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01.
arXiv (math.PR) 2026-06-11

On the structure of the sandpile identity element on Sierpinski gasket graphs

arXiv:2603.12006v2 Announce Type: replace-cross Abstract: We consider the identity of the abelian sandpile group of finite approximation graphs of the Sierpinski gasket, and we show that the second-order term in the scaling limit converges to the path distance to the nearest corner on the Sierpinski gasket. The proof relies on a decomposition of the identity of the sandpile group into the sum of a constant function and the Laplacian of the graph distance on the approximating graphs.

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

Imitating What Works: Simulation-Filtered Modular Policy Learning from Human Videos

The ability to learn manipulation skills by watching videos of humans has the potential to unlock a new source of highly scalable data for robot learning. Here, we tackle prehensile manipulation, in which tasks involve grasping an object before performing various post-grasp motions. Human videos offer strong signals for learning the post-grasp motions, but they are less useful for learning the prerequisite grasping behaviors, especially for robots without human-like hands. A promising way forward is to use a modular policy design, leveraging a dedicated grasp generator to produce stable grasps. However, arbitrary stable grasps are often not task-compatible, hindering the robot's ability to perform the desired downstream motion. To address this challenge, we present Perceive-Simulate-Imitate (PSI), a framework for training a modular manipulation policy using human video motion data processed by paired grasp-trajectory filtering in simulation. This simulation step extends the trajectory data with grasp suitability labels, which allows for supervised learning of task-oriented grasping capabilities. We show through real-world experiments that our framework can be used to learn precise manipulation skills efficiently without any robot data, resulting in significantly more robust performance than using a grasp generator naively.

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

Improved Knowledge Distillation for Land-Use Image Classification

In the present article, an improved Knowledge Distillation (KD) framework has been proposed for efficient compression of deep convolutional neural networks for land-use image classification task. Motivated by the need to achieve competitive classification accuracy while reducing computational complexity, a teacher-student learning paradigm is adopted in which a VGG16 network transfers knowledge to a lightweight MobileNetV2 model. The proposed framework integrates hard supervision from ground truth labels with a soft supervision strategy that combines Kullback-Leibler divergence and Cosine Similarity losses. Experiments conducted on three land-use datasets show that the proposed KD-based method yields improved performance, and achieves an accuracy of 99.04%, outperforming both baseline student training and single-loss distillation approaches, while retaining substantial model compression.

04.
arXiv (CS.CV) 2026-06-16

An Open-Source Monitoring Framework for Data Exploration and Progress Tracking in Multi-Center Radiology Studies

Multi-center studies are crucial for advancing medical and radiological research. Data exploration, collaboration discovery, and study progress monitoring are essential for maximizing their potential. However, in practice these processes often rely on manual communication and shared tables, which quickly become outdated and hinder efficient coordination in large distributed studies. This highlights the need for dedicated monitoring solutions that provide transparent and up-to-date insights into study progress. We propose a lightweight, open-source monitoring architecture for multi-center studies based on the widely used Grafana-Prometheus stack. The framework collects aggregated monitoring metrics from distributed study sites and visualizes them through configurable dashboards. As a real-world deployment example, the framework is integrated into the medical imaging platform Kaapana and evaluated within a large multi-center research network. By deploying our solution within the Germany-wide RACOON consortium, we demonstrate its ability to enable privacy-preserving data exploration and study progress monitoring across all 38 German university clinics. The monitoring framework supports transparent coordination of distributed research activities and can facilitate more efficient management of large-scale multi-center studies. The source code and Kaapana integration are publicly available at https://github.com/MIC-DKFZ/study-monitoring-kaapana.

05.
bioRxiv (Bioinfo) 2026-06-16

Physics-Driven Zero-Shot Reconstruction of Isotropic 3D Fluorescence Microscopy under Undersampled Acquisition

Three-dimensional (3D) imaging represents the development of next generation of fluorescence microscopy. However, routine axial down-sampling makes isotropic resolution unrealistic. Here, we propose DeepUI, a physical zero-shot framework designed to achieve isotropic 3D fluorescence images from a low axial sampling rate. DeepUI fully leverages the intrinsic characteristics of 3D images through physics-guided degradation, which incorporates spatial-frequency joint learning to generate a scaled optical transfer function, combined with noise degradation and an up-sampling branch. Typically requiring just 5 minutes for training and 0.5 minutes for high-throughput and fast prediction, we demonstrate the superior performance of DeepUI to get isotropic results, and the exclusivity to axial down-sampling conditions, even in more challenging conditions, including defocused background, noise, and resolution blur.

