uptake across knowledge-, belief-, and practice-related dimensions, while perceived peer norms for hygiene instruction showed the opposite pattern. Profile membership was not clearly patterned by gender, age band, professional status, or clinical experience. The primary network included 14 non-zero edges out of 36 possible edges, all positive; the strongest partial association linked diagnostic knowledge to diagnostic methods used in practice (partial r = .22). Familiarity, diagnostic knowledge, and general practices occupied more interconnected positions descriptively, but limited centrality stability precluded interpreting them as intervention targets. Conclusions MID uptake in this sample was better represented as a continuum of modestly differentiated profiles than as sharply separated participant types. The findings provide an exploratory map of multidimensional MID uptake and may inform future survey validation, implementation research, and dental education studies. Because the study was cross-sectional, convenience-sampled, and based on self-report, findings should be interpreted as hypothesis-generating rather than causal or population-representative.

09.
arXiv (quant-ph) 2026-06-24

A Hybrid Quantum-Classical Approach for Melt Pool Prediction in Laser Powder Bed Fusion

arXiv:2606.23719v1 Announce Type: new Abstract: Laser powder bed fusion (LPBF) is a promising additive manufacturing technique that suffers from quality assurance concerns. Predicting melt pools from process parameters is crucial for assessing quality prior to manufacturing but remains a difficult problem because of the complex physical processes underlying LPBF. Quantum computers present a new computing paradigm, providing a new approach to information processing using quantum entanglement and superposition. This paper presents a practical demonstration of a hybrid quantum-classical model that leverages quantum computing to improve process parameter feature extraction with a quantum feature encoder. To make the quantum approach computationally feasible for large datasets, we first employ a clustering algorithm to reduce the number of expensive quantum computations. These quantum features are then processed by a classical neural network to predict the melt pool morphology, allowing for more accurate predictions of melt pools. We demonstrate the method using a quantum simulator, analyze the effect of measurement shot noise on the predictive performance of the network, and verify the results using quantum hardware. Finally, by examining which quantum features are most important, we provide insights that can inform the future design of more effective quantum encoding circuits. Ultimately, the performance improvement over purely classical networks validates the hybrid approach, demonstrating an engineering application of quantum computing using noisy and intermediate scale quantum (NISQ) devices.

10.
arXiv (CS.AI) 2026-06-17

Memory as a Wasting Asset: Pricing Flash Endurance for Embodied Agents, and the Limits of Doing So

arXiv:2606.18144v1 Announce Type: new Abstract: A robot's flash endurance is a non-renewable stock: every persisted write spends one of a few thousand program/erase cycles and never refills, yet no fielded robot memory system prices which memories are worth an erase cycle. We treat embodied memory as depreciating capital and price that stock with a single endurance shadow price $\eta$, which makes cost-minimizing placement across a RAM / on-board NVM / cloud hierarchy a threshold in a wear-augmented per-byte index. The index is cost-optimal whatever the sign of the value-write association $\chi$; only when $\chi > 0$ does the optimum turn non-monotone, sending a robot's most valuable memories off its flash. The pivot is thus empirical, and we measure $\chi$ on real robot logs at a pre-specified gate: its sign is a property of the deployment regime – positive on recurrent long-horizon manipulation ($\hat{\chi} \approx +1.0 \times 10^{-3}$, replicated at full power), null on a shorter-horizon suite, and negative on non-recurrent teleoperation. Two boundaries scope the result. The endurance budget is dormant on premium 3,000-P/E TLC at datasheet prices and binding on the commodity QLC/eMMC ($\sim$1,000 P/E) that cheaper edge robots run. And where it binds, a learned wear-aware controller only ties price-based routing on task value, because realized value is tier-invariant across RAM, NVM, and cloud: the rent governs device lifetime and cost, not task performance. Whether wear-aware placement improves task value remains open – $\chi$ is measured against a value proxy, and the non-monotone optimum, while proven, is not yet observed in data.

