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Oct 16

GPCR-Filter: a deep learning framework for efficient and precise GPCR modulator discovery

G protein-coupled receptors (GPCRs) govern diverse physiological processes and are central to modern pharmacology. Yet discovering GPCR modulators remains challenging because receptor activation often arises from complex allosteric effects rather than direct binding affinity, and conventional assays are slow, costly, and not optimized for capturing these dynamics. Here we present GPCR-Filter, a deep learning framework specifically developed for GPCR modulator discovery. We assembled a high-quality dataset of over 90,000 experimentally validated GPCR-ligand pairs, providing a robust foundation for training and evaluation. GPCR-Filter integrates the ESM-3 protein language model for high-fidelity GPCR sequence representations with graph neural networks that encode ligand structures, coupled through an attention-based fusion mechanism that learns receptor-ligand functional relationships. Across multiple evaluation settings, GPCR-Filter consistently outperforms state-of-the-art compound-protein interaction models and exhibits strong generalization to unseen receptors and ligands. Notably, the model successfully identified micromolar-level agonists of the 5-HT1A receptor with distinct chemical frameworks. These results establish GPCR-Filter as a scalable and effective computational approach for GPCR modulator discovery, advancing AI-assisted drug development for complex signaling systems.

Seeing the Unseen: A Frequency Prompt Guided Transformer for Image Restoration

How to explore useful features from images as prompts to guide the deep image restoration models is an effective way to solve image restoration. In contrast to mining spatial relations within images as prompt, which leads to characteristics of different frequencies being neglected and further remaining subtle or undetectable artifacts in the restored image, we develop a Frequency Prompting image restoration method, dubbed FPro, which can effectively provide prompt components from a frequency perspective to guild the restoration model address these differences. Specifically, we first decompose input features into separate frequency parts via dynamically learned filters, where we introduce a gating mechanism for suppressing the less informative elements within the kernels. To propagate useful frequency information as prompt, we then propose a dual prompt block, consisting of a low-frequency prompt modulator (LPM) and a high-frequency prompt modulator (HPM), to handle signals from different bands respectively. Each modulator contains a generation process to incorporate prompting components into the extracted frequency maps, and a modulation part that modifies the prompt feature with the guidance of the decoder features. Experimental results on commonly used benchmarks have demonstrated the favorable performance of our pipeline against SOTA methods on 5 image restoration tasks, including deraining, deraindrop, demoiréing, deblurring, and dehazing. The source code and pre-trained models will be available at https://github.com/joshyZhou/FPro.

  • 6 authors
·
Mar 30, 2024

Searching for Materials with High Refractive Index and Wide Band Gap: A First-Principles High-Throughput Study

Materials combining both a high refractive index and a wide band gap are of great interest for optoelectronic and sensor applications. However, these two properties are typically described by an inverse correlation with high refractive index appearing in small gap materials and vice-versa. Here, we conduct a first-principles high-throughput study on more than 4000 semiconductors (with a special focus on oxides). Our data confirm the general inverse trend between refractive index and band gap but interesting outliers are also identified. The data are then analyzed through a simple model involving two main descriptors: the average optical gap and the effective frequency. The former can be determined directly from the electronic structure of the compounds, but the latter cannot. This calls for further analysis in order to obtain a predictive model. Nonetheless, it turns out that the negative effect of a large band gap on the refractive index can counterbalanced in two ways: (i) by limiting the difference between the direct band gap and the average optical gap which can be realized by a narrow distribution in energy of the optical transitions and (ii) by increasing the effective frequency which can be achieved through either a high number of transitions from the top of the valence band to the bottom of the conduction or a high average probability for these transitions. Focusing on oxides, we use our data to investigate how the chemistry influences this inverse relationship and rationalize why certain classes of materials would perform better. Our findings can be used to search for new compounds in many optical applications both in the linear and non-linear regime (waveguides, optical modulators, laser, frequency converter, etc.).

