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

Domain Generalizable Adaptation of 3D Vision-Language Models via Regularized Fine-Tuning

Domain adaptation remains a central challenge in 3D vision, especially for multimodal foundation models that align 3D point clouds with visual and textual data. While these models demonstrate strong general capabilities, adapting them to downstream domains with limited data often leads to overfitting and catastrophic forgetting. To address this, we introduce ReFine3D, a regularized fine-tuning framework designed for domain-generalizable tuning of 3D large multimodal models (LMMs). ReFine3D combines selective layer tuning with two targeted regularization strategies: multi-view consistency across augmented point clouds and text diversity through synonym-based prompts generated by large language models. Additionally, we incorporate point-rendered vision supervision and a test-time augmentation mechanism with confidence-based aggregation to further enhance robustness. Extensive experiments across different 3D domain generalization benchmarks show that ReFine3D improves base-to-novel class generalization by 1.36%, cross-dataset transfer by 2.43%, robustness to corruption by 1.80%, and few-shot accuracy by up to 3.11%, outperforming prior state-of-the-art methods with minimal added computational overhead.

02.
arXiv (quant-ph) 2026-06-16

Quantum Global Variational Learning for Quantum Error Correction

arXiv:2606.08592v2 Announce Type: replace-cross Abstract: Efficient quantum error correction is essential for the advancement of quantum computing. We propose a quantum neural network with a global structure that reduces the number of unitary matrices required in quantum circuits. This approach resulted in a 97% reduction in training time and up to a 25% improvement in the training completion rate, ultimately achieving a 100% success rate in training while surpassing the error correction performance reported in previous studies. In addition, we demonstrated the enhanced robustness of quantum error correction against internal network noise. Moreover, the fidelity of quantum error correction under internal network noise increased by up to 15% due to the reduced computational load.

03.
arXiv (CS.LG) 2026-06-12

Estimating Individualized Treatment Effects in Acute Ischemic Stroke with Causal Transformation Models (TRAM-DAG): A Multi-Centre Observational Study with External RCT Validation

arXiv:2606.12623v1 Announce Type: cross Abstract: Personalized medicine in acute ischemic stroke requires moving beyond average treatment effects (ATE) to individualized treatment effect (ITE) estimates to support treatment decisions. In acute ischemic stroke, mechanical thrombectomy has been shown to be more effective on average than lysis in randomized controlled trials (RCTs), such as the MR CLEAN study. We aim to identify which individual patients benefit most from mechanical thrombectomy compared to lysis. The outcome of interest is the modified Rankin Scale (mRS) at three months, an ordinal measure of functional disability (0: no symptoms, 6: death). We demonstrate that causal transformation models on directed acyclic graphs (TRAM-DAG) can be used for ITE estimation after being fitted on observational MAGIC multi-center stroke patient data. To ensure comparability with the MR CLEAN population, which we use for validation, we train the TRAM-DAG on a MAGIC sub-population with NIHSS at admission >= 6, corresponding to one inclusion criterion of MR CLEAN. The fitted model is then used to estimate ITEs for stroke patients in the MR CLEAN population. While these ITE estimates cannot be confirmed experimentally, we show that their average is consistent with the trial's reported ATE. Furthermore, the ITE estimates correctly rank trial patients by their observed frequency of a good outcome (mRS at three months

04.
arXiv (CS.LG) 2026-06-19

TetriServe: Efficiently Serving Mixed DiT Workloads

arXiv:2510.01565v4 Announce Type: replace Abstract: Diffusion Transformer (DiT) models excel at generating high-quality images through iterative denoising steps, but serving them under strict Service Level Objectives (SLOs) is challenging due to their high computational cost, particularly at larger resolutions. Existing serving systems use fixed-degree sequence parallelism, which is inefficient for heterogeneous workloads with mixed resolutions and deadlines, leading to poor GPU utilization and low SLO attainment. In this paper, we propose step-level sequence parallelism to dynamically adjust the degree of parallelism of individual requests according to their deadlines. We present TetriServe, a DiT serving system that implements this strategy for highly efficient image generation. Specifically, TetriServe introduces a novel round-based scheduling mechanism that improves SLO attainment by (1) discretizing time into fixed rounds to make deadline-aware scheduling tractable, (2) adapting parallelism at the step level and minimizing GPU hour consumption, and (3) jointly packing requests to minimize late completions. Extensive evaluation on state-of-the-art DiT models shows that TetriServe achieves up to 32% higher SLO attainment compared to existing solutions without degrading image quality.

