Daily Papers

Most human proteins remain undrugged, over 96% of human proteins remain unexploited by approved therapeutics. While structure-based virtual screening promises to expand the druggable proteome, existing methods lack atomic-level precision and fail to predict binding fitness, limiting translational impact. We present AuroBind, a scalable virtual screening framework that fine-tunes a custom atomic-level structural model on million-scale chemogenomic data. AuroBind integrates direct preference optimization, self-distillation from high-confidence complexes, and a teacher-student acceleration strategy to jointly predict ligand-bound structures and binding fitness. The proposed models outperform state-of-the-art models on structural and functional benchmarks while enabling 100,000-fold faster screening across ultra-large compound libraries. In a prospective screen across ten disease-relevant targets, AuroBind achieved experimental hit rates of 7-69%, with top compounds reaching sub-nanomolar to picomolar potency. For the orphan GPCRs GPR151 and GPR160, AuroBind identified both agonists and antagonists with success rates of 16-30%, and functional assays confirmed GPR160 modulation in liver and prostate cancer models. AuroBind offers a generalizable framework for structure-function learning and high-throughput molecular screening, bridging the gap between structure prediction and therapeutic discovery.

Protein fitness optimization involves finding a protein sequence that maximizes desired quantitative properties in a combinatorially large design space of possible sequences. Recent developments in steering protein generative models (e.g diffusion models, language models) offer a promising approach. However, by and large, past studies have optimized surrogate rewards and/or utilized large amounts of labeled data for steering, making it unclear how well existing methods perform and compare to each other in real-world optimization campaigns where fitness is measured by low-throughput wet-lab assays. In this study, we explore fitness optimization using small amounts (hundreds) of labeled sequence-fitness pairs and comprehensively evaluate strategies such as classifier guidance and posterior sampling for guiding generation from different discrete diffusion models of protein sequences. We also demonstrate how guidance can be integrated into adaptive sequence selection akin to Thompson sampling in Bayesian optimization, showing that plug-and-play guidance strategies offer advantages compared to alternatives such as reinforcement learning with protein language models.

We present EgoExo-Fitness, a new full-body action understanding dataset, featuring fitness sequence videos recorded from synchronized egocentric and fixed exocentric (third-person) cameras. Compared with existing full-body action understanding datasets, EgoExo-Fitness not only contains videos from first-person perspectives, but also provides rich annotations. Specifically, two-level temporal boundaries are provided to localize single action videos along with sub-steps of each action. More importantly, EgoExo-Fitness introduces innovative annotations for interpretable action judgement--including technical keypoint verification, natural language comments on action execution, and action quality scores. Combining all of these, EgoExo-Fitness provides new resources to study egocentric and exocentric full-body action understanding across dimensions of "what", "when", and "how well". To facilitate research on egocentric and exocentric full-body action understanding, we construct benchmarks on a suite of tasks (i.e., action classification, action localization, cross-view sequence verification, cross-view skill determination, and a newly proposed task of guidance-based execution verification), together with detailed analysis. Code and data will be available at https://github.com/iSEE-Laboratory/EgoExo-Fitness/tree/main.

Biometric capture devices have been utilised to estimate a person's alertness through near-infrared iris images, expanding their use beyond just biometric recognition. However, capturing a substantial number of corresponding images related to alcohol consumption, drug use, and sleep deprivation to create a dataset for training an AI model presents a significant challenge. Typically, a large quantity of images is required to effectively implement a deep learning approach. Currently, training downstream models with a huge number of images based on foundational models provides a real opportunity to enhance this area, thanks to the generalisation capabilities of self-supervised models. This work examines the application of deep learning and foundational models in predicting fitness for duty, which is defined as the subject condition related to determining the alertness for work.

The rapid evolution of sensors and resource-efficient machine learning models has spurred the widespread adoption of wearable fitness tracking devices. Equipped with inertial sensors, such devices can continuously capture physical movements for fitness technology (FitTech), enabling applications from sports optimization to preventive healthcare. Traditional Centralized Learning approaches to detect fitness activities struggle with data privacy concerns, regulatory restrictions, and communication inefficiencies. In contrast, Federated Learning (FL) enables a decentralized model training by communicating model updates rather than potentially private wearable sensor data. Applying FL to FitTech presents unique challenges, such as data imbalance, lack of labeled data, heterogeneous user activities, and trade-offs between personalization and generalization. To simplify research on FitTech in FL, we present the FedFitTech baseline, under the Flower framework, which is publicly available and widely used by both industry and academic researchers. Additionally, to illustrate its usage, this paper presents a case study that implements a system based on the FedFitTech baseline, incorporating a client-side early stopping strategy and comparing the results. For instance, this system allows wearable devices to optimize the trade-off between capturing common fitness activities and preserving individuals' nuances, thereby enhancing both the scalability and efficiency of privacy-aware fitness tracking applications. The results show that this reduces the overall redundant communications by 13%, while maintaining the overall recognition performance at a negligible recognition cost by 1%. Thus, the FedFitTech baseline creates a foundation for a wide range of new research and development opportunities in FitTech, and it is available as open source at: https://github.com/shreyaskorde16/FedFitTech