11.
arXiv (CS.CL) 2026-06-15

Incentives Of EdTech: A Systematic Review Of EduNLP Research

While the Natural Language Processing community has dedicated significant resources in developing educational technologies (EdTech) that support this shift, it remains unclear whose interests are being best served among the stakeholders of education. In this paper, we present a systematic literature review of 204 papers published in venues of the Association for Computational Linguistics' Special Interest Group on Building Educational Applications in 2024 and 2025, and validate these against EdTech papers from the wider ACL Anthology. By examining stakeholder inclusion and the prioritisation of research tasks, our findings reveal a critical tension: a push and pull between private-sector incentives and the foundational needs of educational infrastructure. Our analysis reveals that teachers are systematically under-represented as beneficiaries of research (33.3%) despite being the most affected, that real-world deployment remains rare (9.8%), and that ethical engagement tends toward acknowledgement rather than action. Drawing on exemplary papers in our corpus, we offer concrete recommendations for more responsible EduNLP research practices.

12.
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.

13.
medRxiv (Medicine) 2026-06-15

An epidemiological scenario for Mass Events During the World Cup

This brief work discusses potential superspreading events that may occur during the World Cup in Mexico. The study is particularly focused on the city of Guadalajara due to a large recent outbreak in January and February and insufficient vaccine coverage prior to 2026. Keywords: Superspreading; measles outbreak; branching process; individual reproduction number; World Cup

14.
arXiv (quant-ph) 2026-06-16

Towards Quantum Limited Spatial Resolution of NV-Diamond Magnetometry

arXiv:2508.13438v2 Announce Type: replace Abstract: Optically addressable ensembles of solid-state defects, such as nitrogen vacancy (NV) centers, are a leading modality for imaging-based magnetometry, thermometry and strain sensing. However, monitoring the fluorescence of individual defects within a sub-diffraction ensemble remains an outstanding challenge that currently limits access to atomic-scale features and dynamics. For compact clusters of NVs, we formulate imaging-based atomic sensing as a low-dimensional multiparameter estimation task in which one seeks to localize each defect and quantify the field strength in its immediate vicinity. In this work, we employ optical spatial mode demultiplexing (SPADE) to enhance localization and brightness estimation accuracy at sub-diffraction scales. Specifically, we develop a two-stage sensing protocol that augments direct imaging by projecting the incoming optical field onto point spread function (PSF)-adapted, i.e., PAD spatial modes and Yuen-Kennedy-Lax (YKL) spatial modes enabling efficient extraction of emitter positions and brightnesses. The YKL-SPADE measurement employed for brightness estimation is shown to be quantum-optimal in the case of two emitters and establishes a new connection between quantum detection and estimation theories. We numerically evaluate the statistical performance of our protocol for sub-diffraction optically detected magnetic resonance (ODMR) and Rabi sensing experiments. Compared to conventional focal plane intensity measurements, our protocol improves emitter localization accuracy by 6$\times$ and brightness estimation accuracy by 2$\times$ for tightly confined ensembles, residing well below the diffraction limit.

15.
arXiv (CS.CL) 2026-06-17

EmoFSM: A Finite State Machine for Emotional Support Conversation

Emotional support conversation (ESC) aims to alleviate people's emotional distress through effective conversations. Although large language models (LLMs) have made remarkable progress in ESC, most of these studies may not define the diagram from a state-model perspective, thereby providing a suboptimal solution for long-term satisfaction. To address such an issue, we leverage the Finite State Machine (FSM) on LLMs, and propose a framework called EmoFSM. Our framework allows a single LLM to bootstrap the planning during ESC, and self-reason the seeker's emotion, support strategy, and the final response upon each conversation turn. Substantial experiments in ESC datasets suggest that EmoFSM outperforms many baselines, including direct inference, self-fine, chain of thought, finetuning, and externally supported methods, even those with many more parameters.

