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01.
arXiv (CS.LG) 2026-06-19

Tracking Representation Dynamics in Large Language Models with Persistent Homology

arXiv:2606.19542v1 Announce Type: new Abstract: Large language models are commonly aligned through supervised fine-tuning, yet little is known about how their internal representations evolve during this process. We study alignment dynamics using persistent homology by tracking the topology of activation spaces throughout fine-tuning. Across four transformer language models ranging from 1B to 7B parameters and three alignment objectives corresponding to helpful, harmless, and mixed training data, we find that the majority of topological reorganization occurs during the earliest stages of training. A dense checkpoint analysis reveals a transient peak in topological activity followed by rapid stabilization. We further show that different alignment objectives induce distinguishable topological trajectories, while instruction-tuned and pretrained models exhibit qualitatively different patterns of evolution. Our results suggest that persistent homology provides a complementary perspective on alignment, revealing representation-level changes that are not apparent from behavioral metrics alone.

02.
arXiv (CS.LG) 2026-06-15

A Longitudinal Attribute-Conditioned Neural Network for Modeling Health-State Transition Probabilities in Temporally Irregular Data: The LANTERN Framework

arXiv:2606.13880v1 Announce Type: new Abstract: Accurate estimation of long-term care transition probabilities is central to disability insurance pricing, reserving, and solvency assessment. Classical actuarial multi-state models commonly rely on Markov, semi-Markov, or proportional-hazard specifications, which provide a direct connection to cohort projection but may be restrictive for irregular longitudinal health data with nonlinear aging patterns and heterogeneous covariate histories. This paper develops a well-calibrated estimator of multi-state transition probabilities for irregular longitudinal health data. The model learns from individual health history, incorporates the time elapsed between observations, and conditions transition probabilities on demographic and socioeconomic attributes. It produces a valid probability distribution over the next observed health state, with four possible states: healthy, mild disability, severe disability, and death. Individual probabilities are aggregated by age group and origin state to form transition matrices compatible with actuarial cohort projection. Using longitudinal data from the Health and Retirement Study, we compare the proposed estimator with logistic regression, gradient-boosted trees, a recurrent neural network, and a last-state persistence benchmark. The evaluation considers probabilistic accuracy, endpoint discrimination and calibration for severe disability and death, risk concentration, and transition matrix error after aggregation. The proposed estimator improves severe disability discrimination relative to logistic regression and gradient-boosted tree benchmarks, maintains strong calibration, and yields the lowest transition matrix error among the evaluated models in the held-out test analysis. Results show that a structured machine learning estimator can support long-term care transition modeling when judged by calibration and projection fidelity, beyond discrimination.

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

HEad and neCK TumOR (HECKTOR) 2025: Benchmark of Segmentation, Diagnosis, and Prognosis in Multimodal PET/CT

Head and neck cancers (HNC) represent a significant global health burden, with accurate tumor delineation being essential for effective radiotherapy planning. The complexity of the oropharyngeal anatomy, combined with the heterogeneous appearance of tumors on imaging, makes manual segmentation time-intensive and subject to inter-observer variability. Beyond segmentation, predicting long-term clinical outcomes, such as recurrence-free survival (RFS), and determining human papillomavirus (HPV) status from noninvasive imaging, remain challenging yet clinically valuable goals. The HECKTOR 2025 challenge addresses these needs by establishing a comprehensive benchmark for automated HNC analysis using multimodal PET/CT imaging and electronic health records. Building on previous editions (2020-2022), this challenge features an expanded multi-institutional dataset comprising over 1,100 patients from 10 centers worldwide. Participants were tasked with three complementary objectives: (1) segmenting primary gross tumor volumes (GTVp) and metastatic lymph nodes (GTVn), (2) predicting recurrence-free survival, and (3) classifying HPV status. The challenge attracted 35 registered teams, with 15 final submissions evaluated on a held-out test set. Top-performing algorithms achieved a mean Dice similarity coefficient of 0.75 for segmentation, a concordance index of 0.66 for survival prediction, and a balanced accuracy of 0.56 for HPV classification. This paper presents a comprehensive analysis of the submitted methodologies, evaluates their performance across different lesion characteristics, and discusses their implications for clinical translation in automated oncology workflows and decision support systems.

