Long-sought chemical inhibitors of β-arrestin proteins
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Long input sequences are central to document understanding and multi-step reasoning in Large Language Models, yet the quadratic cost of attention makes inference both memory-intensive and slow. Context distillation mitigates this by compressing contextual information into model parameters, and recent work such as Doc-to-LoRA amortizes context distillation into a single forward pass that generates one LoRA adapter per document. However, producing a single monolithic adapter for all queries leads to irrelevant-query interference, limited compositional recall, and poor scalability to long-document reasoning. To address these challenges, we propose Doc-to-Atom (Doc2Atom), a compositional parametric memory framework that decomposes each document into semantically typed knowledge atoms. Each atom is compiled into an independent micro-LoRA adapter and a provenance retrieval key. At inference time, a lightweight query router selects and assembles only the relevant atoms into a query-specific adapter, which is then injected into a frozen base model. The entire system is trained end-to-end through a multi-objective distillation framework. Experiments on six diverse QA benchmarks demonstrate that Doc2Atom outperforms Doc-to-LoRA baselines while reducing the memory cost of document internalization.
arXiv:2602.08470v3 Announce Type: replace Abstract: Credal predictors are models that are aware of epistemic uncertainty and produce a convex set of probabilistic predictions. They offer a principled way to quantify predictive epistemic uncertainty (EU) and have been shown to improve model robustness in various settings. However, most state-of-the-art methods mainly define EU as disagreement caused by random training initializations, which mostly reflects sensitivity to optimization randomness rather than uncertainty from deeper sources. To address this, we define EU as disagreement among models trained with varying relaxations of the i.i.d. assumption between training and test data. Based on this idea, we propose CreDRO, which learns an ensemble of plausible models through distributionally robust optimization. As a result, CreDRO captures EU not only from training randomness but also from meaningful disagreement due to potential distribution shifts between training and test data. Empirical results show that CreDRO consistently outperforms existing credal methods on tasks such as out-of-distribution detection across multiple benchmarks and selective classification in medical applications.
arXiv:2601.10490v2 Announce Type: replace Abstract: The stochastic partial differential equation analyzed in this work is the Cahn-Hilliard equation perturbed by an additive fractional white noise (fractional in time and white in space). We work in the case of one spatial dimension and apply Malliavin calculus to investigate the existence of a density for the stochastic solution $u$. In particular, we show that $u$ admits continuous paths almost surely and construct a localizing sequence through which we prove that its Malliavin derivative exists locally, and that its law is absolutely continuous with respect to the Lebesgue measure on $\bf R$, establishing thus that a density exists. A key contribution of this work is the analysis of the stochastic integral appearing in the mild formulation: we derive sharp estimates for the expectation of the $p$-th power ($p \geq 2$) of the $L^{\infty}(D)$-norm of this stochastic integral as well as for the integral involving the $L^{\infty}(D)$-norm of the operator associated with the kernel appearing in the integral representation of the fractional noise, all of which are essential for this study.
Precision agriculture requires the estimation of plant growth stages in real-time. When the plant growth stage is known, the wastage of resources in cultivation, such as nutrients and water, is reduced as only the required resources need to be supplied. Plants at different growth stages, however, have similar morphological features, which can make autonomous growth stage estimation difficult. This paper presents two feature extraction methods for growth stage estimation: one that uses a bank of Gabor filters and morphological operations, and the other that uses pre-trained convolutional neural networks (CNNs) and transfer learning. We test these methods on a publicly available plant growth stage dataset (``bccr-segset``) for two species, canola and radish, grown and captured under indoor conditions. The two proposed feature extraction methods are compared, using support vector machines and boosted trees as classifiers. We find that both methods are suitable for real-time applications, and that CNN features outperform the hand-crafted features, both with regard to speed and accuracy. The best system (VGG-19 features, classified with a radial basis function support vector machine) obtained an accuracy of 98.4% for both species, processing an image in 0.08 seconds.
