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01.
arXiv (math.PR) 2026-06-16

Small moments of the sensitivity of polynomial threshold functions

arXiv:2606.16004v1 Announce Type: new Abstract: In the first version of Chang, Slote, Volberg, and Zhang's paper [BSA_of_PTF], the authors modify a nice recursive approach due to Kane in [Correct_exponent_for_AS] where he bounded the average sensitivity of polynomial threshold functions. In [BSA_of_PTF] Kane's argument was adopted to estimate the boolean surface area of polynomial threshold function. The bridge is a combinatorial averaging lemma considering all balanced partitions. The lemma serves as a substitute for an additive property of average sensitivity. With the lemma, one can apply a Kane-type algorithm to derive a recurrence. Solving the recurrence then gives an upper bound of $e^{C_d \sqrt{\log n}}$ for the boolean surface area. In the second version of the same paper, the authors derive a polylog upper bound for BSA of PTFs. The difference is that they use a tail estimate for the sensitivity function. With the help of a polynomial restriction lemma in [poly_restriction] they sharpen the upper bound. It is noteworthy that when applying the polynomial restriction, each coordinate is put into each part independently with equal probability. As a result, a partition does not necessarily have equal-size blocks. In other words, it may not be balanced. In this note, we first investigate the effect of different partitioning. Second, we use the recursive method in the first version to derive a polylog upper bound for $\mathbb E[s(x)^{\eta}]$ where $\eta < 1/2$. It is interesting to note the phase transition that happens at $\eta=1/2$ in both versions of the proof (but in a completely different form). Section [PhaseTr-s] treats that.

02.
arXiv (CS.CV) 2026-06-11

3D-CBM: A Framework for Concept-Based Interpretability in Generative 3D Modeling

This research introduces a framework for incorporating Concept Bottleneck Models (CBMs) into 3D generative architectures to address the inherent 'semantic gap' in deep geometric learning. As deep models become central to 3D content creation, explainability shifts from a peripheral feature to a fundamental requirement for trust and accountability in safety-critical domains such as healthcare and manufacturing. CBMs provide an intrinsic interpretability solution by constraining latent representations to align with human-defined concepts, yet their application to unstructured 3D data remains largely unexplored. We design, implement, and validate a formal 3D-CBM architecture that maps raw geometric inputs, including point clouds and meshes, into a multi-tiered taxonomy of interpretable primitives and functional attributes. The framework further identifies strategic datasets, such as PartNet and ShapeNet, specialized for concept-based supervision. Experimental results from a 3D part-manipulation proof-of-concept experiment demonstrate the framework's efficacy, achieving a concept prediction accuracy of 88.8\% and a Chamfer Distance of 0.0115. Critically, the model enables precise test-time intervention, allowing for the interactive correction of structural errors. This work establishes a foundation for semantically-steerable 3D generation and invites further exploration into collaborative human-in-the-loop design systems.

03.
arXiv (CS.LG) 2026-06-18

Do as the Romans Do: Learning Universal Behaviors from Heterogeneous Agents

arXiv:2606.18537v1 Announce Type: new Abstract: Humans often acquire new skills by observing others, since observed behaviors implicitly reveal how to act in an environment. However, observations drawn from a heterogeneous population introduce conflicting behavioral signals, making it difficult to determine which behaviors are worth imitating. We address this challenge with General Reward Inference and Disentanglement (GRID), a social learning method that extracts universally useful behaviors from a heterogeneous population of demonstrators pursuing different goals. GRID decomposes per-agent reward functions into a general reward, capturing behaviors shared across all agents, and specific rewards, capturing individual preferences and objectives. Training exclusively on the general reward provides a new paradigm of generalist pretraining. It yields a generalist agent that internalizes universal environmental competencies, such as safety and basic task proficiency, without the mode-averaging bias that afflicts standard learning from demonstration techniques. This generalist serves as a superior prior for fine-tuning to downstream tasks, including preferences unseen during training. Experiments across a synthetic basis function decomposition, multi-agent Craftax, and a continuous autonomous driving simulator (Highway-Env) confirm that GRID successfully disentangles reward structure in a semantically meaningful way, outperforms standard learning from demonstration baselines, and enables more efficient and stable specialization.

