Retraction: Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine
by The PLOS Computational Biology Editors
Academic Intelligence · Curated Daily
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by The PLOS Computational Biology Editors
Continual learning for pre-trained vision-language models requires balancing three competing objectives: retaining pre-trained knowledge, preserving knowledge from a sequence of learned tasks, and maintaining the plasticity to acquire new knowledge. This paper presents KeepLoRA++, balancing these objectives through a unified dual-dimensional knowledge retention mechanism. We analyze knowledge distribution of Transformer architecture from both inter-layer and intra-layer perspectives. The inter-layer perspective examines how retention is distributed across layers, while the intra-layer perspective focuses on the parameter space within each layer. Our analysis reveals a structural property: general transferable knowledge is mainly encoded in the shallow layers and the principal subspace of the parameters, while task-specific adaptations are localized in the deep layers and the residual subspace. Motivated by this insight, KeepLoRA++ introduces a layer-scaled residual gradient adaptation method. New tasks are learned by restricting LoRA parameter updates to the residual subspace, combined with a shallow-to-deep layer scaling, to prevent interference with previously acquired capabilities. Specifically, the gradient of a new task is projected onto a subspace orthogonal to both the principal subspace of the pre-trained model and the dominant directions of previous task features, while simultaneously assigning smaller update magnitudes to shallow layers and larger ones to deeper layers. Our theoretical analysis and empirical evaluations confirm that KeepLoRA++ successfully balances these three competing objectives, consistently outperforming representative baselines across image classification, visual question answering, and video understanding tasks.
This paper presents a two-stage Hybrid Classical-Quantum (HCQ) pipeline for binary Alzheimer's disease (AD) classification from 3D T1-weighted structural MRI volumes, where the classical and quantum components are designed to complement each other rather than operate independently. A supervised 3D $\beta$-variational autoencoder (VAE) is trained end-to-end under voxel-wise reconstruction, KL-divergence, and focal classification losses that compress each 3D MRI volume (resized from 152 x 184 x 152 to 96 x 96 x 96) into a 64-dimensional latent code. Partial Least Squares (PLS) regression selects the six components in the latent code that best separate Alzheimer's Disease (AD) from cognitively normal (CN) subjects and rescales them into rotation angles, which are encoded onto a six-qubit register using the ZZ quantum feature map to give us the respective quantum states. The input to a precomputed-kernel Support Vector Machine (SVM) is an N x N Gram matrix (N = 308), created by calculating the overlap between every pair of quantum states. The novelty of this work lies in the fact that the quantum kernel operates directly on disease-aware features that are learned end-to-end by a supervised autoencoder, rather than on pre-extracted inputs. On 308 ADNI-1 subjects, consisting of 137 AD and 171 CN subjects, the baseline achieved 67.2% accuracy and 0.759 AUC, while the stability-enhanced variant reached 72.1% accuracy and 0.799 AUC with cross-fold variance halved. 3D Grad-CAM further helped validate our model's focus on brain regions linked to Alzheimer's. The HCQ pipeline could serve as a general-purpose framework for diagnostic classification across biomedical imaging domains that present similar challenges for classical approaches.
arXiv:2605.29906v2 Announce Type: replace Abstract: Text-to-motion (T2M) generation has broad applications in character animation, virtual avatars, and human-robot interaction. Existing methods typically generate pose trajectories or motion tokens directly from language, forcing a single model to handle semantic interpretation, long-horizon structure, and low-level physical realization. This coupling makes them costly and often unreliable for long, compositional, or semantically dense prompts. We propose Text2BFM, the first framework that aligns natural language with pretrained Behavioral Foundation Models (BFMs) for T2M generation without relying on heavy end-to-end motion generators. Text2BFM operates in the latent policy space of a frozen BFM, using it as an executable motion prior. A text-aligned variational behavioral bottleneck compresses BFM policy-latent sequences into compact motion representations that are compatible with language and preserve long-horizon behavioral structure. Generation is performed in this compact behavioral manifold with a lightweight conditional generator, and the resulting latent encoded behaviors are decoded into policy latents that drive the pretrained frozen BFM. By decoupling semantic planning from motion execution, Text2BFM achieves efficient, robust T2M generation and strong performance on long, compositional textual descriptions.
