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01.
arXiv (CS.CV) 2026-06-15

HumP-KD: A Hybrid Uncertainty-Aware Multi-Stage Progressive Knowledge Distillation Framework for Efficient Fire Classification

Real-time fire classification systems require models that are simultaneously accurate, computationally efficient, and deployable on resource-constrained hardware. This work proposes HumP-KD, a Hybrid Uncertainty-aware Multi-stage Progressive Knowledge Distillation framework for efficient fire classification. Two datasets, FlameVision and Dataset-II, containing 8,600 and 31,309 images, are used. Various CNN and transformer baselines are applied under standard preprocessing, online augmentation, Gaussian noise and motion blur robustness conditions. The proposed HumP-KD model distills knowledge from two frozen heterogeneous transformer teachers, Swin-Tiny and ViT-Base, along with their Meta-MLP ensemble, into a lightweight MobileViT-S student via three tightly integrated components. Hierarchical Progressive Knowledge Distillation employs a Hierarchical Feature Builder. It generates a fused spatial attention mask to guide distillation toward discriminative regions selectively. Multi-Stage Knowledge Distillation progressively activates three distillation stages across training. On Dataset-II, HumP-KD achieves a mean F1 score of $0.9876 \pm 0.0063$ across 10 independent trials, significantly outperforming the MobileViT-S baseline trained without distillation ($0.9537 \pm 0.0351$), with statistical significance confirmed by both independent t-test ($p = 0.0195$) and Wilcoxon signed-rank test ($W = 1$, $p = 0.0039$). The proposed method also demonstrates strong generalization across datasets and robustness under degraded visual conditions. The student model retains only 4.94M parameters and 19.01Mb model size, representing a $5.7\times$ parameter reduction over Swin-Tiny and a $17.5\times$ reduction over ViT-Base, while achieving 37.72 CPU FPS, making it suitable for real-time deployment.

02.
arXiv (CS.CV) 2026-06-11

From Content to Knowledge: Lightning Fast Long-Video Understanding with Neural Knowledge Representations

We propose a new paradigm for long video understanding by treating a long video as a Neural Knowledge Representation (NKR). NKR represents video contents neither as a stream of tokens nor pre-organized databases, but as an individual small portion of network weights attached to the VLM backbone. The NKR weights are optimized to encapsulate the video's semantic content via a novel Agentic Knowledge Distillation (AKD) process, where an agent automatically synthesizes dense descriptions and question-answer pairs to distill the video's knowledge into the NKR. While AKD serves as a comprehensive, one-time encoding phase, the resulting NKR transforms the video into a portable, reusable asset. At inference, the lightweight NKR is mounted onto a frozen Vision-Language Model (VLM), enabling direct, query-based understanding without reloading or re-encoding the original video. This approach decouples video length from inference cost, offering high amortized efficiency for multi-turn video understanding. Experiments on the LVBench benchmark show our method achieves performance comparable to state-of-the-art approaches while reducing end-to-end latency by over two orders of magnitude, opening new possibilities for interactive long-video understanding.

03.
arXiv (CS.AI) 2026-06-19

Which Pairs to Compare for LLM Post-Training?

arXiv:2606.19607v1 Announce Type: new Abstract: Preference-based post-training has become a central paradigm for aligning language models. A common data-collection strategy is to generate a small set of completions for each prompt and label the resulting comparison pairs. However, human preference labels are often much more expensive than generating additional completions, suggesting a different use of the same labeling budget: generate a larger pool of completions, but label only the most informative comparison pairs. This paper studies which pairs should be compared in preference-based post-training. We formulate comparison curation as a sampling-design problem and evaluate designs by the quality of the final policy under the preference-based post-training objective. We instantiate this framework for Direct Preference Optimization (DPO), analyzing how the choice of labeled pairs propagates through DPO training to downstream policy performance. Our main results provide matching upper and lower bounds on the post-training optimality gap of the DPO-trained policy. The bounds show that comparison selection affects downstream performance through a single design-dependent information matrix, which links label allocation to parameter estimation error and policy suboptimality. This yields an explicit optimization criterion for budgeted comparison curation and motivates practical sampling designs for selecting informative pairs from large generated completion pools. Experiments on synthetic settings and language-model post-training benchmarks show that the proposed designs consistently improve sample efficiency over common comparison-selection heuristics.