04.
bioRxiv (Bioinfo) 2026-06-14

Transposable elements as evolutionary substrates of proteindisorder in the human proteome

Intrinsically disordered regions (IDRs) are central contributors to protein function, evolution and human disease, yet the evolutionary routes that seed new disordered segments within pre-existing proteins are still poorly understood. Sequence insertions provide a powerful mechanism for disorder expansion, but the genomic donors of inserted IDR and its long-term conformational fate remain largely unknown. Transposable elements (TEs), abundant mobile genetic elements with distinctive compositional biases, represent compelling candidates for generating disorder within proteins. Here, we systematically mapped TE-derived segments across human proteins and isoforms, and we found that these insertions are strongly enriched in intrinsic disorder. The structural consequences of their insertion are shaped by TE class and family, reflecting the sequence biases of the elements from which they originate. Recent, Primate specific insertions preferentially generate disordered segments, whereas older insertions more frequently occupy ordered structural contexts, revealing an age-dependent transition in the conformational state of TE-derived sequences. TE-containing isoforms are expressed at lower levels than TE-free isoforms, particularly when insertions are young and disorder-rich, suggesting that intrinsic disorder may constrain the cellular tolerance of newly exonized sequences. These findings identify TEs as a major evolutionary mechanism linking genome mobility to the emergence of new disordered conformational ensembles in the human proteome.

05.
medRxiv (Medicine) 2026-06-16

Care Delivery Gap framework: a proof-of-concept patient-reported measure of guideline-referenced care-process omissions in sickle cell disease

Abstract Background:Sickle cell disease (SCD) is concentrated in sub-Saharan Africa, where delivery of guideline-referenced care remains challenging. Current evaluation approaches rely largely on access indicators and clinical outcomes, which do not directly measure care delivery. We developed the Care Delivery Gap (CDG) framework, a patient-reported approach for identifying care-process omissions, and conducted a proof-of-concept study to assess feasibility and explore variation across income strata. Methods: We conducted a cross-sectional framework-development study involving a proof-of-concept sample of 52 individuals with SCD or caregivers recruited through clinics and moderated SCD communities across Africa, North America, and Europe between June 2025 and March 2026. The CDG framework assessed patient-reported omissions in specialist involvement, follow-up continuity, cardiovascular screening, and biochemical surveillance. Analyses were descriptive. Results: Substantial multi-domain care-process omissions were identified despite high reported healthcare engagement. Across geographic income strata, cardiovascular screening was reported by 4/35 (11%) LMIC versus 16/17 (94%) HIC participants, and regular follow-up within the preceding 12 months by 14/35 (40%) versus 16/17 (94%), respectively. High CDG scores, representing 1 omissions across three or four domains, occurred in 20/35 (57%) LMIC compared with 1/17 (6%) HIC participants. Similar disparities were observed across specialist review and vitamin B12 surveillance domains. Conclusion: A structured patient-reported framework identified multi-domain omissions in guideline-referenced SCD care, including among individuals reporting healthcare access. The divergence between access indicators and reported care delivery suggests that service contact alone may not reflect care quality. The framework provides a feasible foundation for future process-level quality measurement in high-burden settings.

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

C-QUERI: Congressional Questions, Exchanges, and Responses in Institutions Dataset

Questions in political interviews and hearings serve strategic purposes beyond information gathering including advancing partisan narratives and shaping public perceptions. However, these strategic aspects remain understudied due to the lack of large-scale datasets for studying such discourse. Congressional hearings provide an especially rich and tractable site for studying political questioning: Interactions are structured by formal rules, witnesses are obliged to respond, and members with different political affiliations are guaranteed opportunities to ask questions, enabling comparisons of behaviors across the political spectrum. We develop a pipeline to extract question-answer pairs from unstructured hearing transcripts and construct a novel dataset of committee hearings from the 108th–117th Congress. Our analysis reveals systematic differences in questioning strategies across parties, by showing the party affiliation of questioners can be predicted from their questions alone. Our dataset and methods not only advance the study of congressional politics, but also provide a general framework for analyzing question-answering across interview-like settings.