Reports in the biological literature disagree on whether a given model can predict a biological outcome from a given data sample — one study finding a model capable, another, on the same kind of data, finding it is not. This is particularly a challenge in relation to LLMs–where the models are large and opaque, with weights and training data inaccessible.textbf{ }Such disagreements cannot be settled by directly inspecting the model. To address this challenge, we considertextbf{ }an alternative approach: assessing whether the data sample is adequate to support the prediction asserted. For a given dataset, its substrate — the underlying structure of the data — determines what any model can recover, independent of architecture or capacity. At the same time, predicting the present state of a biological process and predicting the direction of its future change are different tasks; the second is supportable among AI models only where the data encode direction as determinable from the state — a property we call encoding — and is unsupportable where the same observed state precedes change in opposite directions — a property we call non-identifiability, in the informational rather than the statistical sense. We introduce two generic metrics, Predictive Blindness Risk (PBR) and Prediction Indeterminacy Measure (PIM), that evaluate a data substrate for predictive accuracy directly — without access to model weights, architecture, or training data — and locate the regions of a data substrate where a predictive claim can be supported and where it cannot. Using human biological subjects, we employ the Yale Brain Metastases Longitudinal Data (1,430 human subjects; 11,892 MRI studies; four sequences) and show that direction of change was non-identifiable across regions encompassing the majority of transitions; a nonlinear AI model gained essentially nothing over majority-direction prediction there while recovering direction near-perfectly where the state encoded it; and model accuracy tracked data-substrate resolvability continuously (Spearman {rho} = -0.95 to -1.00). The metrics adjudicate, before any model is trusted and from the data alone, where claims of predictive accuracy — of state, or of the law of change — can be supported.
arXiv:2606.11632v1 Announce Type: cross Abstract: Agentic infrastructure introduces a critical control-plane authorization problem: non-deterministic reasoning systems can propose high-stakes mutations to production resources, yet existing security mechanisms – such as identity and access management (IAM), policy engines, consensus protocols, and audit logs – either enforce static, context-unaware permissions or merely record actions post-execution. This paper introduces the Sovereign Assurance Boundary (SAB), a certificate-bound runtime admission layer for autonomous execution authority. SAB intercepts agent proposals at an assurance airlock, compiles them into typed execution contracts $C$, and binds these contracts to cryptographic evidence digests $H(E)$ and policy versions. The contracts are then routed through consequence-aware certification paths. Upon successful admission, the system emits a signed Sovereign Assurance Certificate ($\Omega$) that is strictly scoped to a specific execution identity, revocation epoch, and validity window. Finally, a sovereign execution broker verifies $\Omega$ and performs fresh pre-execution revocation and drift checks before invoking infrastructure APIs. We detail the airlock-broker architecture, formalize its admission and revocation invariants, and report preliminary feasibility measurements from a Go prototype evaluated over 2,500 admission attempts. Ultimately, this broker-enforced model prevents autonomous reasoning from directly mutating state, transforming delegated execution authority into a cryptographically verifiable, evidence-bound, revocable, and replayable runtime artifact.
arXiv:2606.13370v1 Announce Type: new Abstract: This study examines training dynamics in a small Llama-style language model trained under a fixed, compute-constrained token budget. Rather than evaluating efficiency solely through endpoint performance, the study uses a quantitative experimental repeated measures design to analyze how validation loss, validation perplexity, rolling volatility, backslide behavior, spike behavior, and between-seed variability change across token-based training intervals. Six independent training runs were conducted on a 4.26-million-parameter model using the TinyStories corpus, CPU-based full-precision training, and a target budget of approximately 20 million cumulative training tokens. Metrics were collected across 21 intervals, producing 126 seed-by-interval observations. Repeated measures ANOVA showed statistically significant interval effects for validation loss, validation perplexity, and rolling volatility. Descriptive trajectories revealed rapid early improvement followed by non-monotonic degradation during later training intervals. Mean validation loss decreased from 8.3552 at initialization to 2.7996 near 4 million tokens, but increased to 3.9010 by the final checkpoint. Validation perplexity followed the same pattern, falling sharply early in training before rising later. Derived telemetry further showed recurrent validation-loss backslides and no interval-summary evidence of a stable phase under the predefined criteria. These findings suggest that compute-aware language model evaluation should examine training trajectories rather than endpoint metrics alone. In constrained compute settings, additional token exposure may increase computational cost without producing proportional generalization gains, and interval-level telemetry can reveal instability, regression, and diminishing returns that final metrics may obscure.