05.
arXiv (CS.LG) 2026-06-11

Discovery and inference beyond linearity for epidemiological data by integrating Bayesian regression, tree ensembles and Shapley values

arXiv:2505.00571v3 Announce Type: replace-cross Abstract: Machine Learning (ML) is gaining popularity in epidemiology and healthcare studies for hypothesis-free discovery of risk and protective factors. ML is strong at discovering nonlinearities and interactions, but this power is compromised by a lack of reliable inference. Although Shapley values provide local measures of features' effects, valid uncertainty quantification for these effects is typically lacking, thus precluding statistical inference. We propose RuleSHAP, a framework that addresses this limitation by combining a dedicated Bayesian sparse regression model with an improved tree-based rule generator and Shapley value attribution. RuleSHAP provides detection of nonlinear and interaction effects, with uncertainty quantification at the individual level as a key contribution. We derive an efficient formula for computing marginal Shapley values within this framework. We apply RuleSHAP to data from an epidemiological cohort to detect and infer several effects for high cholesterol and blood pressure, such as nonlinear interaction effects between features like age, sex, ethnicity, BMI and glucose level. To conclude, we demonstrate the validity of our framework on simulated data.

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

CADET: Physics-Grounded Causal Auditing and Training-Free Deconfounding of End-to-End Driving Planners

作者:

arXiv:2606.14438v1 Announce Type: cross Abstract: End-to-end (E2E) autonomous-driving planners trained by imitation are prone to statistical shortcuts: they associate scene elements that merely co-occur with expert actions (a roadside object, a building facade) with driving decisions, rather than the variables that causally determine them. Such causal confusion silently compromises reliability in long-tail scenarios, and it is difficult to detect, because prevailing open-loop metrics (L2 displacement and collision rate) are dominated by ego status and do not indicate whether a planner depends on spurious cues. Existing remedies based on causal-intervention training require retraining large models and cannot audit a planner that is already deployed. We present CADET, a training-free framework that audits, benchmarks, and repairs spurious reliance in pretrained E2E planners without any parameter update.

07.
arXiv (CS.LG) 2026-06-19

Humanoid Everyday: A Comprehensive Robotic Dataset for Open-World Humanoid Manipulation

arXiv:2510.08807v2 Announce Type: replace-cross Abstract: From loco-motion to dextrous manipulation, humanoid robots have made remarkable strides in demonstrating complex full-body capabilities. However, the majority of current robot learning datasets and benchmarks mainly focus on stationary robot arms, and the few existing humanoid datasets are either confined to fixed environments or limited in task diversity, often lacking human-humanoid interaction and lower-body locomotion. Moreover, there are a few standardized evaluation platforms for benchmarking learning-based policies on humanoid data. In this work, we present Humanoid Everyday, a large-scale and diverse humanoid manipulation dataset characterized by extensive task variety involving dextrous object manipulation, human-humanoid interaction, locomotion-integrated actions, and more. Leveraging a highly efficient human-supervised teleoperation pipeline, Humanoid Everyday aggregates high-quality multimodal sensory data, including RGB, depth, LiDAR, and tactile inputs, together with natural language annotations, comprising 10.3k trajectories and over 3 million frames of data across 260 tasks across 7 broad categories. In addition, we conduct an analysis of representative policy learning methods on our dataset, providing insights into their strengths and limitations across different task categories. For standardized evaluation, we introduce a cloud-based evaluation platform that allows researchers to seamlessly deploy their policies in our controlled setting and receive performance feedback. By releasing Humanoid Everyday along with our policy learning analysis and a standardized cloud-based evaluation platform, we intend to advance research in general-purpose humanoid manipulation and lay the groundwork for more capable and embodied robotic agents in real-world scenarios. Our dataset, data collection code, and cloud evaluation website are made publicly available on our project website.

