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01.
arXiv (CS.AI) 2026-06-11

Irresponsible AI: big tech's influence on AI research and associated impacts

arXiv:2512.03077v2 Announce Type: replace-cross Abstract: The accelerated development, deployment and adoption of artificial intelligence systems has been fuelled by the increasing presence of big tech in the AI field. This trend has been accompanied by growing ethical concerns and intensified societal and environmental impacts. This position paper argues that irresponsible AI development is strongly driven by big tech's influence and involvement in the field. First, we examine the growing and disproportionate influence of big tech in AI research and argue that its drive for scaling and general-purpose systems is fundamentally at odds with the responsible, ethical, and sustainable development of AI. Second, we review key current environmental and societal negative impacts of AI and trace their connections to big tech's influence. Third, we discuss the underlying economic forces driving big tech's actions. Finally, as a call to action, we invite AI researchers to counter big tech's influence in irresponsible AI development through strategies that build on the responsibility of implicated actors and collective action.

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

Geometric Action Model for Robot Policy Learning

Generalist robot policies must follow user instructions while reasoning about how objects, cameras, and robot actions interact in the 3D physical world. Recent vision-language-action models (VLAs) and video world-action models (WAMs) inherit strong semantic or temporal priors from large-scale foundation models, but they still operate primarily on 2D image frames or 2D-derived latent spaces, leaving implicit the 3D geometry required for contact-rich manipulation. We propose the Geometric Action Model (GAM), a language-conditioned manipulation policy that directly repurposes a pretrained geometric foundation model (GFM) as a shared substrate for perception, temporal prediction, and action decoding. GAM splits the GFM at an intermediate layer: the shallow layers serve as an observation encoder, and a causal future predictor inserted at the split layer forecasts future latent tokens conditioned on language, proprioception, and action history. The predicted future tokens are then routed through the remaining GFM blocks for feature propagation and decoding, allowing a single backbone to produce both future geometry and actions. This design equips the GFM with language-conditioned temporal world modeling through minimal architectural modification while preserving its rich geometric priors. Across a broad suite of simulation and real-robot manipulation benchmarks, GAM is more accurate, more robust, faster, and lighter than current foundation-model-scale baselines.

03.
arXiv (CS.LG) 2026-06-15

EM-NeSy: Expectation Maximization for Neurosymbolic Learning

arXiv:2606.14463v1 Announce Type: new Abstract: Neurosymbolic (NeSy) models integrate neural networks and symbolic reasoning for robust and interpretable AI. State-of-the-art NeSy models require that the symbolic component is expressed in a differentiable way, often complicating the use of approximate inference. We propose EM-NeSy which casts probabilistic NeSy learning as an instance of the Expectation-Maximization (EM) algorithm. In the expectation step, we compute the posterior over the neurally predicted symbols conditioned on the label via probabilistic inference. In the maximization step, we update the neural parameters based on this posterior using gradient descent only through the neural component. This formulation unlocks the full potential of the EM algorithm for NeSy learning. It allows NeSy to extend naturally to approximate reasoning without any additional modifications or differentiability requirements of the symbolic component. Furthermore, it recovers the standard end-to-end gradient-based NeSy setting under exact inference. Our experimental results demonstrate the scalability and computational efficiency of EM-NeSy.

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

Source-Grounded Data Generation for Text-to-JSON Learning

From financial filings to clinical records, legacy industries rely heavily on long, unstructured documents to store high-value information. Reliably extracting this information into structured, machine-readable representations is a key prerequisite to making the contents accessible to automated systems. JSON is a natural target for such structured extraction, yet constructing reliable and scalable text-to-JSON training data remains challenging. To address this gap, we propose STAGE (Spreadsheet-grounded Text-to-JSON Artifact GEneration), a source-grounded data generation pipeline that constructs reports and JSON schema by using LLMs for scalable synthesis while validating ground-truth values against the underlying spreadsheet. Evaluations on STAGE-Eval, our source-grounded benchmark with an 851-example test set, show that STAGE produces stronger training data than existing approaches. This improves Qwen3-4B exact match from 31.37% to 74.27% and value accuracy from 45.46% to 90.69%.

