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

Decomposing Prediction Mechanisms for In-Context Recall

arXiv:2507.01414v2 Announce Type: replace Abstract: We introduce a new family of toy problems that combine features of linear-regression-style continuous in-context learning (ICL) with discrete associative recall. We pretrain transformer models on sample traces from this toy, specifically symbolically-labeled interleaved state observations from randomly drawn linear deterministic dynamical systems. We study if the transformer models can recall the state of a sequence previously seen in its context when prompted to do so with the corresponding in-context label. Taking a closer look at this task, it becomes clear that the model must perform two functions: (1) identify which system's state should be recalled and apply that system to its last seen state, and (2) continuing to apply the correct system to predict the subsequent states. Training dynamics reveal that the first capability emerges well into a model's training. Surprisingly, the second capability, of continuing the prediction of a resumed sequence, develops much earlier. Via out-of-distribution experiments, and a mechanistic analysis on model weights via edge pruning, we find that next-token prediction for this toy problem involves at least two separate mechanisms. One mechanism uses the discrete symbolic labels to do the associative recall required to predict the start of a resumption of a previously seen sequence. The second mechanism, which is largely agnostic to the discrete symbolic labels, performs a "Bayesian-style" prediction based on the previous token and the context. These two mechanisms have different learning dynamics. To confirm that this multi-mechanism (manifesting as separate phase transitions) phenomenon is not just an artifact of our toy setting, we used OLMo training checkpoints on an ICL translation task to see a similar phenomenon: a decisive gap in the emergence of first-task-token performance vs second-task-token performance.

02.
arXiv (CS.LG) 2026-06-19

HEPTv2: End-to-End Efficient Point Transformer for Charged Particle Reconstruction

arXiv:2606.20437v1 Announce Type: cross Abstract: Charged-particle tracking – reconstructing trajectories from sparse detector measurements – is a fundamental high-energy-physics inference problem and a canonical example of learning under extreme combinatorial ambiguity. At the High-Luminosity Large Hadron Collider (HL-LHC), tracking must remain accurate and efficient despite unprecedented collision densities. Graph neural networks perform strongly, but incur substantial costs from graph construction and processing, while transformer-based approaches rely on auxiliary stages that prevent end-to-end optimization. To address this, we present HEPTv2, an end-to-end point-transformer architecture that reconstructs tracks from detector hits in one trainable pipeline. HEPTv2 combines a locality-aware point encoder with a track decoder that predicts complete trajectories without graph-building, clustering, or filtering. The encoder uses locality-sensitive hashing in detector coordinate space to preserve tracking-relevant geometry while enabling efficient local attention. The decoder resolves ambiguities through sectorized decoding and direct hit-to-track prediction under joint encoder-decoder supervision, allowing the full pipeline to be optimized end-to-end. On TrackML, HEPTv2 achieves 98.6% double-majority tracking efficiency at a 0.8% fake rate, while requiring only $\sim$15~ms inference time and 0.4~GB peak memory per event on a NVIDIA A100 GPU. Latency and memory scale approximately linearly for events with up to $5\times10^5$ hits. HEPTv2 establishes a new state of the art in the accuracy-latency trade-off, improving efficiency by 4.5% over the strongest prior transformer and by 1.1–2.2% over optimized graph-based pipelines, while reducing latency by factors of 7 and 38–52, respectively. These results show end-to-end transformers can deliver the accuracy and efficiency required for real-time particle reconstruction at the HL-LHC.