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

Quantum Logic Codes: Complete Transversal Logical Clifford Instruction Sets for High-Rate Stabilizer Quantum Error Correcting Codes

Authors:

arXiv:2606.13521v1 Announce Type: new Abstract: We study the structure and transversal logical capabilities of stabilizer quantum error correcting codes. Among our results, we identify universal lower bounds on circuit depth to generate a full logical Clifford algebra, and develop novel constructions of logical transversal gates including a new depth-one transversal phase $\mathrm{\overline{S}}$ gate in the rotated surface code and a depth-one intra-block $\mathrm{\overline{CZ}}$ gate in the 2D-toric code that generalizes to all odd distances and all lengths $L\ge3$, respectively. Finally, we construct a high-rate non-LDPC CSS code family with parameters $[[n,\sqrt{n},\Theta({n^{\beta}})]]$ where $\beta \approx 0.2823$ in one demonstrated case, that provably possesses a constant-depth complete 2-local transversal logical Clifford basis instruction set architecture (ISA) composed of all individually targeted $\mathrm{\overline{S}}$, $\mathrm{\overline{SHS}} = \sqrt{X}$, and $\mathrm{\overline{CZ}}$ gates. This ISA is depth-one for certain subfamilies that we design and generally constant-depth under certain conditions. The code family is built from a small code with parameters $[[n_0, 2, d_0]]$, and is tunable in the standard way: it tiles out to form utility-scale logical qubit counts, and it scales up through concatenation to achieve higher distances and error suppression. We show that this construction preserves the depth-one complete transversal logical Clifford basis ISA when composed with these commuting construction actions, inheriting structure from the core codes so that at scale the complete logical Clifford basis ISA remains depth-one up to depth-two addressable operations between tiled cores. We call these Quantum Logic Codes.

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

TrustedARI: Towards Trust-Native Agentic Routing Infrastructure for Agentic AI

arXiv:2606.15822v1 Announce Type: new Abstract: AI agents increasingly access external models, tools, and services through Agentic Routing Infrastructure (ARI) to manage the overhead of heterogeneous interfaces and fragmented subscriptions. Yet, the architecture of ARI introduces fundamental trust risks: it obtains plaintext access to agent queries and service responses, while leaving agents unable to verify that their queries are routed to intended service providers or that requests and responses remain untampered. To address this problem, we present TrustedARI, the first trust-native agentic routing infrastructure for agentic AI. Architecturally, TrustedARI is built upon three core innovations: (i) an ARI-adapted three-party TLS handshake that enables the agent and ARI to jointly authenticate the service provider through role-specific distribution of TLS key materials; (ii) a privacy-preserving query-construction protocol that allows the agent and ARI to collaboratively construct well-formed queries without exposing their respective private inputs; and (iii) a verifiable billing protocol that supports fair usage-based settlement while preserving the integrity and confidentiality of service responses. We implemented and extensively evaluated a prototype of TrustedARI to validate its performance. Experiments confirm that TrustedARI is highly efficient: our ARI-adapted handshake protocol reduces communication overhead by 39.34% compared to the existing three-party TLS handshake. Furthermore, the privacy-preserving query-construction protocol imposes negligible overhead-averaging 0.19 seconds in computation time and 0.58 MB in communication costs-while the verifiable billing protocol speeds up proof generation by 28.20x. Crucially, TrustedARI is readily deployable without any modification to the service providers.

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

Testing For Distribution Shifts with Conditional Conformal Test Martingales

arXiv:2602.13848v2 Announce Type: replace Abstract: We propose a sequential test for detecting arbitrary distribution shifts that allows conformal test martingales (CTMs) to work under a fixed, reference-conditional setting. Existing CTM detectors construct test martingales by continually growing a reference set with each incoming sample, using it to assess how atypical the new sample is relative to past observations. While this design yields anytime-valid type-I error control, it suffers from test-time contamination: after a change, post-shift observations enter the reference set and dilute the evidence for distribution shift, increasing detection delay and reducing power. In contrast, our method avoids contamination by design by comparing each new sample to a fixed null reference dataset. Our main technical contribution is a robust martingale construction that remains valid conditional on the null reference data, achieved by explicitly accounting for the estimation error in the reference distribution induced by the finite reference set. This yields anytime-valid type-I error control together with guarantees of asymptotic power one and bounded expected detection delay. Empirically, our method detects shifts faster than standard CTMs, providing a powerful and reliable distribution-shift detector.