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

Montreal Forced Aligner and the state of speech-to-text alignment in 2026

The Montreal Forced Aligner (MFA) was released in 2016 and has since become the most widely used tool for forced alignment in research and industry. In the decade since, MFA has undergone substantial development, including expanded coverage across more languages and dialects using larger open-source datasets, harmonized IPA dictionaries, model adaptation, cross-language phone remapping, and support utilities. This paper documents MFA 3.0's developments since version 1.0 and evaluates MFA's performance across English, Japanese, and Korean, benchmarked against classic and neural forced aligners. MFA 3.0 achieves state-of-the-art or near state-of-the-art performance across all four benchmark datasets with mean boundary errors below 15 ms. Adaptation and cross-language remapping are effective for languages outside MFA's training distribution, and pronunciation probability modeling and phonological rules provide gains in specific conditions.

09.
Nature (Science) 2026-06-10

A 5.3-million-year-old deep-sea whale necropolis in the Diamantina Zone

Whale falls are biodiversity oases at seabeds1–6, yet their record from the oceans has remained sparse and fragmentary6,7. Here we report the discovery of a vast whale necropolis in the Diamantina Zone (4,616- to 7,001-m depth), extending about 1,200 km along the sea floor of the southeastern Indian Ocean. This area has a deep and extensive accumulation comprising five modern natural whale-fall communities and 476 fossil cetaceans recorded. We show that carcasses host specialized communities dominated by brittle stars, bone-boring worms and chemosynthesis-based bivalves and that the fossil record in this area comprises both extant and extinct deep-diving beaked whales. Isotopic dating shows that whale falls in this region have occurred since at least 5.3 million years ago. These findings reshape the understanding of the limits and biogeography of whale-fall ecosystems and establish some deep sea floors as a fossil archive for tracing cetacean evolution over geological time. Researchers uncovered an enormous deep-sea accumulation of whale remains in the southeastern Indian Ocean, showing long-term, specialized ecosystems and an extensive fossil record that offers new insight into deep-ocean biodiversity and whale evolutionary history.

10.
arXiv (quant-ph) 2026-06-16

High-dimensional coherence to entanglement transduction under canonical noise

arXiv:2606.16695v1 Announce Type: new Abstract: We develop an analytical framework for coherence-to-entanglement conversion in bipartite high-dimensional quantum systems, so-called qunits. An arbitrary coherent input qunit is coupled to an incoherent ancilla through a generalized controlled-shift operation, producing a maximally correlated bipartite state. By analyzing the partial transpose of the output state, we establish an exact dimension-independent connection between the input coherence and the generated entanglement. We then study how this conversion is affected by three standard noise processes applied after the conversion step: phase damping, global depolarizing noise, and independent amplitude damping. The resulting expressions show that these channels degrade entanglement in qualitatively different ways. Phase damping leads to a uniform attenuation of the entanglement generated from coherence, depolarizing noise introduces pairwise thresholds associated with entanglement sudden death, and amplitude damping produces an asymmetric decay governed by relaxation toward the ground state. For maximally coherent inputs, the general results reduce to simple closed-form behavior, allowing direct comparison of the three noise mechanisms as the system dimension increases. In particular, global depolarizing noise exhibits a dimension-dependent sudden-death threshold, while amplitude damping leads to a smooth suppression in the maximally coherent case. These results provide useful analytical benchmarks for high-dimensional resource conversion and for assessing noisy entanglement generation in qudit-based quantum-information settings.

11.
Nature (Science) 2026-06-17

The EU needs to back its ambition to end animal testing with cash

作者: 未知作者

The European Union has declared that it wants to stop using animals in chemical safety testing. Its goal will need a timeline and a serious funding commitment. The European Union has declared that it wants to stop using animals in chemical safety testing. Its goal will need a timeline and a serious funding commitment.

