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

Frozen Foundation-Model Embeddings Discard Small-Lesion Signal in Chest Radiography: Implications for Pre-Deployment Evaluation

Frozen vision-transformer (ViT) foundation-model embeddings increasingly serve as the substrate for downstream chest-radiography (CXR) pipelines, yet where small-scale, low-contrast signal is retained or lost in the frozen forward pass has not been systematically quantified across architectures, pretraining domains, and objectives. We probed five frozen ViTs (RAD-DINO, DINOv2-B/14, DINOv3 ViT-7B, BiomedCLIP, MedSigLIP) and a frozen DINO-pretrained ResNet-50 architectural control across three large CXR cohorts (NIH-CXR14, MIMIC-CXR, Emory-CXR; aggregate pool n=492,724) and ChestX-Det10 (n=3,543; 1,462 small-lesion bounding boxes across Calcification, Nodule, Mass). Each model was evaluated with a small-scale-perturbation panel and a region-aware bounding-box-stratified probe on real lesions, comparing three pooling modes from the same forward pass: classification token (CLS), patch-mean (mean over all final-layer patch tokens), and bounding-box-restricted patch-local. On the perturbation panel, CLS embeddings sat at the chance floor (area under the ROC curve [AUC] 0.500-0.524); patch-mean was indistinguishable from CLS on iso-blur and reticular-fine cells but rose with CLS on larger directional-blur footprints, while disease AUC on globally decided tasks ranged 0.642-0.913. Patch-local probes recovered AUC ~1.0 from the same forward pass (per-model mean improvement +0.412 to +0.488); the ResNet-50 control reproduced the chance floor. On ChestX-Det10, image-level CLS classification showed within-class small-versus-large stratum gaps up to +0.243 AUC; bounding-box-level patch-local pooling on the same forward pass recovered AUC >= 0.899 on every (model x class) cell. Frozen ViT embeddings silently suppress small-scale signal at the global-aggregation step; the signal is recoverable from patch tokens conditional on a region of interest.

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

Trustworthy Multi-Agent Systems: Mitigating Semantic Drift with the Argent Signaling Protocol

When multi-agent LLM systems produce bad answers, not all failures are equal: some answers are grounded in the right material but incomplete, while others are simply ungrounded and should be stopped. Current retry strategies treat both cases identically (try again and hope for the best), leaving human supervisors unable to tell whether a retry was warranted or whether the system should have halted instead. We introduce the Argent Signaling Protocol (ASP), a compact machine-readable header that accompanies every AI-generated response with structured quality signals: certainty (@C), grounding (@G), stochasticity (@S), and an assumption index that classifies the evidentiary basis of each claim. These signals enable a controller to distinguish repairable failures from containment failures and route each case differently. We evaluate ASP in two modes. In standalone mode, a 27-question document-grounded QA benchmark over the Array BioPharma/Ono license agreement compares baseline prompts against ASP-instrumented controller actions across three local GGUF models. On Qwen~(0.8B), ASP improves pass rate from 11.1% to 33.3% and mean term coverage from 36.7% to 65.4%; on Dobby~(8B), ASP produces 4 fail-to-pass recoveries, raising pass rate from 33.3% to 44.4%; on SmolLM3~(3B), ASP alternates between repair and containment per question. Aggregate improvement is meaningful (12/81 to 21/81 passes). In multi-agent mode, an ASP sidecar sits between a retrieval agent and a downstream decision agent; the sidecar blocks 100% of ungrounded upstream outputs from reaching the downstream agent (24/27 blocked, 0 ungrounded propagations).

