Testing of candidate monoclonal antibody therapeutics in preclinical models is an essential step in drug development. Identification of antibody therapeutic candidates that bind their human targets and cross-react to mouse orthologs is often challenging, especially for targets with low sequence homology. In such cases, surrogate antibodies that bind mouse orthologs must be used.
View Article and Find Full Text PDFThis study experimentally investigates the role of cavitation-induced shock waves in initiating and destabilizing capillary (surface) waves on a droplet surface, preceding atomization. Acoustic emissions and interfacial wave dynamics were simultaneously monitored in droplets of different liquids (water, isopropyl alcohol and glycerol), using a calibrated fiber-optic hydrophone and high-speed imaging. Spectral analysis of the hydrophone data revealed distinct subharmonic frequency peaks in the acoustic spectrum correlated with the wavelength of capillary waves, which were optically captured during the onset of atomization from the repetitive imploding bubbles.
View Article and Find Full Text PDFAnnu Rev Pharmacol Toxicol
January 2025
Although human genetics has substantial potential to illuminate novel disease pathways and facilitate drug development, identifying causal variants and deciphering their mechanisms remain challenging. We believe these challenges can be addressed, in part, by creatively repurposing the results of molecular trait genome-wide association studies (GWASs). In this review, we introduce techniques related to molecular GWASs and unconventionally apply them to understanding , a human coronary artery disease risk locus.
View Article and Find Full Text PDFSignal transducer and activator of transcription 1 (STAT1) gene mutations have broad clinical phenotypes, classified by the inheritance pattern and functional state. Individuals with autosomal dominant STAT1 deficiency are more susceptible to intracellular bacteria, the hallmark of which is Mendelian susceptibility to mycobacterial diseases (MSMDs) that are associated with increased risks of invasive disease by weakly virulent mycobacteria. We report a novel heterozygous missense mutation in exon 23 of the STAT1 gene (NM_007315.
View Article and Find Full Text PDFThe objective of this study is to address the unanswered question whether sustained supersaturation generated from amorphous solid dispersions (ASDs) formulated in insoluble hydrogel carriers will result in better bioavailability over that of spring-and-parachute type of dissolution profiles of ASDs formulated in water-soluble carriers. This was achieved by investigating the effects of supersaturation generation rates and doses on the extent of absorption (i.e.
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