12.
arXiv (CS.AI) 2026-06-15

The Journal of Prompt-Engineered (Moral) Philosophy Or: Why AI-Assisted Ethics Research Requires Process Transparency

作者:

arXiv:2511.08639v4 Announce Type: replace-cross Abstract: Existing AI disclosure mandates in scholarship require that AI assistance be reported but leave transparency philosophically unspecified: they fix the duty without explaining what the duty serves. We argue that ethical inquiry is essentially contested at two independent levels – about what it is, and about what it demands of the inquirer – defeating output-only evaluation and welfare-economic dismissal of the transparency question, and, by extension, reproducibility framings imported from the empirical sciences. The transparency duty is grounded instead in agent-integrity: the legibility, before a community of inquiry, of the identity-constituting commitments that the author's mode of philosophising expresses. Because the standards for evaluating such work are not communally settled, the achievable goal for transparency is not evaluation against agreed criteria but tracking – accumulating the evidentiary record that lets each tradition assess the work on its own terms and makes future normative judgments possible. We develop a documentation-adequacy framework that operationalises Meaningful Human Control through five transparency elements – declaration, navigation, documentation account, process documentation, and development records – demonstrated by the paper itself, whose full documentation record is archived at a persistent identifier. The framework is a first iteration subject to revision, not a settled standard.

13.
arXiv (CS.CV) 2026-06-16

Structure-Semantic Co-optimized Latent Diffusion Model for Fast Visual Anagram Synthesis

Visual anagram is an intriguing form of art creation wherein a single image presents different conceptual interpretations under transformations such as flipping or rotation. Recent work has achieved visual anagram synthesis by leveraging pretrained text-to-image (T2I) diffusion models, yet still suffers from several key limitations including computational inefficiency, suboptimal aesthetic quality, and weak semantic fidelity and expressiveness. This work focuses on generating visual anagrams with substantially improved visual quality at minimal computational cost, thereby advancing intelligent creation of illusionary digital art. To increase image resolution while reducing time overhead, we adapt the cutting-edge parallel denoising algorithm from pixel-based T2I model to the adversarially distilled latent-based one, and accordingly propose a structure-semantic co-optimization (S2CO) framework to counteract the consequent visual degradation. As the core of our approach, S2CO framework comprises three key innovations: (\romannumeral1) null-text structure alignment optimization; (\romannumeral2) semantic enhancement optimization; (\romannumeral3) attention-guided noise fusion. Building upon these components, our method dubbed S2CO-Anagram is able to generate higher-resolution anagram images with noticeably superior visual harmony and semantic faithfulness than related SOTA approaches, all while achieving substantially faster inference speed. Code will be publicly available.

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

General circuit mapping algorithm for neutral atom quantum computers

arXiv:2606.20503v1 Announce Type: new Abstract: Neutral atom quantum computers (NAQC) are emerging as a promising, scalable quantum computing platform because of their long qubit coherence, flexible qubit arrangement, and multiqubit gate capabilities. However, circuit execution often requires physically moving qubits, making compilation a critical optimization challenge. We propose a circuit independent mathematical framework built on graph-theoretic combinatorial optimization that determines the minimal number of required qubit transfers. This model captures spatial constraints specific to NAQC platforms with zone-limited gate operations and multi-qubit gates. From this framework, we encode the qubit mapping problem as a nonlinear integer program and solve it using a genetic algorithm, enabling trade-offs between minimizing the total traveled distance and the number of parallel transfer operations. Compared to the state-of-the-art scalable compiler for zoned architectures, our approach consistently finds fewer transfers. Depending on the optimization focus, our method produces shorter traveled distances or fewer parallel transfer operations. This work provides both theoretical guaranties and a practical tool for efficient, architecture-aware quantum circuit compilation. As a result, practitioners can generate hardware-aware mappings that reduce movement-induced errors and better exploit atom transfer parallelism, directly improving execution efficiency on NAQC devices.