03.
arXiv (CS.AI) 2026-06-16

Who Drifted: the System or the Judge? Anytime-Valid Attribution in LLM Evaluation Pipelines

作者:

arXiv:2606.15474v1 Announce Type: new Abstract: Continuous evaluation of LLM products relies on a strong LLM judge treated as ground truth: a cheap monitor scores every interaction and a team is paged when the score drifts down. But the judge is itself a model behind an API, and a silent version bump or scoring-prompt update changes how it scores – so every drift alarm is ambiguous between a worse product and a changed judge. We resolve the ambiguity with a fixed, human-labeled anchor set that the current judge re-scores at a steady interleave, a second betting e-process on the judge-versus-human gap, and a guard-window rule returning a verdict in {none, system, judge}. We prove anytime-validity, one-way identification (only the judge can move the anchors), an attribution race whose design law is that the anchors must out-run the main process they guard, and process orthogonality. On two real judge changes, a silent version bump is detected as judge drift in 60/60 runs with zero judge-to-system misattribution, and a contaminating strict-prompt change is correctly attributed on 110 of 120 runs at guard width 300 – while the industry-default rolling z-test false-alarms on 75% of drift-free streams. Every experiment replicates on a second domain (TL;DR summarization) with nothing re-tuned, and where the domains differ the differences are the ones the race predicts: the strict-prompt change shifts scores harder there, so the anchors fire faster and attribution becomes perfect (240/240). The monitor runs at approximately 0.64 of the cost of strong-judging every item, or 0.21 in a cheaper-but-deafer regime.

04.
arXiv (CS.LG) 2026-06-15

DTVEM-RE: A Hierarchical Random-Effects Extension of the Differential Time-Varying Effect Model for Person-Specific Multi-Lag Estimation in Intensive Longitudinal Data

arXiv:2606.14116v1 Announce Type: new Abstract: The Differential Time-Varying Effect Model (DTVEM) of Jacobson et al. (2019) is a popular tool for finding the best time lag in intensive longitudinal data, but it assumes everyone shares the same lag structure. The original authors named fixing this as future work, and it clashes with the premise of modern clinical research, which is that people differ. We present DTVEM-RE, an extension that lets each person have their own lag coefficients, with two versions of the confirmatory step: a discrete-time hierarchical Bayesian VAR in Stan, which pools across people and gives calibrated uncertainty, and a continuous-time per-person Ornstein-Uhlenbeck model in ctsem, which handles unevenly spaced beeps directly. We report four results. A simulation shows the Bayesian version recovers the between-person spread tau_a with bias below 0.01 and coverage of 90 to 93 percent. On the Fisher et al. (2017) EMA dataset (N=40), person-specific lag-1 effects vary by an order of magnitude across three mood items, the Bayesian and GAMM estimates agree closely (r=0.87 to 0.92), and DTVEM-RE gives the best one-step-ahead prediction among four discrete-time methods. A multi-lag version shows all nine tau_k values have credible intervals excluding zero, and the lag where people differ most changes across items, something lag-1-only methods like mlVAR cannot detect. Finally, the two versions agree almost exactly on person-specific lag-1 estimates (r >= 0.995), differing only as shrinkage predicts. DTVEM-RE is, to our knowledge, the first person-specific implementation of DTVEM-style lag detection, and it contains standard DTVEM as a special case.

05.
arXiv (CS.AI) 2026-06-12

The Hidden Power of Scaling Factor in LoRA Optimization

arXiv:2606.12883v1 Announce Type: new Abstract: In Low-Rank Adaptation (LoRA), the scaling factor $\alpha$ is often treated as a mere complement to the learning rate, yet its role in optimization remains poorly understood. In this paper, we reveal that the scaling factor $\alpha$ and the learning rate function differently, with $\alpha$ emerging as the dominant driver of effective optimization, delivering gains that cannot be replicated by learning rate scaling alone. Through the synergy of extensive empirical analysis and a theoretical Signal-Drift framework, we uncover three findings into LoRA's scaling mechanism: First, LoRA's spectral suppression smooths the optimization landscape, rendering standard hyperparameters overly conservative and creating an optimization gap. Second, when leveraging this smoothness to accelerate convergence, $\alpha$ outperforms the learning rate by amplifying the task signal without increasing the drift ratio. Third, the optimal scaling factor follows a sublinear relationship with the rank, well characterized by a square-root law with an unexpectedly large coefficient, revealing the insufficient scaling of existing rank-tied heuristics. Based on these insights, we propose LoRA-$\alpha$, a minimalist framework that restores $\alpha$ to its principled regime, making LoRA compatible with standard small learning rates. Extensive evaluations across diverse tasks demonstrate that LoRA-$\alpha$ consistently improves performance while streamlining hyperparameter search, unleashing the learning potential of LoRA.