05.
arXiv (CS.AI) 2026-06-17

Knowledge Reutilization in Meta-Reinforcement Learning

arXiv:2606.18132v1 Announce Type: new Abstract: Meta-reinforcement learning enables fast adaptation by extracting shared structure from related tasks, but existing end-to-end methods often couple task inference with embodiment-specific control. This coupling can obscure non-parametric task semantics, reduce sample efficiency, and limit cross-agent reuse. We propose a meta-knowledge reutilization framework that learns task-level knowledge on a dynamics-simplified agent and transfers it to heterogeneous agents. The framework uses a Bayesian non-parametric prior to organize latent task modes and a high-level policy to generate task-level magnitude guidance. To bridge reusable task knowledge with different embodiments, we introduce a semantic-magnitude interface and a lightweight temporal adaptor, which convert frozen meta-knowledge into temporally aligned subgoals for embodiment-specific low-level controllers. Experiments on multiple locomotion agents show that our framework reduces final-step tracking error by 94.75% – 99.79% compared with recent state-of-the-art baselines and achieves comparable deployment performance with about 23.8% of their interaction data.

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

CisTransCell: Single-Cell Perturbation Prediction via Gene Function, Regulatory Control, and Cellular Context

arXiv:2606.13713v1 Announce Type: cross Abstract: Predicting cellular transcriptional responses to genetic perturbations is a central problem in single-cell biology, especially in the zero-shot setting where the perturbed gene or gene combination is unseen during training. A major difficulty is that perturbation effects are not determined by expression state alone: they depend on how the perturbed gene product influences other genes and proteins, how those downstream factors act on cis-regulatory elements, and which regulatory programs are active in the current cell state. To better capture this biological complexity, we propose CisTransCell, a cell-conditioned multi-modal framework for single-cell perturbation prediction that augments each gene with two complementary priors: a regulatory-sequence prior that captures how the gene is controlled, and a coding-sequence prior that captures what the gene product does. By integrating these priors with cellular expression state, CisTransCell models perturbation response as a cascade from gene function to regulatory control to downstream transcriptional change. Experiments on benchmark single-cell perturbation datasets show that CisTransCell achieves strong performance in zero-shot perturbation prediction.

07.
arXiv (CS.AI) 2026-06-16

The Initial Exploration Problem in Knowledge Graph Exploration

arXiv:2602.21066v2 Announce Type: replace Abstract: Knowledge Graphs (KGs) enable the integration and representation of complex information across domains, but their semantic richness and structural complexity create substantial barriers for lay users without expertise in semantic web technologies. When encountering an unfamiliar KG, such users face a distinct orientation challenge: they do not know what questions are possible, how the knowledge is structured, or how to begin exploration. This paper identifies and theorises this phenomenon as the Initial Exploration Problem (IEP). Drawing on theories from information behaviour and human-computer interaction, including ASK, exploratory search, information foraging, and cognitive load theory, we develop a conceptual framing of the IEP characterised by three interdependent barriers: scope uncertainty, ontology opacity, and query incapacity. We argue that these barriers converge at the moment of first contact, distinguishing the IEP from related concepts that presuppose an existing starting point or information goal. Analysing KG exploration interfaces at the level of interaction primitives, we suggest that many systems rely on epistemic assumptions that do not hold at first contact. This reveals a structural gap in the design space: the absence of interaction primitives for scope revelation, mechanisms that communicate what a KG contains without requiring users to formulate queries or interpret ontological structures. In articulating the IEP, this paper provides a theoretical lens for evaluating KG interfaces and for designing entry-point scaffolding that supports initial exploration.