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

OPD-Evolver: Cultivating Holistic Agent Evolver via On-Policy Distillation

Memory has become a standard substrate for self-evolving agents, yet retaining experience is not the same as learning how to evolve through it. Existing memory agents can store trajectories, retrieve reflections, or accumulate skills, but often lack the holistic competence to select useful experience, act on it, write reusable knowledge, and maintain a growing repository. We introduce OPD-Evolver, a slow-fast co-evolution framework that cultivates such an agent evolver through on-policy self-distillation. In the fast loop, OPD-Evolver interacts with a four-level memory hierarchy to read, use, write, and maintain experience for rapid test-time evolution. In the slow loop, outcome-calibrated memory attribution and privileged hindsight distill these four abilities into the deployable policy. Across multi-domain benchmarks, OPD-Evolver surpasses memory systems such as ReasoningBank by up to 11.5%, and training-based methods such as Skill0 by ~5.8%. Further analysis shows that OPD-Evolver internalizes high-value experience and memory management, enabling OPD-Evolver-9B to challenge giant counterparts such as Qwen3.5-397B-A17B and Step-3.5-Flash, pointing beyond memory-augmented agents toward genuinely qualified agent evolvers.

16.
arXiv (quant-ph) 2026-06-12

Approximability limits for bounded-degree max-LINSAT and implications for decoded quantum interferometry

arXiv:2606.13570v1 Announce Type: new Abstract: For general max-k-XORSAT with $k \geq 3$, no polynomial-time algorithm can do substantially better than random guessing on worst-case instances unless $\mathsf{P} = \mathsf{NP}$: approximating beyond the random-assignment value of $1/2$ is $\mathsf{NP}$-hard. The picture changes when each variable appears in at most $D$ constraints. In that bounded-degree setting, polynomial-time algorithms can provably beat the random baseline by an additive amount of order $1/\sqrt{D}$. For Boolean instances, this scaling is known to be optimal: the matching hardness result is due to Trevisan, while the corresponding algorithmic guarantee was established by Barak et al. Whether the same holds over general finite fields, and what it implies for quantum algorithms, has not been established. We make this connection explicit and extend the hardness to max-E$k$-LINSAT$(q,r)$ with bounded degree $D$ and over arbitrary finite fields $\mathbb{F}_q$, proving that it is $\mathsf{NP}$-hard to exceed $r/q + \mathcal{O}_{q,r}(1/\sqrt{D})$. These results provide the complexity-theoretic benchmark for the bounded-degree instances targeted by decoded quantum interferometry (DQI), QAOA, and classical heuristics. Any quantum advantage on bounded-degree instances is therefore confined to the constant prefactor. We further show that in the context of DQI and on $(k,D)$-regular instances, this prefactor is sensitive to the nature of the decoder: DQI with classical decoders faces an information-theoretic $1/\sqrt{D \log D}$ barrier that prevents it from matching the hardness scaling, while DQI with quantum decoders is compatible with the $1/\sqrt{D}$ scaling – identifying quantum decoding as the key ingredient for matching the complexity-theoretic scaling with DQI.

17.
arXiv (quant-ph) 2026-06-15

Interpreting Bohm-like quantum potentials in "Computing quantum waves exactly from classical action"