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

RelayFormer: A Unified Local-Global Attention Framework for Scalable Image and Video Manipulation Localization

Visual manipulation localization (VML) aims to identify tampered regions in images and videos, a task that has become increasingly challenging with the rise of advanced editing tools. Existing methods face two central issues. The first is resolution diversity. Resizing or padding can distort subtle forensic cues and introduce unnecessary computational cost. The second is the difficulty of extending spatial models for images to spatio-temporal inputs in videos, which often results in maintaining separate architectures for the two data types. To address these challenges, we propose RelayFormer, a unified framework that adapts to varying resolutions and naturally handles both static and temporal visual data. RelayFormer partitions inputs into fixed-size sub-images and introduces Global Local Relay (GLR) tokens that propagate structured context through a relay-based attention mechanism. This design enables efficient exchange of global cues, such as semantic or temporal consistency, while preserving fine-grained manipulation artifacts. Unlike prior approaches that depend on uniform resizing or sparse attention, RelayFormer scales to variable resolutions and video sequences with minimal overhead. Experiments across diverse benchmarks demonstrate superior performance and strong efficiency, combining resolution adaptivity without interpolation or excessive padding, unified processing for images and videos, and a favorable balance between accuracy and computational cost. Code is available at~\href{https://github.com/WenOOI/RelayFormer}{https://github.com/WenOOI/RelayFormer}.

07.
arXiv (quant-ph) 2026-06-11

Coupled integrated photonic quantum memristors using a single photon source made of a colour center

arXiv:2602.14736v2 Announce Type: replace Abstract: Photonic quantum memristors provide a measurement-induced route to nonlinear and history-dependent quantum dynamics. Experimental demonstrations have so far focused on isolated devices or simple cascaded devices configurations. Here, we experimentally realize and characterize a network of two coupled photonic quantum memristors with crossed feedback, implemented on a silicon nitride photonic integrated circuit and fed by a room-temperature single-photon source based on a silicon-vacancy color center SiV$^-$ in a nanodiamond. Each memristor consists of an integrated Mach-Zehnder interferometer whose transfer function is adaptively updated by photon detection events on another memristor, thus generating novel non-Markovian input-output dynamics with an enhanced memristive behaviour compared to single devices. In particular, we report inter-memristor input-output hysteresis curves exhibiting larger form factors and displaying self-intersecting loops, respectively revealing marked bistability and self-intersecting hysteresis geometry. Furthermore, numerical simulations show how these features emerge from the interplay between memory depth and relative input phase, for both intra- and inter-memristor input-output relations. We experimentally test the performance of our system in the NARMA task. Our results establish coupled integrated photonic quantum memristors as scalable nonlinear building blocks and highlight their potential for implementing compact quantum neuromorphic and reservoir computing architectures.

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

The Holistic Storage of Verb+Up Phrases in Text-based and Audio-based Language Models

A crucial aspect of linguistic capability is the ability to trade off between stored representations and abstract knowledge: one must retrieve learned representations, but also generate novel ones by applying productive rules. While recent work has examined abstract knowledge in language models, holistic storage of multi-word units has received far less attention. We probe internal representations in text-based LLMs and an ASR model, testing whether V+up phrasal verbs develop distinct representations as a function of frequency and predictability. All models show evidence of holistic storage driven by frequency and predictability, further supporting usage-based theories of language.