04.
arXiv (math.PR) 2026-06-18

On a class of reflected McKean-Vlasov Stochastic Differential Equations with jumps

arXiv:2606.18433v1 Announce Type: new Abstract: This paper investigates a class of reflected McKean-Vlasov Stochastic Differential Equations driven by both Brownian motion and a compensated Poisson random measure. We establish the existence and uniqueness of solutions and provide moments estimates for the state processes.

05.
arXiv (CS.LG) 2026-06-18

Ensuring Trustworthy Online A/B Testing: Addressing Five Key Questions on CUPED

arXiv:2606.18750v1 Announce Type: cross Abstract: A/B testing has become the gold standard for data-driven decision-making in large-scale online experimentation, providing critical guidance for feature launch, pricing optimization, and user experience enhancement. To maximize statistical sensitivity, many technology companies routinely employ Controlled-experiment Using Pre-Experiment Data (CUPED), a technique that achieves substantial variance reduction while preserving the unbiasedness of estimating the average treatment effect. Despite its widespread adoption, several critical methodological and practical nuances of CUPED remain underexplored. This paper systematically addresses five frequently encountered yet overlooked questions regarding the application of CUPED. First, we provide a comparative analysis of various post-CUPED estimators to identify the optimal adjustment specification. Second, we evaluate the validity of regression-based adjustments and delineate robust variance estimation methods tailored for such frameworks. Finally, we extend our investigation to complex but common scenarios, including multi-arm experiments and two-stage sampling designs. Our findings reveal that in these settings, naive reliance on standard variance estimators can lead to severely misleading inferences. By offering rigorous theoretical insights and extensive experimental validation, this work deepens the conceptual understanding of CUPED. Notably, the recommended methodologies have been successfully deployed and integrated into ByteDance's experimentation platform.

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

Stochastic Adaptive Gradient Descent Without Descent

arXiv:2509.14969v2 Announce Type: replace Abstract: We introduce a new adaptive step-size strategy for convex optimization with stochastic gradient that exploits the local geometry of the objective function only by means of a first-order stochastic oracle and without any hyper-parameter tuning. The method comes from a theoretically-grounded adaptation of the Adaptive Gradient Descent Without Descent method to the stochastic setting. We prove the convergence of stochastic gradient descent with our step-size under various assumptions, and we show that it empirically competes against tuned baselines.

07.
PLOS Computational Biology 2026-06-09

Evolution of phenocopying in a dynamical model of developmental trajectories

by Yuuki Matsushita, Archishman Raju Developmental trajectories are known to be canalized, or robust to both environmental and genetic perturbations. However, even when these trajectories are decanalized by an environmental perturbation outside the range of conditions to which they are robust, they often produce phenotypes similar to known mutants, called phenocopies. This correspondence between the effects of environmental and genetic perturbations has received little theoretical attention. Here, we study an abstract regulatory model that is evolved to follow a specific trajectory. We then study the effects of small and large perturbations to the trajectory, both by changing parameters and by perturbing the state at specific times. We find that the phenomenon of phenocopying emerges in evolved trajectories and is not present in a null model of randomly sampled trajectories. Our results suggest that, in this class of dynamic models, evolution can allow high-dimensional phenotypic landscapes to simultaneously exhibit robustness and phenocopying.

08.
arXiv (CS.AI) 2026-06-12

Beyond Problem Solving: UOJ-Bench for Evaluating Code Generation, Hacking, and Repair in Competitive Programming

arXiv:2606.12864v1 Announce Type: cross Abstract: Despite strong performance in competitive programming, the role of Large Language Models (LLMs) in supporting human learning in the same setting remains largely unexplored. In this work, we introduce UOJ-Bench, a benchmark designed to evaluate not only the problem-solving ability of LLMs, but also their ability to identify errors in human-written code – a crucial educational activity traditionally supported by running test cases over online judge systems. UOJ-Bench consists of three distinct tasks: code generation, code hacking, and code repair, all constructed from real-world code submissions on the Universal Online Judge (UOJ) and evaluated through UOJ's native judging infrastructure. Our results show that under one-shot evaluation, even the strongest models fail to identify errors in more than 50% of a set of submissions that have been found to be incorrect by UOJ users. While test-time scaling improves success rates to above 90%, the substantial computational costs incurred from model inference limit its practicality for large-scale deployment. Despite these limitations, we find that the best-performing models under test-time scaling can uncover errors in over 5% of full-score submissions across roughly 30 problems, suggesting that frontier LLMs can already provide complementary signals beyond standard judging systems.

