Mingyu Li

LG
h-index46
25papers
910citations
Novelty55%
AI Score62

25 Papers

CLNov 4, 2022Code
1Cademy @ Causal News Corpus 2022: Leveraging Self-Training in Causality Classification of Socio-Political Event Data

Adam Nik, Ge Zhang, Xingran Chen et al. · mila

This paper details our participation in the Challenges and Applications of Automated Extraction of Socio-political Events from Text (CASE) workshop @ EMNLP 2022, where we take part in Subtask 1 of Shared Task 3. We approach the given task of event causality detection by proposing a self-training pipeline that follows a teacher-student classifier method. More specifically, we initially train a teacher model on the true, original task data, and use that teacher model to self-label data to be used in the training of a separate student model for the final task prediction. We test how restricting the number of positive or negative self-labeled examples in the self-training process affects classification performance. Our final results show that using self-training produces a comprehensive performance improvement across all models and self-labeled training sets tested within the task of event causality sequence classification. On top of that, we find that self-training performance did not diminish even when restricting either positive/negative examples used in training. Our code is be publicly available at https://github.com/Gzhang-umich/1CademyTeamOfCASE.

LGYesterday
Low-Rank Decay for Grokking in Scale-Invariant Transformers: A Spectral-Geometric View

Mingyu Li

Modern Transformer architectures frequently employ normalization mechanisms such as RMSNorm and Query-Key Normalization, making parts of the model approximately scale-invariant with respect to weight magnitudes. In this regime, standard Frobenius-norm weight decay acts purely along the radial direction of the weight space and cannot directly simplify the function represented by the normalized layer. We study grokking in small algorithmic tasks through this lens and propose \emph{Low-Rank Decay} (LRD), a nuclear-norm-like spectral regularizer whose subgradient -- the polar factor $UV^\top$ -- retains a tangential component even in the scale-invariant setting. This distinction has a concrete dynamical consequence: after the model memorizes the training set and task gradients vanish, L2 decay can no longer reshape the weight spectrum, whereas LRD continues to compress singular values in an $\ell_1$-like fashion. On modular arithmetic tasks, we find that LRD induces rapid effective-rank collapse in Query/Key matrices and expands the data-fraction boundary at which delayed generalization (grokking) occurs. We further provide a spectral-geometric interpretation through the ``needle-to-fan'' expansion of the nuclear-norm subdifferential near low-rank strata.

AIOct 16, 2023Code
EconAgent: Large Language Model-Empowered Agents for Simulating Macroeconomic Activities

Nian Li, Chen Gao, Mingyu Li et al.

The advent of artificial intelligence has led to a growing emphasis on data-driven modeling in macroeconomics, with agent-based modeling (ABM) emerging as a prominent bottom-up simulation paradigm. In ABM, agents (e.g., households, firms) interact within a macroeconomic environment, collectively generating market dynamics. Existing agent modeling typically employs predetermined rules or learning-based neural networks for decision-making. However, customizing each agent presents significant challenges, complicating the modeling of agent heterogeneity. Additionally, the influence of multi-period market dynamics and multifaceted macroeconomic factors are often overlooked in decision-making processes. In this work, we introduce EconAgent, a large language model-empowered agent with human-like characteristics for macroeconomic simulation. We first construct a simulation environment that incorporates various market dynamics driven by agents' decisions regarding work and consumption. Through the perception module, we create heterogeneous agents with distinct decision-making mechanisms. Furthermore, we model the impact of macroeconomic trends using a memory module, which allows agents to reflect on past individual experiences and market dynamics. Simulation experiments show that EconAgent can make realistic decisions, leading to more reasonable macroeconomic phenomena compared to existing rule-based or learning-based agents. Our codes are released at https://github.com/tsinghua-fib-lab/ACL24-EconAgent.

CLOct 31, 2022Code
1Cademy @ Causal News Corpus 2022: Enhance Causal Span Detection via Beam-Search-based Position Selector

Xingran Chen, Ge Zhang, Adam Nik et al.