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

Can LLMs Accurately Score Medical Diagnoses and Clinical Reasoning?

arXiv:2604.14892v3 Announce Type: replace-cross Abstract: Evaluating medical AI systems using expert clinician panels is costly and slow, motivating the use of large language models (LLMs) as alternative adjudicators. Here, we evaluate an LLM Jury, composed of three frontier AI models, for scoring 3334 diagnoses on 300 real-world low- and middle-income country (LMIC) hospital cases. Both LLM- and clinician-generated diagnoses are scored against expert panel diagnoses across four dimensions: diagnosis, differential diagnosis, clinical reasoning, and negative treatment risk. The LLM Jury scores are compared with expert and independent re-scoring panel scores to assess error metrics, inter-rater agreement, severe-risk errors, and the effect of post hoc calibration using isotonic regression. In our data, we find that: (i) the uncalibrated LLM Jury scores preserve ordinal agreement with the expert clinician panel scores, but are systematically lower; (ii) the probability of severe-risk errors is lower for the LLM Jury than the human expert re-score panels; (iii) the LLM Jury combined with LLM diagnoses can be used to identify diagnoses at high risk of error, enabling targeted expert review and improved panel efficiency; (iv) the calibrated LLM Jury scores and rankings of diagnosing agents show excellent agreement with those of the primary expert panels; (v) LLM Jury models show no self-preference bias, they did not score diagnoses generated by their own underlying model or models from the same vendor more (or less) favourably than those generated by other models. Together, these results provide evidence that a calibrated LLM Jury is a trustworthy and reliable proxy for expert clinician evaluation in medical AI benchmarking. Confirming these findings in other clinical settings is an important direction for future work.

09.
arXiv (quant-ph) 2026-06-16

Complete entanglement detection using polynomial invariants

arXiv:2606.16712v1 Announce Type: new Abstract: Existing methods for deciding whether a bipartite quantum state is separable or entangled typically fall into one of two categories: they are either complete but require access to an explicit density matrix followed by numerical optimization, or they can be evaluated directly by measuring the quantum system but are incomplete, in the sense that they cannot detect all forms of entanglement. In this work, we overcome both limitations in a unified framework. First, we bypass numerical optimization by deriving separability criteria in the form of universal bounds on tensor powers of separable states. We prove that these bounds are complete: every entangled state violates them for sufficiently large tensor powers. Second, we explicitly construct a corresponding complete family of nonlinear entanglement witnesses, which can detect all forms of entanglement without requiring an explicit density matrix. The witnesses we construct are moreover basis-independent, in the sense that they are invariant under conjugation by local unitaries. Altogether, our results expand the toolbox for entanglement detection in arbitrary local dimensions in a manifestly invariant way.

10.
medRxiv (Medicine) 2026-06-12

Order-Based Bayesian Network Modeling of Early Detection and Post-Diagnosis Control for Cardiovascular Disease Risk in Type 2 Diabetes

Patients diagnosed with type 2 diabetes (T2D) are at increased risk of developing cardiovascular disease (CVD), the leading cause of morbidity and mortality in this population. Early detection and glycemic control within the first year after diagnosis reduce CVD risk. However, gaps remain in how to operationalize early detection of T2D using Electronic Health Record (EHR) data and quantify its relationship with subsequent CVD risk using longitudinal observations. We developed a probabilistic graph model to analyze the interdependencies between early detection of T2D, post-diagnosis glycemic control, and CVD occurrence. Using a temporally structured Bayesian Network (BN) learned from EHR data of 9,450 primary care patients between 2017 and 2023, we quantified probabilistic dependencies between demographics, diagnostic delay surrogates, glycemic control, and post-diagnosis CVD occurrence. Percentile based thresholds defined risk groups, where individuals with predicted probabilities in the bottom decile ([≤] 10th percentile) were classified as low risk, and those in the top decile ([≥] 90th percentile) as high risk. Results demonstrated heterogeneity in predicted risks across glycemic and cardiovascular outcomes. Predicted probability of developing CVD within the first year after T2D diagnosis ranged from a mean of 5.2% in the low-risk group to 28.9% in the high-risk group, while predicted probabilities of mean Hemoglobin A1c (HbA1c) [≥] 8% during the first year post-diagnosis ranged from 1.6% in low-risk to 55.1% in high-risk group. Patients with HbA1c at diagnosis [≥] 8% had higher predicted probabilities of first-year post-diagnosis mean HbA1c [≥] 8% (53.3% vs. 1.9%) and high HbA1c coefficient of variation (18.7% vs. 3.1%) compared with those with HbA1c [≤] 6.5%. Incorporating early clinical outcomes refined later risk predictions, with long-term CVD risk reaching 33.5% among high-risk individuals. The proposed model achieved predictive performance comparable to conventional machine learning approaches while providing interpretable relationships for risk stratification in primary care populations.