09.
arXiv (CS.CV) 2026-06-11

3D-CBM: A Framework for Concept-Based Interpretability in Generative 3D Modeling

This research introduces a framework for incorporating Concept Bottleneck Models (CBMs) into 3D generative architectures to address the inherent 'semantic gap' in deep geometric learning. As deep models become central to 3D content creation, explainability shifts from a peripheral feature to a fundamental requirement for trust and accountability in safety-critical domains such as healthcare and manufacturing. CBMs provide an intrinsic interpretability solution by constraining latent representations to align with human-defined concepts, yet their application to unstructured 3D data remains largely unexplored. We design, implement, and validate a formal 3D-CBM architecture that maps raw geometric inputs, including point clouds and meshes, into a multi-tiered taxonomy of interpretable primitives and functional attributes. The framework further identifies strategic datasets, such as PartNet and ShapeNet, specialized for concept-based supervision. Experimental results from a 3D part-manipulation proof-of-concept experiment demonstrate the framework's efficacy, achieving a concept prediction accuracy of 88.8\% and a Chamfer Distance of 0.0115. Critically, the model enables precise test-time intervention, allowing for the interactive correction of structural errors. This work establishes a foundation for semantically-steerable 3D generation and invites further exploration into collaborative human-in-the-loop design systems.

10.
arXiv (quant-ph) 2026-06-15

Probing Many-Body Phenomena with Atomically Thin Nuclear Spin Layers in Diamond

arXiv:2510.27374v2 Announce Type: replace Abstract: Quantum simulation aims to recreate complex many-body phenomena in controlled environments, offering insights into dynamics that are otherwise difficult to model. Existing platforms, however, are often complex and costly to scale, typically requiring ultra pure vacuum or low temperatures. Here, we introduce a platform based on a thin, strongly interacting ${}^{13}C$ nuclear spin layer in diamond that allows controlled exploration of many-body dynamics at room temperature. Nearby nitrogen-vacancy centers enable polarization, readout, and, combined with radio-frequency fields, coherent control of the nuclear spins. We demonstrate strong, tunable interactions among the nuclear spins and use the system to probe discrete time-crystalline order across varying interaction ranges. By combining ease of use with operation at ambient temperatures, our work opens new opportunities for investigating strongly correlated many-body effects.

11.
medRxiv (Medicine) 2026-06-11

The impact of pre-stroke statin use on baseline corrected infarct volume and collateral perfusion

Stroke is a leading cause of disability and mortality worldwide, with ischaemic stroke the most prevalent type. Statins, used for cholesterol management, have demonstrated benefits in reducing stroke risk and improving outcomes in preclinical studies. However, the impact of pre-stroke statin use on stroke outcomes remain inconsistent. In this study, we aim to evaluate whether pre-stroke statin use is associated with greater volume of salvaged tissue and improved cerebral collateral perfusion. A retrospective analysis was conducted using data from 281 patients presenting with acute ischemic stroke to the John Hunter Hospital between May 2015 and May 2020. Patients were grouped based on pre-stroke statin use, and clinical variables, including infarct volume and collateral perfusion, were assessed. The primary outcome was salvage volume derived from baseline perfusion lesion volume minus infarct volume at follow-up. Collateral perfusion was measured by the hypoperfusion volume defined by delay time (DT)>6 seconds divided by the hypoperfusion volume defined by DT >2 seconds. Patients on statins at admission were significantly older and had more comorbidities. No significant association was found between pre-stroke statin use and salvage volume or collateral perfusion after adjusting for covariates. Larger initial infarct core was a significant predictor of salvage volume due to larger salvageable tissue volume at baseline. These findings indicate that pre-morbid statin use is not associated with larger salvage volume or improved cerebral collateral perfusion.

