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01.
arXiv (CS.CL) 2026-06-17

AIPatient Arena: EHR-grounded evaluation of large language models in end-to-end clinical consultation workflows

Large language models (LLMs) are increasingly considered for use in clinical consultation tasks, yet most medical evaluations remain static, single-turn, or narrowly outcome-based, limiting their ability to reflect the sequential, uncertain, and interactive nature of real-world care. Here, we propose AIPatient Arena, an EHRs-grounded evaluation framework for assessing the clinical utility of LLMs across eight dimensions of clinical competence. The framework integrates EHR data into patient-specific knowledge graphs, enabling multi-turn physician-patient interactions. We applied AIPatient Arena on a primary cohort of 437 patients and two out-of-distribution validation cohorts of 119 and 67 patients. We observe that LLMs performed well in medical interview questioning skills (QS; mean scores, 4.43-4.99/5), ethical and professional conduct (ET; 4.38-4.93/5), and clarity and transparency of clinical explanations (EX; 3.80-4.72/5). Performance was moderate in information integration (II; 3.19-4.21/5) and medication safety and justification (MS; 3.13-3.78/5), but persistent weaknesses were observed in handling of ambiguous patient responses (HR; 2.57-3.32/5), information coverage (IC; 2.08-3.02/5), and diagnostic accuracy and reasoning (Dx; 2.63-3.55/5). Process-based evaluation revealed recurrent interaction failures, including repetitive questioning, omission of past medical history, and inadequate handling of uncertainty. Richer conversational context improved diagnostic reasoning but yielded limited gains in treatment planning. These findings indicate that final-answer accuracy alone is insufficient for evaluating clinical readiness and highlight the importance of assessing how models gather, interpret, and communicate information throughout a consultation. AIPatient Arena provides an EHR-grounded framework for workflow-oriented pre-deployment evaluation of medical LLMs.

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

Combining Retrieval-Augmented Text Generation with LLMs for Reading Content Recommendations

arXiv:2606.14817v1 Announce Type: cross Abstract: This work presents the design, implementation, and evaluation of a system for generating personalized reading content using Large Language Models (LLMs) combined with Retrieval-Augmented Generation (RAG). The proposed architecture consists of four modules: Input, RAG, Generation, and Judging and enables users to specify both a question and a target reading content complexity. RAG is employed to retrieve relevant information from the Internet, enriching and grounding the content produced by three modern LLMs: Meta LLaMA 4 Scout, LLaMA 3.1 8B Instant, and Google Gemma2 9B. Reading materials are generated using three prompting strategies (Chain-of-Thought, zero-shot, and few-shot), and the LLM-as-a-Judge module automatically evaluates answer quality and alignment with the desired readability level. Experimental results show that RAG consistently improves system performance across all models and prompting techniques, increasing relevance and particularly groundedness by up to 26-35 percentage points. Overall, the findings demonstrate that the RAG-augmented architecture effectively produces reading content tailored to user queries and desired textual complexity.

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

HGCN(O): A Self-Tuning GCN HyperModel Toolkit for Outcome Prediction in Event-Sequence Data

arXiv:2507.22524v3 Announce Type: replace Abstract: We propose HGCN(O), a self-tuning toolkit using Graph Convolutional Network (GCN) models for event sequence prediction. Featuring four GCN architectures (O-GCN, T-GCN, TP-GCN, TE-GCN) across the GCNConv and GraphConv layers, our toolkit integrates multiple graph representations of event sequences with different choices of node- and graph-level attributes and in temporal dependencies via edge weights, optimising prediction accuracy and stability for balanced and unbalanced datasets. Extensive experiments show that GCNConv models excel on unbalanced data, while all models perform consistently on balanced data. Experiments also confirm the superior performance of HGCN(O) over traditional approaches. Applications include Predictive Business Process Monitoring (PBPM), which predicts future events or states of a business process based on event logs.