09.
arXiv (CS.AI) 2026-06-19

The Hidden Evolution of Disguised Visual Context inside the VLM

arXiv:2606.20077v1 Announce Type: cross Abstract: Visual tokens enter Large Language Models (LLMs) as raw, foreign signals. How they are transformed into meaningful representations and interact with the language space depends entirely on the integration architecture. Whether by treating visual tokens as in-context prompts within the input sequence or injecting them directly into the LLM's intermediate layers. A controlled comparison and understanding of how these architectural choices affect visual information and its internal transformation to integrate with the LLM remains underexplored. We provide a fair comparison by evaluating in-context and layer-wise injection VLM integration paradigms under identical training conditions across single image, multi-image, and video benchmarks. In doing so, we uncover a hidden evolution where visual tokens enter the LLM as disguised visual context, raw representations lacking linguistic structure, but are progressively reshaped depending on the integration paradigm, each capturing fundamentally different frequency characteristics of the visual signal. We show that this evolution inside the LLM determines what visual features the VLM can utilize effectively, how visual representations align with the language space, and ultimately how each paradigm performs across different tasks. We further demonstrate that attention allocation alone is insufficient, and that performance is driven by the quality of visual representations at each layer.

10.
medRxiv (Medicine) 2026-06-16

The Target48 Neurodegeneration Panel: A Novel Tool for Profiling Protein Signatures in Neurodegenerative Disorders

Introduction: Novel tools for absolute quantification of established and emerging fluid neuro-biomarkers are required to advance diagnostic studies and improve biological insights. Methods: We conducted an extensive analytical and clinical validation of the Olink Target 48 Neurodegeneration panel (T48 Neuropanel) in 352 paired CSF and plasma samples from cognitively unimpaired controls (CU), Alzheimer dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), n=44 per group. Comparisons with benchmark assays were performed. Results: Good detectability (CSF: 31 out of 42 assays; plasma: 38 out of 42 assays) and technical performance was observed. Benchmark assays showed good correlations, supporting method transformation formulas. Next to emerging biomarkers (MMP10, ITGB2), discriminative performance was excellent in AD: CSF pTau217: AUC=1; FTD: plasma NfL: AUC=0.952; and DLB: CSF DDC: AUC=0.901. Discussion: This analytical and clinical validation of the T48 Neuropanel highlights initial cut-offs and emerging biomarkers to aid clinical studies for the diagnosis, prognosis, and monitoring of neurodegenerative diseases. Highlights: The T48 Neuropanel shows robust analytical performance, with high detectability across both plasma and CSF matrices. The T48 Neuropanel validates established (i.e., pTau217, Abeta42, NfL, and GFAP) and emerging biomarkers (i.e., DDC, MMP10, ITGB2, ITGAM, NPTX2, NPTXR, SMOC1, sTREM1, and sTREM2) in CSF and plasma. CSF NfL, GFAP, ITGB2, and ITGAM and plasma GFAP were dysregulated across AD, FTD, and DLB dementias. -The multiplex design of the T48 Neuropanel enables rich biological interpretation by simultaneously quantifying established and emerging neurodegeneration biomarkers. Importantly, the inclusion of absolute quantification facilitates the establishment of cut-offs, supporting its potential for clinical translation.

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

HeteRo-Select: Informativeness as the Participation Driver in Heterogeneous Federated Learning

arXiv:2508.06692v2 Announce Type: replace Abstract: Federated learning systems typically allocate gradient compression by link speed. This is sensible when bandwidth and data informativeness align. However, under non-IID data, these signals often decorrelate or invert. A bandwidth-driven allocator then risks compressing the most informative gradients hardest. We propose HeteRo-Select, a framework that replaces bandwidth with a per-client informativeness score as the primary driver of compression. The score jointly governs three decisions per round: client selection, compression ratio, and server aggregation weight, with bandwidth retained only as a hard ceiling. Score-proportional selection provably reduces the effective heterogeneity of the chosen subset; score-proportional compression provably lowers aggregate top-$k$ error at fixed traffic. Under the exact FedCG simulation protocol, HeteRo-Select delivers a $1.78\times$ speedup and an $18.2\%$ reduction in traffic on CIFAR-10. The same configuration, unchanged, scales from a $7{,}850$-parameter logistic regression to an $11.27$M-parameter ResNet-18, hitting the accuracy target on three of four benchmarks. When bandwidth and informativeness are deliberately anti-correlated, the method still achieves the target accuracy with less traffic than the normal-bandwidth run.