Much research has been carried out on large language models (LLMs) and LLM-powered agentic workflows. However, many works within the field state emergence of, ascribe to, or assume, generalised anthropomorphic attributes to them (e.g., morality or understanding of natural language). Our goal is not to argue in favour or against the existence of these attributes, but to point out that these conclusions could be incorrect. For this we build and train a simple neural network on the videogame Age of Empires II, and note that any entity in a sufficiently-powerful substrate, such as LEGO or the Greater Boston Area, could also present such attributes. Hence, the purported anthropomorphic attributes of LLMs are empirically non-unique: although some properties (e.g., responses to prompts) could remain invariant, others, such as the interpretation of their perceived behaviour, might change with the substrate. Thus, any empirically-grounded discussion on these attributes requires explicit measurement criteria; otherwise the interpretation is left to the representation. We then show that assuming that these attributes exist or not in a system, independent of the substrate and in a generalised way, leads to either circular or uninformative conclusions. This is regardless of the experimenter's viewpoint on the subject, or whether the outcome shows existence or non-existence. Finally we propose a 'null' assumption, where one assumes LLM non-uniqueness instead of assuming anthropomorphic attributes to set up an experiment, along with examples of it. We also discuss potential objections to our work, briefly survey the field, and prove that Age of Empires II is functionally- and Turing-complete.
Two research teams have created a new, long-awaited type of timekeeper. Two research teams have created a new, long-awaited type of timekeeper.
arXiv:2606.12056v1 Announce Type: new Abstract: Entanglement is a key bottleneck limiting the efficiency of tensor-network and quantum simulations of molecular electronic structures. Here, we systematically assess and extend Clifford disentanglers as a structure-preserving approach to entanglement reduction: they can modify the entanglement structure of qubit wavefunctions while retaining the Pauli-string form of qubit Hamiltonians. To enable a practical search over Clifford transformations, we classify Clifford operators by their action on the Schmidt spectrum across a bipartition, reducing the two- and four-qubit search spaces to 20 and 91392 representatives, respectively. Embedded in an iterative Clifford-augmented matrix product state framework, these transformations reduce the energy errors at fixed bond dimension for the molecular test cases studied and mitigate the dependence on orbital orderings and fermion-to-qubit mappings. We further show that Clifford disentanglers can also benefit quantum simulations such as the shallow-circuit variational quantum eigensolver calculations. Together, these results establish Clifford disentanglers as a useful structure-preserving entanglement-engineering tool for tensor-network and quantum simulations of molecular electronic structure, while also clarifying their correlation dependence and motivating future developments.
Sirtuins are deacetylases implicated in stress responses and longevity in mammals1,2. Although their differential impact on disease for the two sexes has been noted3–7, the underlying reasons are unclear. Here, using Sirt7 as a model in mice, we examine the mechanisms leading to sex differences and find that Sirt7−/− female mice have decreased fitness throughout their lifespan. Notably, SIRT7 preferentially localizes to the sex chromosomes. In female individuals, SIRT7 loss affects X-chromosome inactivation, the first arm of dosage compensation that equalizes X-linked gene expression between males and females8–10. Xist is overexpressed and gene silencing becomes more efficient. However, SIRT7 loss has greatest impact on the active X (Xa) chromosome. The Xa chromosome becomes hyperacetylated at Lys36 of histone H3, structurally disorganized, prone to DNA damage and overexpressed. Increased Xa-chromosome expression leads to genome imbalance and augmented X-chromosome upregulation—the second arm of dosage compensation that balances X-chromosome versus autosomal gene expression. These data reveal an essential crosstalk between sirtuins and the sex chromosomes, with SIRT7 safeguarding X-chromosome integrity and dosage balance with autosomes. We propose that the sex bias in SIRT7 biology can be explained in part by unequal effects on the sex chromosomes. SIRT7 safeguards X-chromosome integrity and dosage balance with autosomes.
arXiv:2404.09829v2 Announce Type: replace Abstract: Chiral quantum optics is central to developing scalable quantum networks, yet existing approaches rely predominantly on linear single-photon regimes. It remains unclear how to generate directional multiphotons. Here we show that giant emitters coupled to nonlinear quantum optical baths enable tunable directional correlated photons, revealing a mechanism for multiphoton directional emission. We demonstrate that the propagation phases of correlated photons, together with the coupling phases of giant emitters, can generate destructive interference in one direction while enhancing emission in the opposite direction, making directionality fully tunable. Building on this mechanism, we introduce a nonlinear cascaded quantum network paradigm mediated by correlated flying qubits, providing a configurable building block enabling distinct many-body applications beyond linear unidirectional setups. These results reveal a rich landscape for engineering multiphoton propagation and correlations through interference in giant emitter-nonlinear bath architectures, offering pathways for quantum networks and strongly correlated light-matter platforms.