Spatial generalization is critical for imitation-learned manipulation policies, but achieving it typically requires scaling demonstrations across diverse object poses, robot configurations, and camera viewpoints. Data augmentation from a few source demonstrations offers a practical alternative to costly real-world collection. Simulation-based augmentation can create controllable variation, but requires complex environment and object setup and may introduce a sim-to-real gap. Recent real-to-real methods avoid these issues by jointly editing 3D observations and action trajectories from real demonstrations, yet they still rely on strong 3D scene parsing and geometry completion, and often produce observations tailored to 3D pointcloud policies rather than RGB-based 2D policies. We propose R2RDreamer, a real-to-real demonstration augmentation framework that preserves the geometric consistency of 3D action-observation editing while moving visual completion to 2D video space. Specifically, R2RDreamer first performs lightweight 3D augmentation by editing incomplete object pointclouds and end-effector trajectories in a shared 3D frame; it then projects the edited scene into masked image-space control videos with occlusion-aware reasoning and uses a dense-control image-to-video model to complete temporally coherent RGB observations. Experiments on spatially shifted manipulation tasks with both 2D diffusion-style policies and vision-language-action policies show that R2RDreamer improves spatial generalization from limited source demonstrations, with analyses validating the contributions of 3D editing, occlusion-aware projection, and video completion.
arXiv:2606.17093v1 Announce Type: new Abstract: Learning-based single-shot fringe projection profilometry (FPP) has been studied mostly at close range. The long-range regime (standoff beyond 1 m) remains largely unaddressed: inverse-square intensity falloff lowers fringe signal-to-noise ratio and degrades physical ground truth, the single-shot problem is ill-posed because fringe-order information is absent from one image, and these architectures have not been studied mechanistically. We present a diagnose-repair-verify study using mechanistic interpretability (MI) and conformal uncertainty quantification (UQ) as convergent diagnostics: they agree on one physical failure locus, driving and verifying an architectural repair. On a photorealistic synthetic benchmark (15,600 fringe images, 50 objects at 1.5-2.1 m), a best UNet baseline reaches 14.54 mm object mean absolute error (MAE). Three probes (linear probing, Grad-CAM, flat-plane out-of-distribution test) converge: the baseline solves the task via object-boundary shape priors rather than fringe-phase decoding. We repair this with PhiCalNet, which outputs wrapped phase rather than depth and applies a fixed differentiable calibration layer mapping phase to depth, removing the shape-prior solution from the hypothesis space architecturally rather than by a loss penalty. A physics-informed loss that enforces the same physics as a soft penalty on a depth-regressing network yields no measurable gain, isolating the architecture as the operative factor. PhiCalNet reduces object MAE 3.3x to 4.46 mm; the residual is carried by 0.103% of pixels at the +/-pi wrap discontinuity. Pixel-wise conformal UQ confirms the diagnosis: rejecting the top 5% of object pixels by snapshot disagreement cuts PhiCalNet RMSE by 64% (20.6->7.4 mm) versus 3.5% for the baseline. MI and UQ converge on the same failure locus.