In this paper, we present our approach and empirical observations for Cause-Effect Signal Span Detection -- Subtask 2 of Shared task 3~\cite{tan-etal-2022-event} at CASE 2022. The shared task aims to extract the cause, effect, and signal spans from a given causal sentence. We model the task as a reading comprehension (RC) problem and apply a token-level RC-based span prediction paradigm to the task as the baseline. We explore different training objectives to fine-tune the model, as well as data augmentation (DA) tricks based on the language model (LM) for performance improvement. Additionally, we propose an efficient beam-search post-processing strategy to due with the drawbacks of span detection to obtain a further performance gain. Our approach achieves an average $F_1$ score of 54.15 and ranks \textbf{$1^{st}$} in the CASE competition. Our code is available at \url{https://github.com/Gzhang-umich/1CademyTeamOfCASE}.

LGMay 31
Soft-NBCE: Entropy-Weighted Chunk Fusion for Long-Context

Shihao Ji, Mingyu Li, Zihui Song

The quadratic complexity of self-attention remains a bottleneck for Large Language Models (LLMs) processing ultra-long contexts. The Naive Bayes Cognitive Engine (NBCE) parallelizes long-context inference by chunking documents and routing to the lowest-entropy chunk at each decoding step. This hard-selection strategy causes semantic fragmentation during cross-chunk reasoning, as abrupt routing changes between adjacent tokens disrupt the model's contextual grounding. We present Soft-NBCE, a lightweight extension that replaces discrete chunk selection with soft entropy-weighted chunk fusion. A temperature-scaled Softmax over predictive entropies assigns continuous weights to all chunks, enabling log-space aggregation across chunk-conditioned distributions. To partially compensate for the conditional independence assumption introduced by chunking, we propose Consistency Distillation, a LoRA-based self-distillation that constrains the chunked logit distribution toward a full-context teacher via KL-divergence. On LongBench multi-hop benchmarks, Soft-NBCE with Consistency Distillation improves consistently over NBCE-style baselines (MuSiQue F1: 0.310 vs.\ 0.275 for Vanilla NBCE; HotpotQA F1: 0.479 vs.\ 0.427) while maintaining retrieval accuracy (NIAH-32K: 0.909) at O(L^2/n) peak memory.

AIMay 31
Expected Value Alignment for Generative Reward Modeling in Formal Mathematics Verification

Shihao Ji, Haotao Tan, Zihui Song et al.

Large Language Models (LLMs) are increasingly used with formal interactive theorem provers such as Lean 4. Scaling these systems with reinforcement learning or search methods requires process reward models (PRMs) that can evaluate intermediate reasoning steps. Existing reward-model designs expose a practical trade-off. Value-head models provide continuous scores but modify the generative model interface, while generative reward models preserve textual rationales but are poorly matched to continuous floating-point regression because numeric values are split across tokens. We introduce Expected Value Alignment (EVA), a reward-modeling procedure that keeps the surface output discrete while extracting continuous scores from the model's token distribution. The model emits integer scores in a structured JSON format, and EVA computes a continuous score as the expectation over the logits of the corresponding anchor tokens. Training combines the causal language modeling objective with an auxiliary mean squared error loss on these expected values. We instantiate EVA in \textit{Leibniz}, a reward model for Lean 4 formal verification, and evaluate it against zero-shot and reward-modeling baselines. The evaluation demonstrates that continuous logit-based scoring significantly reduces discretization artifacts while retaining the interpretability of generative critiques.

LGJul 8, 2024
Improving AlphaFlow for Efficient Protein Ensembles Generation

Shaoning Li, Mingyu Li, Yusong Wang et al.

Investigating conformational landscapes of proteins is a crucial way to understand their biological functions and properties. AlphaFlow stands out as a sequence-conditioned generative model that introduces flexibility into structure prediction models by fine-tuning AlphaFold under the flow-matching framework. Despite the advantages of efficient sampling afforded by flow-matching, AlphaFlow still requires multiple runs of AlphaFold to finally generate one single conformation. Due to the heavy consumption of AlphaFold, its applicability is limited in sampling larger set of protein ensembles or the longer chains within a constrained timeframe. In this work, we propose a feature-conditioned generative model called AlphaFlow-Lit to realize efficient protein ensembles generation. In contrast to the full fine-tuning on the entire structure, we focus solely on the light-weight structure module to reconstruct the conformation. AlphaFlow-Lit performs on-par with AlphaFlow and surpasses its distilled version without pretraining, all while achieving a significant sampling acceleration of around 47 times. The advancement in efficiency showcases the potential of AlphaFlow-Lit in enabling faster and more scalable generation of protein ensembles.