This paper introduces a novel method for real-time exercise classification using a Bidirectional Long Short-Term Memory (BiLSTM) neural network. Existing exercise recognition approaches often rely on synthetic datasets, raw coordinate inputs sensitive to user and camera variations, and fail to fully exploit the temporal dependencies in exercise movements. These issues limit their generalizability and robustness in real-world conditions, where lighting, camera angles, and user body types vary. To address these challenges, we propose a BiLSTM-based model that leverages invariant features, such as joint angles, alongside raw coordinates. By using both angles and (x, y, z) coordinates, the model adapts to changes in perspective, user positioning, and body differences, improving generalization. Training on 30-frame sequences enables the BiLSTM to capture the temporal context of exercises and recognize patterns evolving over time. We compiled a dataset combining synthetic data from the InfiniteRep dataset and real-world videos from Kaggle and other sources. This dataset includes four common exercises: squat, push-up, shoulder press, and bicep curl. The model was trained and validated on these diverse datasets, achieving an accuracy of over 99% on the test set. To assess generalizability, the model was tested on 2 separate test sets representative of typical usage conditions. Comparisons with the previous approach from the literature are present in the result section showing that the proposed model is the best-performing one. The classifier is integrated into a web application providing real-time exercise classification and repetition counting without manual exercise selection. Demo and datasets are available at the following GitHub Repository: https://github.com/RiccardoRiccio/Fitness-AI-Trainer-With-Automatic-Exercise-Recognition-and-Counting.

This research proposes a new database and method to detect the reduction of alertness conditions due to alcohol, drug consumption and sleepiness deprivation from Near-Infra-Red (NIR) periocular eye images. The study focuses on determining the effect of external factors on the Central Nervous System (CNS). The goal is to analyse how this impacts iris and pupil movement behaviours and if it is possible to classify these changes with a standard iris NIR capture device. This paper proposes a modified MobileNetV2 to classify iris NIR images taken from subjects under alcohol/drugs/sleepiness influences. The results show that the MobileNetV2-based classifier can detect the Unfit alertness condition from iris samples captured after alcohol and drug consumption robustly with a detection accuracy of 91.3% and 99.1%, respectively. The sleepiness condition is the most challenging with 72.4%. For two-class grouped images belonging to the Fit/Unfit classes, the model obtained an accuracy of 94.0% and 84.0%, respectively, using a smaller number of parameters than the standard Deep learning Network algorithm. This work is a step forward in biometric applications for developing an automatic system to classify "Fitness for Duty" and prevent accidents due to alcohol/drug consumption and sleepiness.

The ability to accurately model the fitness landscape of protein sequences is critical to a wide range of applications, from quantifying the effects of human variants on disease likelihood, to predicting immune-escape mutations in viruses and designing novel biotherapeutic proteins. Deep generative models of protein sequences trained on multiple sequence alignments have been the most successful approaches so far to address these tasks. The performance of these methods is however contingent on the availability of sufficiently deep and diverse alignments for reliable training. Their potential scope is thus limited by the fact many protein families are hard, if not impossible, to align. Large language models trained on massive quantities of non-aligned protein sequences from diverse families address these problems and show potential to eventually bridge the performance gap. We introduce Tranception, a novel transformer architecture leveraging autoregressive predictions and retrieval of homologous sequences at inference to achieve state-of-the-art fitness prediction performance. Given its markedly higher performance on multiple mutants, robustness to shallow alignments and ability to score indels, our approach offers significant gain of scope over existing approaches. To enable more rigorous model testing across a broader range of protein families, we develop ProteinGym -- an extensive set of multiplexed assays of variant effects, substantially increasing both the number and diversity of assays compared to existing benchmarks.

Communications satellite network (CSN), as an integral component of the next generation of communication systems, has the capability to offer services globally. Data transmission in this network primarily relies on two modes: inter-satellite communication and satellite-to-ground station communication. The latter directly impacts the successful reception of data by users. However, due to resource and task limitations, finding a satisfactory solution poses a significant challenge. The communication satellite-ground station network scheduling problem (CS-GSNSP) aims to optimize CSN effectiveness by devising a plan that maximizes link construction time while considering constraints associated with satellite operation modes. The large number of tasks and numerous constraints in the problem result in a time-consuming evaluation of fitness function values. To address this issue, we propose a fuzzy fitness evaluation method (FFEM) that employs fuzzy or real evaluation methods based on individual similarity degrees. Additionally, we introduce an evolutionary algorithm based on FFEM, called evolutionary algorithm based on FFEM (FFEEA), for iteratively searching high-quality network construction schemes. In FFEEA, an adaptive crossover approach is used for efficient population search. Finally, extensive experiments are conducted to demonstrate that our proposed fuzzy fitness evaluation method and other improvement strategies significantly enhance satellite network service time. The study introduces a novel approach to enhance the efficiency of solving combinatorial optimization problems, such as CS-GSNSP, by mitigating the complexity associated with fitness evaluation.