04.
arXiv (CS.CL) 2026-06-17

The Benchmark Illusion: Pruned LLMs Can Pass Multiple Choice but Fail to Answer

Compressing large language models reduces memory use and inference cost, but it can also create failures that standard benchmarks miss. A pruned model may still perform well on multiple-choice evaluations, yet fail to answer the same question in open generation. We ask what pruning changes: does it erase the correct answer, or does it make the answer harder to produce as the top output? We study this question with multilingual question answering, tracking the same questions before and after pruning. We find a benchmark illusion. Under high-sparsity pruning, especially Wanda, models often fail in greedy open generation while still selecting the correct answer under multiple-choice scoring. In these recognition-only errors, the answer is usually not gone, but demoted: it often reappears with beam search, sampling, or one in-context example. Overall, multiple-choice benchmarks can overstate the usability of compressed LLMs, creating an evaluation blind spot. Compressed models should be tested on what they can produce, not only on what they can recognize.

05.
Nature Biotechnology 2026-06-19

Optimized R2 retroelement complexes for DNA insertion into plant genomes

Traditional approaches for DNA insertion into plant genomes using Agrobacterium tumefaciens result in random integration. Newer genetic engineering methods based on nucleases, prime editors, transposases and recombinases extend capabilities but remain constrained with low efficiencies, off-target integration or limited payload size. Here we adapt the avian Taeniopygia guttata R2 protein (R2Tg) for targeted DNA insertion into plant genomes by engineering R2Tg expression cassettes and RNA payloads carrying intron-disrupted reporters, with optimized ribosomal DNA homology arms and untranslated regions. In Arabidopsis thaliana protoplasts, Nicotiana benthamiana leaves and Solanum lycopersicum seedlings, our R2Tg editor system achieves targeted insertion of full-length payloads ranging from 2.2 kb to 5 kb. In Nicotiana benthamiana leaves, integration occurs, on average, at 1 copy per genome, which is 30 times more efficient than that achieved by Cas9 homology-directed repair. This work establishes an R2Tg ribonucleoprotein platform for targeted DNA insertion into plant genomes, using a multicopy genomic safe-harbor site to enable efficient addition of multikilobase genes. R2 retrotransposons are used to integrate DNA into plant and crop 25S ribosomal DNA sites.

06.
Science (Express) 2026-06-11

Chemically induced skin tumors arise from long-lived stem cells of the upper hair follicle | Science

Authors: Unknown Author

The identification of the cancer cell of origin is a fundamental question in cancer biology. We used fluorescent lineage tracing of independent mouse skin stem cell populations, single cell transcriptomics, and Duplex sequencing, to identify the origin of chemically induced skin tumors. Tumors arose predominantly from Lgr6+ and / or Lrig1+ stem cells of the upper hair follicle, but only very rarely from the Lgr5 + and Krt19 + hair follicle bulge. Lgr6 + stem cells initiated by dimethylbenzanthracene responded to tumor promoter treatment resulting in clonal expansion of initiated cells carrying the canonical Hras Q61L mutation. Spontaneous mutations in Kras also clonally expanded, but did not generate tumors unless the Hras gene was deleted, thus revealing a competitive interaction between Hras and Kras pathways that influences clonal selection.