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

Agentic World Modeling: Foundations, Capabilities, Laws, and Beyond

arXiv:2604.22748v3 Announce Type: replace Abstract: As AI systems move from generating text to accomplishing goals through sustained interaction, the ability to model environment dynamics becomes a central bottleneck. Agents that manipulate objects, navigate software, coordinate with others, or design experiments require predictive environment models, yet the term world model carries different meanings across research communities. We introduce a "levels x laws" taxonomy organized along two axes. The first defines three capability levels: L1 Predictor, which learns one-step local transition operators; L2 Simulator, which composes them into multi-step, action-conditioned rollouts that respect domain laws; and L3 Evolver, which autonomously revises its own model when predictions fail against new evidence. The second identifies four governing-law regimes: physical, digital, social, and scientific. These regimes determine what constraints a world model must satisfy and where it is most likely to fail. Using this framework, we synthesize over 400 works and summarize more than 100 representative systems spanning model-based reinforcement learning, video generation, web and GUI agents, multi-agent social simulation, and AI-driven scientific discovery. We analyze methods, failure modes, and evaluation practices across level-regime pairs, propose decision-centric evaluation principles and a minimal reproducible evaluation package, and outline architectural guidance, open problems, and governance challenges. The resulting roadmap connects previously isolated communities and charts a path from passive next-step prediction toward world models that can simulate, and ultimately reshape, the environments in which agents operate. Code and resources are available at: https://github.com/matrix-agent/awesome-agentic-world-modeling.

17.
Nature (Science) 2026-06-24

Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover

作者:

Metabolism of the hepatic low-density lipoprotein receptor (LDLR) is a key determinant of cholesterol homeostasis1,2. The molecular switches that coordinate LDLR trafficking and turnover in response to nutritional cues, including high dietary cholesterol, remain poorly defined3–6. Here we identify a new pathway regulated by Ral GTPases that links extracellular cholesterol signals to the intracellular trafficking machinery controlling LDLR turnover. Chronic dietary cholesterol activates the Ral proteins by increasing RAS activity, routing LDLR to lysosomes for degradation and inhibiting its recycling independently of transcriptional regulation or PCSK9. Constitutive activation of Ral via RalGAPB deletion or overexpression of constitutively active Ral mutants in hepatocytes reduces LDLR levels and impairs cholesterol clearance. Ral engages the endocytic RalBP1–REPS1 complex to promote LDLR internalization and lysosomal routing, where LDLR is degraded by the lysosomal protease cathepsin A (CTSA). Ral activation directs CTSA towards lysosomes for maturation while limiting its secretion, further promoting LDLR degradation in lysosomes. Genetic variants in this pathway significantly associate with altered cholesterol in humans. Pharmacological inhibition of CTSA activity increases hepatic LDLR function and improves cholesterol clearance, offering a potential new therapeutic strategy for hypercholesterolaemia and cardiovascular disease. Chronic dietary cholesterol activates Ral GTPases, which promote LDLR internalization and lysosomal degradation through RalBP1–REPS1 and CTSA, thereby reducing cholesterol clearance, whereas CTSA inhibition restores LDLR function and may offer a therapeutic strategy for cardiovascular disease.

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

Analyzing Visual Aircraft Representations with Sparse Autoencoders

Vision models can achieve strong performance on classification tasks, but the internal representations supporting their predictions are often difficult to interpret. This work investigates whether sparse autoencoders can decompose intermediate representations of a vision model into interpretable features. We train a ConvNeXt classifier on the FGVC-Aircraft dataset, extract spatial activations from its final feature stage, and train a sparse autoencoder on these activations. The learned sparse features are analyzed using top-activating image patches, activation strength, and class selectivity. Qualitative visual inspection reveals that several features correspond to recognizable aircraft structures and visual patterns. We evaluate a subset of selected features using input-space and feature-space ablations, measuring how blurring image patches and suppressing sparse features affect class logits, classification margins, and prediction confidence. The results suggest that sparse autoencoders can reveal partially interpretable, class-relevant visual features associated with aircraft recognition, while also exposing limitations such as polysemanticity and coarse spatial localization.

19.
arXiv (CS.CL) 2026-06-12

How reliable are LLMs when it comes to playing dice?

We investigate the probabilistic reasoning capabilities of large language models through a controlled benchmarking study on discrete probability problems. We constructed two datasets, respectively a set of standard exercises and a set of counterintuitive exercises, designed to trigger heuristic reasoning, and evaluated 8 state-of-the-art models, each tested with and without Chain-of-Thought prompting. Models achieve an average accuracy of 0.96 on standard problems but only 0.59 on counterintuitive ones. We further provide empirical evidence of token bias: performance drops by over 20% when canonical formulations are replaced by disguised variants. Embedding misleading suggestions in the prompt reduces performance by up to 34%, with no model proving immune. Taken together, the reported findings suggest that current LLMs are not yet genuine probabilistic reasoners, despite their success in advanced mathematical problems.