Motivation: SNARE proteins catalyse membrane fusion across the eukaryotic endomembrane system, from synaptic vesicle exocytosis to intracellular trafficking, endosomal and vacuolar transport, and autophagy, and their accurate domain annotation depends on the quality of profile models and the sequence diversity behind them. The original SNARE domain classification predates the recent expansion of eukaryotic sequence data, leaving its HMM profiles and subgroup coverage unable to resolve divergent and lineage-specific paralogs. Results: We present an updated release of TRACEY built on a resynchronized, non-redundant collection of 18,915 curated SNARE proteins spanning 1,188 species, together with a consolidated set of 83 HMM profiles, including 43 models for newly defined subgroups, reconstructed through an iterative, mixture-model-driven procedure. In direct comparison with the legacy models, at least ~75% of sequences in every overlapping group scored better with the new HMMs, indicating systematic gains in domain detection. A redesigned web interface adds multiparameter querying, FASTA download, and direct scanning of user-submitted sequences against the curated profiles. Availability and implementation: TRACEY is freely available at https://tracey.unil.ch.
arXiv:2606.11341v1 Announce Type: new Abstract: Modular neural network pipelines suffer from error compounding: noise at any module boundary propagates and potentially amplifies through subsequent modules. We introduce energy conservation as a hard physical constraint on inter-module information flow. Activation energy (the squared L2 norm of feature vectors) is enforced to be exactly preserved at every module boundary. Unlike soft energy penalties, conservation is an inviolable law: the network may redistribute energy across neurons but cannot create or destroy it. Four experiments on CIFAR-10 demonstrate: (1) conservation retains 77.4% of clean accuracy at noise sigma=0.2, versus 35.1% for baselines and 30.9% for energy-penalized models (p
Nature staff discuss some of the week’s top science news. Hear the biggest stories from the world of science | 12 June 2026
LLM-based agents have shown increasing potential in automating scientific discovery. Given an optimizable metric and an execution environment, they can propose, validate, and iterate scientific solutions, and have produced results that outperform human-designed approaches. As model capabilities continue to improve, we argue that the bottleneck for autonomous scientific discovery is shifting from prescribing agent workflows to designing agent environments: the resources, constraints, and interfaces that shape agent behavior. We frame this as environment engineering: building environments that amplify productive behaviors, such as open-ended exploration, systematic artifact management, and inter-agent collaboration, while suppressing harmful behaviors, such as reward hacking and high-friction human oversight. We present EurekAgent, an environment-engineered agent system for metric-driven autonomous scientific discovery. EurekAgent engineers the environment along four dimensions: permissions engineering for bounded agent execution and isolated evaluation; artifact engineering for filesystem and Git-based collaboration; budget engineering for budget-aware exploration; and human-in-the-loop engineering for easy human supervision and intervention. EurekAgent sets new state-of-the-art results on multiple mathematics, kernel engineering, and machine learning tasks, including new state-of-the-art 26-circle packing results discovered with less than $11 in total API cost. We open-source our code and results, and call for environment engineering as a core research direction for developing reliable autonomous research agents.
arXiv:2606.19712v1 Announce Type: new Abstract: While much effort has focused on developing and benchmarking high-performance neural networks, less attention has been given to how dataset properties, known to practitioners, can guide efficient model selection. Neural models are typically evaluated on datasets with thousands of classes, yet many real-world applications involve fewer than ten. To address this understudied but common setting, we develop a measure of classification difficulty based on data-side properties and show how it enables more efficient model selection for few-class datasets, where traditional approaches are less effective. We term this phenomenon "few-class distinctiveness". Our metric allows comparison of models and datasets 6 to 29$\times$ faster than repeated training and testing. Leveraging this insight, we extend scaled model families below the smallest published models, achieving greater efficiency at similar accuracy, for example models up to 42% smaller than YOLOv5-nano for a mobile robot task. Targeting resource-constrained applications, we demonstrate few-class model selection across mobile robot, drone, and IoT scenarios, highlighting practical gains in efficiency without sacrificing performance.
