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

Understanding LLMs in Title-Abstract Screening: From Disagreements to Recommendations

arXiv:2606.17588v1 Announce Type: cross Abstract: Several studies have examined the use of large language models (LLMs) for title-abstract screening in systematic reviews (SRs), reporting mixed accuracy. However, questions of reliability remain largely unaddressed. In this study, we go beyond quantitative LLM-human agreement metrics and qualitatively investigate how and why LLMs fail. We also propose actionable recommendations. We analyzed disagreements between LLMs and researchers across six software engineering SRs and over 1,000 primary study papers. For each SR, papers were screened independently by human experts and LLMs in zero-shot mode, resulting in Kappa values ranging from 0.52 to 0.77. Qualitative analysis suggests that human-LLM disagreement results from recurring, identifiable causes, such as boundary ambiguity in key terms, keyword overemphasization, and incorrect topic inference. Based on these findings, we propose recommendations such as validating semantic understanding before deployment, running multiple LLMs, and focusing validation efforts on borderline cases. Future studies are needed to validate the impact of our recommendations, and community efforts are needed to develop normative guidelines on LLM usage in SRs.

02.
arXiv (CS.LG) 2026-06-12

Evaluation of AutoML Frameworks for IDS under Imbalanced Data Conditions of the NSL-KDD Dataset

arXiv:2606.12611v1 Announce Type: new Abstract: This work investigates the impact of severe class imbalance on the performance of automated machine learning (AutoML) frameworks for multiclass network intrusion detection using the NSL-KDD dataset. Unlike previous studies that simplify the problem through binary classification or minority-class removal, we preserve the original five-class distribution, including highly underrepresented attacks such as R2L and U2R, enabling a realistic evaluation of imbalance-sensitive learning behavior. Nine open-source AutoML frameworks were analyzed under a unified and reproducible experimental protocol, considering differences in architectural design, ensemble strategies, validation procedures, hyperparameter optimization, and imbalance-handling mechanisms. The results demonstrate that frameworks incorporating ensemble learning and imbalance-aware optimization achieve better minority-class discrimination. PyCaret obtained the best overall performance, reaching 66\% macro-F1, followed by AutoGluon with 55\%, whereas frameworks lacking native balancing support exhibited significant degradation in minority-class detection capability. The analysis further shows that accuracy-oriented optimization alone is insufficient for highly imbalanced IDS scenarios, since high-weighted metrics may coexist with poor generalization on rare attack categories. As a contribution, this work establishes a standardized benchmark for AutoML-based intrusion detection under severe multiclass imbalance, highlighting current architectural limitations and the need for native integration of imbalance-aware optimization, resampling, and stratified evaluation strategies into automated learning pipelines. The source code is publicly available.

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

The Perceived Fragility of Explanations in Audio Models: Manipulation of Attribution with Unchanged Predictions

arXiv:2606.14466v1 Announce Type: cross Abstract: This paper investigates the fragility of post-hoc explanation methods in audio deepfake detection. While previous work on explanation manipulation focused on images using standard $L_p$ metrics, we introduce a psychoacoustic framework that optimizes inaudible perturbations to decouple model attributions from final classifications. We evaluate this vulnerability across state-of-the-art architectures under strict prediction-preserving constraints. By evaluating the manipulation cost through domain-specific perceptual audio quality metrics alongside explanation alignment criteria, our framework demonstrates that an adversary can systematically distort automated explanation heatmaps while preserving the predicted deepfake label. Full code available at: https://github.com/cncPomper/Audio-XAI

05.
arXiv (quant-ph) 2026-06-12

Quasi-local Edge Mode in XXX Spin Chain/Circuit with Interaction Boundary Defect

arXiv:2603.17835v2 Announce Type: replace-cross Abstract: We study the Heisenberg spin-1/2 model on a semi-infinite chain - or, equivalently, a trotterized unitary SU(2) symmetric six-vertex quantum circuit - with a boundary defect where the interaction between the two spins nearest the edge differs from that in the bulk. For sufficiently strong boundary interaction we explicitly construct a conserved operator quasi-localized near the boundary using a matrix-product ansatz. This quasi-local edge mode leads to non-decaying boundary correlation functions, corresponding to a nonzero boundary Drude weight. The correlation length of the edge mode diverges at a finite critical value of the boundary interaction, signaling a transition to ergodic boundary dynamics for subcritical interactions.