arXiv:2605.20443v3 Announce Type: replace Abstract: The recent posting arXiv:2605.02621 [14], commenting on the article rspa.2025.0413 [7], argues that the proof of Lemma 3.1 in [7] is missing the spatial derivative of the density, which would lead to a Bohm-like quantum potential. This technical note shows why the propagated density is independent of space in the Feynman propagator construction of Lemma 3.1. This is done by extending the proof of Lemma 3.1 explicitly with Bohm-like quantum potential terms along the stationary action paths, and then showing that these terms are exactly zero. In [7], this property can also be verified directly on most examples (double slit, Aharonov-Bohm, potential well, harmonic oscillator, tunneling, EPR, QED), as well as in the derivations of the Pauli, Dirac, and Maxwell equations. For more general nonlinear actions, a time rescaling may be required to guarantee this space independence along stationary paths. In the hydrogen atom example, this time rescaling can be computed in closed form. In contrast to the general wave of the Madelung solution [9] Lemma 3.1 of [7] is defined first for a propagator, and a general wave is then constructed in a second step. Recall that a propagator is a specific quantum wave, which is initialized at $t=0$ with a Dirac impulse at a given initial position or momentum. In turn, a general wave is constructed in a second step by superposing a distribution of initial conditions using the propagator. This key difference is why the Bohm-like quantum potential terms disappear in the construction [7] (specifically, in the first step) while the Bohm potential in the Madelung analysis does not. This fundamental difference is also consistent with the fact that the wave construction in [7] extends naturally to relativistic contexts, while Bohmian non-locality notoriously prevents such extensions. Keywords - Response to arXiv:2605.02621, in relation to rspa.2025.0413

18.
arXiv (CS.CL) 2026-06-15

Harsher on Male? Evaluating LLMs on Gender-Asymmetric Moral Framing Across Diverse Conflict Scenarios

Existing studies on gender bias in LLMs have largely focused on stereotypes, occupational associations, or explicit harmful outputs. In this work, we ask whether LLMs apply consistent response standards to the same negative behavior under matched male-actor and female-actor conditions. We introduce GAMA-Bench, a gender-mirrored benchmark of 1,298 scenarios covering intimate relationship and public social conflicts. It constructs gender-neutral misconduct templates through controlled grids and cross-model review, then compiles them into paired first-person prompts with matched actor-gender and role-reference variations. We further design a structured response-framing protocol to measure how models allocate punishment, empathy, escalation, instruction, and blame. Experiments on 10 representative LLMs reveal a consistent male-disadvantaging asymmetry: male actors receive more punitive, escalatory, and blame-centered framing, whereas female actors receive more therapeutic and empathy-oriented framing for the same misconduct. Further analyses show that this pattern persists across model families, scenario tracks, model scale, and explicit thinking-style reasoning. The official code is available at https://github.com/xufeiqiong/GAMA-Bench.

19.
arXiv (CS.LG) 2026-06-16

Privacy from Symmetry: Orthogonally Equivariant Transformers for LLM Inference

arXiv:2606.16461v1 Announce Type: new Abstract: Running large language models locally is often impractical, pushing inference on sensitive text to third-party providers. Split inference partially mitigates this by keeping tokens on the client and sending only hidden representations, but these representations can still be recovered via nearest-neighbor search against the public embedding table. We propose an orthogonal obfuscation procedure in which the client multiplies embeddings by a secret orthogonal matrix before transmission. To enable correct inference under arbitrary rotations, we introduce ConjFormer, a transformer variant that is exactly $\mathrm{O}(d)$-equivariant via a lightweight normalization change (scalar RMSNorm) together with blockwise orthogonal conjugation of all linear weights. As a result, the server performs the full forward pass entirely in the rotated basis and never observes unrotated hidden states. Experiments on GPT-2 and Llama 3.2 1B models fine-tuned on PubMed show that orthogonal obfuscation eliminates direct cosine nearest-neighbor inversion and reduces token recovery from over 35% top-10 to at most 1.3%, while increasing perplexity by only 0.4% after fine-tuning. These results indicate that enforcing symmetry at the architectural level can provide a practical defense for privacy-preserving LLM inference without noise injection or heavy cryptographic machinery.