07.
arXiv (math.PR) 2026-06-17

Decay of correlations and zeros for the hard-core model

arXiv:2603.17858v2 Announce Type: replace Abstract: In a recent paper the last author proved that absence of complex zeros of the partition function of the hard-core model near a parameter $\lambda>0$ implies a form of correlation decay called strong spacial mixing. In this paper we investigate the reverse implication. We introduce a strengthening of strong spatial mixing that we call very strong spatial mixing (VSSM). Our main result is that if VSSM holds at a parameter $\lambda>0$ for a family of graphs, this implies that the partition function has no zeros near that parameter for each graph in the family. We also demonstrate that a closely related variant of very strong spatial mixing does not imply zero-freeness. As a consequence of our main result, we moreover obtain that VSSM implies spectral independence. Our proof relies on transforming the problem to the analysis of an induced non-autonomous dynamical system given by Möbius transformations.

08.
arXiv (CS.AI) 2026-06-15

CSPO: Constraint-Sensitive Policy Optimization for Safe Reinforcement Learning

arXiv:2606.14415v1 Announce Type: new Abstract: Safe reinforcement learning (Safe RL) aims to maximize expected return while satisfying safety constraints, typically modeled as Constrained Markov Decision Processes (CMDPs). While primal-dual methods scale well to deep RL, they often suffer from delayed constraint correction, leading to oscillatory behavior and prolonged safety violations. In this paper, we propose Constraint-Sensitive Policy Optimization (CSPO), a first-order primal-dual method that incorporates local constraint sensitivity into policy updates. CSPO augments the primal objective with a constraint-sensitive correction derived from the shortest signed distance to the safety boundary, enabling smarter recovery steps back to safety, compensating for delayed Lagrange multiplier updates, reducing oscillations near the boundary, and preserving the KKT solutions of the original constrained problem. Experiments on navigation and locomotion benchmarks demonstrate that CSPO achieves faster safety recovery and high reward preservation, resulting in higher constrained returns compared to state-of-the-art primal-dual and penalty-based methods

09.
arXiv (CS.LG) 2026-06-11

Reliable Error Estimation for PINNs: Lower and Upper A Posteriori Bounds

arXiv:2606.12050v1 Announce Type: new Abstract: Physics-informed neural networks (PINNs) combine machine learning with physical laws to solve differential equations. While existing results provide rigorous a posteriori upper bounds for PINN prediction errors, complete certification also requires complementary lower information in order to obtain computable two-sided error enclosures. In this paper, we derive computable a posteriori lower bounds for PINN errors in ordinary differential equations on suitable certified state-space domains under a localized strong monotonicity condition. We combine these estimates with complementary localized upper bounds under a one-sided Lipschitz condition, which is weaker than the global Lipschitz assumption used in previous work and can yield sharper upper error bands. The resulting bounds depend only on the neural-network approximation, the ODE residual, and local monotonicity and growth constants, and therefore do not require access to the exact solution. For linear time-invariant and time-varying systems, we further derive explicit formulas in terms of the minimal and maximal eigenvalues of the symmetric part of the system matrix. We also discuss the distinction between soft and hard enforcement of initial conditions in PINNs and explain why exact enforcement can make the scalar lower certificate uninformative. To recover nontrivial lower information in the linear setting, we use a signed-residual finite-probe certificate based on coordinate unit vectors. We also formulate a certificate-informed training strategy in which the propagated upper certificate is used as an auxiliary regularizer, while lower certificates remain post-training diagnostics. Altogether, the proposed framework provides rigorous and practically computable error certificates for PINN approximations of ODEs, while making explicit the domains and model classes for which the assumptions can be verified.