SEMay 19Code
A Case for Agentic Tuning: From Documentation to Action in PostgreSQL

Hongyu Lin, Mingyu Li, Weichen Zhang et al.

Documentation has long guided computer system tuning by distilling expert knowledge into per-parameter recommendations. Yet such guides capture only what experts conclude, discarding how they reason. This fundamental gap manifests in three concrete deficiencies: documentation grows stale as software evolves, fails under heterogeneous workloads, and ignores inter-parameter dependencies. We propose shifting from static documentation to dynamic action for system tuning. We introduce PerfEvolve, which translates expert tuning methodologies into executable skills that equip LLM-based agents to perform version-consistency verification, workload-specific profiling, and multi-parameter joint optimization. Evaluated on PostgreSQL under TPC-C and TPC-H benchmarks, PerfEvolve outperforms state-of-the-art documentation-driven tuning baselines by up to 35.2%. The tool is available at https://github.com/ISCAS-OSLab/PerfEvolve.

IMFeb 19
Deeper detection limits in astronomical imaging using self-supervised spatiotemporal denoising

Yuduo Guo, Hao Zhang, Mingyu Li et al.

The detection limit of astronomical imaging observations is limited by several noise sources. Some of that noise is correlated between neighbouring image pixels and exposures, so in principle could be learned and corrected. We present an astronomical self-supervised transformer-based denoising algorithm (ASTERIS), that integrates spatiotemporal information across multiple exposures. Benchmarking on mock data indicates that ASTERIS improves detection limits by 1.0 magnitude at 90% completeness and purity, while preserving the point spread function and photometric accuracy. Observational validation using data from the James Webb Space Telescope (JWST) and Subaru telescope identifies previously undetectable features, including low-surface-brightness galaxy structures and gravitationally-lensed arcs. Applied to deep JWST images, ASTERIS identifies three times more redshift > 9 galaxy candidates, with rest-frame ultraviolet luminosity 1.0 magnitude fainter, than previous methods.

CVFeb 25Code
E-comIQ-ZH: A Human-Aligned Dataset and Benchmark for Fine-Grained Evaluation of E-commerce Posters with Chain-of-Thought

Meiqi Sun, Mingyu Li, Junxiong Zhu

Generative AI is widely used to create commercial posters. However, rapid advances in generation have outpaced automated quality assessment. Existing models emphasize generic esthetics or low level distortions and lack the functional criteria required for e-commerce design. It is especially challenging for Chinese content, where complex characters often produce subtle but critical textual artifacts that are overlooked by existing methods. To address this, we introduce E-comIQ-ZH, a framework for evaluating Chinese e-commerce posters. We build the first dataset E-comIQ-18k to feature multi dimensional scores and expert calibrated Chain of Thought (CoT) rationales. Using this dataset, we train E-comIQ-M, a specialized evaluation model that aligns with human expert judgment. Our framework enables E-comIQ-Bench, the first automated and scalable benchmark for the generation of Chinese e-commerce posters. Extensive experiments show our E-comIQ-M aligns more closely with expert standards and enables scalable automated assessment of e-commerce posters. All datasets, models, and evaluation tools will be released to support future research in this area.Code will be available at https://github.com/4mm7/E-comIQ-ZH.

LGNov 7, 2025
Peptide2Mol: A Diffusion Model for Generating Small Molecules as Peptide Mimics for Targeted Protein Binding

Xinheng He, Yijia Zhang, Haowei Lin et al.

Structure-based drug design has seen significant advancements with the integration of artificial intelligence (AI), particularly in the generation of hit and lead compounds. However, most AI-driven approaches neglect the importance of endogenous protein interactions with peptides, which may result in suboptimal molecule designs. In this work, we present Peptide2Mol, an E(3)-equivariant graph neural network diffusion model that generates small molecules by referencing both the original peptide binders and their surrounding protein pocket environments. Trained on large datasets and leveraging sophisticated modeling techniques, Peptide2Mol not only achieves state-of-the-art performance in non-autoregressive generative tasks, but also produces molecules with similarity to the original peptide binder. Additionally, the model allows for molecule optimization and peptidomimetic design through a partial diffusion process. Our results highlight Peptide2Mol as an effective deep generative model for generating and optimizing bioactive small molecules from protein binding pockets.