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

A Bifurcation Theory Framework for Gradient Descent on the Edge of Stability

作者:

arXiv:2606.15551v1 Announce Type: new Abstract: The Edge of Stability (EoS) phenomenon, where gradient descent operates with sharpness exceeding the classical convergence threshold yet the loss decreases over long timescales, is ubiquitous in modern deep learning but remains poorly understood in realistic settings. Prior rigorous analyses have been largely confined to scalar or low-dimensional losses with specific structural forms. In this work, we develop a bifurcation theory framework for gradient descent on the edge of stability that applies directly to overparameterized neural networks. By decomposing the training dynamics into components normal and tangent to the manifold of minimizers, we show that stable EoS training arises from a flip bifurcation in the normal direction, governed by the sign of the first Lyapunov coefficient, while the tangent dynamics drift toward regions of decreasing sharpness. Under mild spectral and geometric assumptions on the loss landscape, we prove convergence to the minimizing manifold when training at the EoS threshold. As a corollary, we recover and unify prior results: we show that the product-stability condition of Gan (2026) is an instance of our framework.

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

PLATE: Plasticity-Tunable Efficient Adapters for Geometry-Aware Continual Learning

arXiv:2602.03846v2 Announce Type: replace-cross Abstract: We develop a continual learning method for pretrained models that requires no access to old-task data, addressing a practical barrier in foundation model adaptation where pretraining distributions are often unavailable. Our key observation is that pretrained networks exhibit substantial geometric redundancy, and that this redundancy can be exploited in two complementary ways. First, redundant neurons provide a proxy for dominant pretraining-era feature directions, enabling the construction of approximately protected update subspaces directly from pretrained weights. Second, redundancy offers a natural bias for where to place plasticity: by restricting updates to a subset of redundant neurons and constraining the remaining degrees of freedom, we obtain update families with reduced functional drift on the old-data distribution and improved worst-case retention guarantees. These insights lead to \textsc{PLATE} (Plasticity-Tunable Efficient Adapters), a continual learning method requiring no past-task data that provides explicit control over the plasticity-retention trade-off. PLATE parameterizes each layer with a structured low-rank update $\Delta W = B A Q^\top$, where $B$ and $Q$ are computed once from pretrained weights and kept frozen, and only $A$ is trained on the new task. The code is available at https://github.com/SalesforceAIResearch/PLATE.

14.
arXiv (CS.AI) 2026-06-17

StepGuard: Guarding Web Navigation via Single-Step Calibration

arXiv:2606.17871v1 Announce Type: new Abstract: Web navigation requires agents to follow natural language goals, interact with web pages, and produce accurate answers. While recent advances leverage vision-language models and reinforcement learning, existing methods still suffer from single-step fragility due to reward misalignment and error propagation. To tackle the reward entanglement, we design Dynamic Dual-Policy Optimization (DDPO), which dynamically switches between a navigation-first mode for exploration and an answer-first mode for question-answering to mitigate reward conflict. To calibrate the single-step error, we propose Confidence-Guided Adaptive Navigation Reflection (CANR), a mechanism that estimates per-step confidence, triggers reflection only when necessary, and uses contrastive rewards to encourage self-correction to calibrate the single-step inaccuracy. With the above as the main components, we finally develop our StepGuard, a new framework of Guarding Web Navigation via Single-Step Calibration. Experiments demonstrate that our approach significantly improves navigation and answer accuracy, setting new state-of-the-art performance on standard web navigation benchmarks.

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

A Compositional Framework for Open-ended Intelligence

arXiv:2606.15386v1 Announce Type: new Abstract: Open-ended intelligence is the capacity to adapt to novel problems and environments that are substantially different from those in training. We formalize open-ended intelligence as the closure induced by a finite primitive set \(P\) and a set of composition operators \(C\). We characterize properties of the induced closure \(\mathcal{L}(P,C)\) that support unbounded compositional generation across families of tasks and worlds. A mathematics of open-ended intelligence requires two pillars: a minimal set of representational primitives (e.g., states, actions) and algorithmic primitives (e.g., nearest neighbor), together with composition motifs (e.g., recursion, sequencing) that reflect an acquired compositional grammar. The closure of these two pillars enables the generation of infinite adaptive responses across a wide range of settings. The mathematics supports complementary research agendas, including evaluation metrics for explanation and interpretability, as well as building architectures where compositional generalization is native. We propose next primitive prediction as a novel architectural objective, where the training objective encourages the acquisition of reusable algorithmic primitives and their compositional grammar, such that new solutions are generated through recombination. Curriculum learning and self-play enable lifelong learning and expansion of the closure by discovering reusable primitives and transition motifs across families of tasks and worlds. We ground the framework through case studies in physics, evolution, and neuroscience.