12.
arXiv (CS.AI) 2026-06-18

A Variational Framework for LLM Generator-Regulator Games

Authors:

arXiv:2606.18424v1 Announce Type: cross Abstract: This paper develops a variational framework for regulated language generation. Starting from autoregressive token sampling, we derive the induced distribution over complete messages and relate it to an entropy-regularized Gibbs law. Regulation is modeled as an optimal discriminator whose convex-dual value is an f-divergence, and the generator-regulator interaction is formulated as a saddle-point problem. The framework applies to moderation, censorship, AI deception detection, compliance auditing, phishing defense, and manipulation control, where regulation concerns a distribution over possible messages rather than a single output. The equilibrium clarifies the tradeoff among utility, entropy, regulatory alignment, and finite-length detectability. Two finite-vocabulary case studies, censorship filtering and phishing defense, illustrate how the theory can be evaluated through utility, entropy, divergence, receiver-side scores, and detection probability.

13.
arXiv (CS.AI) 2026-06-15

YeasierAgent: Agentic Social Sandbox as a Canvas for Intent-Driven Creation of Platform-Agnostic Symbiotic Agent-Native Applications

Authors:

arXiv:2606.13722v1 Announce Type: new Abstract: This paper introduces YeasierAgent, an application-building paradigm based on symbiotic agents, narrative worlds, and scene-aware interaction. It challenges the conventional device-coupled model of software by redefining applications as collaborative spaces among users, agents, and worlds. We present a system architecture that achieves two primary contributions: (1) enabling the rapid, cross-platform construction of agent-native applications by utilizing platform-agnostic interactive units (agents, scenes, dialogue) rather than fixed graphical layouts; and (2) unifying the emotional companionship and practical tool execution attributes of intelligent agents within a single experiential sandbox. By integrating automated generation, user-created worlds, and spatial multi-agent collaboration, YeasierAgent formalizes the category of Symbiotic Agent-Native Applications, demonstrating a shift from isolated, tool-specific chatbots toward cohesive, socially embedded computational environments.

14.
Nature (Science) 2026-06-10

Human migration has surged since 2000 — these maps reveal where people are going

Authors:

Modelling with artificial-intelligence tools has filled gaps in migration data, revealing detailed global population movements from 1990 to 2023. Modelling with artificial-intelligence tools has filled gaps in migration data, revealing detailed global population movements from 1990 to 2023.

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

Physics-conforming Latent Twins

arXiv:2606.15053v1 Announce Type: new Abstract: Surrogate models are central to scientific machine learning, where they enable fast prediction, simulation, inference, and control for complex physical systems. For time-dependent problems, however, accurate interpolation of training trajectories is not sufficient: reliable surrogates should also respect the conservation laws, invariants, admissibility conditions, and dissipative structures that give those trajectories physical meaning. We introduce Physics-conforming Latent Twins, a framework for learning latent surrogate solution operators whose dynamics satisfy selected physical principles by design. The method builds on the Latent Twin formulation by jointly learning an encoder, a decoder, and a latent flow map between arbitrary time-indexed states, while constraining the latent dynamics to preserve or dissipate prescribed structural quantities. We develop a constraint-transfer viewpoint that connects physical structure in the original state space with compatible constraints in latent space, and prove structure-preservation bounds showing how latent enforcement improves control of physical defects after decoding. We also derive algebraic conditions for latent flow maps that preserve linear and quadratic invariants or enforce dissipative inequalities. Numerical experiments on representative ODE and PDE benchmarks demonstrate improved constraint satisfaction, structural fidelity, and qualitative long-time behavior while maintaining accurate surrogate prediction.

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

No Universal Purification in Quantum Mechanics

arXiv:2509.21111v2 Announce Type: replace Abstract: Many central tasks in fundamental physics and quantum information processing are possible only insofar as mixed quantum states can be made purer. In this work, we prove that the linearity and positivity of quantum mechanics impose general restrictions on quantum purification, unveiling a new fundamental principle of quantum information processing. We first establish that no quantum operation can transform a finite number of copies of an unknown quantum state or channel into an exactly pure output that depends non-trivially on the input, thereby ruling out an important form of universal purification in both static and dynamical settings. Building on this, we show that, upon relaxing the requirement of exact purity, one can establish quantitative sample-complexity lower bounds for approximate purification that hold for arbitrary physically allowed strategies, whose scaling matches the performance of purification-related tasks across several different areas of quantum information processing. Moreover, this lower bound leads to a generalized standard quantum limit for learning arbitrary functions of a quantum state, greatly extending earlier results based on quantum Fisher information and revealing a deep connection between purification and quantum learning. Extending this principle to other important settings, we establish, for the first time, an exponential sample-complexity lower bound for approximate pure dilation state preparation and a no-go theorem for approximate bosonic Gaussian state purification with passive Gaussian operations, establishing much more stringent limitations under practical operational constraints.