CRMar 19
Confidential Databases Without Cryptographic Mappings

Wenxuan Huang, Zhanbo Wang, Mingyu Li

Confidential databases (CDBs) are essential for enabling secure queries over sensitive data in untrusted cloud environments using confidential computing hardware. While adoption is growing, widespread deployment is hindered by high performance overhead from frequent synchronous cryptographic operations, which causes significant computational and memory bottlenecks. We present FEDB, a novel CDB design that removes cryptographic operations from the critical path. FEDB leverages crypto-free mappings, which maintain data-independent identifiers within the database while securely mapping them to plaintext secrets in a trusted domain. This paradigm shift reduces the runtime overhead by up to 78.0 times on industry-standard benchmarks including TPC-C and TPC-H.

LGOct 12, 2025Code
ProteinAE: Protein Diffusion Autoencoders for Structure Encoding

Shaoning Li, Le Zhuo, Yusong Wang et al.

Developing effective representations of protein structures is essential for advancing protein science, particularly for protein generative modeling. Current approaches often grapple with the complexities of the SE(3) manifold, rely on discrete tokenization, or the need for multiple training objectives, all of which can hinder the model optimization and generalization. We introduce ProteinAE, a novel and streamlined protein diffusion autoencoder designed to overcome these challenges by directly mapping protein backbone coordinates from E(3) into a continuous, compact latent space. ProteinAE employs a non-equivariant Diffusion Transformer with a bottleneck design for efficient compression and is trained end-to-end with a single flow matching objective, substantially simplifying the optimization pipeline. We demonstrate that ProteinAE achieves state-of-the-art reconstruction quality, outperforming existing autoencoders. The resulting latent space serves as a powerful foundation for a latent diffusion model that bypasses the need for explicit equivariance. This enables efficient, high-quality structure generation that is competitive with leading structure-based approaches and significantly outperforms prior latent-based methods. Code is available at https://github.com/OnlyLoveKFC/ProteinAE_v1.

IVApr 12, 2025Code
PathSeqSAM: Sequential Modeling for Pathology Image Segmentation with SAM2

Mingyang Zhu, Yinting Liu, Mingyu Li et al.

Current methods for pathology image segmentation typically treat 2D slices independently, ignoring valuable cross-slice information. We present PathSeqSAM, a novel approach that treats 2D pathology slices as sequential video frames using SAM2's memory mechanisms. Our method introduces a distance-aware attention mechanism that accounts for variable physical distances between slices and employs LoRA for domain adaptation. Evaluated on the KPI Challenge 2024 dataset for glomeruli segmentation, PathSeqSAM demonstrates improved segmentation quality, particularly in challenging cases that benefit from cross-slice context. We have publicly released our code at https://github.com/JackyyyWang/PathSeqSAM.

CLJul 17, 2025
A Survey of Context Engineering for Large Language Models

Lingrui Mei, Jiayu Yao, Yuyao Ge et al.

The performance of Large Language Models (LLMs) is fundamentally determined by the contextual information provided during inference. This survey introduces Context Engineering, a formal discipline that transcends simple prompt design to encompass the systematic optimization of information payloads for LLMs. We present a comprehensive taxonomy decomposing Context Engineering into its foundational components and the sophisticated implementations that integrate them into intelligent systems. We first examine the foundational components: context retrieval and generation, context processing and context management. We then explore how these components are architecturally integrated to create sophisticated system implementations: retrieval-augmented generation (RAG), memory systems and tool-integrated reasoning, and multi-agent systems. Through this systematic analysis of over 1400 research papers, our survey not only establishes a technical roadmap for the field but also reveals a critical research gap: a fundamental asymmetry exists between model capabilities. While current models, augmented by advanced context engineering, demonstrate remarkable proficiency in understanding complex contexts, they exhibit pronounced limitations in generating equally sophisticated, long-form outputs. Addressing this gap is a defining priority for future research. Ultimately, this survey provides a unified framework for both researchers and engineers advancing context-aware AI.