The worldwide surge of authoritarianism, combined with the increasing central role in users' everyday lives, raises the question of to what extent specific models exhibit or promote authoritarian attitudes and characteristics. We introduce AuAu, a comprehensive benchmark that aims to assess the risk of LLMs generating responses with authoritarian tendencies. This benchmark combines three evaluation approaches: (i) psychometric questions from an extensive pool of 15 human validated instruments; (ii) contextual behavior vignettes probing intended actions in concrete situations; and (iii) responses to realistic user prompts. Unlike prior work, AuAu evaluates not only a general closeness towards authoritarianism but also the established sub-concepts Authoritarian Aggression, Authoritarian Submission, and Conventionalism. Evaluating 17 models from China, the EU, Russia, and the USA, we find that all tested models exhibit substantial authoritarian response rates under the psychometric evaluation, though rates drop significantly in increasingly more realistic downstream task. We further find that an authoritarian system prompt easily manipulates 15 out of 17 models to promote increased authoritarianism. Our results underscore the need for continued, systematic auditing of LLM-based AI systems to detect and ultimately mitigate undesired authoritarian tendencies in generated output. Our code and data are available at: https://github.com/andreaseinwiller/AuAu
arXiv:2606.11469v1 Announce Type: cross Abstract: We study the task of density estimation, where we hope to accurately estimate a probability density from $n$ samples. A textbook method for density estimation in total variation distance is the minimum-distance estimator approach, where we conclude both the algorithm and the analysis merely from bounding the VC dimension of a particular concept class (the so-called Yatracos class). While this technique has originally yielded sharp guarantees primarily for total variation distance, in this work we extend the minimum-distance estimator approach for learning within Hellinger distance. Our main observation is that we may produce an analogous recipe for Hellinger (where we only require bounding the VC dimension of a related concept class) by drawing connections to recent results yielding reverse data processing inequalities. This recipe is flexible enough to accommodate fast algorithms originally designed for total variation distance; by modifying the approach of Acharya et al. (2017) we conclude the first near-linear time algorithm for learning classes including univariate mixtures of log-concave densities and mixtures of Gaussians (with arbitrary variances), with near-optimal sample complexity.
arXiv:2606.20142v1 Announce Type: new Abstract: This paper introduces RACL, a Reasoning-Agent Control Layer for metaheuristics. RACL places a reasoning agent above an existing optimizer. The agent does not replace the optimizer and does not modify business constraints. Instead, it controls the optimizer's internal search behavior by observing operational memory, reasoning over past behavior, formulating bounded hypotheses, testing interventions, evaluating outcomes, applying guardrails, consolidating useful policies and explaining its decisions. The experiment uses vehicle routing as a testbed, but the contribution is not a new routing solver, a particular ALNS configuration or a specific set of routing rules. The contribution is the RACL method: a way for a reasoning agent to discover, validate, consolidate and explain algorithmic control rules for a metaheuristic. In the current experimental setting, RACL improves or ties the Operational Memory Policy in 21 of 21 feasible cases and improves or ties a non-reasoning Stagnation-Triggered Policy in 18 of 21 feasible cases, with an average RACL vs STP cost delta of -0.641%. In the Sevilla-9/10 runtime sample, RACL improves average cost by -8.337% versus Fixed and -1.605% versus STP without showing material computational overhead. During the proof-of-concept, Codex was used as an in-the-loop reasoning agent observing executions, interpreting logs and proposing live bounded interventions. The policy proxy was later used only to make quantitative evaluation reproducible.
arXiv:2512.17753v2 Announce Type: replace-cross Abstract: We show that for a large class of planar $1$-dimensional random fractals $S$, the Favard length $\operatorname{Fav}(S(r))$ of the neighborhood $S(r)$ is comparable to $\log^{-1}(1/r)$, matching a universal lower bound; up to now, this was only known in expectation for a few concrete models. In particular, we show that there exist $1$-Ahlfors regular sets with the fastest possible Favard length decay. For a wide class of planar one-dimensional "grid random fractals", including fractal percolation and its Ahlfors-regular variants, we further show that $\operatorname{Fav}(S(r))/\log(1/r)$ converges almost surely, and we identify the limit explicitly. Furthermore, we prove that for some $1$-dimensional Ahlfors-regular random fractals $S$, the Favard length of $S(r)$ decays instead like $\log\log(1/r)/\log(1/r)$, showing that the $1/\log(1/r)$ decay is not universal among random fractals, as might be expected from previous results.