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

Deep Q-Learning on Hölder Spaces

Authors:

arXiv:2606.16846v1 Announce Type: cross Abstract: We study the operator-theoretic core of Q-learning in continuous-time stochastic control with continuous states and actions. In value-based reinforcement learning, each Q-learning or DQN update is built from a Bellman optimality target; our analysis isolates this target in a diffusion setting and studies its regularity and approximation complexity. Under uniform ellipticity and Hölder-regular coefficients, we show that a Bellman update maps bounded inputs into an anisotropic regularity class, smoothing the state variable while leaving only Lipschitz dependence on the action variable. This yields a compact family of Bellman iterates and motivates a tensor-product DeepONet architecture adapted to the mixed regularity of the problem. We then derive explicit approximation and resource bounds, together with a stiffness–complexity trade-off as the time step $\delta \to 0$. The resulting theory makes a direct contribution to Q-learning theory at the level of Bellman target regularity and approximation in continuous stochastic control. At the same time, we do not claim a full convergence theorem for practical sampled Q-learning with exploration, replay, and stochastic gradient updates.

18.
medRxiv (Medicine) 2026-06-22

The circulating blood proteome of childhood acute leukemia

The circulating blood proteome provides a systemic readout of disease biology and holds promise for advancing diagnostics and disease monitoring in pediatric leukemia. Here, we profiled 3072 proteins in diagnostic serum from 54 children with acute lymphoblastic leukemia (ALL), 21 with acute myeloid leukemia (AML), and 12 healthy controls using the Olink Proximity Extension Assay. We observed profound alterations in circulating protein levels in leukemia patients compared with controls and identified immunophenotype-specific proteins, including SIGLEC15 in B-cell precursor ALL (BCP-ALL), NOTCH1 in T-ALL, and CEBPA in AML, all which remained high even in patients with low (

19.
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.

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

Cognitive Debt: AI as Intellectual Leverage and the Dynamics of Systemic Fragility

Authors:

arXiv:2606.15078v1 Announce Type: new Abstract: We develop a formal theory of cognitive debt: the stock of unverified reasoning obligations that accumulates when individuals use AI as a substitute rather than a complement for first-principles cognition. The model features two state variables per agent, cognitive capital and cognitive debt, and a multiplicative production technology in which cognitive capital functions as collateral that determines the return to AI adoption. We establish six propositions. Rational agents incur positive cognitive debt because the costs are deferred, partially external, and masked by short-run productivity gains. Tranquil periods lower subjective risk assessments, raise AI substitution intensity, and compound leverage, generating a cognitive Minsky moment in which subjective risk falls while true systemic fragility rises. Expected crisis losses are convex in aggregate leverage. Post-crisis, output-target pressure can produce a false-correction loop in which agents patch AI failures with more AI. The decentralised equilibrium over-adopts substitutive AI relative to the social optimum because of systemic risk, cognitive public goods, and arms-race externalities. In a two-type heterogeneous-agent economy, high-cognitive-capital agents adopt AI more intensively and may eventually erode their unaided cognitive capital below that of initially lower-skilled agents.

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

Co-Scraper: query-aware DOM Pruning and Reusable Scraper Synthesis for Lightweight Web Data Extraction

arXiv:2606.14821v1 Announce Type: cross Abstract: The abundant and heterogeneous nature of web content necessitates automated information extraction, and generating scrapers that can be reused across similar web pages offers an effective solution for scalable data extraction. In this work, we propose Co-Scraper, a two-stage framework capable of handling the hierarchical complexity of long HTML documents. By integrating a query-aware DOM pruning mechanism with stable extraction strategy induction, Co-Scraper can effectively transforms web content into executable programmatic wrappers using a fine-tuned Qwen3-8B model. On the test set of SWDE, Co-Scraper achieves state-of-the-art performance with an F1 score of 94.78% and a reuse success rate of 90.39%. This framework significantly enhances the accuracy and resilience of data extraction, providing a highly efficient approach for web data acquisition tasks.