20.
arXiv (quant-ph) 2026-06-11

Single Photon Cross-Phase Shifts Can Be Enhanced by Localization in both Frequency and Time

arXiv:2606.11516v1 Announce Type: new Abstract: Single-photon optical nonlinearities face a fundamental trade-off: maximum nonlinearity requires both spectral resonance (narrow bandwidth) and high peak intensity (short duration), constraints that are incompatible due to the time-energy uncertainty relation. We demonstrate experimentally that this limitation does not need to exist in cases involving post-selection. We measure a cross-phase shift (XPS) produced by a resonant photon from a narrow-band source that is first transmitted through a cold atomic cloud and then localized in time through detection. The peak size of this XPS is greatly enhanced compared to that of Gaussian single-photon-level pulses without post-selection, benefiting from the narrow bandwidth of the resonant prepared state and the high intensity of the post-selected state simultaneously. We measure enhancements in the peak XPS of 6$\pm$1 at an optical depth (OD) of 2.4$\pm$0.1, and our results are in qualitative agreement across a range of optical depths with the recently developed weak value theory of atomic excitation [Thompson et al., APL Quantum 2, 036108 (2025)] for such post-selected photons. This work uncovers new consequences of having simultaneous knowledge of frequency and time, raising new foundational questions about how a particle behaves, and interacts with other systems, when its preparation and post-selection are non-commuting.

21.
Nature (Science) 2026-06-24

Small-molecule modulation of β-arrestins

β-Arrestins are multifunctional regulators of G-protein-coupled receptor (GPCR) signalling and orchestrate diverse downstream signalling events and physiological responses across the GPCR superfamily1–3. Although GPCR pharmacology has advanced to target orthosteric and allosteric sites, as well as G proteins and GPCR kinases, direct chemical tools to modulate β-arrestin activities have remained conspicuously absent. Here we report the identification of small-molecule inhibitors that selectively target β-arrestins and delineate their mechanism of action through integrated pharmacological, biochemical, biophysical and structural analyses. These inhibitors disrupt β-arrestin engagement with agonist-activated GPCRs, impairing desensitization, internalization and β-arrestin-dependent physiological functions while sparing G protein–receptor coupling. Cryo-electron microscopy, molecular dynamics simulations and structure-guided mutagenesis reveal that one modulator, Cmpd-5, engages a pocket within the central crest of β-arrestin1 formed by the middle, C and lariat loops, a critical receptor-binding interface, stabilizing a distinct conformation that is incompatible with full β-arrestin–receptor engagement. Together, these findings establish a mechanistic framework for β-arrestin modulation, reveal a novel allosteric site for structure-based drug design, and open new avenues for transducer-targeted, pathway-specific GPCR therapeutic agents. Integrated pharmacological, biochemical, biophysical and structural analyses of small-molecule β-arrestin inhibitors show how they block β-arrestin engagement with activated GPCRs, revealing their mechanism of action and uncovering a previously unrecognized allosteric regulatory site.

22.
arXiv (CS.AI) 2026-06-17

Towards Leveraging AutoML for Sustainable Deep Learning: A Multi-Objective HPO Approach on Deep Shift Neural Networks

arXiv:2404.01965v3 Announce Type: replace-cross Abstract: Deep Learning (DL) has advanced various fields by extracting complex patterns from large datasets. However, the computational demands of DL models pose environmental and resource challenges. Deep shift neural networks (DSNNs) offer a solution by leveraging shift operations to reduce computational complexity at inference. Following the insights from standard DNNs, we are interested in leveraging the full potential of DSNNs by means of AutoML techniques. We study the impact of hyperparameter optimization (HPO) to maximize DSNN performance while minimizing resource consumption. Since this combines multi-objective (MO) optimization with accuracy and energy consumption as potentially complementary objectives, we propose to combine state-of-the-art multi-fidelity (MF) HPO with multi-objective optimization. Experimental results demonstrate the effectiveness of our approach, resulting in models with over 80\% in accuracy and low computational cost. Overall, our method accelerates efficient model development while enabling sustainable AI applications.