07.
arXiv (quant-ph) 2026-06-11

Dynamically Optimal Unraveling Schemes for Simulating Lindblad Equations

arXiv:2509.19887v2 Announce Type: replace Abstract: Stochastic unraveling schemes are powerful computational tools for simulating Lindblad equations, offering significant reductions in memory requirements. However, this advantage is accompanied by increased stochastic uncertainty, and the question of optimal unraveling remains open. In this work, we investigate unraveling schemes driven by Brownian motion or Poisson processes and present a comprehensive parametric characterization of these approaches. For the case of a single Lindblad operator and one noise term, this parametric family provides a complete description for unraveling scheme with pathwise norm-preservation. We further analytically derive dynamically optimal quantum state diffusion (DO-QSD) and dynamically optimal quantum jump process (DO-QJP) that minimize the growth rate of the variance of an observable locally in time. Compared to jump process ansatz, DO-QSD offers two notable advantages: firstly, the variance for DO-QSD can be rigorously shown not to exceed that of any jump-process ansatz locally in time; secondly, it has very simple expressions. Numerical results demonstrate that the proposed DO-QSD scheme may achieve substantial reductions in the variance of observables and the resulting simulation error.

08.
arXiv (math.PR) 2026-06-16

Pathwise structure of the three-dimensional attractive one-point interaction diffusion

作者:

arXiv:2606.08008v2 Announce Type: replace Abstract: We study the pathwise behavior of the three-dimensional attractive one-point interaction diffusion whose law was constructed by Cranston, Koralov, Molchanov and Vainberg, corresponding to the singular Schrödinger Hamiltonian \[ \frac12\Delta+\frac{\beta}{2}\delta_0, \qquad \beta>0. \] We identify a local stochastic differential equation satisfied by the process away from the origin and use it to construct a natural submartingale whose increasing component in the Doob-Meyer decomposition is supported on the set of times at which the process visits the origin. In particular, we show that the process visits the origin with positive probability and that the law conditioned on avoiding the origin is three-dimensional Wiener measure.

09.
bioRxiv (Bioinfo) 2026-06-20

Seed variation impacts clustering stability in Single-Cell RNA-Seq and can be mitigated by StAbility-BasEd-Reassignment (SABER)

Single-cell RNA-seq clustering is commonly treated as reproducible once a random seed is fixed, yet the choice of seed itself may alter cell assignments and downstream interpretation. We systematically quantified seed-induced clustering variability by running Louvain and Leiden clustering across 100 seeds in Seurat and Scanpy on 28 single-cell RNA-seq datasets from the Human Cell Atlas and IMMUcan. Using Element-Centric Consistency, we found that seed choice affected a substantial fraction of cells, with Scanpy showing more unstable assignments than Seurat on average, 40.46% versus 26.78% unstable cells, respectively. This increased stability came at a marked computational cost: Seurat required approximately 19-fold higher median memory than Scanpy. Seed-dependent clustering variability also propagated to cell-type annotation, particularly among transcriptionally related populations including macrophage/monocyte, endothelial/epithelial and T/NK cell states. To mitigate this instability, we developed StAbility-BasEd Reassignment (SABER), a Scanpy-based framework that identifies seed-sensitive cells across repeated clusterings and reassigns them to stable cluster cores using cosine similarity. SABER improved clustering quality while preserving annotation concordance and reduced median memory usage 3.5-fold compared with Seurat-Louvain. Our results identify seed choice as an underappreciated source of variability in single-cell analysis and provide a scalable strategy to improve clustering robustness.

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

UniTemp: Unlocking Video Generation in Any Temporal Order via Bidirectional Distillation

Autoregressive video diffusion models have emerged as a promising approach for long video generation, achieving strong performance in streaming settings. However, existing methods are restricted to forward temporal generation, whereas practical video creation often requires flexible generation order, e.g., conditioning on future context to extend backward, or on both past and future context for inbetween generation. We bridge this gap by training an autoregressive model that supports generation in arbitrary temporal directions. A key technical challenge arises from the Causal 3D VAE widely used in video diffusion models, which encodes latents strictly conditioned on past context. While suited for forward generation, this causal structure causes inter-block discontinuities when generation proceeds backward. To address this, we introduce blockwise anchor latents, a set of auxiliary latents that restore the missing past context at block boundaries during backward generation. Built on this design, we propose UniTemp, a bidirectional distillation framework that trains a single autoregressive student model for any-direction video generation. At inference time, UniTemp conditions on arbitrary past and/or future frames, improving controllability for both bidirectional and inbetween generation. Experiments show that UniTemp maintains competitive performance on short and long video generation compared to forward-only methods, while enabling diverse workflows such as bidirectional video extension, inbetween generation, looping video generation, scene transition, and visual story generation. Project website: https://lzhangbj.github.io/projects/unitemp/