20.
Nature (Science) 2026-06-17

Structure of the pre-initiation complex explains CMGE biogenesis

When cells enter S phase, bidirectional DNA replication is initiated through the kinase-regulated recruitment of three activators (Cdc45, GINS and Pol ε) to a duplex-DNA-loaded double hexamer of minichromosome maintenance (MCM) ATPases. Together, these proteins form two CMGE helicases that establish divergent replication forks as they become separated1. Here, to gain an understanding of CMGE biogenesis, we reconstituted the pre-initiation complex with purified yeast proteins. The cryo-electron-microscopy structure shows a set of firing factors caught in the act of assembling two symmetrical CMGEs. We show how stepwise complex formation reshapes MCM in preparation for DNA opening, and we explain how ATP promotes firing-factor ejection and CMGE maturation. We find that although Sld2 facilitates the recruitment of GINS to MCM, as expected, it also aids the efficient separation of the CMGE dimer, and is essential for the ejection of the lagging strand from MCM. These findings have direct implications for our understanding of the metazoan Sld2 orthologue, RECQL4, and point to a replication-fork establishment mechanism that is conserved across eukaryotes. Cryo-electron microscopy and biochemical reconstitution experiments in yeast provide insight into the assembly of the CMGE complex, a helicase that establishes bidirectional DNA replication in eukaryotic cells, and elucidate the role of the firing factor Sld2.

21.
arXiv (CS.AI) 2026-06-17

Patients With Personality: Realistic Patient Simulation through Controlled Diversity and Selective Disclosure

arXiv:2606.17441v1 Announce Type: cross Abstract: Simulating realistic patient interactions is a key requirement to testing clinical applications of LLMs at scale without time-consuming and expensive user studies. However, existing approaches often lack realism and controllability, often oversharing information unprompted, and failing to capture the wide variability of patient behavior. Here, we introduce PatientsWithPersonality (PWP), a patient simulation framework that generates realistic yet diverse virtual patient responses through explicit personality parametrization over a latent patient state. Grounded in HEXACO, a six-dimensional personality space used to quantify and parameterize human behavioral traits, our approach enables fine-grained control over conversational style, cooperativeness, and information disclosure within a unified framework. In a clinician evaluation, PWP is judged nearly as realistic as recorded human actors and clearly ahead of prior simulators, while being flagged as "too informative" far less often. Conditioning on HEXACO axes yields personas whose configured traits are recoverable by both clinicians and an autorater, span a substantially wider behavioral footprint than the closest baseline, and prevent oversharing. Altogether, our framework paves the way for more accurate and informative LLM benchmarking through our realistic and steerable patient simulator.

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

The Dark Regulome: Disentangling Predictability from Regulation in Genomic Foundation Models

High-grade gliomas integrate into neural circuits through functional synapses with neurons, raising the question of which noncoding elements shape synaptogenic gene expression in tumor cells. The regulatory program written across the dark genome, what we call the $dark regulome$, is the natural substrate to probe, and sequence foundation models offer a zero-shot route through in-silico mutagenesis (ISM); yet likelihood-based scoring is tautologically coupled to local sequence predictability, leaving the regulatory interpretation underdetermined. Across three architecturally distinct foundation models (Caduceus-Ph, HyenaDNA, Enformer) and 30,448 dark genome elements at 92 glioma-relevant loci, we introduce a residualization-and-permutation diagnostic that separates predictability-driven from regulation-driven RIS variance. A sharp 10kb proximal-regulatory horizon survives every control we apply, but the LM-derived element-class hierarchy does not: a six-feature linear baseline matches Caduceus top-decile membership at AUC $= 0.985$. Cross-architecture decomposition cleanly separates a sequence-predictability layer (the two language models co-rank long well-predicted transposable elements) from a regulatory-output layer (Enformer alone retains residual cCRE-discriminative signal), with literally zero overlap between the two top-100 lists. Conservation, brain cis-eQTL, and STRING-PPI cross-checks then anchor what biology survives: top-100 elements across all three models are $3.3\times$ enriched per model for matching brain eQTLs ($p_\mathrm{emp} < 5\times 10^{-3}$), while a tempting transposable-element regulatory layer and a striking NRXN1+NLGN1 protein-pair convergence both fail proper permutation tests once those tests are constructed. We deliver the diagnostic as a general methodological tool for any ISM-based regulatory study.