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

Probing Dec-POMDP Reasoning in Cooperative MARL

arXiv:2602.20804v2 Announce Type: replace Abstract: Cooperative multi-agent reinforcement learning (MARL) is typically framed as a decentralised partially observable Markov decision process (Dec-POMDP), a setting whose hardness stems from two key challenges: partial observability and decentralised coordination. Genuinely solving such tasks requires Dec-POMDP reasoning, where agents use history to infer hidden states and coordinate based on local information. Yet it remains unclear whether popular benchmarks actually demand this reasoning or permit success via simpler strategies. We introduce a diagnostic suite combining statistically grounded performance comparisons and information-theoretic probes to audit the behavioural complexity of baseline policies (IPPO and MAPPO) across 37 scenarios spanning MPE, SMAX, Overcooked, Hanabi, and MaBrax. Our diagnostics reveal that success on these benchmarks rarely requires genuine Dec-POMDP reasoning. Reactive policies match the performance of memory-based agents in over half the scenarios, and emergent coordination frequently relies on brittle, synchronous action coupling rather than robust temporal influence. These findings suggest that some widely used benchmarks may not adequately test core Dec-POMDP assumptions under current training paradigms, potentially leading to over-optimistic assessments of progress. We release our diagnostic tooling to support more rigorous environment design and evaluation in cooperative MARL.

10.
arXiv (CS.AI) 2026-06-18

Two-Phase Bilevel Search for the Moving-Target Traveling Salesman Problem with Moving Obstacles

arXiv:2606.18730v1 Announce Type: cross Abstract: The Moving-Target Traveling Salesman Problem (MT-TSP) seeks a minimum cost trajectory for an agent that departs from a static depot, visits a set of moving targets, each within one of their assigned time windows, and returns to the depot. In this article, we study the Moving-Target Traveling Salesman Problem with Moving Obstacles (MT-TSP-MO), a generalization of the MT-TSP where the agent trajectory must avoid moving obstacles. We present a Mixed-Integer Conic Programming (MICP) formulation that can be solved using off-the-shelf solvers, as well as a fast and scalable Two-Phase Bilevel Search (TPBS) algorithm that computes high-quality feasible solutions for the problem. We evaluate our approaches against an existing baseline algorithm on a broad range of problem instances with up to 40 targets and 40 obstacles. The results demonstrate that both the proposed methods significantly outperform the baseline with respect to success rates, solution costs, and computation time.

11.
arXiv (CS.AI) 2026-06-16

Intrinsic Computational Functionalism and Simulated Consciousness

arXiv:2606.15348v1 Announce Type: cross Abstract: A common objection to artificial or simulated consciousness is that a simulated brain is no more conscious than simulated water is wet. We address this from the perspective of Intrinsic Computational Functionalism (ICF): if consciousness is computationally constituted, it depends not on externally imposed descriptions but on the computational structures a system physically realizes in virtue of its own causal-dynamical organization. In previous work we developed Canonical Functionalism as a mathematically precise special case of this anti-interpretivist program, identifying functional states by their complete future input-output roles under a fixed interface. Here we argue that this input-output construction, though important, is incomplete: as a behavioral boundary case of ICF, it makes lookup tables and unfolded systems that preserve the same boundary behavior canonically equivalent. A consciousness-relevant canonical representation must instead include internal mechanisms, interventions, and joint readouts belonging to the relevant intrinsic organization. We therefore define a mechanism-enriched canonical structure and use it to formulate Intrinsic Causal-Computational Realization (ICCR), a realization relation preserving physical implementation, intrinsic state individuation, transition structure, intervention profiles, and the relevant agent-body-world boundary. The central result is conditional: if conscious properties are invariants of intrinsic causal-computational organization, then any system satisfying ICCR realizes the same consciousness-relevant properties, whether biological, artificial, or simulated. We discuss objections including biological naturalism and integrated information theory. We conclude that to deny consciousness to a simulation, one must identify a consciousness-relevant intrinsic causal-computational structure that the simulation fails to realize.