11.
arXiv (math.PR) 2026-06-11

On the $d$-rigidity phase transition in random graphs

作者:

arXiv:2605.25711v2 Announce Type: replace-cross Abstract: We study generic $d$-dimensional rigidity in sparse random graphs. Our main result is that for every $d\ge 2$, the Erdős–Rényi random graph $G\sim G(n,c/n)$ undergoes a $d$-rigidity phase transition at the known, explicit, $d$-orientability threshold $c_d$: If $cc_d$, then $G$ is a.a.s. not independent in the generic $d$-rigidity matroid, and we give a sharp asymptotic estimate for its rank. In addition, the $d$-rigidity closure of $G$ has a giant clique of linear size, which contains all but at most $o(n)$ vertices of the $((d+1)+d)$-core of the graph. More generally, we compute, up to a $1+o(1)$ factor, the generic $d$-rigidity rank of random graphs with a given degree distribution. For example, we show that the uniform $n$-vertex $k$-regular graph a.a.s. has rank $\min(k/2,d)n+o(n).$ Our approach is to estimate the rigidity rank of a random graph from its Galton–Watson local weak limit, using a parameter that we call local flexibility.

12.
arXiv (CS.AI) 2026-06-16

CoAgent: Concurrency Control for Multi-Agent Systems

arXiv:2606.15376v1 Announce Type: cross Abstract: Multi-agent LLM systems – coding agents, devops agents, document agents – now routinely run several agents in parallel against the same git tree, Kubernetes cluster, or document. As soon as two of them mutate shared state, they enter the regime classical concurrency control has studied for decades, but classical mechanisms fit LLM agents poorly. A single agent transaction spans minutes of inference, read sets are broad and opaque rather than statically inferable, and the live state agents act on admits neither fork nor buffer, so writes take effect the moment they execute. Locks block long inference intervals; OCC abort-and-retry discards minutes of work on every conflict. This paper builds concurrency control on a capability classical transactions lack: the LLM inside each agent can judge whether a conflicting write invalidates its plan, and can repair exactly the operations that depended on it. Control therefore turns advisory: the runtime informs, the agent repairs. Our protocol, MTPO (Monotonic Trajectory Pre-Order), fixes a serialization order at launch, serves each read the order-filtered value, and applies writes speculatively in place; a one-way notification asks an affected reader to re-judge and patch its plan, while the framework mechanically undoes and reorders misplaced writes through the saga-style inverse each tool registers in advance. At quiescence the run is serializable in the pre-decided order. We realize MTPO as CoAgent, toolcall middleware whose privileged ToolSmith grows footprint-declared, undoable tools online. On ten contended workloads, CoAgent stays within 5\% of serial correctness at a $1.4\times$ speedup and near-serial token cost, where 2PL and OCC surrender nearly all concurrency gains; on a bash-only target system, it grows a 25-tool library online and lifts the task pass rate from 45/71 to 63/71 at $0.80\times$ the time and $0.86\times$ the cost.

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

E-mem: Multi-agent based Episodic Context Reconstruction for LLM Agent Memory

arXiv:2601.21714v5 Announce Type: replace Abstract: The evolution of Large Language Model (LLM) agents towards System~2 reasoning, characterized by deliberative, high-precision problem-solving, requires maintaining rigorous logical integrity over extended horizons. However, prevalent memory preprocessing paradigms suffer from destructive de-contextualization. By compressing complex sequential dependencies into pre-defined structures (e.g., embeddings or graphs), these methods sever the contextual integrity essential for deep reasoning. To address this, we propose E-mem, a framework shifting from Memory Preprocessing to Episodic Context Reconstruction. Inspired by biological engrams, E-mem employs a heterogeneous hierarchical architecture where multiple assistant agents maintain uncompressed memory contexts, while a central master agent orchestrates global planning. Unlike passive retrieval, our mechanism empowers assistants to locally reason within activated segments, extracting context-aware evidence before aggregation. Evaluations on the LoCoMo benchmark demonstrate that E-mem achieves over 54\% F1, surpassing the state-of-the-art GAM by 7.75\%, while reducing token cost by over 70\%.