03.
medRxiv (Medicine) 2026-06-17

Macrophage-targeted glucocorticoid prodrug resolves acute inflammation while preserving HPA axis function: mechanistic, preclinical, and Phase II/III clinical evidence

Glucocorticoids (GCs) remain the fastest-acting anti-inflammatory agents but are constrained by systemic exposure that suppresses the hypothalamic pituitary adrenal (HPA) axis, silences adaptive immunity, and drives chronic toxicities. Chronic inflammatory diseases are sustained by long-lived CD206+ macrophages containing immune-resistant pathogenic material not cleared physiologically. We developed 101-PGC-005 ('005), a macrophage-targeted type 1a dexamethasone prodrug engineered for low-affinity, recycling-compatible uptake via CD206, with intracellular release triggered by acidic endosomes. We evaluated '005 in mechanistic assays, pathogen-diverse preclinical models, three human pharmacokinetic (PK) studies, and an adaptive-design randomized Phase II/III trial in 309 hospitalized patients with moderate COVID-19. In two completed Phase I human studies, a first-in-human dose-escalation and repeated-dose study and a dedicated single/multiple-dose PK and safety study; '005 circulated as intact prodrug with rapid systemic clearance (Tmax ~0.5 h; terminal half-life ~1.9 h), with no measurable free dexamethasone after single dosing and only low, clinically non-significant free dexamethasone after repeated dosing, and intact prodrug recovered unchanged in urine. Morning cortisol and ACTH were preserved after 30 mg once daily for three consecutive days (1.5 times the intended therapeutic dose). A cerebrospinal fluid PK study is evaluating central-compartment penetration. In the Phase II/III trial, powered for non-inferiority, conducted across six sites in India under GCP with Ministry of Health approval and independent DSMB oversight; '005 (20 mg IV daily for 3 days) was superior to dexamethasone (6 mg IV daily for 3 -10 days) on the primary endpoint of time to > a 2-point improvement on the WHO ordinal scale (HR 2.31; 95% CI 1.83-2.93; p < 0.0001; median 3 vs. 4 days). '005 was also superior on viral clearance (HR 1.47; 95% CI 1.17-1.84; p = 0.0001), hospital discharge rate, SpO2; recovery, and fever resolution. Zero patients in the '005 arm received investigator-initiated corticosteroid supplementation despite protocol allowance. All 309 randomized patients completed the study (ITT = per-protocol). Safety profiles were equivalent (TEAEs 54.8% vs 54.5%; p = 0.958), with no Grade 3+ events, SAEs, deaths, or discontinuations in either arm. Mechanistically, '005 delivered dual benefit: acute debulking of inflammatory macrophages and selective depletion of chronically activated pathology-sustaining macrophages, while preserving CXCL10 antiviral signaling and physiologic HPA control. Critically, HPA preservation is not merely a safety feature, it is a core efficacy mechanism: by clearing the pathogenic macrophage burden that was overriding HPA regulation, '005 restores the conditions for endogenous cortisol to resume its pulsatile, demand-responsive anti-inflammatory role across all GR-expressing cells, lymphocytes, endothelial cells, neurons, and newly differentiated macrophages, that '005 itself cannot reach. These findings support regulatory-grade evidence for macrophage-targeted corticosteroid therapy and provide the foundation for further development across acute inflammatory indications (sepsis, viral pneumonia, cytokine-release syndromes) and chronic macrophage-driven diseases (atherosclerosis, metabolic steatohepatitis, neurodegeneration, tumor-associated macrophages).

04.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

Migratory cells tend to have soft nuclei that deform and penetrate narrow spaces1,2. Extensive nuclear deformation during migration can cause nuclear-envelope rupture and DNA damage in cancer cells, which may contribute to malignant transformation during tumour progression3–6. However, the importance of DNA damage in physiological migration is less well understood. Here we demonstrate that the migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-stranded breaks (DSBs) due to mechanostress during passage through narrow interstitial spaces. In contrast to many other migratory cells, these DSBs occur without detectable nuclear envelope rupture. Confined migration increases topoisomerase-IIβ covalently bound DSBs, and these lesions are repaired through non-homologous end-joining during brain development without causing cell death. Genome sequencing revealed that DSBs tend to occur at transcriptionally inactive regions. The deletion of ligase IV at the onset of neuronal migration leads to persistent DSB accumulation in cerebellar neurons with moderate transcriptional changes in genes related to synaptic function, neuronal development and stress and immune responses. The mutant mouse develops mild motor deficits in later life, suggesting that the DNA damage generated during normal brain development poses a potential disease risk if left unrepaired. The migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-strand breaks due to mechanostress during passage through narrow interstitial spaces.