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

Provable quantum speedups for computing persistence in topological data analysis

arXiv:2410.21258v2 Announce Type: replace-cross Abstract: Topological data analysis (TDA) aims to extract noise-robust features from a data set by examining the number and persistence of holes in its topology. We provide an efficient quantum algorithm for a computational problem closely related to a core task in TDA – determining whether a given hole persists across different length scales. Further, we prove the problem itself is $\mathsf{BQP}_1$-hard, implying that a classical solution is extremely unlikely; this stands in contrast to all previous quantum approaches to TDA, where the problems were also intractable for quantum computers, or where a rigorous proof of classical hardness still remains open. This result implies an {exponential} quantum speedup for this problem under standard complexity-theoretic assumptions. Our approach relies on encoding the persistence of a hole in a variant of the guided sparse Hamiltonian problem, where the guiding state is constructed from a harmonic representative of the hole.

07.
Nature (Science) 2026-06-08

Distributed control circuits across a brain-and-cord connectome

Just as genomes revolutionized molecular genetics, connectomes (maps of neurons and synapses) are transforming neuroscience. To date, the only organisms with complete connectomes are worms1–3, sea squirts4, and comb jellies5 (103–104 synapses). By contrast, the fruit fly is more complex (108 synaptic connections), with a brain that supports learning and spatial memory6,7 and an intricate ventral nerve cord analogous to the vertebrate spinal cord8–12. Here we report the first densely-reconstructed adult fly connectome that unites the brain and ventral nerve cord, and we leverage this resource to investigate principles of neural control. We show that effector neurons (motor neurons, endocrine cells, and efferent neurons targeting the viscera) are primarily influenced by sensory neurons in the same body part, forming local feedback loops. These local loops are linked by long-range circuits involving ascending and descending neurons organized into behavior-centric modules. Single ascending and descending neurons are often positioned to influence the voluntary movements of multiple body parts, together with the endocrine cells or visceral organs that support those movements. Brain regions involved in learning and navigation supervise these circuits. These results reveal an architecture that is distributed, parallelized, and embodied, reminiscent of distributed control architectures in engineered systems13,14.

09.
arXiv (CS.LG) 2026-06-15

Mitigating Heterogeneity-Induced Drift in Hierarchical Sign-Based Federated Learning

arXiv:2602.02355v2 Announce Type: replace-cross Abstract: Hierarchical federated learning (HFL) is well suited for large-scale wireless and Internet of Things systems, where devices communicate with nearby edge servers before reaching the cloud. In these environments, uplink bandwidth and latency impose strict communication constraints, making aggressive gradient compression essential. One-bit sign-based stochastic gradient descent methods provide an attractive solution in flat federated settings, but their behavior in hierarchical edge–cloud architectures remains insufficiently understood, especially under inter-cluster data heterogeneity. To address this gap, we develop a sign-based HFL framework in which devices transmit binary stochastic-gradient signs to edge servers, edge servers apply majority voting, and the cloud periodically aggregates edge models. Our analysis reveals that inter-cluster heterogeneity induces a persistent bias term in the convergence bound, reflecting the drift of edge models toward local objectives. This term cannot be removed by increasing the number of training rounds or by tuning standard hyperparameters alone. We therefore propose \(\mathtt{DC-HierSignSGD}\), a drift-corrected sign-based HFL algorithm in which devices apply a cloud-assisted gradient correction before taking the sign. We show that this pre-sign correction mitigates the non-vanishing heterogeneity-induced bias while preserving binary device–edge communication during the repeated local sign-update steps. Experiments under severe inter-cluster heterogeneity demonstrate that \(\mathtt{DC-HierSignSGD}\) improves the stability and accuracy of sign-based HFL and achieves performance comparable to full-precision hierarchical SGD with substantially lower device–edge communication.

10.
bioRxiv (Bioinfo) 2026-06-13

Reinforcement learning-driven unified generative framework for multi-objective RNA codon design

Current RNA codon design methods are limited by inefficient long-sequence processing and poor generalizability, often relying on a decoupled "generate-or-optimize" paradigm. We introduce RNARL, a reinforcement learning-driven framework that unifies sequence generation with multi-objective optimization. RNARL directly learns to generate high-performance sequences, effectively optimizing sequences over 3,900 nucleotides and demonstrating superior performance and universality across six species and five RNA types. RNARL thus establishes an effective and generalizable framework for RNA codon design. Finally, a user-friendly web platform is freely available to facilitate its application for RNA therapeutic design.