23.
arXiv (CS.LG) 2026-06-11

Analytic Bijections for Smooth and Interpretable Normalizing Flows

arXiv:2601.10774v2 Announce Type: replace Abstract: A key challenge in normalizing flows is finding expressive invertible scalar bijections. Existing approaches face trade-offs: affine transformations are smooth and analytically invertible but lack expressivity; monotonic splines offer local control but are only piecewise smooth and act on bounded domains; residual flows achieve smoothness but need numerical inversion. We introduce three families of analytic bijections that are globally smooth ($C^\infty$), defined on all of $\mathbb{R}$, and analytically invertible in closed form, combining the favorable properties of prior approaches. Beyond serving as drop-in replacements in coupling flows, where they match or exceed spline performance, we develop radial flows: a novel architecture using direct parametrization that transforms the radial coordinate while preserving angular direction. Radial flows exhibit exceptional training stability, produce geometrically interpretable transformations, and on targets with radial structure can achieve comparable quality to coupling flows with $1000\times$ fewer parameters. We provide comprehensive evaluation on 1D and 2D benchmarks, and demonstrate applicability to higher-dimensional physics problems through experiments on $\phi^4$ lattice field theory, where our bijections outperform affine baselines and enable problem-specific designs that address mode collapse.

24.
arXiv (CS.AI) 2026-06-12

Contextual Invertible World Models: A Neuro-Symbolic Agentic Framework for Colorectal Cancer Drug Response

arXiv:2603.02274v3 Announce Type: replace-cross Abstract: Precision oncology is currently limited by the small-N, large-P paradox, where high-dimensional genomic data is abundant but pharmacological response samples are sparse. While deep learning achieves predictive accuracy, it frequently fails to provide the mechanistic clarity required for clinical adoption. We present the Contextual Invertible World Model (CIWM), a Neuro-Symbolic Agentic Framework that bridges this gap by integrating a quantitative machine learning emulator with a Large Language Model reasoning layer. Utilising a stringently curated, high-fidelity data engineering pipeline on the Sanger GDSC dataset (\( N=83 \)), we isolate true biological signals from in vitro artifacts to establish a rigorous baseline predictive correlation for complex transcriptomics (\( r=0.268 \)). Through Inverse Reasoning, we perform in silico CRISPR perturbations across the colorectal landscape. The framework autonomously overturns classical mechanistic assumptions, identifying a hierarchical dominance of mutant KRAS over the APC/Wnt-axis in driving 5-fluorouracil resistance (\( \Delta=-0.0469 \)) via a "KRAS Shield" mapped to MAPK/PI3K networks. Furthermore, the agentic layer identified a "PIK3CA Paradox", revealing that repairing PIK3CA inadvertently increases chemoresistance (\( \Delta=+0.0085 \)) by triggering a compensatory feedback loop that hyperactivates the dominant MAPK survival pathway.

25.
Nature Biotechnology 2026-06-11

Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT

作者:

Spatially resolved CRISPR screening in vivo has been limited to small perturbation panels and subsets of protein-coding RNAs. We present Perturb-DBiT, a method for co-sequencing of spatial total RNA whole transcriptomes and single guide RNAs (sgRNAs) on the same tissue section in situ. In a human cancer metastatic colonization model, we applied large (80,000+) sgRNA panels across tumor colonies in multiple consecutive tissue sections alongside their corresponding total RNA transcriptomes. We linked perturbations affecting long noncoding RNA covariation, microRNA–mRNA interactions and distinct amino acid-specific tRNA alterations to tumor migration and growth. By integrating transcriptional pseudotime trajectories, we further observed the impact of perturbations on clonal dynamics and cooperation. In an immune-competent syngeneic mouse model, investigation of the tumor immune microenvironment indicated distinct, synergistic effects on immune infiltration and suppression. Perturb-DBiT provides a spatially resolved comprehensive view of perturbation responses in complex tissues, including small and large RNA regulation, tumor proliferation, migration, metastasis and immune interactions. In vivo CRISPR genetic perturbations are spatially mapped at scale.