QMMay 1, 2024
F$^3$low: Frame-to-Frame Coarse-grained Molecular Dynamics with SE(3) Guided Flow Matching

Shaoning Li, Yusong Wang, Mingyu Li et al.

Molecular dynamics (MD) is a crucial technique for simulating biological systems, enabling the exploration of their dynamic nature and fostering an understanding of their functions and properties. To address exploration inefficiency, emerging enhanced sampling approaches like coarse-graining (CG) and generative models have been employed. In this work, we propose a \underline{Frame-to-Frame} generative model with guided \underline{Flow}-matching (F$3$low) for enhanced sampling, which (a) extends the domain of CG modeling to the SE(3) Riemannian manifold; (b) retreating CGMD simulations as autoregressively sampling guided by the former frame via flow-matching models; (c) targets the protein backbone, offering improved insights into secondary structure formation and intricate folding pathways. Compared to previous methods, F$3$low allows for broader exploration of conformational space. The ability to rapidly generate diverse conformations via force-free generative paradigm on SE(3) paves the way toward efficient enhanced sampling methods.

LGMay 27, 2025
Designing Cyclic Peptides via Harmonic SDE with Atom-Bond Modeling

Xiangxin Zhou, Mingyu Li, Yi Xiao et al.

Cyclic peptides offer inherent advantages in pharmaceuticals. For example, cyclic peptides are more resistant to enzymatic hydrolysis compared to linear peptides and usually exhibit excellent stability and affinity. Although deep generative models have achieved great success in linear peptide design, several challenges prevent the development of computational methods for designing diverse types of cyclic peptides. These challenges include the scarcity of 3D structural data on target proteins and associated cyclic peptide ligands, the geometric constraints that cyclization imposes, and the involvement of non-canonical amino acids in cyclization. To address the above challenges, we introduce CpSDE, which consists of two key components: AtomSDE, a generative structure prediction model based on harmonic SDE, and ResRouter, a residue type predictor. Utilizing a routed sampling algorithm that alternates between these two models to iteratively update sequences and structures, CpSDE facilitates the generation of cyclic peptides. By employing explicit all-atom and bond modeling, CpSDE overcomes existing data limitations and is proficient in designing a wide variety of cyclic peptides. Our experimental results demonstrate that the cyclic peptides designed by our method exhibit reliable stability and affinity.

DCMar 16
Guaranteeing Semantic and Performance Determinism in Flexible GPU Sharing

Zhenyuan Yang, Wenxin Zheng, Mingyu Li

GPU sharing is critical for maximizing hardware utilization in modern data centers. However, existing approaches present a stark trade-off: coarse-grained temporal multiplexing incurs severe tail-latency spikes for interactive services, while fine-grained spatial partitioning often necessitates invasive kernel modifications that compromise behavioral equivalence. We present DetShare, a novel GPU sharing system that prioritizes determinism and transparency. DetShare ensures semantic determinism (unmodified kernels yield identical results) and performance determinism (predictable tail latency), all while maintaining complete transparency (zero code modification). DetShare introduces GPU coroutines, a new abstraction that decouples logical execution contexts from physical GPU resources. This decoupling enables flexible, fine-grained resource allocation via lightweight context migration. Our evaluation demonstrates that DetShare improves training throughput by up to 79.2% compared to temporal sharing. In co-location scenarios, it outperforms state-of-the-art baselines, reducing P99 tail latency by 15.1% without compromising throughput. Furthermore, through workload-aware placement and our TPOT-First scheduling policy, DetShare decreases average inference latency by 69.1% and reduces Time-Per-Output-Token (TPOT) SLO violations by 21.2% relative to default policies.

OSOct 6, 2025
A Case for Declarative LLM-friendly Interfaces for Improved Efficiency of Computer-Use Agents

Yuan Wang, Mingyu Li, Haibo Chen

Computer-use agents (CUAs) powered by large language models (LLMs) have emerged as a promising approach to automating computer tasks, yet they struggle with graphical user interfaces (GUIs). GUIs, designed for humans, force LLMs to decompose high-level goals into lengthy, error-prone sequences of fine-grained actions, resulting in low success rates and an excessive number of LLM calls. We propose Goal-Oriented Interface (GOI), a novel abstraction that transforms existing GUIs into three declarative primitives: access, state, and observation, which are better suited for LLMs. Our key idea is policy-mechanism separation: LLMs focus on high-level semantic planning (policy) while GOI handles low-level navigation and interaction (mechanism). GOI does not require modifying the application source code or relying on application programming interfaces (APIs). We evaluate GOI with Microsoft Office Suite (Word, PowerPoint, Excel) on Windows. Compared to a leading GUI-based agent baseline, GOI improves task success rates by 67% and reduces interaction steps by 43.5%. Notably, GOI completes over 61% of successful tasks with a single LLM call.