  • 6 authors
·
Sep 4, 2018

MDTransformer: A Hardware-Software Co-Design of Mode-Division Photonic Transformer Accelerator with Inverse-Designed Coherent Crossbar

Recently, photonic transformer accelerators (PTAs) have successfully achieved significant speedup and energy efficiency improvements over electronic accelerators for expediting Transformer inference. However, state-of-the-art rely on expensive multi-wavelength light generation and large dot-product units due to active phase-shifter components, thus making their approach inefficient and impractical. To address this, we propose MDTransformer, a novel hardware-software co-design of PTA based on mode-division optical dataflow and operations. Specifically, MDTransformer performs complex matrix operations using spatial-mode interference, that leverages the inverse-designed multi-mode couplers, crossings, and Mach-Zehnder IQ modulators into a compact mode-division photonic tensor core (MPTC), capable of executing matrix multiplications in the optical domain. Its each guided mode (i.e., TE0-TE3) acts as an independent computational lane, enabling four-fold parallelism-per-waveguide without spectral filtering or free-spectral-range limitations. Moreover, its coherent detection and IQ modulation jointly encode amplitude and phase, realizing complex-valued arithmetic for full-range operations in transformers. MDTransformer offers analog multiplication with sub-4-bit effective precision and inter-modal crosstalk below -30 dB. Its inverse-designed approach also offers scalable and full compatibility with single-laser continuous-wave operation at 1550 nm. Experimental results show that MDTransformer achieves 40.4% area reduction, 63.6% power saving, 40.6% energy saving, and comparable latency over the state-of-the-art PTA across different workloads (i.e., DeiT-Tiny/Small/Base and BERT-Base/Large). These results show that MDTransformer offers a practical solution for high-performance and energy-efficient transformer-based systems.

  • 5 authors
·
Jul 27

Influence of astrocyte feedback and noise on breathing neural clusters

Astrocytes are increasingly recognized as active regulators of neural dynamics, yet their role in large-scale synchronization remains incompletely understood. Building on the discovery of breathing cluster synchronization in neuron-astrocyte networks, we investigate whether this phenomenon persists under more biologically realistic conditions by incorporating thermosensitive neuronal dynamics, intrinsic electric-field interactions, stochastic perturbations, and delayed astrocytic feedback. Through systematic numerical simulations of a network containing structurally symmetric neuronal subsets, we show that breathing clusters characterized by intermittent alternations between synchronized and desynchronized states, remain robust across a broad range of biophysical conditions. The results reveal a non-monotonic dependence on astrocytic attenuation and feedback parameters, with intermediate values maximizing rhythmic switching through a slow push-pull regulatory mechanism. Temperature and electric-field effects primarily modulate neuronal excitability and the tolerance of the breathing state to noise, while elevated stochastic perturbations progressively destabilize cluster coherence. In contrast, the phenomenon exhibits remarkable robustness to biologically realistic astrocytic delays. Importantly, our findings indicate that the emergence of breathing synchronization remains fundamentally governed by the interplay between network symmetry and astrocyte-mediated feedback, whereas temperature, electric fields, and noise act as modulators of its stability and temporal organization. These results establish breathing cluster synchronization as a robust organizing principle of astrocyte-regulated networks and provide a quantitative framework for understanding how glial regulation shapes cortical state-switching under realistic physiological conditions.