arXiv:2606.07362v2 Announce Type: replace Abstract: As scalable inference services become popular, the cold start latency of an inference engine becomes important. Today, vLLM has evolved into the de facto inference engine of choice for many inference workloads. Although popular, due to its complexity and rapid evolution, there has not been a systematic study of its startup latency. With major architectural innovations such as the V1 API and the introduction of torch.compile, this paper presents the first detailed performance characterization of vLLM startup latency. We break down the startup process into six foundational steps and demonstrate that it is predominantly CPU bound. Each step exhibits consistent and interpretable scaling trends with respect to model-level and system-level parameters, enabling fine-grained attribution of latency sources. Building on these insights, we develop a lightweight analytical model that accurately predicts vLLM startup latency for a given hardware configuration, providing actionable guidance for resource planning in large-scale inference environments. All benchmarking datasets, analysis tools, and prediction scripts are open sourced at https://github.com/upb-cn/vllm-startup-profiler.
arXiv:2309.15769v3 Announce Type: replace-cross Abstract: Recent advances in deep learning have highlighted the phenomenon of benign overfitting in overparameterized statistical models, sparking significant interest in understanding its foundations. Owing to its simplicity and practical relevance, the ordinary least squares (OLS) interpolator has become a key object of study for gaining theoretical insight into this phenomenon. While the properties of OLS are well understood in classical underparameterized settings, its behavior in the overparameterized regime – unlike that of ridge regression or the lasso – remains comparatively less explored. We contribute to this growing literature by deriving new algebraic and statistical results for the minimum $\ell_2$-norm OLS interpolator. In contrast to much of the existing work, which focuses on prediction risk, we center our analysis on parameter estimation and inference, which are fundamental for many statistics and causal inference applications. Specifically, we establish overparameterized analogues of (i) the leave-$k$-out formulas, (ii) the omitted variable bias formula, and (iii) the Frisch-Waugh-Lovell theorem. Under the Gauss-Markov model, we further extend the Gauss-Markov theorem and analyze variance estimation under homoskedasticity in the overparameterized setting. Collectively, these results provide a systematic framework for studying parameter estimation and inference in overparameterized linear models, offering a novel perspective on benign overfitting beyond its implications for prediction.
arXiv:2606.07001v2 Announce Type: replace-cross Abstract: High-quality training data is essential to large language models (LLMs) and typically requires extensive and costly manual curation. Existing automatic data preparation methods rely on predefined pipelines or customized human instructions, which limits their adaptability to diverse data distributions and lacks principled guidance from high-quality examples. In this paper, we introduce DataEvolver, the first self-evolving data preparation system that automatically constructs pipelines to transform raw data into high-quality data. DataEvolver employs a multi-level mechanism to ensure both pipeline executability and effectiveness. At the operator level, it incrementally expands the operator set to construct a logical plan while resolving dependency conflicts. At the pipeline level, it instantiates logical plans into executable code and iteratively refines pipeline orchestration through a feedback loop that reduces the distribution gap between prepared data and high-quality examples. Experiments on seven benchmarks show that DataEvolver substantially improves data quality and achieves an average 10\% gain in downstream LLM performance compared with training on original data, highlighting new opportunities for the iterative co-evolution of LLMs and data.
arXiv:2606.14954v1 Announce Type: cross Abstract: We develop a general framework for analyzing representation costs of parametric data-fitting methods through their parameter-space regularizers. From this abstract perspective, we define representation costs for arbitrary parametric models and reveal their induced (native) function spaces. This unifies recent function-space views of data-fitting methods. We also prove that many natural results hold in this abstract setting, including representer theorems for parametric methods on their native spaces. The framework also rigorously connects parametric methods with their equivalent nonparametric descriptions under sufficient overparameterization. Classical methods and their native spaces, such as kernel methods / reproducing kernel Hilbert spaces, wavelets / Besov spaces, and shallow neural networks / variation spaces emerge as special cases of our abstract framework. A byproduct of "axiomatizing" the study of representation costs is that we also immediately obtain new results for deep neural networks: For depth-$L$ feedforward ReLU networks, their induced native spaces are $p$-normable quasi-Banach spaces with $p = 2/L$. This reveals that the inductive bias of deep neural networks (as given by the representation cost) cannot be captured by norms for depths $L > 2$.