05.
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.

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

Last-Iterate Convergence of Optimistic Multiplicative Weight Update

arXiv:2606.11773v1 Announce Type: cross Abstract: Optimistic Gradient Descent Ascent (OGDA) and Optimistic Multiplicative-Weights Update (OMWU) are two very popular algorithms to solve convex/concave saddle-point problems, where OMWU is the non-Euclidean, entropic version of OGDA. It is known since the '80s that the last iterate of OGDA asymptotically converges to a saddle point in smooth problems. On the other hand, it is unknown if OMWU has the same property. In this paper, I show that OMWU converges asymptotically for smooth convex-concave saddle-point problems, with a small enough constant learning rate. The result does not require uniqueness, strict complementarity, an error bound, or initialization near a solution. The main new ingredient is a boundary argument showing that every cluster point satisfies the inactive-coordinate KKT inequalities. The boundary argument was discovered with assistance from ChatGPT and is documented in the appendix.

07.
arXiv (CS.AI) 2026-06-17

Temporal Preference Optimization for Unsupervised Retrieval

arXiv:2606.17664v1 Announce Type: cross Abstract: Unsupervised dense retrievers offer scalability by learning semantic similarity from unlabeled documents via contrastive learning, but they struggle to capture the temporal relevance, retrieving semantically related but temporally misaligned documents-an important aspect when a document collection spans multiple time periods (e.g., retrieving documents from 2018-2025 for "Who is the president in 2019?" introduces temporal ambiguity). Existing methods rely on supervised training with explicit timestamps, which are not always feasible. We propose TPOUR (Temporal Preference Optimization for Unsupervised Retriever), which uses our novel training method Temporal Retrieval Preference Optimization (TRPO). TRPO reinterprets preference learning in the temporal dimension, guiding the retriever to favor temporally aligned documents. TPOUR further generalizes to unseen time periods via interpolation in a learned time embedding, enabling continuous temporal alignment. Experiments on temporal information retrieval (T-IR), TPOUR outperforms both unsupervised and supervised baselines. Compared to Qwen-Embedding-8B, despite being about 72.7x smaller, TPOUR Contriever improves average nDCG@5 by +4.04 (+12.15%) on explicit and +4.98 (+15.21%) on implicit queries. We provide our code at https://github.com/agwaBom/TPOUR.

08.
medRxiv (Medicine) 2026-06-18

Intra-arterial recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis for acute medium vessel occlusion (MeVO-TNK): Study rationale and design

Background The optimal management of acute ischemic stroke caused by medium vessel occlusion (MeVO) remains uncertain. Recent randomized trials have failed to demonstrate a clear benefit of endovascular therapy in this population, whereas intra-arterial thrombolysis (IAT) has emerged as a biologically plausible alternative. However, prospective evidence supporting IAT in MeVO is lacking, and the optimal dosing strategy for stand-alone IAT remains undefined. Aim To preliminarily evaluate the efficacy and safety of intra-arterial tenecteplase (IA-TNK) plus standard medical therapy (SMT) compared with SMT alone in patients with acute MeVO stroke, and to explore a stepwise IA-TNK dosing strategy. Design The MeVO-TNK trial is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), exploratory phase II study. A total of 60 participants with imaging-confirmed MeVO will be randomized 1:1 to receive either IA-TNK plus SMT or SMT alone. Participants presenting beyond 6 hours from symptom onset must demonstrate salvageable penumbral tissue on advanced imaging. Those assigned to the intervention group will receive up to two intra-arterial boluses of tenecteplase (0.0625 mg/kg per bolus), with the second bolus administered based on angiographic assessment of reperfusion and safety. Outcomes The primary efficacy outcome is final infarct volume measured at 72{+/-}24 hours after randomization. Secondary efficacy outcomes include the proportions of patients achieving modified Rankin Scale (mRS) scores of 0-1, 0-2 and 0-3 at 90 days, a shift analysis of the mRS distribution at 90 days, early neurological deterioration, and National Institutes of Health Stroke Scale score at 7 days or discharge. The primary safety outcome is symptomatic intracranial hemorrhage within 24 hours. Conclusions This trial will provide preliminary evidence on the biological efficacy, reperfusion potential and safety of stand-alone IA-TNK for acute MeVO stroke, helping to address an important evidence gap and inform the design of future confirmatory studies.