04.
bioRxiv (Bioinfo) 2026-06-11

Revealing trajectories of multi-modal voxel-level changes in neurodegenerative diseases using latent event mapping

Neurodegenerative diseases are driven by pathological mechanisms that can be indirectly measured in vivo using multi-modal neuroimaging. However, current computational methods that aim to reconstruct trajectories of voxel-level changes in the brain are either not computationally scalable or fully interpretable, limiting their ability to reveal associations between disease progression and underlying mechanisms. Here we introduce Latent Event Mapping (LEMING), a generative unsupervised modelling technique that learns a latent map of disease events along a common pseudo-timeline of events. We apply LEMING to amyloid PET and structural MRI data from the Alzheimer's Disease Neuroimaging Initiative to reveal the first voxel-level trajectories of events in Alzheimer's disease. Notably, we show how LEMING can provide new insights into progression-dependent disease mechanisms. We find that acetylcholine receptor density is significantly positively associated with both late-stage amyloid and atrophy events, suggesting that either these receptors are targeted later in disease progression, or that amyloid does not play an active role. This has strong implications for therapeutics that target acetylcholine receptors, particularly for early-stage intervention strategies.

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

Learned JPEG Compression for DNN Vision

JPEG, a lossy image compression technique designed for human viewers, has maintained its dominance for decades. However, in the era of artificial intelligence (AI), a substantial portion of image data, often compressed by JPEG, is and will continue to be consumed by deep neural networks (DNNs) instead of humans, thus creating a need to optimize JPEG for DNN inference performance. To this end, we propose learned JPEG compression for DNN vision (J4D), a novel training framework for determining JPEG encoding parameters to minimize compression rate while maximizing DNN inference performance. The major challenge of solving this optimization problem lies in representing the JPEG codec and compression rate in closed form. By incorporating a differentiable soft quantizer based on a probabilistic quantization scheme, we not only obtain a differentiable proxy for the JPEG codec, but are also able to compute the entropy of the coded source analytically, which is a close estimate of the actual compression rate. Equipped with both the differentiable JPEG codec and the information-theoretic rate estimator, we are then able to solve the aforementioned optimization problem with backpropagation. After training, the learned encoding parameters will be subsequently used in actual JPEG encoding based on probabilistic quantization. Extensive experimental results across multiple datasets and DNN architectures demonstrate that J4D consistently and significantly outperforms the default JPEG and other competitive JPEG codecs optimized for DNNs. Notably, compared to the default JPEG, J4D achieves an increase in accuracy by as much as 11.60% at the same rate, or a reduction of compression rate up to 80.05% at the same accuracy. Additionally, with the help of J4D, we show the potential to design universal JPEG encoding parameters for various DNN architectures for the first time.

07.
bioRxiv (Bioinfo) 2026-06-11

A high-quality chromosome-scale reference genome assembly for Asparagus racemosus var. CIM-Shakti (Shatavari), a medicinal plant of Ayurvedic importance

Asparagus racemosus Wild., commonly known as Shatavari, is an important medicinal plant in Ayurveda and is valued for its steroidal saponins, particularly shatavarin compounds, which contribute to its adaptogenic, galactagogue, immunomodulatory, and therapeutic properties. Despite its medicinal and economic importance, genomic resources for this species have remained limited, restricting molecular breeding, pathway discovery, and comparative evolutionary studies within Asparagaceae. Here, we report a high quality chromosome scale reference genome assembly of A. racemosus var. CIM Shakti generated using PacBio HiFi long read sequencing and Omni C chromatin conformation scaffolding. The pseudo haploid assembly spans 817 Mb across 53 scaffolds, with a scaffold N50 of 98.50 Mb, L50 of 5, and a largest scaffold of 113.80 Mb. Ten major chromosome scale pseudomolecules were resolved, corresponding to the haploid chromosome complement of A. racemosus. The assembly showed high gene space completeness, with BUSCO completeness of 99.8% against the Eukaryota dataset and 98.0% against the Embryophyta dataset. BlobToolKit profiling further supported assembly quality, with GC content of approximately 39 to 40% and no major evidence of contamination. EDTA based repeat annotation identified 580.93 Mb of interspersed repetitive elements, accounting for 71.06% of the 817.57 Mb genome assembly. The repeat landscape was dominated by LTR retrotransposons, particularly Gypsy elements, which accounted for 25.01% of the assembly, followed by unclassified LTR elements at 26.58% and Copia elements at 4.84%. Structural and functional annotation identified 29,199 protein coding genes represented by 29,199 transcript models, 138,433 exons, and 125,201 CDS features. The annotation was structurally robust, with an average gene length of 4,605.1 bp, 4.74 exons per transcript, and 97.80% of transcripts containing multiple exons. The CIM Shakti reference genome provides a foundational genomic resource for investigating steroidal saponin biosynthesis, sex chromosome evolution, repeat driven genome expansion, and comparative genomics in Asparagaceae. This assembly will support future studies on medicinal trait improvement, conservation genomics, and genomics assisted breeding of climate resilient Shatavari cultivars.