Recent progress in vision-language models has enabled the processing of increasingly long video sequences, but the ability to handle extended token streams does not translate to understanding of narrative structure in long videos. Existing long video benchmarks focus on needle-in-a-haystack retrieval rather than evaluating how low-level actions form events, how events interact across time, and how narratives progress, for example, whether a model can connect an early setback, such as a job loss to a later relationship breakup, despite long gaps, intervening scenes, or flashbacks that reframe what occurred. We introduce NEST (Narrative Event Structures in Time for Long Video Understanding), a dataset of 1005 full-length movies (avg. 98 minutes), each annotated with 102 multimodal narrative events grounded in visual content, dialogue, and audio. NEST captures multimodal narrative events with structured annotations grounded in visual content, dialogue, and audio, and links them through relations that reflect narrative structure, including temporal ordering, hierarchical composition, and long-range dependencies. We introduce baselines for event trigger detection (ETD), event localization (EL), event argument extraction (EAE), and event relation extraction (ERE). The benchmark is highly challenging for grounded event discovery, with ETD below 8%, EL under 6%, and EAE below 11%. In contrast, ERE is more tractable once events are given, reaching 35.45% F1 zero-shot and 44.42% F1 after fine-tuning.
arXiv:2606.11303v1 Announce Type: cross Abstract: We investigate the nonequilibrium dynamics of a one-dimensional interacting system across a transition from a charge-density-wave (CDW) phase to a symmetry-protected topological (SPT) phase. Starting from a CDW initial state, we study both sudden quenches and slow ramps into the SPT regime. While the CDW order melts under both protocols, the fate of topological order is sharply different. Following a sudden quench, long-range SPT order does not emerge because the post-quench state contains a finite density of excitations above the topological ground state. In contrast, slow ramps allow the system to follow the instantaneous ground state away from the critical region, enabling the buildup of SPT order with deviations governed by Kibble-Zurek defect production. The dynamics is solvable via a unitary mapping to a quadratic fermionic Hamiltonian, allowing us to compute the Loschmidt echo, correlation functions, and string correlator. The Loschmidt rate function exhibits cusps signaling dynamical quantum phase transitions, while the correlation dynamics reveal the contrasting mechanisms governing quenches and ramps across the transition. These results demonstrate that entering the topological regime is not sufficient for the emergence of topological order; the decisive factor is the suppression of excitation production during the evolution.
arXiv:2606.19984v1 Announce Type: new Abstract: Reservoir computing offers a lightweight framework for forecasting dynamical systems but may struggle to capture long-range dependencies due to limited representational capacity. Conventional reservoir computing recurrently uses trainable reservoirs with hyperparameter sensitivity, while the next-generation reservoir computing removes recurrence at the cost of rapidly growing feature dimensions. Here, we develop Kolmogorov-Arnold Reservoir Computing (KARC), which replaces reservoirs with explicit basis-function expansions inspired by the Kolmogorov-Arnold representation theorem. We rigorously show that KARC is a lightweight design of Kolmogorov-Arnold networks (KANs), preserving the potential expressive capacity of KANs while admitting efficient closed-form training of reservoir computing. At comparable cost, KARC outperforms existing reservoir computing methods on challenging benchmarks including partial differential equations. It can also be integrated with generative diffusion models for text-to-image generation. This work thus establishes a principled bridge between reservoir computing and KANs, enabling efficient and high-fidelity dynamical system forecasting.
Multilingual benchmarks are central to evaluating large language models (LLMs) across languages, but they suffer from three issues: exhaustive evaluation scales linearly with the number of languages, automatic translation introduces errors that are easily missed at scale, and some items conflate general and culture-specific knowledge. We address all three with a unified statistical framework, Multilingual-IRT, which extends Item Response Theory with per-language difficulty deviations, split discriminability separating content from language effects, and per-language ability residuals. Fitting Multilingual-IRT on 25 LLMs across 29 languages of MMLU-Pro-X, we show that its fitted parameters support three practical applications: predicting unobserved (item, LLM, language) instances with 11-16% lower binary cross-entropy than the strongest accuracy-based baseline, surfacing candidate translation errors distributed across all 28 non-English languages, whereas accuracy-based baselines concentrate detections in a few languages, and recovering culture-specific items that accuracy-based baselines miss.