Many moments in the real world do not wait for a user to ask. A fire starts on a security monitor, an expression flickers across a video call, or a product a viewer wants flashes by in a livestream. Yet today's large models remain mostly turn-based by design: they answer only when addressed, and even video-call apps that appear interactive still operate as question-answer systems, reacting only when polled or prompted. We argue for a different paradigm: a model that is present in the world like a person. It continuously watches what is happening now, decides on its own whether to speak or stay silent, interacts in real time, and delegates to a background model when the problem is hard. To advance interaction models and their adoption across domains, we make two fully open-sourced contributions. First, we release JoyAI-VL-Interaction, an 8B-scale, vision-first VL-interaction model. The model makes the response decision internally, choosing each second to stay silent, respond, or delegate to a background model, and it excels at vision-triggered responsiveness and time awareness. We pair it with a transferable training recipe, from which capabilities we never trained for emerge, such as guiding a shopper through changing app screens or improvising a lecture from a slide deck. Second, we release a complete, deployable system built around that model. The system streams any ongoing video into the model, making it genuinely present in the world. All other components are pluggable, including ASR/TTS modules, memory, visualization UI, and a background brain that can connect to any API or agent. Across six real-world scenarios, human raters prefer JoyAI-VL-Interaction over the in-app video-call assistants of Doubao and Gemini by a wide margin. To our knowledge, this is the first open, vision-driven interaction model released together with its training recipe, data, and complete deployable system.
The use of ‘base editing’ to precisely tweak human embryos has divided researchers. Plus, the number of lives saved by less-polluting cars in China and how to tip the world towards a sustainable future. The use of ‘base editing’ to precisely tweak human embryos has divided researchers. Plus, the number of lives saved by less-polluting cars in China and how to tip the world towards a sustainable future.
arXiv:2606.24585v1 Announce Type: new Abstract: While the validity of LLMs' use in the legal context remains subject to ethical and legal debate, legal professionals are already experimenting with personal LLMs, if only for translation and reformulation. However, even such a seemingly innocuous use can introduce biases through case processing speed if LLM assistants selectively refuse assistance on certain topics. To better anticipate such biases, we investigate several modern small LLMs that are most likely to be used as on-device assistants, to assess the impact of overrefusal on legal prompts. Surprisingly, we find that authority-style prefixes (``you are acting as an assistant of the national supreme court'', ``[...] defense lawyer'') systematically increase refusal rates by 2–20x over the no-prefix baseline, while a known role-play jailbreak prefix shows mixed effects, sharply increasing refusals in some models and barely shifting them in others. The finding suggests that small on-prem deployable LLMs are unstable under contextual framings that a real institutional user might naturally introduce, and further investigation is essential to minimize opportunities for bias.
arXiv:2606.17147v1 Announce Type: cross Abstract: Renormalisation is traditionally understood to be a Wilsonian memoryless process in which ultraviolet (UV) degrees of freedom gradually decouple, leaving an autonomous infrared (IR) description. However this need not be the case: in UV/IR mixed theories correlations between widely separated scales can persist. In this work I recast UV/IR mixing as a Hilbert-space phenomenon, realised as correlations across renormalisation scales. This formulation is implemented using the Born-Reciprocal Tensor Network (BRTN), a new configuration of tensor network that is globally symmetric under phase-space reciprocity. On this network I prepare the vacuum and reproduce the expected radiative corrections. The resulting renormalisation geometry exhibits memory, with a bridge linking reciprocal representations of IR physics, whose cross-bridge entanglement provides a precise criterion for the viability of an effective description. I analyse when this criterion is met, and show that there is a large-volume limit, with the fundamental scale held fixed, in which the obstruction to a local description scales away: Wilsonian behaviour is restored and renormalisation forgets. The BRTN therefore provides a concrete and calculable platform for UV/IR mixing.