08.
arXiv (CS.LG) 2026-06-11

Beyond the Golden Teacher: Enhancing Graph Learning through LLM-GNN Co-teaching

arXiv:2606.11583v1 Announce Type: new Abstract: Text-attributed graphs (TAGs) underlie real-world applications such as citation networks, social media, and e-commerce. Few-shot graph learning on TAGs is hard: with only a handful of labels per class and the rest of the graph unannotated, neither GNNs nor LLMs can learn well on their own. GNNs read topology and fail on cold nodes; LLMs read text and fail on text-ambiguous nodes. Existing LLM-GNN methods all follow the same recipe: designate one model as the golden teacher and use its outputs (e.g., features or pseudo-labels) to supervise the other. We argue this golden-teacher assumption breaks under sparse supervision: neither model is golden, and treating either as such transfers its blind spots into the student. We therefore ask: can we avoid designating either model as the golden teacher, and still perform effective graph learning? We answer with LLM-GNN Co-Teaching, a bidirectional co-teaching framework in which neither model is fixed as teacher. The GNN and LLM exchange their most confident pseudo-labels under an architecture-specific small-loss criterion, and both update every round. Supervision is then mined from the trajectory: whenever a node moves from cross-model contradiction at round t to cross-model agreement at round t+1, the LLM's two answers on the same input form a preference pair (old contradicting self < new peer-endorsed self) for DPO training. We call this Round-based Pseudo-Label Preference Optimization (RPL-PO). On six benchmarks, LLM-GNN Co-Teaching consistently outperforms GNN-as-Judge and all prior methods, with absolute 3-shot gains of 7.86% on Cora and 7.73% on ogbn-arxiv; improvements carry over to 5-shot and to zero-shot cross-dataset transfer. Error-structure analysis further shows that abandoning the golden-teacher assumption substantially improves the LLM's graph learning capability on challenging samples.

09.
arXiv (CS.AI) 2026-06-16

Prototyping an AI-powered Tool for Energy Efficiency in New Zealand Homes

arXiv:2509.05364v2 Announce Type: replace-cross Abstract: Residential buildings contribute significantly to energy use, health outcomes, and carbon emissions. In New Zealand, housing quality has historically been poor, with inadequate insulation and inefficient heating contributing to widespread energy hardship. Recent reforms, including the Warmer Kiwi Homes program, Healthy Homes Standards, and H1 Building Code upgrades, have delivered health and comfort improvements, yet challenges persist. Many retrofits remain partial, data on household performance are limited, and decision-making support for homeowners is fragmented. This study presents the design and evaluation of an AI-powered decision-support tool for residential energy efficiency in New Zealand. The prototype, developed using Python and Streamlit, integrates data ingestion, anomaly detection, baseline modeling, and scenario simulation (e.g., LED retrofits, insulation upgrades) into a modular dashboard. Fifteen domain experts, including building scientists, consultants, and policy practitioners, tested the tool through semi-structured interviews. Results show strong usability (M = 4.3), high value of scenario outputs (M = 4.5), and positive perceptions of its potential to complement subsidy programs and regulatory frameworks. The tool demonstrates how AI can translate national policies into personalized, household-level guidance, bridging the gap between funding, standards, and practical decision-making. Its significance lies in offering a replicable framework for reducing energy hardship, improving health outcomes, and supporting climate goals. Future development should focus on carbon metrics, tariff modeling, integration with national datasets, and longitudinal trials to assess real-world adoption.