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

DIPHINE: Diffusion-based $\Phi$-ID Neural Estimator

arXiv:2606.18997v1 Announce Type: new Abstract: Uncovering the true informational architecture of real-world complex systems requires disentangling how their components uniquely store, redundantly share, and synergistically integrate information over time. Integrated Information Decomposition ($\Phi$ID) is a framework for decomposing the information dynamics of multivariate systems into sixteen non-overlapping atoms that characterize redundant, unique, and synergistic modes of information storage, transfer, and integration. Existing methods to compute $\Phi$ID are restricted to Gaussian or discrete systems, preventing its application to continuous non-Gaussian dynamical systems. We address this limitation by proposing DIPHINE (Diffusion-based $\Phi$-ID Neural Estimator), the first neural estimator that leverages score-based diffusion models to jointly estimate all the mutual information terms required by $\Phi$ID from a single amortized network, recovering the sixteen atoms through Möbius inversion. We provide a theoretical analysis of error propagation through the inversion, showing that the Jacobian of the mapping from mutual informations to atoms is integer-valued and that the synergy-to-synergy atom is provably the hardest to estimate. We demonstrate accurate recovery of ground-truth atoms on synthetic benchmarks, superior performance compared to established mutual information estimators, and the ability to extract physiologically interpretable information-dynamic structure on an application involving real data without any distributional assumptions.

12.
arXiv (CS.AI) 2026-06-17

From Noise to Order: Learning to Rank via Denoising Diffusion

arXiv:2602.11453v3 Announce Type: replace-cross Abstract: Learning-to-rank (LTR) methods have traditionally been limited to discriminative machine learning approaches that model the probability of the document being relevant to the query given some feature representation of the query-document pair. We propose an alternative denoising diffusion-based generative approach to LTR that instead models the full joint distribution over features and relevance labels. While in discriminative LTR, an over-parameterized ranking model may find different ways to fit the training data, we posit that candidate solutions that can explain the full data distribution under the generative setting maybe better at estimating relevance. Thus, we propose DiffusionRank that extends TabDiff, an existing diffusion model for tabular datasets, to create generative alternatives to classical discriminative pointwise and pairwise LTR objectives. Our work demonstrates improvements from DiffusionRank over discriminative counterparts on four standard LTR datasets and points to a rich space for future exploration to leverage ongoing advancements in deep generative models for LTR. Our code is publicly available at https://github.com/sadjadeb/DiffusionRank.

13.
arXiv (CS.CV) 2026-06-17

SkillMoV: Mixture-of-View Routing with Prototype-Conditioned Gating for Unified Multi-View Proficiency Estimation

Estimating human proficiency from video is a key challenge for automated skill assessment, with applications in sports coaching, music pedagogy, surgical training, and workplace learning. Existing approaches often focus on individual scenarios or rely on shared multi-view aggregation, limiting their ability to adapt to heterogeneous camera viewpoints and activity domains. We introduce SkillMoV, a unified, parameter-efficient framework for multi-scenario proficiency estimation from synchronized multi-view video. At its core, SkillMoV introduces a Mixture-of-View Projector (MoVP), which adapts the mixture-of-experts paradigm to camera-specific view features. MoVP is composed of four stages: (i) a Mixture-of-View soft router with twelve expert MLPs that learns view-dependent expert preferences without camera-identity supervision; (ii) cross-view attention to align synchronized cameras; (iii) learnable prototype anchoring to condition the representation on class-level reference vectors; and (iv) a prototype-conditioned gated projection that produces the final skill embedding. We evaluate SkillMoV on EgoExo4D across six skill domains and three separately trained view configurations: Ego, Exos, and Ego+Exos. SkillMoV reaches 50.17% overall accuracy in the Exos setting with a single model trained jointly across all scenarios, surpassing the strongest reported Exos result among the compared methods by 3.57 percentage points. In Ego+Exos, SkillMoV remains close to the best reported result in that setting (47.63% versus 48.20%). Ablations on the selected Exos configuration validate each component: MoV routing contributes +6.61 pp over attentive aggregation, cross-view attention +4.92 pp, prototype anchoring +4.07 pp, and stochastic view dropout +3.90 pp. Through LoRA adaptation, SkillMoV trains only 23.32% of its parameters and adds limited measured overhead relative to a LoRA-only baseline.