14.
arXiv (quant-ph) 2026-06-12

Intermediate State Formation of Topologically Associated Chromatin Domains using Quantum Annealing

arXiv:2505.23289v2 Announce Type: replace Abstract: Topologically Associating Chromatin Domains are spatially distinct chromatin regions that regulate transcription by segregating active and inactive genomic elements. Empirical studies show that their formation correlates with local patterns of epigenetic markers, yet the precise mechanisms linking 1D epigenetic landscapes to 3D chromatin folding remain unclear. Recent models represent chromatin as a spin system, where nucleosomes are treated as discrete-state variables coupled by interaction strengths derived from genomic and epigenetic data. Classical samplers struggle with these models due to high frustration and dense couplings. Here, we present a quantum annealing (QA) approach to efficiently sample chromatin states, embedding an epigenetic Ising model into the topology of D-Wave quantum processors. Rather than reconstructing exact TAD size distributions or insulation scores, our method reproduces statistical features, such as mean marker incidences and intra-/inter-nucleosome correlations, while generating configurations that exhibit TAD-like structural motifs. These results demonstrate QA as an alternative to explore the chromatin architecture and provide a foundation in epigenetic modeling.

15.
arXiv (CS.CL) 2026-06-16

Automatic Summarization of Doctor-Patient Encounter Dialogues Using Large Language Model through Prompt Tuning

Automatic text summarization (ATS) is an emerging technology to assist clinicians in providing continuous and coordinated care. This study presents an approach to summarize doctor-patient dialogues using generative large language models (LLMs). We developed prompt-tuning algorithms to instruct generative LLMs to summarize clinical text. We examined the prompt-tuning strategies, the size of soft prompts, and the few-short learning ability of GatorTronGPT, a generative clinical LLM developed using 277 billion clinical and general English words with up to 20 billion parameters. We compared GatorTronGPT with a previous solution based on fine-tuning of a widely used T5 model, using a clinical benchmark dataset MTS-DIALOG. The experimental results show that the GatorTronGPT- 20B model achieved the best performance on all evaluation metrics. The proposed solution has a low computing cost as the LLM parameters are not updated during prompt-tuning. This study demonstrates the efficiency of generative clinical LLMs for clinical ATS through prompt tuning.

16.
arXiv (CS.CV) 2026-06-17

Looped World Models

Current world models face a fundamental tension: faithful long-horizon simulation demands deep computation, but deeper models are expensive to deploy and prone to compounding errors. We resolve this by introducing Looped World Models (LoopWM), which are the first looped architectures for world modelling. Our method iteratively refines latent environment states through a parameter-shared transformer block. This yield up to 100x parameter efficiency over conventional approaches with adaptive computation that automatically scales depth to match the complexity of each prediction step. Orthogonal to scaling model size and training data, LoopWM establishes iterative latent depth as a new scaling axis for world simulation, which might significantly push the community forward.

17.
arXiv (CS.AI) 2026-06-11

JailbreakOPT: Tool-Assisted Iterative Jailbreak Prompt Optimization

arXiv:2606.11425v1 Announce Type: cross Abstract: Jailbreak attacks expose persistent safety weaknesses in large language models (LLMs), but existing stateless single-turn methods face a trade-off: hand-crafted prompts are expressive but static, while iterative prompt optimization can adapt but often relies on low-level mutations that require many target queries. We propose JailbreakOPT, a tool-assisted framework for improving iterative single-turn jailbreak prompt optimization. JailbreakOPT organizes diverse atomic jailbreak prompts into an attack tool library and composes them through a unified intra-episode optimization abstraction to generate stronger standalone attack prompts. To reuse experience across attack episodes, JailbreakOPT further frames tool selection as a contextual bandit problem and applies contextual Thompson sampling to guide exploration and exploitation based on past outcomes. Experiments across multiple target LLMs and attack goals show that JailbreakOPT improves attack success rate (ASR) while reducing the number of attacks until success (No.A) compared with atomic single-turn attacks and existing iterative optimization baselines. This paper may contain offensive or harmful content.