Protein design, a grand challenge of the day, involves optimization on a fitness landscape, and leading methods adopt a model-based approach where a model is trained on a training set (protein sequences and fitness) and proposes candidates to explore next. These methods are challenged by sparsity of high-fitness samples in the training set, a problem that has been in the literature. A less recognized but equally important problem stems from the distribution of training samples in the design space: leading methods are not designed for scenarios where the desired optimum is in a region that is not only poorly represented in training data, but also relatively far from the highly represented low-fitness regions. We show that this problem of "separation" in the design space is a significant bottleneck in existing model-based optimization tools and propose a new approach that uses a novel VAE as its search model to overcome the problem. We demonstrate its advantage over prior methods in robustly finding improved samples, regardless of the imbalance and separation between low- and high-fitness training samples. Our comprehensive benchmark on real and semi-synthetic protein datasets as well as solution design for physics-informed neural networks, showcases the generality of our approach in discrete and continuous design spaces. Our implementation is available at https://github.com/sabagh1994/PGVAE.

Vision-language models have shown impressive progress in recent years. However, existing models are largely limited to turn-based interactions, where each turn must be stepped (i.e., prompted) by the user. Open-ended, asynchronous interactions, where an AI model may proactively deliver timely responses or feedback based on the unfolding situation in real-time, are an open challenge. In this work, we present the QEVD benchmark and dataset, which explores human-AI interaction in the challenging, yet controlled, real-world domain of fitness coaching -- a task which intrinsically requires monitoring live user activity and providing immediate feedback. The benchmark requires vision-language models to recognize complex human actions, identify possible mistakes, and provide appropriate feedback in real-time. Our experiments reveal the limitations of existing state-of-the-art vision-language models for such asynchronous situated interactions. Motivated by this, we propose a simple end-to-end streaming baseline that can respond asynchronously to human actions with appropriate feedback at the appropriate time.

The ability to engineer novel proteins with higher fitness for a desired property would be revolutionary for biotechnology and medicine. Modeling the combinatorially large space of sequences is infeasible; prior methods often constrain optimization to a small mutational radius, but this drastically limits the design space. Instead of heuristics, we propose smoothing the fitness landscape to facilitate protein optimization. First, we formulate protein fitness as a graph signal then use Tikunov regularization to smooth the fitness landscape. We find optimizing in this smoothed landscape leads to improved performance across multiple methods in the GFP and AAV benchmarks. Second, we achieve state-of-the-art results utilizing discrete energy-based models and MCMC in the smoothed landscape. Our method, called Gibbs sampling with Graph-based Smoothing (GGS), demonstrates a unique ability to achieve 2.5 fold fitness improvement (with in-silico evaluation) over its training set. GGS demonstrates potential to optimize proteins in the limited data regime. Code: https://github.com/kirjner/GGS

With the increasing awareness of health and the growing desire for aesthetic physique, fitness has become a prevailing trend. However, the potential risks associated with fitness training, especially with weight-loaded fitness actions, cannot be overlooked. Action Quality Assessment (AQA), a technology that quantifies the quality of human action and provides feedback, holds the potential to assist fitness enthusiasts of varying skill levels in achieving better training outcomes. Nevertheless, current AQA methodologies and datasets are limited to single-view competitive sports scenarios and RGB modality and lack professional assessment and guidance of fitness actions. To address this gap, we propose the FLEX dataset, the first multi-modal, multi-action, large-scale dataset that incorporates surface electromyography (sEMG) signals into AQA. FLEX utilizes high-precision MoCap to collect 20 different weight-loaded actions performed by 38 subjects across 3 different skill levels for 10 repetitions each, containing 5 different views of the RGB video, 3D pose, sEMG, and physiological information. Additionally, FLEX incorporates knowledge graphs into AQA, constructing annotation rules in the form of penalty functions that map weight-loaded actions, action keysteps, error types, and feedback. We conducted various baseline methodologies on FLEX, demonstrating that multimodal data, multiview data, and fine-grained annotations significantly enhance model performance. FLEX not only advances AQA methodologies and datasets towards multi-modal and multi-action scenarios but also fosters the integration of artificial intelligence within the fitness domain. Dataset and code are available at https://haoyin116.github.io/FLEX_Dataset.

We introduce UbiPhysio, a milestone framework that delivers fine-grained action description and feedback in natural language to support people's daily functioning, fitness, and rehabilitation activities. This expert-like capability assists users in properly executing actions and maintaining engagement in remote fitness and rehabilitation programs. Specifically, the proposed UbiPhysio framework comprises a fine-grained action descriptor and a knowledge retrieval-enhanced feedback module. The action descriptor translates action data, represented by a set of biomechanical movement features we designed based on clinical priors, into textual descriptions of action types and potential movement patterns. Building on physiotherapeutic domain knowledge, the feedback module provides clear and engaging expert feedback. We evaluated UbiPhysio's performance through extensive experiments with data from 104 diverse participants, collected in a home-like setting during 25 types of everyday activities and exercises. We assessed the quality of the language output under different tuning strategies using standard benchmarks. We conducted a user study to gather insights from clinical physiotherapists and potential users about our framework. Our initial tests show promise for deploying UbiPhysio in real-life settings without specialized devices.