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

A Formal Framework for Declarative Agentic AI in Business Process Analysis

arXiv:2606.15291v1 Announce Type: new Abstract: Agentic AI opens new opportunities for automating Business Process (BP), enabling autonomous decision-making and dynamic adaptation. However, realising this potential requires BP entities and their interactions to be defined with formal precision. This paper presents a formal framework for Agentic BP analysis through the AGO methodology. AGO captures the modelling perspective in terms of who is acting (Agents), why it is carried out (Goals), and what the relevant entities are (Objects). Grounded in set theory and mathematical logic, we formally define the AGO entity types and their interactions, organising all definitions into a BP Knowledge Base (BPKB). The resulting BPKB supports structured querying, incremental updates, and automatic generation of BP workflows, while ensuring soundness and completeness of the derived paths.

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

Adaptive and Explicit safe: Triggering Latent Safety Awareness in Large Reasoning Models

arXiv:2606.16808v1 Announce Type: new Abstract: While Large Reasoning Models (LRMs) excel at complex tasks, they remain highly vulnerable to sophisticated jailbreaks and direct harmful queries. To address this vulnerability, prior works depend heavily on external manual data annotation for safety alignment. However, we observe that LRMs can inherently identify safety risks when being re-presented with original queries alongside their own reasoning trajectories – a capability we term Latent Safety Awareness. To leverage this safety awareness, we first employ Supervised Fine-Tuning (SFT) to explicitly induce safe tags to trigger safety analysis and guidance following the initial reasoning content for unsafe queries, while preserving standard responses for general queries to ensure adaptive triggering. Subsequently, we apply Direct Preference Optimization (DPO) to further enhance the correctness and stability of the safety analysis and guidance. Notably, responses required for both training stages are entirely generated by models being optimized. With (Safe Trigger) SFT and DPO, experimental results demonstrate significant safety enhancement. For example, the Attack Success Rate (ASR) of DeepSeek-R1-Distill-Llama-8B, on average, drops 24.65% and 36.72% on harmful and jailbreak benchmarks, respectively. Finally, our Safe Trigger method exerts almost no negative impact on general performance or user experience.

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

A Tutorial on World Models and Physical AI

作者:

arXiv:2606.12783v1 Announce Type: new Abstract: World modeling is emerging as a central principle for building intelligent systems capable of prediction, reasoning, and decision making. A central distinction can be drawn between explicit world models, which learn structured dynamics for rollout-based reasoning and planning, and implicit world models, which encode predictive structure within scalable learned representations. These complementary paradigms provide a foundation for physical AI in domains such as robotics and autonomous driving, enabling intelligence beyond reactive control under real-world constraints. Recent foundation models further suggest a pathway toward unified systems integrating perception, prediction, and action. Despite rapid progress, major challenges remain in hierarchical reasoning, long-horizon planning, and autonomous goal formation, which are critical for advancing toward artificial general intelligence. This tutorial presents a coherent framework in which diverse world modeling approaches are unified through shared predictive structure and differentiated by how such structure is represented and exploited.

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

AtomMem: Building Simple and Effective Memory System for LLM Agents via Atomic Facts

Large language models (LLMs) demonstrate strong reasoning and generation abilities, but their fixed context windows limit long-term information accumulation and reuse across multi-session interactions. Existing memory-augmented systems often construct memory in a coarse and unstable manner, relying on inefficient memory representations or unstable unconstrained updates. To address these challenges, we propose AtomMem, a long-term memory system designed for value-dense storage and stable memory evolution. AtomMem introduces a Fact Executor, which selectively extracts high value atomic facts from long form interactions to serve as highly efficient memory representations. Subsequently, AtomMem organizes these facts into hierarchical event structures and temporal profiles, capturing coherent episodic contexts and tracking dynamically evolving user attributes over time. During retrieval, the system activates an associative memory graph to connect fragmented memories. Experiments on the LoCoMo benchmark confirm that AtomMem achieves state-of-the-art performance across various reasoning tasks, offering a scalable and economically viable solution for deploying intelligent personalized agents.