  • 3 authors
·
Oct 2

DreamClear: High-Capacity Real-World Image Restoration with Privacy-Safe Dataset Curation

Image restoration (IR) in real-world scenarios presents significant challenges due to the lack of high-capacity models and comprehensive datasets. To tackle these issues, we present a dual strategy: GenIR, an innovative data curation pipeline, and DreamClear, a cutting-edge Diffusion Transformer (DiT)-based image restoration model. GenIR, our pioneering contribution, is a dual-prompt learning pipeline that overcomes the limitations of existing datasets, which typically comprise only a few thousand images and thus offer limited generalizability for larger models. GenIR streamlines the process into three stages: image-text pair construction, dual-prompt based fine-tuning, and data generation & filtering. This approach circumvents the laborious data crawling process, ensuring copyright compliance and providing a cost-effective, privacy-safe solution for IR dataset construction. The result is a large-scale dataset of one million high-quality images. Our second contribution, DreamClear, is a DiT-based image restoration model. It utilizes the generative priors of text-to-image (T2I) diffusion models and the robust perceptual capabilities of multi-modal large language models (MLLMs) to achieve photorealistic restoration. To boost the model's adaptability to diverse real-world degradations, we introduce the Mixture of Adaptive Modulator (MoAM). It employs token-wise degradation priors to dynamically integrate various restoration experts, thereby expanding the range of degradations the model can address. Our exhaustive experiments confirm DreamClear's superior performance, underlining the efficacy of our dual strategy for real-world image restoration. Code and pre-trained models will be available at: https://github.com/shallowdream204/DreamClear.

  • 7 authors
·
Oct 24, 2024 3

Spatially Encoded Polaritonic Ultra-Strong Coupling in Gradient Metasurfaces with Epsilon-Near-Zero Modes

We introduce a platform to achieve ultra-strong coupling (USC) between light and matter using widely available materials. USC is a light-matter interaction regime characterized by coupling strengths exceeding 10% of the ground state energy. It gives rise to novel physical phenomena, such as efficient single-photon coupling and quantum gates, with applications in quantum sensing, nonlinear optics, and low-threshold lasing. Although early demonstrations in plasmonic systems have been realized, achieving USC in dielectric platforms, which offer lower losses and high Q-factors, remains challenging due to typically low mode overlap between the photonic field and the material resonance. Here we leverage dielectric dual gradient metasurfaces supporting quasi-bound states in the continuum to spatially encode both the spectral and coupling parameter space and demonstrate USC to an epsilon-near-zero (ENZ) mode in an ultra-thin SiO2 layer. The strong out-of-plane electric fields in our tapered bar structure overlap exceptionally well with those of the ENZ mode, resulting in a normalized coupling strength of 0.101 and a mode splitting equivalent to 20% of the ENZ mode energy; a four- to five-fold increase compared to previous approaches. The strong field confinement of our approach opens new possibilities for compact and scalable polaritonic devices, such as tunable frequency converters and low-energy optical modulators.

  • 7 authors
·
Feb 19, 2025

SPARK: Jailbreaking T2V Models by Synergistically Prompting Auditory and Recontextualized Knowledge

Jailbreak attacks can circumvent model safety guardrails and reveal critical blind spots. Prior attacks on text-to-video (T2V) models typically add adversarial perturbations to obviously unsafe prompts, which are often easy to detect and defend. In contrast, we show that benign-looking prompts containing rich, implicit cues can induce T2V models to generate semantically unsafe videos that both violate policy and preserve the original (blocked) intent. To realize this, we propose SPARK, a jailbreak framework that leverages T2V models cross-modal associative patterns via a modular prompt design. Specifically, our prompts combine three components: neutral scene anchors, which provide the surface-level scene description extracted from the blocked intent to maintain plausibility; latent auditory triggers, textual descriptions of innocuous-sounding audio events (e.g., creaking, muffled noises) that exploit learned audio-visual co-occurrence priors to bias the model toward particular unsafe visual concepts; and stylistic modulators, cinematic directives (e.g., camera framing, atmosphere) that amplify and stabilize the latent trigger's effect. We formalize attack generation as a constrained optimization over the above modular prompt space and solve it with a guided search procedure that balances stealth and effectiveness. Extensive experiments over 7 T2V models demonstrate the efficacy of our attack, achieving a +23% improvement in average attack success rate in commercial models.

  • 9 authors
·
Mar 5