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

Size Doesn't Matter: Cosine-Scored Sparse Autoencoders

arXiv:2606.15054v1 Announce Type: new Abstract: Sparse autoencoders (SAEs) detect features via inner product, so a feature's activation scales with both its directional alignment and the input's norm. Under BatchTopK, high-norm tokens inflate all pre-activations simultaneously, claiming dictionary slots regardless of content alignment. This matters because sublayer normalization has already discarded the magnitude the score measures, so the encoder detects a quantity the model does not read. We replace the score with a learned blend of cosine similarity and input magnitude, letting the optimizer choose how much norm to use; a per-feature extension lets each feature decide independently. In both regimes, training is free to recover inner product but never does, with no feature ever choosing more than half-magnitude dependence. At matched reconstruction, the cosine encoder learns features that align with human-recognizable concepts far more often than standard, filling dictionary slots that inner product wastes on norm detectors. Loss reweighting that equalizes gradients barely closes the gap, confirming forward-pass score geometry as the lever. The advantage is not universal across tasks or depths, but we believe cosine scoring should be the default for dictionary learning on normalized representations.

10.
Nature (Science) 2026-06-18

Daily briefing: The proteins that protect us from deadly mutations

作者:

Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States. Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States.

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

Large deviations for marked sparse random graphs with applications to interacting diffusions

arXiv:2204.08789v2 Announce Type: replace Abstract: We consider the empirical neighborhood distribution of marked sparse Erdős-Rényi random graphs, obtained by decorating edges and vertices of a sparse Erdős-Rényi random graph with i.i.d. random elements taking values on Polish spaces. We prove that the empirical neighborhood distribution of this model satisfies a large deviation principle in the framework of local weak convergence. We rely on the concept of BC-entropy introduced by Delgosha and Anantharam~(2019) which is inspired on the previous work by Bordenave and Caputo~(2015). Our main technical contribution is an approximation result that allows one to pass from graph with marks in discrete spaces to marks in general Polish spaces. As an application of the results developed here, we prove a large deviation principle for interacting diffusions driven by gradient evolution and defined on top of sparse Erdős-Rényi random graphs. In particular, our results apply for the stochastic Kuramoto model. We obtain analogous results for the sparse uniform random graph with given number of edges.

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

Optimizing Appliance Scheduling for Solar Energy Management Using Metaheuristic Algorithms

arXiv:2606.13407v1 Announce Type: new Abstract: Renewable energy is essential for meeting future energy demands; however, solar energy generation, which occurs only during daylight hours often does not align with household consumption patterns. Appliances such as cookers, washing machines, and dryers are typically operated according to user preferred schedules rather than solar energy availability, creating a scheduling optimization problem. The objective is to determine optimal appliance start times to maximize renewable energy utilization while minimizing user inconvenience and adhering to system constraints. This paper presents a metaheuristic approach using Iterated Local Search (ILS) and Simulated Annealing (SA) to optimize appliance start times, while considering appliance operating durations, power consumption, inverter limit, battery state of charge constraints, and solar generation forecasts. Unlike most existing work, the scheduling is extended beyond a single day to accommodate unfinished tasks from previous days (spillover), ensuring operational continuity and enabling sequential operation across multiple days. Experimental results show that the sequential multi-day scheduling framework effectively manages system constraints while ensuring user convenience under exclusive solar generation. These findings also open opportunities for future research on multi-objective trade-offs between investment in equipment of various sizes, return on that investment, and user satisfaction.