arXiv:2606.17545v1 Announce Type: new Abstract: Simulation based solvers for optimal stopping problems must discretize the stopping decision. Under classical dynamic programming, a coarse exercise grid with only a few stopping opportunities can materially undervalue the optimal expected reward, whereas on a very fine grid, approximation errors accumulate through the backward recursion. To remove this limitation, we develop a new reinforcement-learning inspired algorithm that enables us to learn the exercise rule at arbitrarily fine time resolution. Our CARLOS (Continuous-time Adaptive Reinforcement Learning for Optimal Stopping) algorithm utilizes an aggregate deep neural network (ADNN) to learn a joint space-time decision boundary. Starting from a coarse time grid, we progressively increase the frequency of stopping opportunities, while in parallel training the ADNN to refine its timing-value estimates. We moreover design an adaptive sampling strategy that gradually concentrates training effort near the stopping boundary. Benchmarked results show that CARLOS delivers higher prices than existing Bermudan solvers, approaching the American upper bound, and achieves high computational efficiency relative to non-RL comparators.
arXiv:2606.20306v1 Announce Type: new Abstract: Quantum batteries have been proposed as locally precharged work sources for superconducting quantum technologies, suggesting a route to reduce continuously supplied microwave drives. Here we ask whether the pump tone of a quantum-limited parametric amplifier can be replaced, or strongly duty-cycled, by a finite bosonic quantum battery. Quantizing the pump of a nondegenerate parametric amplifier exposes a resource distinction hidden in the classical description: stored pump energy can generate signal-idler photons, but pump phase coherence is required to generate a phase-locked amplifier field. In a closed trilinear model, coherent and phase-randomized coherent pumps with the same photon-number distribution produce comparable pair numbers, yet only the coherent pump produces anomalous two-mode coherence and an EPR-squeezed interference dip. Including leakage, we collect the emitted fields into cascaded temporal modes. At matched collector bandwidth, the coherent pump gives \(I_{\min}^{(f)}=0.553\), whereas the phase-randomized pump gives \(I_{\min}^{(f)}=1.94\) at nearly identical collected energy. Weak amplitude squeezing slightly improves the dip by reducing finite-pump number fluctuations while preserving the coherent displacement. Thus battery-powered parametric amplification requires phase-coherent stored energy, possibly assisted by number-noise reduction, rather than stored energy alone.
Motivation: Proteolysis-targeting chimeras (PROTACs) enable targeted protein degradation through ternary complex formation with E3 ubiquitin ligase. However, the rational design of PROTACs remains highly challenging due to limited structure-activity relationship data and the vast conformational diversity of linkers. Existing computational approaches can be broadly divided into structure-based ternary modelling methods and fragment-based linker generation models. Although these approaches have advanced PROTAC design, they typically neglect key physicochemical constraints and linker-length control during the generation process, causing the generated PROTACs to lack balanced structural properties required for effective ternary complex formation with drug-like characteristics. Results: To address these limitations, we propose DesignMaster, a diffusion-based generative framework that explicitly incorporates linker length and physicochemical properties as controllable conditioning signals. DesignMaster employs an E(3)-equivariant graph Transformer with a gated multi-condition fusion module to inject linker length and physicochemical constraints throughout the diffusion process, enabling fine-grained and constraint-aware molecular generation. Experiments on PROTAC-DB 2.0 and 3.0 demonstrate that DesignMaster outperforms state-of-the-art baselines, with a 3.2% improvement in validity and a 34.4% improvement in recovery. The Case study shows DesignMaster achieves a 51.78% reduction in RMSD when predicting the linker of PROTAC BCPyr targeting 6W7O, highlighting its potential for practical structure-guided PROTAC design. Availability: The source code and datasets are available at https://github.com/ABILiLab/DesignMaster.