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

When Dynamics Models Read the Wrong Time Steps: Label-Free Event Credit Re-Anchoring for Robust Global Readouts

作者:

arXiv:2606.17572v1 Announce Type: new Abstract: Learned dynamics models often answer global physical questions, such as fault severity or impact stiffness, by pooling a per-step feature sequence into one readout vector. This sequence-to-global interface creates an under-studied temporal credit problem: with only trajectory-level supervision, a model can predict accurately in training conditions while reading from abundant smooth correlates rather than the brief physical events that determine the target. We call this failure temporal credit dilution. It is not exposed by the training loss and is not removed by standard physics-informed residuals, because the error lies in where the global readout assigns functional credit. We introduce Credit-in-Event, an interface-level probe for measuring how much pooled credit lands on event steps, and prove in closed form that a pooled linear reader routes credit to a spurious background channel as the event fraction shrinks. We then propose CREST, a training-free and label-free readout that estimates a transient event core from learned features and re-anchors the pooled representation through event-versus-rest contrast. Across simulated gear and impact systems, recurrent and attention encoders, and public bearing vibration data, CREST reduces out-of-distribution error while restoring event credit. Ablations show that stable-step selection and receptive-field shrinking fail, confirming that the gain comes from event-core credit re-anchoring rather than a generic locality or stability prior.

11.
arXiv (CS.AI) 2026-06-25

WinDOM: Self-Family Distillation for Small-Model GUI Grounding

arXiv:2606.25964v1 Announce Type: new Abstract: Small ($\sim$2B) GUI-grounding agents are attractive for on-device deployment, accessibility tooling, and low-cost iteration, but at this scale they face two open recipe questions: how to obtain bounding-box training data without expensive human annotation, and how to combine supervised fine-tuning with reinforcement learning. We address both, with the explicit goal of pushing small-model performance rather than scaling up. WinDOM is a $54{,}425$-record grounding corpus harvested by driving an open-source Windows 11 web reimplementation under headless Playwright, with bounding boxes read directly off the DOM and no OCR or human annotation. Self-Family Distillation (SFD) is a single rejection-sampling cold-start parameterised only by the teacher choice: either an EMA of the student (no external model) or a frozen larger same-family teacher. We then treat the saturation depth of the SFD cold-start as an explicit GRPO hyperparameter. On a Qwen3.5-2B student, the under-saturated cold-start is a better GRPO initialiser than the converged one: SFD-4B with Early-init RL gains $+5.4$ OOD-mean ($+3.5$ ScreenSpot-Pro, $+7.0$ OSWorld-G, $+5.8$ ScreenSpot-V2) over the base. The same-size EMA mode lands within roughly one OOD-mean point of the cross-size $4$B variant ($65.2$ vs $66.3$) without an external teacher.

13.
arXiv (CS.AI) 2026-06-18

SwitchBraidNet: Quantisation-Aware Lightweight Architecture for Hybrid Brain-Computer Interface

arXiv:2606.18816v1 Announce Type: cross Abstract: Hybrid brain-computer interfaces (BCIs) that integrate motor imagery (MI) and steady-state visual evoked potentials (SSVEP) provide high-dimensional neural decoding but typically exceed the computational limits of embedded hardware. To address this, we propose SwitchBraidNet, a compact EEG classification architecture designed for low-power deployment. The model employs a dual-path temporal braid to extract multiscale oscillatory features, an adaptive squeeze-and-excitation spatial switch for electrode gating, and a log-variance readout layer for direct band-power encoding. Furthermore, through systematic quantisation-aware training on the OpenBMI dataset, we compared SwitchBraidNet against four established baselines across FP32, FP16, and INT8 precisions. Experimental results demonstrate superior efficiency and performance, achieving MI accuracy of 69.49% (FP16), SSVEP accuracy of 93.48% (FP32), and a hybrid information transfer rate of 64.82 bits/min (FP16). With an INT8 footprint of only 3.03 KB, SwitchBraidNet maintains high accuracy across varying numerical precisions, demonstrating its suitability for low-power embedded BCI deployment.