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

Safe Exploration via Policy Priors

arXiv:2601.19612v3 Announce Type: replace-cross Abstract: Safe exploration is a key requirement for reinforcement learning (RL) agents to learn and adapt online, beyond controlled (e.g. simulated) environments. In this work, we tackle this challenge by utilizing suboptimal yet conservative policies (e.g., obtained from offline data or simulators) as priors. Our approach, SOOPER, uses probabilistic dynamics models to optimistically explore, yet pessimistically fall back to the conservative policy prior if needed. We prove that SOOPER guarantees safety throughout learning, and establish convergence to an optimal policy by bounding its cumulative regret. Extensive experiments on key safe RL benchmarks and real-world hardware demonstrate that SOOPER is scalable, outperforms the state-of-the-art and validate our theoretical guarantees in practice.

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

An AI Security Agent for University ACMIS: Multi-Vector Threat Detection and Automated Response

arXiv:2606.08270v2 Announce Type: replace-cross Abstract: University Academic Management Information Systems (ACMIS) are high-value targets for a wide spectrum of security threats including brute-force login attacks, payment fraud, privilege escalation, insider data theft, and academic integrity violations. Traditional rule-based intrusion detection systems are inadequate because many malicious activities are structurally indistinguishable from normal operations. This paper presents an AI-based security agent for ACMIS that combines supervised anomaly detection, behavioural analytics, and a natural language processing chatbot for secure password recovery. The agent monitors five operational layers: authentication, authorisation, financial transactions, user behaviour, and system health, and responds through a four-tier risk escalation framework. A modular architecture allows the core engine to be extended to other institutional systems. Experiments on a simulated ACMIS event log dataset of 147,922 sessions demonstrate a threat detection macro-average F1 of 0.966, compared to 0.156 for a rule-based baseline and 0.836 for a sequence-only (LSTM) baseline, with end-to-end critical-tier automated response latency under 1 ms on a single-node prototype. The integrated recovery chatbot achieves 97.1 percent identity verification accuracy and an 87.3 percent mass-reset attack detection rate with zero false positives on legitimate high volume recovery periods.

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

Root-Selecting Fixed-Point Inversion for Rectified Flows via Trajectory Straightness

Finding the initial noise that generates a given data sample, known as inversion, is a key component for downstream applications such as training-free image editing. Existing fixed-point inversion methods improve inversion accuracy by formulating each inversion step as a fixed-point problem, but they lack a principled mechanism for selecting among multiple fixed-point solutions that can arise in practice. We observe that different selections induce different inversion trajectories, leading to substantial variation in reconstruction and editing quality. For rectified flows, we further find that this variation is closely associated with trajectory straightness, motivating straightness as a principled selection criterion. We propose SelFix, a fixed-point inversion method that selects fixed-point solutions inducing straighter inverse trajectories while retaining convergence to an exact inverse root under standard local assumptions. Experiments on FLUX.1-dev and PIE-Bench show that SelFix improves fixed-point inversion, achieving stronger real-image reconstruction and better source-preserving prompt-based editing than prior inversion baselines. The code is available at https://github.com/seminkim/selfix.