11.
arXiv (CS.LG) 2026-06-16

Brownian Kernel Ladders

arXiv:2606.15812v1 Announce Type: new Abstract: Constructing mathematically tractable function spaces that capture hierarchical compositional representations remains a central challenge in statistical learning theory. We introduce Brownian kernel ladders (BKLs), a recursively defined hierarchy of integral reproducing kernel Hilbert spaces generated through Brownian-kernel integral constructions. Starting from linear functionals, each layer is obtained by integrating Brownian kernels over probability measures supported on subsets of the previous layer, yielding a recursive function-space model in which depth is encoded directly through the hierarchy. Based on this framework, we define canonical BKL spaces together with an associated complexity functional. We establish several analytical and statistical properties of these spaces. In particular, we show that BKL spaces form quasi-Banach spaces, satisfy depth-dependent Hölder regularity estimates, and exhibit strict monotonicity with respect to depth. We further prove existence results for regularized empirical risk minimization and derive Gaussian complexity bounds that remain uniformly controlled with respect to both the ambient dimension and the hierarchy depth. A key ingredient of the analysis is a combinatorial proof technique based on recursive subset decompositions and Brownian-kernel threshold representations. These estimates yield excess-risk guarantees of near-parametric order for regularized empirical risk minimization over BKL spaces. Our results provide a mathematically tractable hierarchical function-space framework for studying compositional representations in deep learning.

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

Recursive Agent Harnesses

Recursive language models (RLMs) showed that recursion over model calls is an effective strategy for long-context reasoning, and production coding agents have begun to write code that spawns subagents at scale, most recently in Anthropic's dynamic workflows. We name and study the pattern between these two lines of work, where the recursive unit is a full agent harness with filesystem tools, code execution, and planning rather than a model call with no tools. We call this the Recursive Agent Harness (RAH) and frame it as harness recursion, the code-first extension to the model recursion of RLMs. A parent agent generates and runs an executable script that spawns subagent harnesses in parallel for fine-grained workloads and uses structured function calls for small subtasks. We provide a controlled evaluation on long-context reasoning. With the backbone held fixed at GPT-5 to match the published Codex and RLM baselines, RAH improves the Codex coding-agent baseline from 71.75% to 81.36% on Oolong-Synthetic (199 samples, 13 context-length buckets up to 4M tokens), a gain attributable to the harness rather than the model. With a stronger backbone, Claude Sonnet 4.5, the same design reaches 89.77%.

13.
arXiv (CS.LG) 2026-06-19

On the Oracle Complexity of Interpolation-Based Gradient Descent

arXiv:2606.19878v1 Announce Type: new Abstract: Recent work on first-order optimizers for empirical risk minimization (ERM) has suggested that smoothness of ERM loss functions in the training data, rather than in the optimization parameters, can be leveraged to improve the oracle complexity of gradient descent (GD) methods. In this paper, we propose an inexact gradient method, piecewise polynomial interpolation-based gradient descent (PPI-GD), which approximates the full gradient in each iteration by querying the first-order oracle at equidistant points in the data domain to construct polynomial interpolants of the resulting gradient samples over appropriately sized patches of the data domain. We analyze the oracle complexity of PPI-GD for strongly convex and non-convex loss functions when the data space dimension is bounded by a polylogarithmic function of the number of training samples, and find it to outperform several GD variants in key regimes when the loss function is sufficiently smooth. Furthermore, our analysis extends several techniques from the error analysis of bicubic spline interpolants to the setting of $d$-variate tensor product polynomial interpolants which may be of independent interest in interpolation analysis.

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

Observation of alignment tensor effects in metastability-exchange collisions with highly polarized 3He ensembles

arXiv:2606.20330v1 Announce Type: new Abstract: Highly polarized 3He ensembles prepared by metastability-exchange optical pumping (MEOP) have been widely used in precision measurements and fundamental physics. Metastability-exchange (ME) collisions, serving as the basis of MEOP, are traditionally described in terms of atomic orientation, while the significant contributions of metastable alignment tensor at high polarization remain unexplored. In this work, we develop a linearized model under mean-field approximation to investigate alignment tensor effects in highly polarized 3He , which originate from the metastable F = 3/2 manifold and are revealed through ME-induced relaxation and frequency shift. By means of free-induction-decay (FID) measurements, a pronounced dependence on nuclear polarization is experimentally observed in the response of the ground-state-metastable hybrid 3He ensembles to the external magnetic field. Furthermore, after obtaining the characteristics of tensor-induced phenomena, we demonstrate good agreement between the experiment and the theory. This work advances the understanding of nuclear spin dynamics in highly polarized 3He using MEOP. It further provides applications in systematic error correction of high-accuracy magnetometry, as well as in optimal protocol for the generation of nuclear spin-squeezed states.