18.
arXiv (CS.AI) 2026-06-11

Bimanual Robot Manipulation via Multi-Agent In-Context Learning

arXiv:2604.20348v2 Announce Type: replace-cross Abstract: Language Models (LLMs) have emerged as powerful reasoning engines for embodied control. In particular, In-Context Learning (ICL) enables off-the-shelf, text-only LLMs to predict robot actions without any task-specific training while preserving their generalization capabilities. Applying ICL to bimanual manipulation remains challenging as the high-dimensional joint action space and tight inter-arm coordination constraints rapidly overwhelm standard context windows. To address this, we introduce BiCICLe (Bimanual Coordinated In-Context Learning), the first framework that enables standard LLMs to perform few-shot bimanual manipulation without fine-tuning. BiCICLe frames bimanual control as a multi-agent leader-follower problem, decoupling the action space into sequential, conditioned single-arm predictions. Evaluated on 13 tasks from the TWIN benchmark, BiCICLe achieves 70.5% average success rate, outperforming the best training-free baseline by 6.1 percentage points and surpassing most supervised methods. We also demonstrate superior real-world performance on 3 tasks without hardware-specific retraining.

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

S$^2$COPE: Self-Supervised Concept Discovery via Preference Learning

Current representation learning paradigms force a fundamental compromise: self-supervised methods scale to massive datasets but yield opaque features, whereas interpretable models remain bottlenecked by the need for dense human annotation. We introduce Self-Supervised Concept discOvery via Preference lEarning (\model), a label-free framework that resolves this dilemma. Instead of treating Vision-Large-Language Models (VLLMs) as static feature extractors, \model leverages them as active participants in a self-supervised preference optimization loop. By autonomously hypothesizing, validating, and reinforcing candidate visual attributes directly from raw imagery, our framework discovers novel, structured concepts without a single label. Extensive experiments across natural, medical, and physics domains demonstrate that \model successfully extracts domain-specific concepts where standard VLLMs often fail to generate. By amortizing concept discovery directly into the VLLM backbone through our self-supervised preference objective – rather than relying on static generation and disjoint filtering – we achieve up to a 24-point absolute improvement in downstream top-1 classification accuracy on unseen data. Our work suggest that interpretability can emerge through a model's autonomous interaction with incidental visual structures, without any human supervision.

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

MiniFool – Physics-Constraint-Aware Minimizer-Based Adversarial Attacks in Deep Neural Networks

arXiv:2511.01352v2 Announce Type: replace Abstract: In this paper, we present a new algorithm, MiniFool, that implements physics-inspired adversarial attacks for testing neural network-based classification tasks in particle and astroparticle physics. While we initially developed the algorithm for the search for astrophysical tau neutrinos with the IceCube Neutrino Observatory, we apply it to further data from other science domains, thus demonstrating its general applicability. Here, we apply the algorithm to the well-known MNIST data set and furthermore, to Open Data data from the CMS experiment at the Large Hadron Collider. The algorithm is based on minimizing a cost function that combines a $\chi^2$ based test-statistic with the deviation from the desired target score. The test statistic quantifies the probability of the perturbations applied to the data based on the experimental uncertainties. For our studied use cases, we find that the likelihood of a flipped classification differs for both the initially correctly and incorrectly classified events. When testing changes of the classifications as a function of an attack parameter that scales the experimental uncertainties, the robustness of the network decision can be quantified. Furthermore, this allows testing the robustness of the classification of unlabeled experimental data.

