Neoantigen-targeting vaccines have achieved breakthrough success in cancer immunotherapy by eliciting immune responses against neoantigens, which are proteins uniquely produced by cancer cells. During the immune response, the interactions between peptides and major histocompatibility complexes (MHC) play an important role as peptides must be bound and presented by MHC to be recognised by the immune system. However, only limited experimentally determined peptide-MHC (pMHC) structures are available, and in-silico structure modelling is therefore used for studying their interactions. Current approaches mainly use Monte Carlo sampling and energy minimisation, and are often computationally expensive. On the other hand, the advent of large high-quality proteomic data sets has led to an unprecedented opportunity for deep learning-based methods with pMHC structure prediction becoming feasible with these trained protein folding models. In this work, we present a graph neural network-based model for pMHC structure prediction, which takes an amino acid-level pMHC graph and an atomic-level peptide graph as inputs and predicts the peptide backbone conformation. With a novel weighted reconstruction loss, the trained model achieved a similar accuracy to AlphaFold 2, requiring only 1.7M learnable parameters compared to 93M, representing a more than 98% reduction in the number of required parameters.
The effect of theophylline on sleep quality and cognitive performance in patients with obstructive lung disease has been the subject of controversy. To examine the direct effects of theophylline on sleep quality and cognitive performance, without confounding effects from bronchodilatation, we have undertaken a study of the drug in healthy subjects. A double-blind, placebo-controlled crossover protocol was used to study the effect of oral sustained-release theophylline (Theodur) on subjective sleep quality, objective sleep quality, and cognitive performance. Overnight sleep studies were carried out on Nights 13 and 14 of each 2-wk study limb, and cognitive performance tests administered on Days 1 and 13 of each limb. A total of 18 subjects satisfactorily completed the study (8 males, median age 37, range 24 to 67 yr). Theophylline levels were median 10.2, range 2.3 to 13.3 micrograms/ml on Day 1 and 14.7, range 9.6 to 17.5 micrograms/ml on Day 13. No significant difference was observed between theophylline and placebo on subjective or objective sleep quality or on acute or medium-term cognitive performance. We conclude that theophylline does not affect sleep quality or cognitive performance in normal adults.
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