10.
arXiv (CS.LG) 2026-06-16

Beyond the Smile: A Hybrid Convolutional VAE for Crypto Volatility Surfaces

arXiv:2606.16961v1 Announce Type: new Abstract: We present a convolutional variational autoencoder for cryptocurrency implied-volatility surfaces, together with a deployable predictor that combines it with a quadratic smile re-fit through a deterministic per-tenor routing rule. Trained on 6,034 fully-filled hourly Binance Options surfaces of BTC and ETH spanning May-October 2023 and parameterised on a common $6 \times 7$ tenor-delta grid, the model attains a hidden-cell surface-completion RMSE in the 0.94-1.56 vol-point range across both markets and mask rates 10-50%. The hybrid predictor attains 0.83 vol points at 50% masking against 7.00 for the smile re-fit alone, an eightfold reduction obtained at no additional inference cost. Under structurally-correlated hole patterns that emulate the withdrawal of an entire tenor of strikes, the smile re-fit incurs 9.6-13.1 vol points of error while the learned model remains at 1.5-1.9, isolating a regime in which the generative model is the only viable predictor. Joint training on BTC and ETH improves the in-distribution model on both markets by 9-27% relative to the better-performing single-symbol counterpart, indicating a substantially shared vol-surface manifold across the two largest cryptocurrencies over the observation window. The hybrid is calendar- and butterfly-arbitrage-free at the listed strikes, a property that the parametric smile re-fit alone fails at high mask rates. The per-snapshot reconstruction error of the trained model flags the late-October ETF-anticipation rally and the August $17$, $2023$ flash crash as elevated-error periods without supervision. All training and evaluation infrastructure is released to support reproducible follow-on work.

11.
bioRxiv (Bioinfo) 2026-06-11

Combinatorial docking and molecular generation to navigate over 100-billion molecules for prospective ligand discovery

Commercially available make-on-demand libraries now exceed 100 billion compounds, requiring over 50 years to screen on 2,000 CPU cores using conventional docking. We present two complementary approaches to address this challenge. CombiDOCK, a combinatorial docking framework, enables exhaustive screening at the 100-billion scale within 40 days. MINT-Dock, a generative framework, accelerates navigation of this space by integrating CombiDOCK with Monte Carlo Tree Search. Benchmarked on 46 diverse targets, CombiDOCK matched full-molecule docking accuracy, and MINT-Dock achieved a 4,800-fold enrichment over random selection. Compared with prior billion-scale brute-force campaigns against {sigma}2, VMAT2, and VAChT, prospective CombiDOCK screens of the 100-billion-molecule library yielded higher hit rates and more potent ligands, while MINT-Dock achieved comparable outcomes across single- and multi-target objectives with >20-fold computational cost reductions. Docking-predicted poses of the best VAChT-binding compounds were confirmed by cryo-EM structures. These methods provide exhaustive and generative paths for navigating the trillion-molecule frontier of drug discovery.

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

Neural Variability Enhances Artificial Network Robustness

arXiv:2606.13801v1 Announce Type: new Abstract: Neural responses in cortex exhibit substantial trial-to-trial variability in response to repeated stimuli, while peripheral sensory neurons respond far more consistently, leading many to wonder whether stochasticity may carry meaning. Existing work has argued that noise and signal correlations may be optimized for discrimination in animals, whereas artificial neural network (ANN) studies have shown similar benefits of noise in machine learning tasks, although most ANN work has neglected the effects of correlations. Here we investigate whether correlated noise improves the robustness of artificial neural networks to adversarial attacks and naturalistic image modifications. Using the covariance of activations under modified versus clean inputs, we find that structured noise may significantly improve network robustness. Robustness to naturalistic image modifications benefits most from structure, but this structure transfers poorly across modification types. In contrast, noise structure from adversarial attacks can generalize to other kinds of attacks. These results suggest that structured noise in ANN activations generally improves robustness, establishing a biologically plausible strategy for creating robust artificial neural networks that only relies on local information.

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

Valid Inference with Synthetic Data via Task Exchangeability

arXiv:2606.13629v1 Announce Type: cross Abstract: There is a proliferation of work arguing for the use of synthetic data in scientific research. For example, social scientists are arguing for the use of LLM-generated "silicon samples" in pilot studies; AI evaluations increasingly rely on "LLM-as-a-judge" outputs; and proteomics research is accelerated by generative models that produce synthetic protein structures. These developments raise an intriguing possibility: synthetic data may help researchers ask more questions, run more studies, and accelerate discovery. But they also raise a fundamental concern: synthetic data can be biased, noisy, and misspecified. In this work, we propose statistical principles for using synthetic data in scientific research with provable validity guarantees. The key insight is a new technical condition that we call task exchangeability. Informally, this is a requirement that the researcher can identify historical tasks, for which real data is available, such that their current task of interest is exchangeable with the historical tasks in an appropriate mathematical sense. We develop methods for valid inference under task exchangeability, together with extensions that provide guarantees even beyond exchangeability. We demonstrate the framework on public opinion surveys with silicon samples and AI evaluation with autoraters.