15.
arXiv (quant-ph) 2026-06-11

Fabricating fiber cavity mirror substrates compatible with high coupling efficiency

arXiv:2606.12168v1 Announce Type: cross Abstract: Fiber optical cavities offer small mode volumes and correspondingly strong light-matter interactions in an open Fabry-Perot geometry. However, existing fabrication techniques do not reliably produce substrates with surface profiles amenable to high mode matching between the cavity mode and fiber core, thereby limiting the achievable collection efficiency. Here we present a technique to fabricate fiber mirror substrates while using $in situ$ reflectometry to constrain the achievable mode matching prior to coating. By measuring the back-reflection from freshly cleaved fiber tips, we pre-select 138 fibers compatible with 96.5-99.5% mode matching, and after a single CO$_2$ laser ablation pulse, these fibers remained compatible with 95.3-99.2\%. This simple technique provides rapid feedback during each stage of substrate fabrication, greatly enhancing the yield of viable fiber mirror substrates prior to (expensive) coating runs.

16.
arXiv (CS.LG) 2026-06-11

Critic Architecture Matters: Dual vs. Unified Critics for Humanoid Loco-Manipulation

arXiv:2606.11891v1 Announce Type: cross Abstract: Multi-objective reinforcement learning for humanoid robots must coordinate locomotion and manipulation within a single policy. A natural design choice is whether to use a single (unified) critic that estimates the combined value of all objectives, or separate (dual) critics with disjoint reward signals. We present a controlled comparison on the Unitree G1 humanoid (23 active DoF) in NVIDIA Isaac Lab, training loco-manipulation policies through a sequential curriculum spanning 13 levels from stationary reaching to walking with variable-orientation targets. In standardized evaluation, dual-critic policies reach targets 3.5$\times$ faster (6.5 vs. 22.6 simulation steps), achieve 2$\times$ higher throughput (14.3 vs. 7.0 validated reaches per 1,000 steps), and attain higher validated reach rates (65.2% vs. 53.8%) compared to the unified-critic policy. Notably, additional anti-gaming reward mechanisms provide no further improvement beyond the architectural change alone (60.9% vs. 65.2%). These results have direct implications for the emerging paradigm of RL fine-tuning of imitation-learned policies: when refining a pre-trained manipulation policy with RL, a unified critic risks suppressing the learned behavior through competing locomotion gradients. These findings demonstrate that critic architecture is a primary - and often overlooked - design choice in multi-objective humanoid RL, with greater impact than reward engineering on reaching efficiency.

17.
arXiv (CS.LG) 2026-06-18

N(CO)$^2$: Neural Combinatorial Optimization with Chance Constraints to Solve Stochastic Orienteering

arXiv:2606.18514v1 Announce Type: cross Abstract: Neural combinatorial optimization (NCO) offers a promising alternative to traditional heuristic-based methods for solving complex graph optimization problems by proposing to learn heuristics through data. This class of problems frequently arises in automation, as it can be used to model a variety of applications. While NCO has been extensively studied for deterministic combinatorial optimization problems, there are only a few works that aim to solve stochastic combinatorial optimization problems. In this work, we present N(CO)$^2$: Neural Combinatorial Optimization with Chance cOnstraints to solve the Stochastic Orienteering Problem (SOP) without the use of hand-crafted heuristics. By integrating a reinforcement learning (RL) framework, the model optimizes path selection under uncertainty, effectively balancing exploration and exploitation. Empirical results demonstrate that our method generalizes well across diverse SOP instances, achieving competitive performance compared to the state-of-the-art mixed-integer linear program (MILP) for the task. The proposed approach reduces human effort in heuristic design while enabling adaptive and efficient decision-making in uncertain environments.