LGSep 19, 2025
Communications to Circulations: Real-Time 3D Wind Field Prediction Using 5G GNSS Signals and Deep Learning

Yuchen Ye, Chaoxia Yuan, Mingyu Li et al.

Accurate atmospheric wind field information is crucial for various applications, including weather forecasting, aviation safety, and disaster risk reduction. However, obtaining high spatiotemporal resolution wind data remains challenging due to limitations in traditional in-situ observations and remote sensing techniques, as well as the computational expense and biases of numerical weather prediction (NWP) models. This paper introduces G-WindCast, a novel deep learning framework that leverages signal strength variations from 5G Global Navigation Satellite System (GNSS) signals to forecast three-dimensional (3D) atmospheric wind fields. The framework utilizes Forward Neural Networks (FNN) and Transformer networks to capture complex, nonlinear, and spatiotemporal relationships between GNSS-derived features and wind dynamics. Our preliminary results demonstrate promising accuracy in real-time wind forecasts (up to 30 minutes lead time). The model exhibits robustness across forecast horizons and different pressure levels, and its predictions for wind fields show superior agreement with ground-based radar wind profiler compared to concurrent European Centre for Medium-Range Weather Forecasts (ECMWF) Reanalysis v5 (ERA5). Furthermore, we show that the system can maintain excellent performance for localized forecasting even with a significantly reduced number of GNSS stations (e.g., around 100), highlighting its cost-effectiveness and scalability. This interdisciplinary approach underscores the transformative potential of exploiting non-traditional data sources and deep learning for advanced environmental monitoring and real-time atmospheric applications.

LGJul 6, 2025
Zero-Shot Cyclic Peptide Design via Composable Geometric Constraints

Dapeng Jiang, Xiangzhe Kong, Jiaqi Han et al.

Cyclic peptides, characterized by geometric constraints absent in linear peptides, offer enhanced biochemical properties, presenting new opportunities to address unmet medical needs. However, designing target-specific cyclic peptides remains underexplored due to limited training data. To bridge the gap, we propose CP-Composer, a novel generative framework that enables zero-shot cyclic peptide generation via composable geometric constraints. Our approach decomposes complex cyclization patterns into unit constraints, which are incorporated into a diffusion model through geometric conditioning on nodes and edges. During training, the model learns from unit constraints and their random combinations in linear peptides, while at inference, novel constraint combinations required for cyclization are imposed as input. Experiments show that our model, despite trained with linear peptides, is capable of generating diverse target-binding cyclic peptides, reaching success rates from 38% to 84% on different cyclization strategies.

GAJun 19, 2025
Can AI Dream of Unseen Galaxies? Conditional Diffusion Model for Galaxy Morphology Augmentation

Chenrui Ma, Zechang Sun, Tao Jing et al.

Observational astronomy relies on visual feature identification to detect critical astrophysical phenomena. While machine learning (ML) increasingly automates this process, models often struggle with generalization in large-scale surveys due to the limited representativeness of labeled datasets -- whether from simulations or human annotation -- a challenge pronounced for rare yet scientifically valuable objects. To address this, we propose a conditional diffusion model to synthesize realistic galaxy images for augmenting ML training data. Leveraging the Galaxy Zoo 2 dataset which contains visual feature -- galaxy image pairs from volunteer annotation, we demonstrate that our model generates diverse, high-fidelity galaxy images closely adhere to the specified morphological feature conditions. Moreover, this model enables generative extrapolation to project well-annotated data into unseen domains and advancing rare object detection. Integrating synthesized images into ML pipelines improves performance in standard morphology classification, boosting completeness and purity by up to 30\% across key metrics. For rare object detection, using early-type galaxies with prominent dust lane features ( $\sim$0.1\% in GZ2 dataset) as a test case, our approach doubled the number of detected instances from 352 to 872, compared to previous studies based on visual inspection. This study highlights the power of generative models to bridge gaps between scarce labeled data and the vast, uncharted parameter space of observational astronomy and sheds insight for future astrophysical foundation model developments. Our project homepage is available at https://galaxysd-webpage.streamlit.app/.