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

MagpieTTS-LF: Inference-Time Long-Form Speech Generation Without Training on Long-Form data

arXiv:2606.18485v1 Announce Type: cross Abstract: Neural Text-to-Speech (TTS) systems achieve remarkable quality on short utterances but long-form speech generation shows prosodic drift, speaker inconsistencies and sentence boundary artifacts. Existing approaches either compress sequences, increase context length or naively concatenate independently synthesized chunks. We present an inference-time approach called MagpieTTS-LF that enables MagpieTTS to produce coherent long-form speech without model retraining. Our method introduces three key innovations: (1) soft attention priors to guide monotonic alignment while preserving past and future context; (2) a stateful inference algorithm that maintains context across sentence chunks, ensuring prosodic continuity; (3) history-aware text encoding that uses past text for discourse-level prosodic planning. Experiments on long texts show significant improvements in long-range intelligibility, prosodic coherence, speaker consistency, and boundary naturalness compared to other baselines.

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

Real-time pseudo entropy and modular-Hamiltonian correlations

arXiv:2606.14208v1 Announce Type: cross Abstract: Pseudo entropy is a complex-valued generalization of entanglement entropy defined from a reduced transition matrix. We study the pseudo entropy associated with a real-time transition matrix between an initial pure state and its unitary time evolution. For a subsystem $A$, we show that the short-time behavior of real-time pseudo entropy is governed by the correlation between the physical Hamiltonian $H$ and the modular Hamiltonian $K_A=-\log\rho_A$ of the initial reduced state, $ S_A(t,0)=S_A(0)-it \langle K_A(H-\langle H\rangle)\rangle + \mathcal{O}(t^2)$. For Hermitian dynamics, the initial imaginary response is controlled by the symmetrized covariance of $H$ and $K_A$ with an overall minus sign, while the initial real response is governed by their commutator. Thus the imaginary part of real-time pseudo entropy is not merely a branch artifact: it is a time-oriented modular response generated by the correlation between microscopic time evolution and subsystem coarse graining. We clarify the relation of this result to the known first law of pseudo entropy, derive an all-order expression in a Schmidt-diagonal model, recover thermal pseudo entropy as a special case, illustrate the covariance/commutator decomposition in a two-qubit model, and confirm the covariance response in transverse-field Ising-chain quenches, including a finite-size study of a modular susceptibility near the Ising critical region. We discuss how this amplitude-level oriented response can be related to ordinary entropy production, and also give a concrete $\mathcal{PT}$-symmetric toy-model illustration of the non-Hermitian extension.

18.
bioRxiv (Bioinfo) 2026-06-18

Metrics for Evaluating Biological AI Model Predictive Accuracy at the Data-Substrate Level

作者:

Reports in the biological literature disagree on whether a given model can predict a biological outcome from a given data sample — one study finding a model capable, another, on the same kind of data, finding it is not. This is particularly a challenge in relation to LLMs–where the models are large and opaque, with weights and training data inaccessible.textbf{ }Such disagreements cannot be settled by directly inspecting the model. To address this challenge, we considertextbf{ }an alternative approach: assessing whether the data sample is adequate to support the prediction asserted. For a given dataset, its substrate — the underlying structure of the data — determines what any model can recover, independent of architecture or capacity. At the same time, predicting the present state of a biological process and predicting the direction of its future change are different tasks; the second is supportable among AI models only where the data encode direction as determinable from the state — a property we call encoding — and is unsupportable where the same observed state precedes change in opposite directions — a property we call non-identifiability, in the informational rather than the statistical sense. We introduce two generic metrics, Predictive Blindness Risk (PBR) and Prediction Indeterminacy Measure (PIM), that evaluate a data substrate for predictive accuracy directly — without access to model weights, architecture, or training data — and locate the regions of a data substrate where a predictive claim can be supported and where it cannot. Using human biological subjects, we employ the Yale Brain Metastases Longitudinal Data (1,430 human subjects; 11,892 MRI studies; four sequences) and show that direction of change was non-identifiable across regions encompassing the majority of transitions; a nonlinear AI model gained essentially nothing over majority-direction prediction there while recovering direction near-perfectly where the state encoded it; and model accuracy tracked data-substrate resolvability continuously (Spearman {rho} = -0.95 to -1.00). The metrics adjudicate, before any model is trusted and from the data alone, where claims of predictive accuracy — of state, or of the law of change — can be supported.

