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The increasing availability of coarse-scale climate simulations and the need for ready-to-use high-resolution variables drive the climate community to the challenge of reducing computational resources and time for downscaling purposes. To this end, statistical downscaling is gaining interest as a potential strategy for integrating high-resolution climate information obtained through dynamical downscaling over limited years, providing a clear understanding of the gains and losses in combining dynamical and statistical downscaling. In this regard, several questions can be raised: (i) what is the performance of statistical downscaling, assuming dynamical downscaling as a reference over a shared time window; (ii) how much the performance of statistical downscaling is affected by changes in the number of years available for training; (iii) how does the climate normal considered for the training affect the predictions.
View Article and Find Full Text PDFregionalpcs improve discovery of DNA methylation associations with complex traits.
Nat Commun
January 2025
Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
We have developed the regionalpcs method, an approach for summarizing gene-level methylation. regionalpcs addresses the challenge of deciphering complex epigenetic mechanisms in diseases like Alzheimer's disease. In contrast to averaging, regionalpcs uses principal components analysis to capture complex methylation patterns across gene regions.
View Article and Find Full Text PDFMolecular basis of proton sensing by G protein-coupled receptors.
Cell
December 2024
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, CA 94148, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94115, USA. Electronic address:
Three proton-sensing G protein-coupled receptors (GPCRs)-GPR4, GPR65, and GPR68-respond to extracellular pH to regulate diverse physiology. How protons activate these receptors is poorly understood. We determined cryogenic-electron microscopy (cryo-EM) structures of each receptor to understand the spatial arrangement of proton-sensing residues.
View Article and Find Full Text PDFResearch review and transcriptomic insights into Benzalkonium chloride inhalation and disease association.
Ecotoxicol Environ Saf
January 2025
College of Pharmacy, Korea University, Sejong 30019, South Korea. Electronic address:
The widespread use of disinfectants, particularly during the coronavirus disease (COVID-19) pandemic, has significantly increased human exposure to biocides, raising concerns about their potential health risks, especially when inhaled. Benzalkonium chloride (BKC), a quaternary ammonium compound commonly used as a disinfectant and preservative, is a notable example because it is frequently used in household products and medical settings. Despite its broad usage, limited research has been conducted on the respiratory and systemic toxicities of BKC.
View Article and Find Full Text PDFIntegration of paper-based colorimetric microdevice and magnetic nanoparticles affinity for high-throughput capture of antimicrobial resistance-reversing agent from complex natural products.
Biosens Bioelectron
December 2024
Department of Pharmaceutical Analysis, School of Pharmacy, Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China. Electronic address:
Efficient analysis of active ingredient in complex natural products is crucial for drug discovery, but developing a simple method for this is challenging. The discovery of drugs against bacterial resistance is urgent because drug-resistant bacteria produce β-lactamases, which inactivate antibiotics and increase infection risks, particularly the AmpC β-lactamase. Here, an integrated analytical model based on colorimetric sensing and magnetic nanoparticles (MNPs) affinity chromatography was developed for screening AmpC β-lactamase inhibitors.
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