Phase plates can in principle overcome the poor image contrast in electron cryo–microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous designs have been unstable and compromised the high-resolution signal. They have thus been unable to surpass results achieved by standard cryo-EM. Here, we show that the laser phase plate (LPP), installed in a custom, modern Titan Krios microscope, enhances the resolution in single-particle reconstruction of small proteins by improving specimen-motion correction, recovery of information from the early frames, as well as particle visualization, 3D classification, and alignment. These advances use standard defocus ranges and reconstruction procedures, but open the door to LPP-tailored protocols offering further improvements by leveraging the LPP demonstrated here.
As Vision-Language Models are increasingly deployed in safety-critical applications, the trustworthiness of their explanations becomes crucial. Explainable AI (XAI) methods for Vision-Language Models often suffer from semantic hallucination, where attribution maps highlight prominent image regions even when prompted with incorrect text descriptions (e.g., highlighting a dog when prompted ``cat''). Although this problem is widespread, a formal mathematical analysis of XAI methods and CLIP embeddings is largely missing in the literature. We demonstrate that this phenomenon is not specific to a single architecture but is a fundamental consequence of Linear Semantic Leakage in high-dimensional embedding spaces. We propose a unified theoretical framework, Linear Semantic Attribution (LSA), which generalizes across discriminative methods. We introduce OSP, a geometric intervention that utilizes the residual property of OMP to disentangle unique semantic signals from shared concepts. We prove theoretically and demonstrate empirically that OSP minimizes hallucination by orthogonalizing the query vector against distractor concepts, rendering the attribution model blind to shared features while preserving fidelity for correct prompts. Our code is available at: https://github.com/emirhanbilgic/Orthogonal-Semantic-Projection
arXiv:2606.20526v1 Announce Type: new Abstract: Neurosymbolic systems such as DeepProbLog combine neural perception with probabilistic logic, but standard inference is associational. Counterfactual reasoning additionally requires a causal semantics for interventions and evidence. We introduce DeepSWIP, a single-world counterfactual semantics for DeepProbLog programs. Using neural materialization, we reduce fixed-context neural predicates to ordinary ProbLog choices, apply Single World Intervention Programs (SWIPs), and compute counterfactuals by weighted model counting (WMC) over a single transformed program. Under finite grounding and unique-supported-model assumptions, DeepSWIP is exact relative to the learned materialized FCM. The standard quotient-WMC form of ProbLog conditionals identifies active neural probabilities and explains intervention cleaning, calibration sensitivity, and rare-evidence instability. Experiments on MPI3D confirm the transformation against a DeepTwin construction against 12,000 queries, as predicted and a 2.14$\times$ inference speedup from avoiding the Twin's endogenous duplication. A SUMO HOV experiment shows that neural calibration degradation biases plug-in estimates, while a correctly scoped randomized-policy AIPW estimator removes most first-order bias for population mean and ATE estimands. Code is at https://github.com/saibib/deep_SWIP.
arXiv:2606.17283v1 Announce Type: cross Abstract: Achieving reproducibility, quantity, and diversity in vulnerability datasets has long been viewed as an inherent three-way trade-off, where improving one dimension often comes at the cost of the others. In practice, reproducibility has been the dimension most often neglected. This has limited what can be automatically extracted from historical bug datasets, and has reduced their utility for downstream security research. In this work, we propose a method to produce a new security dataset which ensures reproducibility for diverse vulnerabilities at scale by identifying the key obstacles to large-scale bug reproduction and addressing them with general solutions. Using this method, we introduce full reproducibility to the largest open source software vulnerability dataset (OSS-Fuzz) and construct the ARVO dataset (an Atlas of Reproducible Vulnerabilities in Open-source software). ARVO is a large-scale dataset consisting of over 6,100 real-world vulnerabilities across 311 projects. Focusing on reproducibility, ARVO differs from existing datasets by providing each vulnerability in a form that can be consistently rebuilt, triggered, and analyzed across versions. Reproducibility also enables automatic identification of the corresponding patch for each vulnerability and supports direct interaction with vulnerabilities after code changes, capabilities that existing large-scale datasets do not provide. In our evaluation, ARVO successfully reproduces 81% of vulnerabilities and achieves 89.4% accuracy on the located patches. We also discuss ARVO's influence on both upstream practices and downstream security research.