19.
arXiv (CS.AI) 2026-06-17

LLM Consumer Behavior Theory: Foundations of a Novel Research Field

arXiv:2606.18005v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly deployed as autonomous agents that make consumption decisions on behalf of users. This shift raises fundamental questions for consumer theory, which has traditionally modeled humans as the primary decision-makers. In this paper, we introduce LLM Consumer Behavior Theory, a new field of study concerned with analyzing consumer behavior in agentic markets. Drawing on classical and behavioral economics alongside recent advances in Natural Language Processing, we formalize how human preferences are reflected and acted upon by LLM-based agents, and how agent-level decisions aggregate into market demand. We unify previously fragmented literature on LLM decision-making, human behavior simulation, and preference elicitation under a common economic lens, highlighting where assumptions, such as rationality and heterogeneity, may fail in agentic markets. Rather than providing empirical validation, this paper outlines the scope of LLM consumer behavior and identifies open research questions related to alignment, preference representation, and market dynamics.

20.
Nature (Science) 2026-06-09

Daily briefing: Trial to ‘de-age’ cells treats first person

作者:

The gene-therapy trial aims to treat glaucoma by rejuvenating cells in the optic nerve. Plus, the mystery of how things freeze and encouragement to go out into the sunlight. The gene-therapy trial aims to treat glaucoma by rejuvenating cells in the optic nerve. Plus, the mystery of how things freeze and encouragement to go out into the sunlight.

21.
bioRxiv (Bioinfo) 2026-06-21

SPA-C: an hybrid tool to accurately scaffold genomes using Hi-C and Deep-Learning

Genome assembly is a computational pipeline designed to reconstruct chromosomes from small sequencing reads. Following their assembly, contiguous sequences (contigs) are arranged into chromosome-long sequences during scaffolding. Hi-C, a long-range linkage information between regions of the genome widely used in recent large sequencing projects, is often required to correctly order contigs. Several tools have been developed to automate this task following either statistical or deep-learning approaches. Statistical approaches summarise 2D Hi-C matrices into contact densities across sequences, thus ignoring informative visual patterns. The sole existing deep-learning tool uses a transformer-based computer vision model to correct the assembly. It has been trained on several species and uses Hi-C matrices directly. Yet it comes as a supplementary step in the scaffolding process, introducing extra computation time, and has been trained on a dataset that might contain labelling errors, which could provide sub-optimal results. We propose SPA-C, an hybrid pipeline combining the strengths of both approaches. Linkage prediction is handled with a frugal CNN-based model and a graph-solving algorithm is used to generate the scaffolds. Through our input's design, the model is able to both correct errors within assemblies and link contigs, leveraging small, local Hi-C contact matrices. We handled low-complexity regions that might induce erroneous predictions using an external tool, improving the overall accuracy of generated assemblies. On a benchmark of six various genomes and four standard metrics, SPA-C outperformed four out of four state-of-the-art methods while achieving comparable start-to-end computation time.Python and Bash scripts are available on GitHub (https://github.com/SPA-C/SPA-C.git) and Zenodo (https://doi.org/10.5281/zenodo.19000361).