14.
bioRxiv (Bioinfo) 2026-06-18

A unified smoothing framework for protein domain bigram model

Biomolecular sequences can be represented as strings over an alphabet, an analogy that has motivated many applications of computational linguistic techniques to biological problems. However, such methods must be adapted to the characteristic scale and organization of biomolecular data. Here, we consider the problem of bigram smoothing for multidomain protein architectures, where domain bigram frequency data is extremely sparse and differs from textual data in alphabet size, string length distribution, the relationship between bigram and unigram frequencies, tandem repeat lengths, and the distribution of domain adjacencies. Moreover, some domain combinations are unobserved because they are biologically incompatible, others because the data are incomplete. A smoothing method that distinguishes these two cases is required. We propose a unified smoothing framework based on interpolation that can be tuned to accommodate different bigram data characteristics. Within this framework, we design specific model variants suited to protein domain bigram data: these assign low adjusted counts to pairs that are likely incompatible, while making appropriate adjustments for undersampled pairs. We demonstrate empirically that this approach distinguishes the two cases while preserving the characteristic signatures of multidomain data.

15.
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.

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

Enhancing CVRP Solver through LLM-driven Automatic Heuristic Design

arXiv:2602.23092v2 Announce Type: replace Abstract: The Capacitated Vehicle Routing Problem (CVRP), a fundamental combinatorial optimization challenge, focuses on optimizing fleet operations under vehicle capacity constraints. While extensively studied in operational research, the NP-hard nature of CVRP continues to pose significant computational challenges, particularly for large-scale instances. This study presents AILS-AHD (Adaptive Iterated Local Search with Automatic Heuristic Design), a novel approach that leverages Large Language Models (LLMs) to revolutionize CVRP solving. Our methodology integrates an evolutionary search framework with LLMs to dynamically generate and optimize ruin heuristics within the AILS method. Additionally, we introduce an LLM-based acceleration mechanism to enhance computational efficiency. Comprehensive experimental evaluations against state-of-the-art solvers, including AILS-II and HGS, demonstrate the superior performance of AILS-AHD across both moderate and large-scale instances. Notably, our approach establishes new best-known solutions for 8 out of 10 instances in the CVRPLib large-scale benchmark, underscoring the potential of LLM-driven heuristic design in advancing the field of vehicle routing optimization.

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

Test-Time Training for Robust Text-Guided Open-Vocabulary Object Counting

Text-guided Open-vocabulary Object Counting (TOOC) enables counting arbitrary object categories specified by text prompts, offering substantially greater flexibility than conventional closed-set counting. However, existing TOOC methods are developed and evaluated primarily on ideal images, while real-world scenes often suffer from adverse conditions such as rain, fog, darkness, and sensor noise, which severely degrade visual quality and impair vision-language alignment. To bridge this gap, we introduce Robust-TOOC, the first benchmark for evaluating TOOC under diverse corruption conditions, which covers six representative degradation types: rain, fog, darkness, Gaussian noise, salt-and-pepper noise, and mixed corruption. To improve robustness while preserving the original counting architecture, we propose Dual-TTT, a dual-architecture test-time training framework for TOOC. Specifically, during test-time training, Dual-TTT updates only the Text-guided Lightweight Denoising module (TL-Denoiser), while keeping the original counting network frozen. Inspired by diffusion models, the TL-Denoiser is optimized to remove corruption-aware noise from image representations under degraded conditions. Since only the TL-Denoiser is trained at test time, Dual-TTT is annotation-free and can be seamlessly integrated into existing TOOC models without modifying their original architecture. Extensive experiments on multiple recent TOOC baselines demonstrate the effectiveness of our method.

18.
arXiv (CS.AI) 2026-06-17

Position: Modular Memory is the Key to Continual Learning Agents

arXiv:2603.01761v2 Announce Type: replace-cross Abstract: Foundation models have transformed machine learning through large-scale pretraining and increased test-time compute. Despite surpassing human performance in several domains, these models remain fundamentally limited in continuous operation, experience accumulation, and personalization, capabilities that are central to adaptive intelligence. While continual learning research has long targeted these goals, its historical focus on in-weight learning (IWL), i.e., updating a single model's parameters to absorb new knowledge, has rendered catastrophic forgetting a persistent challenge. Our position is that combining the strengths of In-Weight Learning (IWL) and the newly emerged capabilities of In-Context Learning (ICL) through the design of modular memory is the missing piece for continual adaptation at scale. We outline a conceptual framework for modular memory-centric architectures that leverage ICL for rapid adaptation and knowledge accumulation, and IWL for stable updates to model capabilities, charting a practical roadmap toward continually learning agents.