22.
arXiv (CS.CL) 2026-06-19

CogniFold: Always-On Proactive Memory via Cognitive Folding

Existing agent memory remains predominantly reactive and retrieval-based, lacking the capacity to autonomously organize experience into persistent cognitive structure. Toward genuinely autonomous agents, we introduce CogniFold, a brain-inspired "always-on" agent memory designed for the next generation of proactive assistants. CogniFold continuously folds fragmented event streams into self-emerging cognitive structures, bootstrapping progressively higher-level cognition from incoming events and accumulated knowledge. We ground this by extending Complementary Learning Systems (CLS) theory from two layers (hippocampus, neocortex) to three, adding a prefrontal intent layer. Emulating the prefrontal cortex as the locus of intentional control and decision-making, CogniFold achieves this through graph-topology self-organization: cognitive structures proactively assemble under the stream, merge when semantically similar, decay when stale, relink through associative recall, and surface intents when concept-cluster density crosses a threshold. We evaluate structural formation using CogEval-Bench, demonstrating that CogniFold uniquely produces memory structures that match cognitive expectations and concept emergence. Furthermore, across eight downstream benchmarks – two probing long-term conversational memory (LoCoMo, LongMemEval) and six spanning other cognitive domains – we validate that CogniFold simultaneously performs robustly on conventional memory tasks. Our code is available at https://github.com/OpenNorve/CogniFold.

23.
bioRxiv (Bioinfo) 2026-06-11

GeroQubit: a lightweight, honesty-first de-novo design platform for geroscience-native small molecules with calibrated uncertainty

Authors:

Computational molecule generation has outpaced its own credibility. We present GeroQubit, a GPU-free de-novo design platform that organizes candidates along a target x tissue x hallmark model and reports every signal alongside its measured baseline. We treat our tissue aging-signature readout as a mechanistic structural prior that we explicitly disclose is not validated against lifespan, and we surface efficacy only through a structure-to-lifespan k-NN whose weak but real signal (leave-one-out rho ~ 0.145) is wrapped in empirically-calibrated conformal intervals (90% target, 90.3% measured coverage). On a held-out retrospective recovery of ~1,940 ChEMBL binders against decoys, the score reaches ROC-AUC 0.945 with ~20x enrichment at 1% (BEDROC 0.91) and survives a scaffold-disjoint split - yet we report that it collapses to near-random (AUC 0.62) on genuinely novel chemotypes. Molecules are assembled reaction-first, so every candidate carries a verified synthetic route and atom-level synthon provenance; ADMET is handled as a multi-objective Pareto problem. We frame the disclosed weak signals and the hard-case failures not as flaws but as the honest, decision-useful output the field's own critics demand.

24.
arXiv (math.PR) 2026-06-18

Random Schrödinger operators on manifolds and abstract bounds for multiplier-type operators

arXiv:2606.19075v1 Announce Type: cross Abstract: We study random Schrödinger operators on closed Riemannian manifolds with Anderson-type potentials. We prove high-probability spectral inclusion bounds showing that eigenvalues remain close to those of the Laplacian, with deviations controlled by a norm of the potential coefficients. Compared with deterministic bounds, this yields a square-root cancellation gain. The proof is based on a general principle showing that randomisation improves operator norm bounds for multiplier-type operators, which we formulate in both discrete and continuous settings.

25.
medRxiv (Medicine) 2026-06-22

Histologically validated diffusion MRI signatures of neuroinflammation and neurodegeneration in Alzheimer disease

Noninvasive neuroinflammation measurement remains a major barrier for Alzheimer disease (AD) therapeutics. We present generalized diffusion basis spectrum imaging (g-DBSI), a diffusion MRI framework that decomposes the tissue signal into biologically interpretable microstructural compartments. In postmortem Knight ADRC brains, g-DBSI-derived restricted isotropic fraction (RIF) and restricted anisotropic fraction (RAF) mapped cellularity and neurofilament density, while their ratio (RIF/RAF) tracked inflammatory cell density and peri-plaque amyloid-beta with higher specificity and regional consistency than RIF alone. In 112 living Knight ADRC participants stratified by PET amyloid, g-DBSI metrics showed amyloid-dependent trajectories: in low-amyloid individuals, RIF and RAF rose together with amyloid, consistent with early neuropil expansion and glial elaboration, whereas in high-amyloid individuals, RIF/RAF increased, and RAF declined, indicating established neuroinflammatory remodeling and neurofilament loss. CSF proteomics linked RIF/RAF to glia-enriched immune and vascular pathways, supporting g-DBSI as a clinically compatible MRI biomarker of neuroinflammation and neurodegeneration in AD.