Background and Aims: Machine learning has shown potential in predicting ablation targets for ventricular tachycardia (VT) in an animal model. This study progresses to externally validating deep learning approaches for human data. Methods: The development and external validation dataset included 21 and 13 patients, respectively, with structural VT undergoing catheter ablation. In the development datasets, electrophysiological studies were conducted using the AdvisorTM HD grid (EnsiteTM X), while both CARTO and Ensite Precision were used in the validation dataset. In each patient, VT ablation targets were defined as mapping points within 8 mm of VT isthmuses. Three advanced machine learning models were trained using cardiac mapping data acquired in both omnipolar and unipolar configurations during sinus rhythm and ventricular pacing. Discrimination was evaluated using nested leave-one-out cross-validation at patient level. Results: Overall, graph convolutional networks (GCNs), which integrate intracardiac signal waveforms with three-dimensional electroanatomical geometries, achieved the highest performance, with optimal results obtained from unipolar electrograms acquired in sinus rhythm (median AUC 0.793, sensitivity 83.6%, specificity 69.0%). This may be partly explained by the inclusion of repolarization dynamics in unipolar electrograms and the higher point density of sinus rhythm maps. Comparable performance was observed in the external dataset. Conclusion: This study demonstrates that graph convolutional networks applied to sinus rhythm EGM waveforms collected during substrate mapping can localise critical components of VT re-entry circuits. This approach has potential to provide fast and accurate ablation guidance without the need to induce and map VT, improving safety and efficacy of VT catheter ablation.
arXiv:2606.13374v1 Announce Type: cross Abstract: The voter model is a classical stochastic process that models how opinions might spread through a network: at each step, every node lazily adopts the opinion of a random neighbour; eventually all nodes share the same opinion (consensus). Stronger connectivity should yield faster consensus. Berenbrink, Giakkoupis, Kermarrec, and Mallmann-Trenn (ICALP 2016) make this precise via the network's conductance: if the network has $m$ edges, minimum degree $d_{\min}$, and conductance at least $\phi$, then the voter model reaches consensus in expected $O(m/(d_{\min}\phi))$ steps. Their results extend to dynamic networks with fixed vertex degrees by considering the network's conductance at each time step. We introduce temporal conductance $\Phi$, a more general connectivity measure for dynamic networks. Unlike static conductance, which collapses to $0$ whenever some snapshot is disconnected, $\Phi$ captures connectivity through edges that appear at different times. We generalise the results of Berenbrink et al. from static conductance to temporal conductance, showing that the expected consensus time of the standard voter model is at most $O(m/(d_{\min}\Phi))$. Moreover, we prove that this bound is tight up to constant factors. We expect temporal conductance to be a useful primitive for analysing other dynamics on temporal networks, and potentially time-inhomogeneous Markov chains more generally.
Lossless compression and probabilistic sequence modeling are two faces of the same coin: a model that assigns high probability to a sequence can encode it in few bits via arithmetic coding. We exploit this duality to evaluate genomic language models as compressors of DNA, using compression primarily as an objective probe of generative sequence modeling rather than as a deployable storage system. We release DNAGPT2, a family of ten GPT-2-small models pretrained for one epoch on a single A40 using the DNABERT2 multi-species corpus that differ only in byte-pair encoding vocabulary size. Coupled with arithmetic coding, the best model reaches 1.47 bits per base (bpb) on the T2T human genome, fourth in the Cobilab compression benchmark and ahead of every general-purpose compressor. Our results suggest that NLP-style tokenization choices may be suboptimal for DNA: a 32-token BPE vocabulary compresses better than larger vocabularies. We also find that, in this benchmark, published long-context genomic LMs underperform a much shorter-context BPE GPT-2; we discuss in Section 5 that this is not a controlled context-length ablation, since the compared models also differ in architecture, training data, parameter count, and tokenization. Finally, we compute a per-nucleotide information-content map of the human genome and show that exons, introns, intergenic regions, and Alu repeats have statistically distinct information profiles.