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

An End-to-End Hybrid Framework for Rumour Detection in Low-Resources Algerian Dialect

The rapid growth of social media has intensified the spread of rumours. This issue is more challenging in the Algerian context due to the informal and code-switched nature of dialectal content, the scarcity of annotated resources, and the limited effectiveness of standard Arabic NLP tools on dialect text. This paper presents an end-to-end rumour detection hybrid framework for Algerian dialect social media content. We build a domain-specific annotated dataset by combining real social media posts, synthetic data, and the FASSILA corpus, with automatic labeling based on a similarity-based annotation process. A transliteration pipeline is also introduced to generate parallel datasets in Arabic script and Arabizi. We evaluate multiple approaches, including classical machine learning, deep learning, transformers, and hybrid models. Experimental results show that a hybrid approach combining transformer embeddings with a classical classifier achieves the best performance, reaching an F1-score of 0.84. We also find that domain-specific pre-training is more important than model size, with social media-trained models outperforming larger models trained on formal Arabic corpora. These results demonstrate the feasibility of rumour detection in low-resource Algerian dialect settings.

14.
arXiv (CS.AI) 2026-06-11

WeaveBench: A Long-Horizon, Real-World Benchmark for Computer-Use Agents with Hybrid Interfaces

arXiv:2606.09426v2 Announce Type: replace Abstract: Computer-use agents (CUAs) increasingly operate in runtimes that combine visual desktop control, command-line execution, code editing, browsers, and external tools. Existing benchmarks, however, often evaluate these interfaces as separable capabilities, leaving long-horizon cross-interface orchestration under-tested. Thus, we introduce WeaveBench, a long-horizon hybrid-interface benchmark with 114 tasks across 8 real-world work domains, grounded in real user requests and publicly verifiable artifacts. Each task requires agents to combine GUI observations/actions with CLI/code operations within a single trajectory. We evaluate these tasks on a real Ubuntu desktop inside deployed CLI-agent runtimes, augmented with a minimal desktop-control plugin. We also propose a companion trajectory-aware judge that inspects deliverables, files, screenshots, logs, and action traces, while detecting shortcut behaviors such as fabricated visual evidence or hard-coded metrics. Across frontier model-runtime pairings, the best PassRate reaches only 41.2%, showing the benchmark remains far from saturated. The trajectory-aware judge further reveals that outcome-only grading substantially overestimates agent performance. Overall, WeaveBench exposes a critical gap in CUA evaluation and provides an effective testbed to measure whether agents can orchestrate GUI, CLI, and code operations across long-horizon real-world tasks.

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

HAMON: Passive Optical Sequence Mixing for Long-Horizon Forecasting

arXiv:2606.17028v1 Announce Type: cross Abstract: Simple linear and frequency-domain models remain surprisingly competitive in long-horizon time-series forecasting, and recent mechanistic evidence suggests that standard forecasting benchmarks may not require the dense superposed representations that make transformers powerful in other domains. This raises a substrate-level question: if the core forecasting operator is often low-complexity and approximately linear, does it need to be implemented as learned digital temporal mixing? We introduce HAMON, a passive diffractive optical forecasting core in which historical values are encoded onto an optical aperture, future positions are left dark, and cascaded trainable phase masks with free-space diffraction shape the forecast directly in the output field. At inference, prediction is performed by a single passive optical propagation pass with no trainable digital sequence-mixing layer. Across standard benchmarks, HAMON outperforms the strongest digital baselines considered on ETTm2 at all horizons and on ETTh2 at all but the longest horizon, improving MSE by up to 14\% and doing so consistently across horizons rather than at isolated points. It is competitive on Weather and trails the strongest baselines on the remaining ETT settings and on the high-channel-count Traffic and Electricity datasets. Phase encoding, intensity-compatible readout, and phase-scrambling ablations, together with a TorchOptics cross-simulator check, indicate that the forecasts arise from the data-bearing optical field rather than from a digital forecasting head. Because the passive core uses standard Fourier optics, HAMON defines a concrete target for optical hardware and for passive physical sequence mixing.