23.
medRxiv (Medicine) 2026-06-22

Toward less intrusive pubertal assessment: longitudinal evaluation of tanner and non-tanner metrics in East African adolescents

Background: Accurate pubertal assessment is essential in pediatric endocrinology and adolescent health research. While Tanner staging remains the gold standard, its subjective nature and invasive genital examination limit feasibility and acceptability, especially in longitudinal studies and culturally sensitive settings. This study evaluated less intrusive pubertal assessment combinations that maintain discriminative accuracy. Methods: We conducted a longitudinal study among 200 uncircumcised, sexually naive males aged 15-17 years in Southwestern Uganda, with quarterly follow-up over three years. Clinicians assessed Tanner staging metrics (pubic hair, testicular volume, penile length, scrotal color), axillary hair, and serum testosterone. Markov transition models estimated Tanner stage progression. Ordinal logistic regression and area under the receiver operating characteristic curve (AUC) analyses quantified discriminative performance of individual and combined metrics. Results: At baseline, participants were distributed across Tanner stages II (6.0%), III (13.5%), IV (55.0%), and V (25.5%). Among individual metrics, pubic hair distribution best predicted overall Tanner stage (AUC=0.867), while penile length was least predictive (AUC=0.833). The full four-metric Tanner model achieved high discrimination (AUC=0.993). However, a less intrusive combination of pubic hair and scrotal color achieved comparable discrimination (AUC=0.942), improving to AUC=0.953 with axillary hair and age. Markov modeling demonstrated frequent bidirectional transitions between Tanner stages IV and V, reflecting variability in longitudinal staging. Conclusions: A minimally intrusive assessment combining pubic hair, scrotal color, axillary hair, and age reliably predicts pubertal stage, offering an acceptable alternative to traditional Tanner staging for research and surveillance contexts where genital manipulation is impractical or unethical.

24.
Nature Biotechnology 2026-06-23

Mapping and engineering the human cell–cell interactome

Efforts to systematically understand how cell interactions tune tissue-level function have motivated transformative advances in single-cell transcriptomics and spatial profiling. Although these technologies can measure molecular states in individual cells and their spatial mapping within tissues, they also reveal that there exists a fundamental knowledge gap of how cells influence each other in context. In this Perspective, we propose an initiative to map and engineer the human cell–cell interactome: a functional atlas of how all major human cell types communicate. We highlight how recent innovations can make this vision achievable. As a first moonshot, we propose the ‘Billion Cell×Cell Project’, which systematically characterizes the outcomes of defined cell–cell dyads across diverse cell types and conditions. We envision this multistage initiative will produce progressively deeper insights and unlock additional avenues for therapeutic discovery. We call on the scientific community to join us in building the tools, datasets and models that will decode and rewrite the language of life between cells. Di Carlo and colleagues discuss technologies required to map and engineer the human cell–cell interactome and the therapeutic avenues such an atlas could unlock.

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

Minim: Privacy-Aware Minimal View for Agents via Trusted Local Sanitization

arXiv:2606.13949v1 Announce Type: new Abstract: Modern LLM-powered autonomous agents increasingly rely on rich user interface (UI) state observations to achieve reliable action grounding in complex digital environments. However, many deployments transmit the full UI state to remote inference servers even when most elements are irrelevant to the current task, which can leak sensitive but unnecessary context such as authentication codes, private notifications, and background application states. We propose MINIM, a trusted local broker that performs privacy-aware minimization on the client side before any observation leaves the device. Grounded in Contextual Integrity (CI), MINIM learns a dual-score representation for each UI element by predicting an inherent sensitivity score (s) and a task-conditioned necessity score (n). These scores drive a ternary disclosure policy that keeps essential elements, abstracts sensitive attributes when needed, and removes task-irrelevant content. We optimize a CI-aware objective that penalizes necessity errors more strongly on high-risk content, enabling aggressive pruning while preserving task-critical information. Experiments on real-world UI observations derived from WebArena show that MINIM substantially reduces task-irrelevant sensitive leakage while preserving task-critical semantic context and the interactive affordances required for reliable agent actions.