14.
arXiv (CS.CV) 2026-06-18

Revealing Hidden Vulnerabilities in Autoencoders through Gradient Signal Restoration

Adversarial robustness of deep autoencoders (AEs) has received less attention than that of discriminative models, although their compressed latent representations induce ill-conditioned mappings that can amplify small input perturbations and destabilize reconstructions. Existing white-box attacks for AEs, which optimize norm-bounded adversarial perturbations to maximize reconstruction damage, often converge to suboptimal perturbations, thereby potentially overstating AE robustness. We show that this limitation is linked to vanishing adversarial loss gradients during backpropagation through ill-conditioned layers, associated with near-zero singular values in their intermediate weight matrices. To address this, we propose GRILL (Gradient Signal Restoration in Ill-Conditioned Layers), a framework designed to mitigate gradient degradation and improve the reliability of adversarial robustness evaluation in encoder-decoder architectures. GRILL is designed to mitigate adversarial gradient degradation during optimization, enabling attacks to better approximate high-distortion perturbations under fixed norm constraints. Through extensive experiments across multiple AE architectures, under both sample-specific and universal attacks, as well as standard and adaptive attack settings, we show that GRILL significantly increases attack effectiveness, thereby exposing vulnerabilities hidden by existing attack limitations. Beyond AEs, we provide preliminary evidence that modern multimodal encoder-decoder architectures exhibit similar vulnerabilities.

15.
Nature (Science) 2026-06-08

Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding

Authors:

Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in ~40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging. Here, we programmed CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage activities3,4, to selectively kill cancer cells by targeting cancer-specific transcripts. This approach limits cell growth by inducing trans shredding of chromatin, triggering DNA damage responses and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides a new approach to precision disease treatments for undruggable targets.

16.
medRxiv (Medicine) 2026-06-15

Supporting people to access social security payments through the Special Rules for End of Life: a qualitative study of the perspectives of patients, carers and health care professionals

Background: People living with terminal illness face a double financial burden from additional costs and loss of earning for themselves and their carers. Social security benefits are intended to help alleviate some of this financial pressure, and in the UK and other countries people are eligible for fast-tracked access to financial support via the Special Rules for End of Life. One in 3 people who are eligible miss out on this support, yet there is limited evidence on the reasons for this take-up deficit. Objectives: The aim of this study is to understand the barriers and facilitators to claiming benefits for terminally ill people from the perspectives of patients, carers, and health care professionals. Methods: This is a qualitative study combining i) focus groups with healthcare professionals recruited via professional networks and social media, and ii) interviews with patients and carers recruited in hospital and hospice settings. We analysed the data using Practical Thematic Analysis Results: Fifty-five multidisciplinary healthcare professionals participated in 11 focus groups, and we interviewed 10 patients and carers. We constructed five descriptive themes to summarise the data: Navigating priorities and uncertainty; positive impacts alongside a sense of shame and stigma; talking about money, difficulties and dividends; everybodys, yet nobodys, responsibility; and sticking points in the system. Conclusion: The themes reveal several challenges that may contribute to people not taking up this financial support. However, discussions about access to benefits were also seen as a core part of holistic care, a positive way to offer support and a gateway to other discussions about end-of-life care preferences and decisions. Recommendations for policy and practice include evaluating the adoption of a diagnostic rather than a prognostic eligibility criteria, integrating discussions about benefits into existing processes such as advance care planning, and improving education and support for clinicians.