14.
arXiv (CS.CL) 2026-06-16

Can Agents Read the Room? Benchmarking Visual Social Intelligence in Multimodal Simulation

Social interaction depends on both language and visible social signals, such as facial expressions, posture, gaze, and emotional shifts. Yet existing social-agent benchmarks are largely text-based and rarely test whether multimodal agents can use visual cues to guide interaction. We introduce \textsc{\benchmarkname{}}, a benchmark evaluating visual social intelligence in multimodal social simulation. It contains 240 scenarios, 585 role instances, and 2,340 role-task instances, combining aligned textual-visual evidence, structured role profiles, and four role-level tasks: expression task, characteristic task, interaction regulation task, and interaction outcome task. Evaluating seven recent MLLMs under verbalized-vision and direct-vision reveals a clear gap between local role enactment and interaction management: role-specific expression and conflict handling are near saturation, whereas interaction regulation and visually grounded outcome achievement remain substantially more difficult. The code is released at https://github.com/JunsWan/AgentViSS, and the dataset is available at https://huggingface.co/datasets/JunsWan/AgentViSS.

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

HiT-JEPA: A Hierarchical Self-supervised Trajectory Embedding Framework for Similarity Computation

The representation of urban trajectory data plays a critical role in effectively analyzing spatial movement patterns. Despite considerable progress, the challenge of designing trajectory representations that can capture diverse and complementary information remains an open research problem. Existing methods struggle in incorporating trajectory fine-grained details and high-level summary in a single model, limiting their ability to attend to both long-term dependencies while preserving local nuances. To address this, we propose HiT-JEPA (Hierarchical Interactions of Trajectory Semantics via a Joint Embedding Predictive Architecture), a unified framework for learning multi-scale urban trajectory representations across semantic abstraction levels. HiT-JEPA adopts a three-layer hierarchy that progressively captures point-level fine-grained details, intermediate patterns, and high-level trajectory abstractions, enabling the model to integrate both local dynamics and global semantics in one coherent structure. Extensive experiments on multiple real-world datasets for trajectory similarity computation show that HiT-JEPA's hierarchical design yields richer, multi-scale representations. Code is available at: https://anonymous.4open.science/r/HiT-JEPA.

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

Telenor Nordics Customer Service self-help corpus

作者:

This paper presents a multilingual customer service self-help corpus comprising 1,122 manually validated documents in Finnish, Danish, Norwegian, and Swedish, totaling 274,599 words and 1,884,833 characters. The documents have been sourced from the public self-help pages of four Nordic telecommunications operators and subsequently filtered for person-identifiable information and relevance through a combined LLM and human annotation pipeline. Domain-specific datasets for Nordic languages remain scarce, particularly in customer service: a domain of growing importance for retrieval-augmented generation, cross-lingual transfer learning, and emerging agent-based service architectures. An analysis of the corpus reveals substantial variation in document length and structure across operators, reflecting distinct editorial strategies, as well as broad topical coverage spanning network hardware, mobile services, TV and streaming, billing, and account management. The dataset is publicly available under a CC-BY-NC-SA-4.0 license at https://zenodo.org/records/20732652, intended to support reproducible research in Nordic NLP and information retrieval.

17.
medRxiv (Medicine) 2026-06-18

Age as a moderator of a brief alcohol intervention among injury patients in Northern Tanzania

Background: Alcohol use is a leading modifiable risk factor for injury in sub-Saharan Africa. In Tanzania, young people ([&le;]24 years) experience greater alcohol-related harm despite drinking less frequently than adults. Punguza Pombe kwa Afya Yako (PPKAY) is a culturally adapted, brief intervention for injury patients in Tanzania. This study examined whether age moderates its effectiveness. Methods: We conducted an exploratory secondary analysis of baseline and 3-month data from the PPKAY randomized trial among injury patients aged [&ge;]18 years at Kilimanjaro Christian Medical Centre, Tanzania. Eligible participants reporting alcohol use before injury, AUDIT [&ge;]8, or positive breathalyzer were randomized to usual care or PPKAY with SMS boosters. The primary outcome was binge drinking days. Count outcomes were analyzed using negative binomial regression with robust SEs and continuous outcomes using mixed-effects models. Effect modification was assessed using a three-way interaction (Time x intervention x Age). Results: Among 543 participants (mean age 36.8 years; 16.2% aged 18–24), age moderated the intervention effect for drinking days (IRR = 0.27, 95% CI 0.07 – 0.98; p = 0.046) and drinks consumed (IRR = 0.17, 95% CI 0.04 – 0.77; p = 0.021). The intervention reduced 4 drinking days (95% CI -7.1 to -0.8) and 27.5 drinks (95% CI -42.8 to -12.2) among young people, while adults showed reductions in both arms, without intervention-specific effect. Conclusion: The effects of ED-based brief alcohol interventions are not uniform, varying across both age groups and alcohol-related outcomes. We found a greater responsiveness in drinking frequency and quantity reported among young people.