16.
arXiv (CS.LG) 2026-06-11

Urban Heat MiniCubes: An AI-Ready dataset for urban heat research

arXiv:2606.11534v1 Announce Type: cross Abstract: Urban heat is amplified by impermeable surfaces and heterogeneous built environments, yet street-level variability remains difficult to quantify because multi-sensor observations are rarely available in consistent, analysis-ready form at the necessary spatiotemporal scales. We present "Urban Heat MiniCubes," a publicly available, FAIR-oriented dataset designed for machine learning applications in urban heat research. The dataset provides harmonized 90 x 90 km gridded data cubes for 48 cities in the Western Hemisphere spanning 2022-2023, with variables reprojected and collocated to a common grid to reduce preprocessing (e.g., reprojection, resampling, and spatiotemporal alignment). Urban Heat MiniCubes includes two complementary modalities: (i) higher-spatial-resolution, lower-frequency observations from Landsat 8/9 (e.g., surface reflectances) and Sentinel-1 (e.g., synthetic aperture radar backscatter), and (ii) higher-temporal-frequency, coarser observations from GOES-R (e.g., longwave infrared brightness temperatures) and a microwave land surface temperature product. We document variables and metadata and provide technical assessment using inter-variable analyses and autoencoder-based reconstruction-error summaries across pixel classes (e.g., water and cloud). Potential use cases and limitations are also discussed.

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

Mean-Field Parallel Decoding for Discrete Diffusion Language Models

arXiv:2606.15805v1 Announce Type: new Abstract: Discrete diffusion language models enable parallel token generation, offering a pathway to low-latency decoding. However, selecting tokens independently by marginal confidence limits effective parallelism: tokens that appear reliable in isolation can form incompatible configurations when several positions are updated at once. We introduce a training-free decoding framework that coordinates these parallel updates. At each forward pass, the method assigns a commit score to each masked position and refines these scores using pairwise interactions derived from the model's predictive distributions. A variational relaxation yields a simple fixed-point update that suppresses conflicting simultaneous commitments within a single forward pass. This mechanism allows the decoder to commit more tokens in parallel while maintaining competitive generation quality. The method is lightweight, requires no auxiliary model or retraining, and drops into existing diffusion decoding pipelines without modification. Experiments on reasoning and code-generation benchmarks show consistent improvements in the quality-latency trade-off.

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

MUFFLe: Efficient Model Update Compression via Generalized Deduplication for Federated Learning

arXiv:2606.14354v1 Announce Type: new Abstract: Federated learning is well suited to edge environments but is often limited by the uplink cost of transmitting model updates. This Work-in-Progress paper presents MUFFLe, a communication-efficient update compression scheme that integrates generalized deduplication (GD) into the FedAvg pipeline. MUFFLe deduplicates repeated patterns across the update vector, yielding a fixed-rate, variable-count compression scheme. Preliminary experiments on IID MNIST with 20 clients show that MUFFLe reaches the target accuracy of $92.93\%$ with 38~MB cumulative uplink communication, compared with 75~MB for 8-bit quantization, 86~MB for Top-$k$ sparsification, and 310~MB for uncompressed FedAvg. These results demonstrate the feasibility of applying GD to communication-efficient federated learning.

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

Do we have the knowledge we need? Rethinking human-AI decision-making in corporations

arXiv:2606.15575v1 Announce Type: new Abstract: Organizational knowledge is fragmented across a variety of software systems, tacit expertise, and manual documents that have traditionally been designed for human consumption. As AI systems are increasingly deployed and granted decision-making roles, they require access to this knowledge. This raises two questions: how should organizations store and maintain knowledge so that it remains accessible to both humans and future AI systems, and how should agency be allocated between humans and AI across tasks with different risks and levels of uncertainty? In this position paper, we describe how organizational knowledge evolves and contribute a framework that maps task attributes and knowledge availability to recommended agency allocations and control mechanisms. We illustrate the applicability of the framework on two different manufacturing tasks: a routine operation (visual quality inspection) and a one-off strategic decision (factory location), and conclude with opportunities for future research.