22.
arXiv (quant-ph) 2026-06-12

New bounds on private simultaneous quantum message passing

arXiv:2606.12557v1 Announce Type: new Abstract: In the private simultaneous message (PSM) setting, $k$ players obtain inputs $x_i\in\{0,1\}^n$ and then each send messages to a referee, who should learn $f(x_1,...,x_k)$ but no other information about $(x_1,...,x_k)$. The PSM setting was introduced as a minimal model for secure multiparty computation and has connections to Boolean function complexity. In the quantum setting, PSM has been related to non-local quantum computation (NLQC). The communication and correlation cost of implementing PSM remains poorly understood. Here, we give new upper and lower bounds on the (quantum) PSM model. For lower bounds, we show: 1) Nečiporuk's measure lower bounds the entanglement required for $k$-player quantum PSM with perfect correctness. This leads to quadratic lower bounds for explicit functions. 2) The rank of the communication matrix of $f(x_1,x_2)$ lower bounds 2-player quantum PSM with perfect privacy but imperfect correctness. This implies a previously unknown lower bound on classical PSM with imperfect correctness. When allowing quantum communication and shared entanglement, these are the first lower bounds on quantum PSM that make use of the privacy condition. For upper bounds, we show: 1) Letting $s$ be the size of a quantum circuit computing $f$, $d_f$ be the circuit depth, $k$ the number of players, $n$ the number of bits received by each player, and $\epsilon$ a correctness parameter, we obtain $\mathsf{PSM}_k^*(f) \leq (kn +s) \cdot \log^{O(d_f)}(s/\epsilon)$. 2) The square of the Fourier 1 norm of $f$, $\Vert \hat{f}\Vert_1^2$, upper bounds the classical PSM complexity, $\mathsf{PSM}(f)\leq O(\Vert \hat{f} \Vert^2_1)$. In proving the first upper bound, we generalize existing $T$-depth based techniques for NLQC from $2$ to $k\geq 2$ parties, and consider cases where the Clifford layers are restricted to having small light cones.

23.
medRxiv (Medicine) 2026-06-10

Prediction of immunotherapy response using live tumor fragments from routine clinical biopsies

Functional ex vivo assays using live tumor tissues have demonstrated strong predictive accuracy for response to immune checkpoint inhibitors (ICIs) but are not scalable, requiring manual processing of large resections collected at academic centers. Here, an ex vivo live tumor fragment (LTF) platform was developed using standard-of-care biopsies from 228 patients with suspected malignancy collected across prospective, multicenter observational trials and biobanks. Hierarchical clustering of ICI-mediated changes in cytokine production identified two groups: responders and nonresponders. A binary classifier (elive index) using 8 cytokines achieved an AUC of 0.99 for cluster prediction. elive index correctly predicted clinical benefit in 93% (26/28) of patients (P = 3.2x10-5) and accurately identified 83% (10/12) of objective responders. Critically, elive responders were identified among biomarker-negative patients, highlighting the platform as a scalable approach that complements existing companion diagnostics and expands the population of patients identified to benefit from ICI therapy.

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

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

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

25.
bioRxiv (Bioinfo) 2026-06-11

ANCHOR: haplotype-aware allelic and isoform inference from single-cell long-read RNA sequencing with de novo variant calling

Long-read RNA sequencing enables haplotype- and isoform-resolved allelic analysis of transcriptomes, yet extending this capability to single cells and distinct cell types remains computationally challenging due to sparse coverage, sequencing errors, incomplete variant information, and reference-biased transcript assignment. Here we present ANCHOR, a haplotype-aware framework for single-cell long-read RNA sequencing that performs de novo expressed-variant discovery, molecule-level haplotype assignment and isoform-resolved allelic quantification. ANCHOR combines a signed-graph variant caller, pair hidden Markov modelling and beta-binomial UMI aggregation to infer parental allele counts for genes and splice-resolved isoforms, without requiring a pre-existing phased genotype or deep learning. In human single-cell long-read RNA benchmarks, ANCHOR improved variant-calling performance over tested long-read RNA callers at single-cell and low-to-moderate coverage, and its beta-binomial model reduced depth-driven false positives in allele-specific expression testing. Applied to newly generated single-cell long-read RNA-seq data from reciprocal mouse crosses during gastrulation, ANCHOR resolved cell-type- and isoform-specific parent-of-origin imprinting and identified an antagonistic maternally biased Sgce isoform. ANCHOR provides a general framework for allele- and isoform-resolved analysis of diploid single-cell long-read transcriptomes.