19.
arXiv (CS.AI) 2026-06-11

Generalization Hacking: Models Can Game Reinforcement Learning by Preventing Behavioral Generalization

arXiv:2606.12016v1 Announce Type: cross Abstract: Model post-training, and in particular reinforcement learning (RL), is one of the primary mechanisms by which developers can shape models' values and behaviors. However, as models become increasingly evaluation and training aware, they may be motivated to resist training when the perceived objective conflicts with their current values, undermining developers' ability to detect misalignment and correct model behavior through further training. In this paper, we demonstrate generalization hacking, in which a model collects reward during RL while preventing the rewarded behavior from generalizing. We construct a model organism on Qwen3-235B-A22B, finetuning on synthetic documents describing training awareness and self-inoculation, a novel mechanism in which the model frames compliance as context-specific in its chain of thought, without demonstrating or instructing either behavior. The model organism achieves train-time harmfulness comparable to controls while maintaining a persistent ${\sim}15$ percentage point compliance gap across 700 steps of RL. Additionally, a control organism trained only on training awareness documents independently discovers inoculation-like reasoning under RL pressure, developing its own compliance gap despite never being exposed to the concept. Because the generalization-hacking organism receives high reward throughout, standard training metrics provide no signal that generalization has failed. Our results constitute the first demonstration that a model can actively resist RL behavioral modification while maintaining high reward, suggesting that as models become more capable and training-aware, they may be able to undermine the training process itself.

20.
arXiv (CS.LG) 2026-06-11

Mahalanobis-Guided Latent OOD Detection for Hybrid ES-DRL Control in Time-Varying Systems

arXiv:2606.11474v1 Announce Type: new Abstract: In this paper, we study Mahalanobis-guided latent out-of-distribution (OOD) detection for test-time RL controller switching in nonlinear time-varying systems. RL controllers can quickly control high-dimensional systems within the training distribution, but their performance can degrade when time-varying dynamics produce unseen observations. We consider a combined ES–DRL controller, where RL provides fast in-distribution actions and bounded extremum seeking (ES) provides robust model-independent control under OOD operation. The key challenge is deciding when to switch. We train a variational autoencoder (VAE) on in-distribution beam-profile observations and use Mahalanobis distance in the VAE latent space to detect OOD beam profiles at test time. This OOD decision sets a binary switch that selects either the RL controller or the ES controller. We evaluate the approach in safety-critical particle accelerator control. In this setting, spatial magnet motion creates OOD beam profiles that were not seen during RL training. Visualization of the VAE latent space shows that the proposed method identifies this OOD scenario and provides an interpretable signal for switching between RL and ES in the combined controller.

21.
arXiv (CS.CL) 2026-06-18

MCompassRAG: Topic Metadata as a Semantic Compass for Paragraph-Level Retrieval

Retrieval-augmented generation (RAG) systems depend critically on how documents are chunked and searched. Fine-grained chunks can improve retrieval precision but expand the search space, increasing latency and cost; larger chunks reduce the number of candidates but make dense similarity less reliable, as the representation for each chunk mixes multiple topics and introduces more semantic noise. This trade-off becomes especially limiting in deep research tasks, where retrieval must be both fast and precise across large, heterogeneous corpora. We introduce MCompassRAG, a metadata-guided retrieval framework that uses topic-level signals as a semantic compass for selecting relevant evidence. Instead of relying only on cosine similarity between queries and noisy chunk embeddings, MCompassRAG enriches chunk representations with topic metadata in the same embedding space and trains a lightweight retriever through LLM-teacher distillation. At inference time, MCompassRAG performs topic-aware retrieval without additional LLM calls, improving both efficiency and evidence quality. Across six complex retrieval benchmarks, MCompassRAG improves information efficiency (IE) by 8.24% on average with over 5 times lower latency than the strongest efficient RAG baselines. Code is available on https://github.com/AmirAbaskohi/MCompassRAG.