20.
arXiv (CS.LG) 2026-06-16

Taming Curvature: Architecture Warm-Up for Stable Transformer Training

arXiv:2606.16768v1 Announce Type: new Abstract: Training billion-parameter Transformers is often brittle, with transient loss spikes and divergence that waste compute. Even though the recently developed Edge of Stability (EoS) theory provides a powerful tool to understand and control the stability of optimization methods via the (preconditioned) curvature, these curvature-controlling methods are not popular in large-scale Transformer training due to the complexity of curvature estimation. To this end, we first introduce a fast online estimator of the largest (preconditioned) Hessian eigenvalue (i.e., curvature) based on a warm-started variant for power iteration with Hessian-vector products. We show theoretically, and verify empirically, that the proposed method makes per-iteration curvature tracking feasible at billion parameter scale while being more accurate. Using this tool, we find that training instabilities coincide with surges in preconditioned curvature and that curvature grows with depth. Motivated by these observations, we propose architecture warm-up: progressively growing network depth to carefully control the preconditioned Hessian and stabilize training. Experiments on large Transformers validate that our approach enables efficient curvature tracking and reduces instabilities compared to existing state-of-the-art stabilization techniques without slowing down convergence.

21.
medRxiv (Medicine) 2026-06-16

A Poisson Process Life Expectancy framework for optimising patient lifetime during chemotherapy

Cancer therapy balances between two competing objectives - treatment efficacy against the tumour and the risk of treatment related severe adverse events, including patient death. Most existing optimal control theory (OCT) formulations rely on optimising heuristic cost functionals that lack direct clinical interpretability. In clinical practice treatment efficacy and patient tolerability are primarily assessed through survival metrics and adverse event rates. Here we introduce the Continuous Lifetime Payoff (CLP), a novel OCT objective functional that directly links treatment decisions to patient survival. It explicitly incorporates tumour dynamics, tumour eradication, and patient mortality from tumour progression, drug-related toxicity and age. We fit age-related mortality from life tables and infer parameters from simulated survival data. The CLP provides a clinically grounded framework for optimising chemotherapy regimens.

22.
bioRxiv (Bioinfo) 2026-06-18

segSHAPE: RNA secondary structure prediction from nanopore direct RNA sequencing

RNAs adopt complex structures that regulate key biological processes, making accurate structure prediction essential. Chemical probing coupled with Nanopore direct RNA sequencing (DRS) offers a route to single-molecule structural inference, but current tools are limited by inaccurate signal-to-sequence alignment, which degrades modification-rate estimation and downstream structure prediction. Here we introduce segSHAPE for RNA secondary structure prediction from Nanopore DRS data (both RNA002 and RNA004 chemistries), a probe-agnostic framework that improves signal alignment using prior information of basecalling and per-read signal baseline shift correction, learns position-specific k-mer raw signal parameters, and estimates per-nucleotide modification rates with an unsupervised anomaly detector. On three public RNA002 DRS datasets spanning different chemical probes (AcIm, NAI-N3) and RNAs from 421 to 1552 nt, segSHAPE achieves the highest F1 score and Matthews correlation coefficient (MCC) on all RNAs, exceeding the strongest baseline by 3.4 to 5.8 percentage points in MCC. It additionally captures the ligand-induced conformational change of the thiamine pyrophosphate (TPP) riboswitch RNA directly from RNA002 DRS data using the DEPC probe. On a public RNA004 DRS dataset, segSHAPE improves over the sm-PORE-cupine baseline by 17 ROC-AUC points in modification rate estimation and by 6.7 MCC points in structure prediction. These results establish segSHAPE as a unified, probe-agnostic pipeline for RNA structure prediction from Nanopore DRS data.