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

Bayesian Inference and Decision Audits for Public Archives of Frontier AI Evaluations

作者:

arXiv:2606.17005v1 Announce Type: new Abstract: Public AI evaluations are often read as terminal leaderboards, yet the underlying evidence is a selective time series shaped by reporting rules, benchmark revisions, and missingness. Repeated public archives for LiveBench and Open LLM Leaderboard v2 serve as the primary longitudinal record; LMArena provides a preference stress test; and GAIA and tau-bench contribute limited agentic pilots. Together, these archives instantiate a Bayesian inference problem: under a fixed reporting convention, one constructed terminal-only example over $1{,}000$ systems is compatible with two pre-terminal histories, yielding times of $23.03$ or $75.13$ to reach within $0.05$ of the ceiling under the same terminal-tail model. In synthetic posterior comparisons, action-facing diagnostics differ across observation regimes. The candidate selection-aware frontier model fails synthetic recovery, objective-archive prediction, preference transfer, and uncertainty calibration; correspondingly, fixed audit gates reject its stronger claims. An archive-and-adjudication protocol reconstructs public evaluation histories, isolates a verified timing boundary, and falsifies unsupported frontier claims.

22.
medRxiv (Medicine) 2026-06-22

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes

OBJECTIVE To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

23.
arXiv (CS.AI) 2026-06-16

Learning in the Recurrent State: Gradient Descent with Linear Recurrent Networks

arXiv:2410.11687v3 Announce Type: replace-cross Abstract: Linear recurrent networks (LRNNs) offer linear-time sequence modeling, but standard recurrent updates do not directly expose the supervised products needed for in-context gradient descent. We propose a sufficient constructive inductive bias for LRNNs: equip a diagonal recurrent state with multiplicative readout and a short sliding-window cross-product self-attention update. The resulting architecture, Gradient-based Recurrent In-context Learner (GRIL), can implement minibatch gradient descent on a task-specific linear predictor during a single forward pass. The same design extends to multi-step updates and cross-entropy classification, with a limited MLP-based extension to non-linear regression. Empirically, trained GRILs recover the behavior and parameters predicted by the construction on synthetic ICL tasks, and the same architectural bias yields useful performance on Long Range Arena and language modelling. These results present windowed cross-product self-attention as a practical, testable inductive bias for LRNNs that learn in context through gradient-descent-like updates.

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

scLLM-DSC: LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering for Single-Cell RNA Sequencing

arXiv:2606.13007v1 Announce Type: cross Abstract: Clustering is fundamental to scRNA-seq analysis, serving as a cornerstone for identifying cell populations and resolving tissue heterogeneity. However, existing methods focus on mining numerical statistical patterns, suffering from semantic agnosticism by neglecting the intrinsic biological functions encoded by genes. While Large Language Models (LLMs) offer promising semantic capabilities, their direct adaptation to cell clustering is hindered by the structural mismatch between generative pre-training objectives and discriminative downstream tasks. To bridge this gap, we propose scLLM-DSC, a novel LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering framework. Diverging from data-driven paradigms, scLLM-DSC establishes a semantically-grounded representation by synergizing two views: a Knowledge-Driven Semantic View derived from NCBI gene priors and contextualized Cell2Sentence embeddings, and a Structure-Aware Topological View extracted via a graph-guided encoder. Crucially, we introduce a cross-modal contrastive alignment mechanism to enforce consistency between biological semantics and transcriptomic features within a unified latent space. Extensive benchmarks demonstrate that scLLM-DSC significantly outperforms eleven state-of-the-art baselines in clustering accuracy.

25.
arXiv (CS.LG) 2026-06-12

Adjusted Cup-Product Neural Layer

arXiv:2606.13568v1 Announce Type: new Abstract: Many important observables in physics and geometry are cup products of cochains. The adjusted cup product neural layer has been introduced in this paper. It is a neural primitive that hard wires the cup product with an adjustment term from higher gauge theory. This creates a readout that is gauge invariant by design. Their main theoretical result shows that on a closed cycle the output relies entirely on the adjustment coefficient. Setting this coefficient to zero removes the output completely regardless of other parameters. Thus the adjustment is the only source of gauge invariant signal. They prove this observable is a nonzero quadratic form and is exactly invariant under one and two gauge transformations.