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

Combating Data Laundering in LLM Training

arXiv:2604.01904v3 Announce Type: replace-cross Abstract: Post-hoc unauthorized-training data detection for large language models (LLMs) typically assumes a query-with-originals regime: rights holders query a target LLM with raw proprietary data and assess whether the model assigns them stronger memorization-based detection signals, e.g., higher confidence or lower loss, than held-out non-training reference texts. We show that this regime becomes brittle under data laundering, where the target LLM is trained on semantics-preserving but stylistically or structurally transformed surrogates of proprietary data to obfuscate provenance. Since training-time exposure occurs in the laundered form, memorization signals may no longer appear on the originals, collapsing the candidate-reference signal separation that standard detectors rely on. We counter this threat by studying laundering-aware detection with raw proprietary data, a held-out reference corpus, and query access to the target LLM, while the laundering transformation is undisclosed. Since exact recovery of the laundered corpus is infeasible, we infer a detection-useful synthesis process via an auxiliary LLM that maps originals into training-like queries. To make this search tractable, we introduce Synthesis Data Reversion (SDR), which constrains the unbounded space of natural-language transformations through a goal-details abstraction: a high-level transformation goal, e.g., "lyrical rewriting", and fine-grained details, e.g., "with vivid imagery". SDR identifies the most likely goal and iteratively refines details so synthesized queries elicit stronger target-model detection signals. Evaluated on the MIMIR benchmark against diverse laundering practices and target LLM families (Pythia, Llama2, and Falcon), SDR consistently restores detection signals, offering a practical auditing layer against data laundering.

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

From Frames to Temporal Graphs: In-Context Egocentric Action Recognition with Vision-Language Models

Action reasoning in egocentric video requires capturing fine-grained transitions of hand-object interactions, a task where general-purpose Vision-Language Models (VLMs) often struggle when operating directly on raw pixels. We propose to decouple visual perception from symbolic reasoning by converting videos into Temporal Action Graphs. In a multi-stage prompting pipeline, we first generate dense natural language narratives over short temporal windows as a semantic bottleneck, then formalize them into structured, open-vocabulary graph representations. On the EGTEA and Epic-Kitchens-100 datasets, the symbolic representation unlocks efficient in-context learning: few-shot graph demonstrations yield substantial accuracy gains over zero-shot frame and graph-based inference alike. Even in the zero-shot setting, graph-based reasoning remains competitive with pixel-based inference despite potential pretraining contamination favoring the latter. Across 11 open-weight VLMs from 6 model families ranging from 2B to 235B parameters, our findings indicate that current VLMs are more effective as symbolic reasoners than as direct visual observers. By projecting video into the language domain, we provide a scalable, fine-tuning-free alternative to end-to-end approaches that better leverages these models' latent reasoning strengths. The code will be made public.

19.
arXiv (CS.CL) 2026-06-15

Natively Unlearnable Large Language Models

Unlearning aims to remove the influence of specific training data sources, but this has proved challenging because the contributions of different sources are entangled within the model. Isolating source contributions to disjoint parameters makes removal easier, though it obstructs joint learning across sources. We propose NULLs (Natively Unlearnable LLMs), a model class that satisfies the two opposing goals of isolating source-specific contributions and learning jointly across sources, by training a set of shared backbone neurons alongside a pool of sparsely activated sinks. During training, information specific to a source naturally concentrates in its sinks while information shared across sources accumulates in the backbone. A source is then unlearned at deployment by disabling its corresponding sinks, with no gradient updates and no access to the retained data. We show that NULLs scales to Wikipedia's ~6M articles, isolating each as an independent source. Unlearning a single article removes knowledge specific to it while preserving facts shared with semantically related articles, closely matching retraining from scratch. We note that unlearning with NULLs is also robust: in a case study of unlearning the Harry Potter books, NULLs resists both adversarial extraction and relearning that reverses post-hoc unlearning. Finally, NULLs preserves general language capabilities, matching a standard transformer on downstream benchmarks. Together, these results suggest that source-level unlearning need not be an afterthought. It can be built natively into LLM training while retaining the benefits of shared representation learning.