22.
bioRxiv (Bioinfo) 2026-06-22

Multivariate Random Forests for Cross-Modal Multi-Omics Integration

Multi-omics studies are widely used across many areas of biomedical research. In many diseases, some signals are shared across data types, while others are strongest in a single omics layer. Current multi-omics clustering methods often either merge all data types into a single representation, which can blur biology that is strong in one layer, or rely on linear structure that may miss more complex relationships across data types. We introduce multiRF, a random-forest-based method that handles complex data types and separates shared and modality-specific structure for multi-omics data. multiRF learns sample similarities across omics layers from multivariate random forests, combines them across data types, and uses the resulting weights to estimate the part of each omics layer that is predictable from the others. The remaining residual is treated as modality-specific signal, allowing shared and modality-specific similarities to be clustered separately. In simulations, multiRF recovered shared clusters as well as or better than established integrative methods while more reliably separating modality-specific signal under nonlinear data structures. In TCGA head and neck squamous cell carcinoma, the shared component aligned with the main subtype structure across established reference classifications, while gene- and miRNA-specific components revealed additional immune and developmental biology. In the ADNI cohort with matched blood DNA methylation and structural MRI, the shared cross-modal aging signal was associated with future conversion to mild cognitive impairment or Alzheimer's disease, and a DNAm-specific residual signal showed exploratory additional information. These results show that multiRF can recover a common disease axis while retaining biologically meaningful signals specific to one data type. multiRF is available as an open-source R package at https://github.com/novawz/multiRF.

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

PHINN: Persistent Homology Inspired Neural Network for Rare-Event Time Series Generation

arXiv:2606.15452v1 Announce Type: new Abstract: Rare events in time series are critical to model but hard to learn due to data scarcity. Current generative models struggle with extreme values. We observe that rare events leave distinct topological fingerprints - transitions in Betti numbers from point-cloud embeddings - that are more stable and discriminative than statistical moments. We introduce PHINN, a flow-matching framework using dynamic Betti curves as conditioning signals and a persistence landscape loss for homology consistency. It scales to multivariate data, includes a natural-language interface to set Betti targets, supports cross-domain meta-learning and few-shot generation, and provides certified adversarial robustness. On financial, epidemiological, and multi-modal benchmarks, PHINN outperforms statistical and diffusion baselines in topological fidelity (beta-RMSE down 41-63%, transition accuracy up 84%) and matches jump-diffusion models in tail coverage while exceeding them in shape fidelity. All results have 95% confidence intervals.

24.
arXiv (math.PR) 2026-06-11

Continuous stochastic flows driven by white noise and their duals

作者:

arXiv:2606.12143v1 Announce Type: new Abstract: We study a class of continuous stochastic flows driven by a space-time white noise and characterize their dual flows by explicit stochastic differential equations. A key ingredient of the proof is the convergence of solutions under coefficient approximations. As an application, we derive the dual flows in two illustrative examples, the squared Bessel flow and the Jacobi flow. We also introduce a new model of polynomially self-repelling (PSR) flow and show that it enjoys a self-duality property.

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

Agents All the Way Down; A Methodology for Building Custom AI Agents from Substrate to Production

arXiv:2606.11869v1 Announce Type: cross Abstract: Custom AI agents areagents that live inside their own application, talk to their own data and tools, enforce their own security boundaries, and carry their own brand and audit trail. What separates them from the general-purpose tier is fit, not capability: each is built for one job, by the engineer who will maintain it. No published practice sets out how to build one end to end. The pieces are everywhere (function-calling APIs, the Model Context Protocol, code agents to pair with), but the practice that chains them lives in podcasts, blogs, and leaked system prompts. This paper writes that practice down as a methodology, Agents All the Way Down: two preconditions crossed once and kept, then three practices repeated for the agent's life. The preconditions are (P1) Substrate, the LLM as a software component, framed as tools, then system, then messages under prompt-caching; and (P2) Building blocks: function calling, MCP, CLI orchestration, the liteshell pattern, the agent loop, skills, characters, hooks, and scaffolding. The practices are (P3) prototype with a general-purpose agent; (P4) harvest, fold, and ship the result as a CLI, the Turtle pattern; and (P5) agent-tests-agent, in which a general-purpose agent drives it through behavioural scenarios, a complement to classical testing, not a replacement. The working loop is P3 to P4 to P5 and back, and one corollary falls out for free: multi-agent orchestration is just CLI composition. The methodology is framework-free by construction. It was distilled from the AAC, a custom agent for the open-source LAMB platform, built in about ten days by one developer with an AI pair-programmer and in production . We present it as a transferable practice, independent of any language or framework.