18.
bioRxiv (Bioinfo) 2026-06-19

ContinuumCellAgent: A Framework-Guided Agent for Long-Horizon Scientific Research

AI-scientist systems are beginning to automate parts of scientific research. We present ContinuumCellAgent, an autonomous agent that executes literature review, hypothesis formation, computational experimentation, manuscript drafting, and adversarial peer review as a single unattended run. Existing AI scientist systems remain difficult to diagnose because they lack modularity, systematic prompt grounding, and observability into long-running behavior. ContinuumCellAgent addresses these gaps with a modular supernode architecture for stage-wise backend swapping, protocols grounded in curated research-method checklists that also define reviewer rubrics, and a diagnostics layer that records file-based artifacts, message traces, and state transitions. We evaluate the system on open-domain QA benchmarks and biomedical/longevity case studies, showing that it can produce checkable research artifacts while exposing pipeline dynamics for rigorous AI co-scientist research.

19.
Nature (Science) 2026-06-24

The mutational landscape of STING-induced immunity

作者:

Stimulator of interferon genes (STING) is an evolutionary conserved immune signalling protein with key roles in host defence, cancer, senescence and inflammation1–3. Downstream of STING, type I interferon, inflammatory cytokine signalling and non-canonical autophagy are governed by a multilayered mechanism integrating ligand-induced structural transitions, protein–protein interactions and coordinated intracellular trafficking4–13. Despite its central role in immunity and relevance as therapeutic target14, the sequence elements that govern STING (in)activation in cells remain incompletely&nbsp;understood. Here we developed a massively parallel assay to systematically chart the sequence-function landscape of STING. Profiling thousands of single amino-acid variants, we identified structural and functional determinants that shape the&nbsp;immunostimulatory capacity of STING and its ability to translate ligand recognition into distinct signalling outputs. Cryogenic-electron microscopy structures of select STING hyperactive variants revealed new regulatory principles dictating conformational transition from inactive to signalling-competent states of STING. Mutational effects are widespread across the functional landscape and can sensitize STING towards the natural ligand 2′3′-cGAMP15–18 or decouple interferon induction from non-canonical autophagy, demonstrating a diversity of possible responses that can be accessed through single point substitutions. Finally, our data showed the clinical and evolutionary relevance of naturally occurring STING protein variants. Collectively, these findings define molecular principles that tune STING activity and chart the landscape of its functional potential across immune contexts. A massively parallel assay systematically charts the sequence-function landscape of the STING signalling protein, and the findings define molecular principles that tune STING activity and show its functional potential across immune contexts.

20.
arXiv (CS.CL) 2026-06-19

Med-R2: Perception and Reflection-driven Complex Reasoning for Medical Report Generation

Automated medical report generation (MRG) is increasingly used to reduce the burden of manual reporting and for decision support. Large vision-language models (LVLMs) hold great promise for automated MRG due to their fine-grained image-text alignment and advanced text-generation capabilities. Currently, state-of-the-art MRGs primarily focus on adapting pre-trained LVLMs with direct supervised fine-tuning (SFT), a fine-tuning strategy with medical image-report pairs. However, several factors limit the performance of these LVLMs. Firstly, direct SFT enables LVLMs to generate medical reports directly without an intermediate thinking process of pathological feature perception and diagnostic reasoning. This causes a potential failure to perceive pathological features and thus leads to misdiagnosis. Secondly, direct SFT lacks the incorporation of radiology-specific knowledge guidance, causing LVLMs to misinterpret perceived pathological features and make incorrect diagnoses. To address these gaps, we propose a novel fine-tuning strategy named Med-R2. We introduce a perception-driven long reasoning process that precedes report generation and incorporates radiology-specific knowledge as guidance. Additionally, to alleviate potential perceptual errors in complex reasoning, a reflection mechanism is introduced to refine the perception of pathological features and the generated report. Our experiments demonstrate that Med-R2 effectively enhances the capability of pathological features perception and diagnosis accuracy for MRG via fine-tuned LVLMs.