18.
Nature (Science) 2026-06-17

Spatial distribution of the proteome in the human body and in cancers

作者:

A detailed, spatially resolved quantitative map of the human proteome is essential for a deeper understanding of human biology and disease1–4. Here we present a comprehensive human proteomic landscape, generated by profiling more than 13,000 proteins across 2,856 samples using data-independent acquisition mass spectrometry. The dataset spans 58 major tissue types, 251 specific tissue subtypes and 25 distinct carcinomas. This resource enables the depiction of spatially resolved proteome trajectories across tissue types and physiological states, including fetal, tumour, adjacent non-tumour and healthy adult tissue, thereby providing insight into both developmental processes and oncogenic progression. Furthermore, quantitative proteomics comparisons across diverse tissue types and states facilitate the indication of organ-specific toxicity, the identification of repurposable anticancer drug candidates and the prioritization of therapeutic targets for cancers. This study establishes a quantitative resource for navigating the proteome in the human body and in common cancers. A spatially resolved map of the human proteome across a variety of healthy tissues and cancers provides wide-ranging insights in developmental biology and oncology, and could aid the identification of therapeutic targets and development of treatments for cancer.

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

Matrix Product Operator Encodings of the Magnus Expansion and Dyson Series

arXiv:2605.21597v2 Announce Type: replace Abstract: We introduce a matrix product operator (MPO) encoding of the Magnus expansion and the Dyson series for one-dimensional quantum lattice models with time-dependent Hamiltonians. The MPO construction can be made accurate up to arbitrary order in the time step, it can be applied to both finite and infinite systems, and it can handle long-range interactions. The resulting MPO can be combined with state-of-the-art time evolution algorithms based on matrix product states, allowing for drastic improvements in simulating evolution under time-dependent Hamiltonians. Our MPO construction can also be used for the optimization of quantum circuits in the context of quantum simulation of time-dependent Hamiltonians.

20.
arXiv (CS.LG) 2026-06-11

Multi-agent rendezvous in fluid flows via reinforcement learning

arXiv:2606.11274v1 Announce Type: cross Abstract: Rendezvous is a critical task for multi-agent systems, requiring agents to coordinate to meet at an unspecified location. However, achieving this in fluid environments presents a challenge, as it remains unclear how agents can exploit underlying fluid kinematics to facilitate convergence. In this study, we adopt a multi-agent reinforcement learning (MARL) approach to develop physics-informed rendezvous strategies in vortical flows. Compared to a naive strategy, where agents navigate toward their counterparts, MARL strategies significantly improve the rendezvous rate. MARL strategies also show transferability across varying vortex intensities, vortex scales, and swarm sizes. By breaking the symmetry of the state-action map, MARL strategy leverages a non-intuitive mechanism that prevents agents from becoming trapped in separate vortices, thereby enhancing rendezvous success. Additionally, a heuristic strategy is extracted from the learned strategy and also outperforms the naive strategy. Furthermore, a theoretical analysis demonstrates that fluid deformation impedes the rendezvous process. Large finite-time Lyapunov exponents identify where fluid effects separate adjacent agents, suggesting that targets should be planned in weak-deformation regions. Our findings reveal the important role that agent-fluid interactions play in multi-agent tasks and highlight the MARL capability to explore swarm intelligence in complex flow environments.

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 (quant-ph) 2026-06-16

Quantifying Coherence-to-Entanglement Conversion Efficiency under Noisy Operations

arXiv:2606.16916v1 Announce Type: new Abstract: We investigate the noise-limited conversion of local quantum coherence into bipartite entanglement in a minimal two-qubit protocol comprising a coherent single-qubit input, an incoherent ancilla, an ideal CNOT operation, and subsequent environmental noise. Employing the $l_1$-norm of coherence and the entanglement negativity as resource quantifiers, we establish an exact closed-form correspondence between local single-qubit input coherence and the two-qubit entanglement generated in the noiseless limit, showing that the output negativity is precisely one half of the initial $l_1$-coherence. We then derive analytic expressions for the surviving entanglement and the associated coherence-to-entanglement conversion efficiency under two representative noise mechanisms: independent phase damping and global two-qubit depolarizing noise. The two channels exhibit qualitatively distinct degradation behavior. Phase damping induces a universal multiplicative suppression of the generated entanglement, yielding a coherence-independent conversion efficiency and no finite-noise entanglement sudden death. In contrast, global depolarization introduces an isotropic mixing contribution that shifts the partial-transpose spectrum, producing coherence-dependent degradation and a finite sudden-death threshold. We show that maximally coherent inputs not only maximize the entanglement generated by the CNOT protocol but also optimize its robustness against depolarizing noise. Direct density-matrix simulations validate the analytic results to numerical precision. These findings provide a compact analytic benchmark for assessing how different noise mechanisms constrain coherence-to-entanglement conversion in elementary quantum-information protocols and near-term quantum devices.