23.
medRxiv (Medicine) 2026-06-18

Plasma proteomics reveals clinical and mechanistic heterogeneity among individuals who develop coronary artery disease

BACKGROUND: Individuals who develop coronary artery disease (CAD) are clinically and mechanistically heterogeneous, and understanding this variation is crucial for precise risk stratification and tailored interventions. However, the molecular mechanisms that connect these two kinds of heterogeneity remain unclear, limiting progress toward biologically grounded risk stratification and targeted interventions. Here, we investigated the heterogeneity of individuals who develop CAD by leveraging plasma proteomic signatures, placed individuals along continuous metabolic gradients and revealed the molecular programs underlying these patterns, thereby linking mechanistic variation to clinical heterogeneity. METHODS AND RESULTS: From 42,803 UK Biobank participants, including 3,713 individuals who developed CAD within 10 years (incident CAD), we first identified a 320-protein panel from 2,923 baseline proteins that improved prediction of incident CAD beyond clinical risk scores. Using reverse graph embedding, we reduced the proteomic data to two dimensions and mapped each incident case onto the resulting two-dimensional latent proteomic space. These proteomic dimensions show significant associations with cardiometabolic and kidney-related clinical markers. The patterns were replicated in the EPIC-Norfolk study. Phenome-wide Cox regression analyses further linked these proteomic dimensions to 10-year incidence rates for various diseases, including type 2 diabetes, obesity, and chronic kidney disease (CKD). Furthermore, adding the proteomic dimensions to clinical variable-based Cox regression model improved prediction of 10-year incidence of CKD and other diseases, demonstrating the value of proteomic dimensions beyond conventional clinical risk factors. Moreover, individuals with prevalent CAD (diagnosed before proteomic sampling) exhibited high, metabolically adverse dimension values, indicating that these axes capture cumulative metabolic burden. Pathway enrichment analyses implicated altered extracellular matrix organization and immune programs among the proteins contributing to the proteomic dimensions. CONCLUSIONS: Our findings demonstrate that plasma proteomic signatures can dissect the heterogeneity of individuals who develop CAD in continuous phenotypic gradients, improve prediction of CAD and comorbidities, and map underlying biological mechanisms.

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

The Stable Recovery Manifold: Geometric Principles Governing Recoverability in Continual Learning

arXiv:2606.13637v1 Announce Type: new Abstract: Catastrophic forgetting is often viewed as the destruction of previously learned knowledge during sequential learning. Building on the Accessibility Collapse framework, we investigate the geometric structure of recoverability in continual learning. Using Split CIFAR-100 and a sequentially trained ResNet-18, we analyze recoverability, representational drift, and recovery complexity across ten tasks. We introduce Recovery Subspace Dimensionality (k_t), a measure of the minimum number of singular directions required to preserve 90 percent of full probe performance. Contrary to our Recoverability Diffusion hypothesis, recovery dimensionality remains stable throughout training (mean k_t = 8.0) despite substantial representational drift. Principal-angle drift strongly predicts recoverability (r = -0.862), and a simple geometric model explains 82.2 percent of recoverability variance. These findings support the Stable Recovery Manifold hypothesis, suggesting that forgotten knowledge remains compactly decodable despite representational reorganization. The results indicate that catastrophic forgetting is primarily an accessibility and manifold-alignment problem rather than information destruction.

25.
arXiv (quant-ph) 2026-06-11

Machine-learned, finite temperature Fermi-operator expansions suitable for GPUs and AI-hardware

arXiv:2605.08523v2 Announce Type: replace Abstract: We present several finite-temperature recursive Fermi-operator expansion schemes based on the second-order spectral projection (SP2) method. Our approach builds on a previous observation that the electronic structure problem, as formulated through a recursive SP2 expansion, can be mapped onto the architecture of a deep neural network. Using this perspective, we generalize SP2 to finite electronic temperatures by constructing machine learning models that determine optimized recursive expansion coefficients. The same approach is also applied to the prediction of the electronic entropy for fractional occupation numbers. The coefficients are trained for a specified chemical potential and electronic temperature and are not available in closed analytical form. However, by employing an appropriate affine rescaling strategy to the Hamiltonian matrix, we eliminate the need to retrain the model for different temperatures and chemical potentials. Our approach avoids explicit diagonalization and relies solely on highly optimized matrix-matrix multiplication kernels. Compared to state-of-the-art diagonalization, we achieve an order-of-magnitude speedup in the single-particle finite-temperature density matrix calculation for small and moderately sized matrices on modern GPUs and dense matrix multiply units.