21.
PLOS Computational Biology 2026-06-04

CIPHER: An end-to-end framework for designing optimized aggregated spatial transcriptomics experiments

by Zachary Hemminger, Haley De Ocampo, Fangming Xie, Zhiqian Zhai, Jingyi Jessica Li, Roy Wollman Motivation Most imaging-based spatial transcriptomics methods measure individual genes, which limits scalability and typically requires integration with scRNA-seq to recover full cellular states. Recent approaches such as CISI, FISHnCHIPs, and ATLAS address this limitation by measuring aggregate transcriptional signatures, where multiple genes are pooled into each channel to increase throughput. While aggregate measurements improve scalability, they shift the problem from gene selection to feature design. For effective integration with scRNA-seq, these signatures must be not only discriminative in transcriptional space but also straightforward to measure, with balanced signal, sufficient dynamic range, and robustness to experimental noise. By optimizing decoding accuracy in isolation, existing methods leave substantial performance on the table. Results We present CIPHER (Cell Identity Projection using Hybridization Encoding Rules), a neural-network framework that jointly optimizes the experimental encoding matrix, i.e., the way that genes are aggregated to signatures, and the downstream cell embedding. CIPHER integrates the physical limits of imaging assays directly into its loss function, shaping the latent space to maximize discriminability while maintaining robustness to measurement noise and signal constraints. Using a large-scale mouse brain scRNA-seq reference, we show that CIPHER-designed encodings yield latent spaces with improved cell-type separability, uniform signal utilization, and greater resilience to hybridization variability, resulting in higher decoding accuracy from both simulated and experimental data. Conclusion CIPHER formulates aggregate signature design as a joint optimization problem over decoding accuracy and experimental measurability. This enables systematic, scRNA-seq-aligned feature design for scalable spatial transcriptomics based on aggregate measurements. Availability Code and documentation are available at https://github.com/wollmanlab/Design/.

22.
arXiv (math.PR) 2026-06-24

Deep numerical schemes for systems of Ergodic BSDEs with applications to regime-switching forward utilities

arXiv:2606.24271v1 Announce Type: cross Abstract: In this paper, we introduce two neural-network-based numerical schemes for solving systems of coupled ergodic Backward Stochastic Differential Equations (eBSDEs), motivated by the approximation of optimal strategies within the framework of forward utilities in a regime-switching stochastic factor model. Our approach builds on the representation of such models through systems of eBSDEs introduced in [HLT20]. We first establish a link between the solution of the system of ergodic BSDEs and that of an associated multidimensional BSDE with random terminal time, given by the hitting time of the positive recurrent stochastic factor. Building on this representation, we introduce a locally additive deep learning scheme obtained by minimizing aggregated local error terms. We then present a new Deep Galerkin Method (DGM) inspired algorithm that minimizes the residual of the associated ergodic PDE system, relying on a representation of the ergodic cost. Finally, we apply this framework to regime-switching forward utilities in a stochastic factor model. We first derive a general consistency SPDE that characterizes regime-switching forward utilities and retrieve their representation with systems of ergodic BSDEs in the homothetic case. Numerical experiments demonstrate the performance of the proposed methods, with a particular focus on the impact on forward preferences of taking into account regime switches.