BMApr 24, 2025
Deciphering the unique dynamic activation pathway in a G protein-coupled receptor enables unveiling biased signaling and identifying cryptic allosteric sites in conformational intermediates

Jigang Fan, Chunhao Zhu, Xiaobing Lan et al.

Neurotensin receptor 1 (NTSR1), a member of the Class A G protein-coupled receptor superfamily, plays an important role in modulating dopaminergic neuronal activity and eliciting opioid-independent analgesia. Recent studies suggest that promoting \{beta}-arrestin-biased signaling in NTSR1 may diminish drugs of abuse, such as psychostimulants, thereby offering a potential avenue for treating human addiction-related disorders. In this study, we utilized a novel computational and experimental approach that combined nudged elastic band-based molecular dynamics simulations, Markov state models, temporal communication network analysis, site-directed mutagenesis, and conformational biosensors, to explore the intricate mechanisms underlying NTSR1 activation and biased signaling. Our study reveals a dynamic stepwise transition mechanism and activated transmission network associated with NTSR1 activation. It also yields valuable insights into the complex interplay between the unique polar network, non-conserved ion locks, and aromatic clusters in NTSR1 signaling. Moreover, we identified a cryptic allosteric site located in the intracellular region of the receptor that exists in an intermediate state within the activation pathway. Collectively, these findings contribute to a more profound understanding of NTSR1 activation and biased signaling at the atomic level, thereby providing a potential strategy for the development of NTSR1 allosteric modulators in the realm of G protein-coupled receptor biology, biophysics, and medicine.

QMJan 25, 2025
ILETIA: An AI-enhanced method for individualized trigger-oocyte pickup interval estimation of progestin-primed ovarian stimulation protocol

Binjian Wu, Qian Li, Zhe Kuang et al.

In vitro fertilization-embryo transfer (IVF-ET) stands as one of the most prevalent treatments for infertility. During an IVF-ET cycle, the time interval between trigger shot and oocyte pickup (OPU) is a pivotal period for follicular maturation, which determines mature oocytes yields and impacts the success of subsequent procedures. However, accurately predicting this interval is severely hindered by the variability of clinicians'experience that often leads to suboptimal oocyte retrieval rate. To address this challenge, we propose ILETIA, the first machine learning-based method that could predict the optimal trigger-OPU interval for patients receiving progestin-primed ovarian stimulation (PPOS) protocol. Specifically, ILETIA leverages a Transformer to learn representations from clinical tabular data, and then employs gradient-boosted trees for interval prediction. For model training and evaluating, we compiled a dataset PPOS-DS of nearly ten thousand patients receiving PPOS protocol, the largest such dataset to our knowledge. Experimental results demonstrate that our method achieves strong performance (AUROC = 0.889), outperforming both clinicians and other widely used computational models. Moreover, ILETIA also supports premature ovulation risk prediction in a specific OPU time (AUROC = 0.838). Collectively, by enabling more precise and individualized decisions, ILETIA has the potential to improve clinical outcomes and lay the foundation for future IVF-ET research.

CRFeb 10, 2018
Aurora: Providing Trusted System Services for Enclaves On an Untrusted System

Hongliang Liang, Mingyu Li, Qiong Zhang et al.

Intel SGX provisions shielded executions for security-sensitive computation, but lacks support for trusted system services (TSS), such as clock, network and filesystem. This makes \textit{enclaves} vulnerable to Iago attacks~\cite{DBLP:conf/asplos/CheckowayS13} in the face of a powerful malicious system. To mitigate this problem, we present Aurora, a novel architecture that provides TSSes via a secure channel between enclaves and devices on top of an untrusted system, and implement two types of TSSes, i.e. clock and end-to-end network. We evaluate our solution by porting SQLite and OpenSSL into Aurora, experimental results show that SQLite benefits from a \textit{microsecond} accuracy trusted clock and OpenSSL gains end-to-end secure network with about 1ms overhead.