23.
arXiv (CS.CL) 2026-06-18

Beyond Tokenization: Direct Timestep Embedding and Contrastive Alignment for Time-Series Question Answering

Recent advances in large language models (LLMs) have given rise to time-series question answering (TSQA), which formulates time-series analysis as natural-language question answering. However, directly feeding raw numerical series into LLMs suffers from a tokenization bottleneck: Byte Pair Encoding fragments continuous values into unstable tokens whose embeddings lack meaningful metric structure, resulting in the loss of magnitude, scale, and trend information. Prior methods use patch-based encoders that split the series into fixed windows, locking in one granularity that breaks patterns and hides exact timesteps, through a separate module that rarely transfers across datasets with different lengths or sampling rates. To address this challenge, we propose CADE (Contrastive Alignment with Direct Embedding), a novel framework for TSQA built upon two key components: direct timestep embedding and semantic alignment. The proposed framework maps each timestep directly into the LLM embedding space through a point-wise linear encoder and MLP projector, preserving exact index-level access while eliminating the need for patching and padding. To further bridge the semantic gap between time-series and language representations, we introduce a novel one-directional supervised contrastive loss that aligns time-series embeddings with frozen class-name text anchors. Experimental results on the public Time-MQA benchmark demonstrate that our framework consistently improves performance across six TSQA tasks, outperforming both open-source and proprietary LLM baselines.

24.
arXiv (CS.LG) 2026-06-18

ActiTect: A Generalizable Machine Learning Pipeline for REM Sleep Behavior Disorder Screening through Standardized Actigraphy

arXiv:2511.05221v3 Announce Type: replace Abstract: Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of $\alpha$-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. While wrist-worn actimeters hold significant potential for detecting RBD in large-scale screening efforts by capturing abnormal nocturnal movements, they become inoperable without a reliable and efficient analysis pipeline. This study presents ActiTect, a fully automated, open-source machine learning tool to identify RBD from actigraphy recordings. To ensure generalizability across heterogeneous acquisition settings, our pipeline includes robust preprocessing and automated sleep-wake detection to harmonize multi-device data and extract physiologically interpretable motion features characterizing activity patterns. Model development was conducted on a cohort of 78 individuals, yielding strong discrimination under nested cross-validation (AUROC = 0.95). Generalization was confirmed on a blinded local test set (n = 31, AUROC = 0.86) and on two independent external cohorts (n = 113, AUROC = 0.84; n = 57, AUROC = 0.94). To assess real-world robustness, leave-one-dataset-out cross-validation across the internal and external cohorts demonstrated consistent performance (AUROC range = 0.84-0.89). A complementary stability analysis showed that key predictive features remained reproducible across datasets, supporting the final pooled multi-center model as a robust pre-trained resource for broader deployment. By being open-source and easy to use, our tool promotes widespread adoption and facilitates independent validation and collaborative improvements, thereby advancing the field toward a unified and generalizable RBD detection model using wearable devices.

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

Handling Feature Heterogeneity with Learnable Graph Patches

arXiv:2606.17667v1 Announce Type: cross Abstract: In recent years, the rapid development of foundation models and graph pre-training technologies has spurred increasing interest in constructing a universal pre-trained graph model or Graph Foundation Model (GFM). However, a significant challenge is that existing models are unable to address feature heterogeneity in graph data without textual information, which hinders the transferability of graph models across different datasets. To bridge this gap, we propose the concept of learnable graph patches, which we regard as the smallest semantic units of any graph data. We decompose the graph into learnable graph patches by unfolding the node features and constructing corresponding patch structures separately. We then design a framework that mines transferable information from graph data across domains. Specifically, after extracting graph patches, we propose a patch encoder to extract knowledge from each unit and a patch aggregator to learn how the units are combined into a whole. Due to its domain-agnostic nature, the model can be applied to downstream data across different domains. Furthermore, we analyze the connection between our method and existing graph models, as well as the transferability of the node embeddings it generates. Empirically, our method not only achieves the capability to use multi-domain graphs for pre-training, but also shows enhanced performance across various downstream datasets and tasks. Moreover, we observe consistent improvement in downstream performance as the volume of pre-training data increases.