23.
arXiv (CS.CL) 2026-06-12

If LLMs Have Human-Like Attributes, Then So Does Age of Empires II

Much research has been carried out on large language models (LLMs) and LLM-powered agentic workflows. However, many works within the field state emergence of, ascribe to, or assume, generalised anthropomorphic attributes to them (e.g., morality or understanding of natural language). Our goal is not to argue in favour or against the existence of these attributes, but to point out that these conclusions could be incorrect. For this we build and train a simple neural network on the videogame Age of Empires II, and note that any entity in a sufficiently-powerful substrate, such as LEGO or the Greater Boston Area, could also present such attributes. Hence, the purported anthropomorphic attributes of LLMs are empirically non-unique: although some properties (e.g., responses to prompts) could remain invariant, others, such as the interpretation of their perceived behaviour, might change with the substrate. Thus, any empirically-grounded discussion on these attributes requires explicit measurement criteria; otherwise the interpretation is left to the representation. We then show that assuming that these attributes exist or not in a system, independent of the substrate and in a generalised way, leads to either circular or uninformative conclusions. This is regardless of the experimenter's viewpoint on the subject, or whether the outcome shows existence or non-existence. Finally we propose a 'null' assumption, where one assumes LLM non-uniqueness instead of assuming anthropomorphic attributes to set up an experiment, along with examples of it. We also discuss potential objections to our work, briefly survey the field, and prove that Age of Empires II is functionally- and Turing-complete.

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

Can Language Model Agents be Helpful Circuit Explainers in Mechanistic Interpretability?

arXiv:2606.24026v1 Announce Type: new Abstract: Mechanistic interpretability has made substantial progress in automatically localizing circuits, but explaining what localized components do remains labor-intensive and difficult to standardize. In this work, we study whether language model (LM) agents can assist with this explanation problem once a circuit has already been identified. We introduce AgenticInterpBench, a benchmark for circuit explanation built from 84 semi-synthetic transformer circuits with 163 component-level annotations. We propose HyVE (Hypothesize, Validate, Explain), an agentic explainer that analyzes each component through an iterative loop of observation, hypothesis generation, and causal validation, eventually producing a component-level explanation and a circuit-level task description. Across four LM backbones, HyVE recovers useful component- and task-level explanations, but no backbone is uniformly best. Our analysis shows that strong backbones usually form observation-grounded hypotheses, while failures more often arise later in the validation loop, through incomplete validation plans, code execution errors, or unresolved hypotheses. A case study on an arithmetic circuit in Llama-3-8B shows that the same formulation can extend beyond semi-synthetic benchmarks to naturally trained models. Overall, LM agents are promising circuit explainers, but reliable validation remains the key obstacle.

25.
arXiv (quant-ph) 2026-06-12

Toward quantum-noise-limited interferometric measurements of optical nonlinearity in vacuum

arXiv:2602.10896v2 Announce Type: replace-cross Abstract: Quantum Electrodynamics predicts that the vacuum must behave as a nonlinear optical medium: the vacuum optical index should increase when it is stressed by intense electromagnetic fields. The DeLLight (Deflection of Light by Light) project aims to measure it by using intense and ultra-short laser pulses. The experiment uses a Sagnac interferometer to amplify the tiny deflection signal of a low-intensity probe pulse crossing the vacuum refractive-index gradient produced by an external high-intensity pump pulse. The measurement of the amplified signal by a CCD camera requires a high spatial resolution, which is limited by the ultimate quantum noise of the CCD. However, interferometric phase noise induced by the mechanical vibrations of the interferometer is also amplified and degrades spatial resolution. To overcome this, we propose a new method named High-Frequency Phase Noise Suppression (HFPNS), based on the addition of a delayed replica (5 ns) of the probe pulse. The delayed pulse, which is not affected by the pump but is subject to the same vibration noise, enables offline subtraction of correlated phase noise. In this work, we present an experimental proof-of-concept on a prototype interferometer operating with a limited amplification factor ($\mathcal{A}\simeq25$), about 10 times smaller than the required value of the final experiment. We have succeeded in reducing phase noise by a factor of 40, resulting in a residual noise level 2.3 times higher than the expected quantum noise. The residual noise is linked to delay-line instabilities and incident beam pointing fluctuations present during these tests. This result validates HFPNS as a robust method for future quantum-noise-limited interferometric measurements of vacuum optical nonlinearity, though additional stabilization and higher interferometric amplification are still needed.