20.
arXiv (CS.AI) 2026-06-18

A CEFR-Inspired Classification Framework with Fuzzy C-Means To Automate Assessment of Programming Skills in Scratch

arXiv:2604.00730v2 Announce Type: replace-cross Abstract: Context: Schools, training platforms, and technology firms increasingly need to assess programming proficiency at scale with transparent, reproducible methods that support personalized learning pathways. Objective: This study introduces a pedagogical framework for Scratch project assessment, aligned with the Common European Framework of Reference (CEFR), providing universal competency levels for students and teachers alongside actionable insights for curriculum design. Method: We apply Fuzzy C-Means clustering to 2008246 Scratch projects evaluated via Dr.Scratch, implementing an ordinal criterion to map clusters to CEFR levels (A1-C2), and introducing enhanced classification metrics that identify transitional learners, enable continuous progress tracking, and quantify classification certainty to balance automated feedback with instructor review. Impact: The framework enables diagnosis of systemic curriculum gaps-notably a "B2 bottleneck" where only 13.3% of learners reside due to the cognitive load of integrating Logic Synchronization, and Data Representation–while providing certainty–based triggers for human intervention.

21.
bioRxiv (Bioinfo) 2026-06-11

PhyloZoo: a unified framework for phylogenetic network analysis in Python

作者:

Reticulate evolutionary processes (events in which lineages merge, such as hybridization, recombination, and horizontal gene transfer) are widespread across nature but cannot be represented by phylogenetic trees alone. Phylogenetic networks have therefore become an important modelling tool, yet existing software is typically tied to specific inference paradigms and provides limited support for working with multiple network representations in a unified and programmable environment. PhyloZoo is an open-source Python framework that lowers the barrier to developing practical, easy-to-use software for phylogenetic network analysis. It provides data structures and algorithms covering the main representations used in the field, together with dedicated visualization tools and robust I/O for all major phylogenetic file formats. A particular emphasis lies on semi-directed phylogenetic networks, which explicitly represent root uncertainty and have so far received limited support in existing software. By offering a shared foundation for developing interoperable tools and a combinatorial layer that supports computational proofs and theoretical exploration, PhyloZoo enables reproducible workflows for applied, methodological, and theoretical studies of reticulate evolution. Availability and implementation: PhyloZoo is implemented in Python and installable from PyPI, with source code, documentation, and examples available at https://github.com/nholtgrefe/phylozoo.

22.
arXiv (quant-ph) 2026-06-17

Singular Vector Finite Element Basis Functions for Tetrahedra in Complex Electromagnetic Geometries

arXiv:2606.18140v1 Announce Type: cross Abstract: Electromagnetic finite element method (FEM) implementations using traditional basis functions struggle to accurately represent field behavior near singular features such as conducting wedges. To combat this, specialized singular basis functions have been introduced to directly model the singular fields in these regions, leading to substantially improved performance. While these efforts have been pursued extensively in 2D, few functions have been developed for 3D elements. In this work, we develop basis functions for this in tetrahedra. Unlike prior functions, these basis functions are additive, meaning they are included alongside the standard vector basis functions to achieve more robust performance. Further, these functions are designed to be adaptable to tetrahedra touching several unique singular features by using combinations of basis functions singular with respect to each node and edge in the element, making them applicable to highly complex geometries. Higher-order interpolatory versions of the basis functions for modeling singular behavior with greater accuracy are also provided. These basis functions lead to substantial improvements in accuracy relative to the standard basis functions, and allow otherwise expensive simulations to be performed at far lower costs. As an application example, we perform simulations to extract critical quantities for designing superconducting qubits that significantly depend on the behavior of singular fields. In Ansys HFSS, this took 21.27 hours and a peak memory usage of 6.23 TB with 800 processors available, while using our singular basis functions achieved comparable results in 196 seconds while using 27.24 GB of memory and only 16 processors. Due to these benefits, our singular basis functions could be applied to enable design optimization of electromagnetic geometries with dominantly singular behavior, such as superconducting qubits.