20.
arXiv (CS.CV) 2026-06-17

Revisiting Structural Dependency in Autoregressive Multi-Task Table Recognition via Order-Independent Cell-Level Representations

Multi-task table recognition jointly addresses table structure prediction, cell localization, and cell content recognition within a unified framework. Existing approaches often rely on autoregressive decoders to generate table structures and reuse their hidden states for cell localization and content recognition. This autoregressive generation process can make cell representations order-dependent, degrading global consistency across cells. This paper proposes a structural refinement module that produces order-independent cell features through non-causal attention. This design enables parallel inference of cell contents while conditioning each cell on global context encoded in the refined features. Experiments on two large datasets demonstrate consistent gains in cell localization and end-to-end recognition, while reducing overall inference time by around threefold.

21.
arXiv (CS.AI) 2026-06-16

PISA: A Pragmatic Psych-Inspired Unified Memory System for Enhanced AI Agency

arXiv:2510.15966v2 Announce Type: replace Abstract: Memory systems are fundamental to AI agents, yet existing work often lacks adaptability to diverse tasks and overlooks the constructive and task-oriented role of AI agent memory. Drawing from Piaget's theory of cognitive development, we propose PISA, a pragmatic, psych-inspired unified memory system that addresses these limitations by treating memory as a constructive and adaptive process. To enable continuous learning and adaptability, PISA introduces a trimodal adaptation mechanism (i.e., schema updation, schema evolution, and schema creation) that preserves coherent organization while supporting flexible memory updates. Building on these schema-grounded structures, we further design a hybrid memory access architecture that seamlessly integrates symbolic reasoning with neural retrieval, significantly improving retrieval accuracy and efficiency. Our empirical evaluation, conducted on the existing LOCOMO benchmark and our newly proposed AggQA benchmark for data analysis tasks, confirms that PISA sets a new state-of-the-art by significantly enhancing adaptability and long-term knowledge retention.

22.
bioRxiv (Bioinfo) 2026-06-11

Calibrated Uncertainty Quantification for Patient-Level AML Drug Sensitivity Prediction Using Split Conformal Prediction

Accurate prediction of ex vivo drug sensitivity in acute myeloid leukemia (AML) patients from transcriptomic data is a critical challenge for precision oncology. Existing computational approaches have explored uncertainty quantification in cancer drug response prediction primarily using cell line data, while patient-level AML models typically rely on heuristic confidence measures rather than statistically calibrated uncertainty estimates. Here, we present a framework applying split conformal prediction to patient-level AML drug response modeling using the BeatAML 2.0 cohort. We trained Elastic Net and XGBoost regressors on bulk RNA-seq gene expression profiles from 318 AML patients, analyzing 34,764 patient-drug observations across 122 compounds. Baseline models achieved median Pearson R values of 0.291 (Elastic Net) and 0.281 (XGBoost) across 122 drugs. Wrapping these models with split conformal prediction yielded well-calibrated prediction intervals across three confidence levels: empirical coverages of 81.4%, 90.7%, and 95.5% against nominal targets of 80%, 90%, and 95%, respectively. Analysis of prediction interval widths revealed substantial drug-class-specific uncertainty patterns, with HDAC and BCL-2 inhibitors exhibiting markedly higher uncertainty than MDM2 inhibitors, suggesting a potential association between transcriptomic predictability and drug mechanism of action, although several drug classes were represented by only a small number of compounds. Predictive uncertainty was not significantly associated with ELN2017 molecular risk classification (Kruskal-Wallis p=0.395) or NPM1 mutation status (p=0.788). These results demonstrate that statistically valid uncertainty quantification can be achieved for patient-level AML drug response prediction despite substantial biological heterogeneity. to the best of our knowledge, no published study has applied split conformal prediction to patient-level ex vivo drug sensitivity prediction in the BeatAML cohort, providing a principled alternative to heuristic confidence scoring approaches. Keywords: Acute myeloid leukemia (AML); Ex vivo drug sensitivity; Conformal prediction; Uncertainty quantification; Precision oncology; BeatAML; Transcriptomic biomarkers; Machine learning.