23.
bioRxiv (Bioinfo) 2026-06-18

A data-driven rediscovery of the specificity-conferring code of adenylation domains in nonribosomal peptide synthetases

Nonribosomal peptide synthetases (NRPSs) are large modular enzymes that assemble structurally diverse peptides, many of pharmacological importance, including antibiotics and immunosuppressants. Within each NRPS module, the adenylation (A) domain selects the substrate to be incorporated, a choice governed by a small set of residues lining the binding pocket. For two decades, computational prediction of A-domain substrate specificity has relied on residue sets - most prominently the Stachelhaus code and the 34-residue "8 Angstrom code" - that were defined by spatial proximity to the substrate rather than by demonstrated predictive value. Here we revisit which residues govern substrate specificity from a purely data-driven perspective. We assembled a non-redundant dataset of 5,366 A-domain sequences (4,693 bacterial and 673 fungal) and used information-theoretic measures to rank alignment positions by their statistical association with substrate identity, without restricting candidate positions to any predefined structural shell. This procedure yielded two compact, kingdom-specific codes: IG15B (15 positions) for bacterial and IG13F (13 positions) for fungal A-domains. Both match or exceed the predictive accuracy of the 34-residue 8 Angstrom code while using fewer than half its positions, and both independently recover the majority of the classical Stachelhaus positions. Notably, our analysis identifies four positions (242, 280, 281, and 284) that lie outside all conventional codes yet carry non-redundant specificity information and co-localize with classical determinants on two helices flanking the binding pocket. These positions provide new candidate sites for the rational engineering of A-domain specificity.

24.
arXiv (CS.CV) 2026-06-16

A Dual-Branch Collaborative Framework for Joint Optimization of Underwater Image Enhancement and Object Detection

Due to wavelength dependent light absorption and scattering, underwater images usually suffer from color distortion and blurred details, which limits underwater object detection performance. Existing underwater image enhancement methods mainly focus on visual quality improvement, while it is still difficult to balance enhancement quality, processing efficiency, and downstream detection performance. Therefore, this paper proposes an efficient dual-branch underwater image enhancement framework for object detection. The detail enhancement branch improves brightness and local contrast to recover texture details in dark regions. The color restoration branch uses adaptive compensation to reduce color distortion and improve color gradation. By combining the complementary outputs of the two branches, the proposed framework provides clearer and more informative images for object detection. On the UIEB and EUVP datasets, the proposed method achieves UIQM scores of 2.249 and 2.576. When applied to the YOLOv8 detection task on the URPC dataset, the proposed method improves mAP50 by 2.1\% compared with the baseline. Extensive experiments show that our method improves object detection in complex underwater scenes, while balancing enhancement quality and processing efficiency.

25.
medRxiv (Medicine) 2026-06-17

Sao Tome and Principe on the verge of eliminating lymphatic filariasis as a public health problem: evidence from IDA impact assessment surveys

Background Accelerated efforts to eliminate lymphatic filariasis (LF) as a public health problem have been supported by the introduction of the triple-drug regimen of ivermectin, diethylcarbamazine and albendazole (IDA) in endemic settings. In Sao Tome and Principe, nationwide mass drug administration (MDA) with diethylcarbamazine and albendazole was implemented in 2018, followed by IDA in 2019 and 2020. This study assesses progress towards elimination using post-MDA impact assessment surveys conducted after cessation of treatment. Methods Cross-sectional surveys were conducted among adults aged 20 years and older in 2022 and again between December 2024 and January 2025. Circulating filarial antigen (CFA) was detected using the filarial test strip (FTS). Individuals who tested positive were examined for microfilaremia using nocturnal calibrated thick blood smear microscopy. Additionally, programme data on MDA coverage and morbidity were obtained from national surveillance records. Results Three rounds of nationwide MDA achieved high epidemiological coverage (86.4% in 2018, 74.2% in 2019 and 80.0% in 2020). The impact assessment surveys conducted in 2022 evaluated 14 132 adults, with 21 individuals (0.15%) testing positive for CFA, while the follow-up survey conducted between December 2024 and January 2025 assessed 14 653 adults and detected seven positive cases (0.05%). No microfilariae were detected among the 28 antigen-positive individuals examined using nocturnal calibrated thick blood smears. National morbidity records documented 190 cases of lymphoedema and nine cases of hydrocoele. Conclusions Infection indicators remain well below WHO decision thresholds, suggesting that LF transmission is unlikely to be sustained. Sao Tome and Principe appears to be close to eliminating LF as a public health problem. However, strengthening morbidity management services will be essential to support the preparation of the national elimination dossier.