23.
arXiv (CS.AI) 2026-06-19

BIM-Edit: Benchmarking Large Language Models for IFC-Based Building Information Modeling

arXiv:2606.20146v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly applied to computer-aided design (CAD) to generate design artifacts from textual instructions. In engineering practice, this requires more than creating new geometry, models must also understand existing scenes, edit them correctly, and preserve semantics and relations. However, many CAD benchmarks focus on creating new models rather than editing existing ones, and mostly evaluate geometric correctness. We introduce BIM-Edit, a benchmark for evaluating LLMs on natural-language editing of Building Information Models (BIM) represented in the Industry Foundation Classes (IFC) format. BIM provides a challenging testbed because building models encode geometry together with semantic and relational structure. BIM-Edit contains 324 editing tasks spanning 11 realistic building models and 36 synthetic scenes. Tasks are expressed using three instruction categories - direct, spatial, and topological - covering both explicit and scene-grounded edits. We evaluate outputs along three dimensions: geometric accuracy, semantic validity, and topological consistency. Across evaluated LLMs, the best-performing model achieves only 49.5% average score across the three metrics, and no model fully solves more than 3.4% of tasks. These results demonstrate a substantial gap between current LLM capabilities and the requirements of structured engineering design workflows.

24.
arXiv (CS.CL) 2026-06-19

From Texts to Scores: Tracing the Emergence of Essay Quality Representations in Large Language Models

Recent advances in Large Language Models (LLMs) have substantially transformed Automated Essay Scoring (AES), yet the internal mechanisms underlying LLM-based scoring remain poorly understood. In this work, we systematically analyze the hidden representations of eight LLMs across two English essay datasets (ASAP++, CSEE) and one Portuguese dataset (ENEM). Using linear probing, cross-prompt generalization, dimensionality reduction, and neuron-level analyses, we find consistent evidence that essay quality information is encoded in a linearly accessible form within LLM representations. These representations emerge progressively across layers, remain robust across prompting strategies, and partially transfer across essay prompts despite differences in scoring rubrics. In addition, nonlinear probes provide only marginal and inconsistent improvements over linear probes, suggesting that most essay quality information is already linearly decodable. We further identify individual ``essay scoring neurons'' whose activations strongly correlate with essay scores and whose behavior is sensitive to targeted intervention. Moreover, the layer-wise distribution of these neurons systematically shifts with essay length, with longer essays relying more heavily on deeper layers. Overall, our findings provide evidence that LLMs encode structured representations related to essay quality and offer new insights into the interpretability of LLM-based AES systems.

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

AnalogFed: Privacy-Preserving Discovery of Analog Circuits at Scale with Federated Generative AI

arXiv:2507.15104v2 Announce Type: replace-cross Abstract: Recent advances in generative AI (GenAI) have shown transformative potential for modern hardware design. However, existing GenAI-driven approaches fall short of enabling large-scale electronic design automation (EDA) due to the proprietary and siloed nature of hardware datasets, which cannot be centralized for model training. Achieving at-scale GenAI-driven EDA, therefore, requires a novel privacy-preserving framework that can leverage distributed data without compromising confidentiality. This work introduces AnalogFed, the first privacy-preserving framework for large-scale analog circuit topology discovery using federated learning (FedL) and GenAI. AnalogFed establishes the feasibility of collaborative analog topology design while addressing key security challenges: it mitigates membership inference attacks (MIAs) through a novel input perturbation strategy based on dummy token injection, and defends against model inversion attacks with customized, efficient homomorphic encryption. Extensive experiments demonstrate AnalogFed's effectiveness and efficiency, achieving strong privacy protection without degrading model utility. This framework lays the foundation for scalable, multi-party collaboration in next-generation hardware design automation with GenAI.