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Abstract This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the CTSA Program led by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) at the United States. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers. Our analysis reveals that 53% of institutions identified data security as a primary concern, followed by lack of clinician trust (50%) and AI bias (44%), which must be addressed to ensure the ethical and effective implementation of GenAI technologies. 

In the Biochemistry Authentic Scientific Inquiry Lab (BASIL) course-based undergraduate research experience, students use a series of computational (sequence and structure comparison, docking) and wet lab (protein expression, purification, and concentration; sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]; enzyme activity and kinetics) modules to predict and test the function of protein structures of unknown function found in the Protein Data Bank and UniProt. BASIL was established in 2015 with a core of 10 faculty members on six campuses, with the support of an educational researcher and doctoral student on a seventh campus. Since that time, the number of participating faculty members and campuses has grown, and we have adapted our curriculum to improve access for all who are interested. We have also expanded our curriculum to include new developments that are appearing in computational approaches to life science research. In this article, we provide a history of BASIL, explain our current approach, describe how we have addressed challenges that have appeared, and describe our curriculum development pipeline and our plans for moving forward in a sustainable and equitable fashion. 

Northern northeastern Brazil (NEB) is a climate change hotspot due to its high biological and social vulnerability to ongoing and future hydroclimate changes. Precipitation in this region is influenced by the Intertropical Convergence Zone (ITCZ), which is largely controlled by the strength of the Atlantic Meridional Overturning Circulation (AMOC). Accordingly, the projected weakening of the AMOC due to anthropogenic global warming may substantially change NEB hydroclimate. Heinrich Stadials (HS), past millennial-scale events during which the AMOC was significantly weaker, provide important insights into the AMOC-ITCZ dynamics. This is especially true for those HS that occurred under similar to modern boundary conditions. HS10 (ca. 110 thousand years ago) was the first HS of Marine Isotope Stage 5, providing an ideal target for investigating AMOC-ITCZ dynamics under relatively warm climate conditions. Here we investigate the response of the surface and deep western equatorial Atlantic (WEA) circulation, as well as NEB precipitation to HS10. Therefore, we use foraminiferal carbon and oxygen stable isotopes and bulk sediment major elemental data from a marine sediment core retrieved from the WEA. Our results record a weakening of the AMOC during HS10 and show a concurrent increased WEA upper stratification and precipitation over NEB. We suggest that the mechanism controlling the WEA upper ocean stratification during HS depends on the background climate. Furthermore, we infer that the southward shift of the ITCZ during HS10 was more limited if compared to the shifts that occurred under colder climate background. Our findings provide useful insights into how a weakening of the AMOC under a relatively warm climate can impact the ITCZ and tropical South American precipitation. 

ABSTRACT Secondary fermentation in beer can result in undesirable consequences, such as off-flavors, increased alcohol content, hyperattenuation, gushing, and the spontaneous explosion of packaging. Strains ofSaccharomyces cerevisiae var. diastaticusare a major contributor to such spoilage due to their production of extracellular glucoamylase enzyme encoded by theSTA1gene.Saccharomycesyeasts can naturally produce antifungal proteins named “killer” toxins that inhibit the growth of competing yeasts. Challenging diastatic yeasts with killer toxins revealed that 91% of strains are susceptible to the K1 killer toxin produced byS. cerevisiae. Screening of 192 killer yeasts identified novel K2 toxins that could inhibit all K1-resistant diastatic yeasts. Variant K2 killer toxins were more potent than the K1 and K2 toxins, inhibiting 95% of diastatic yeast strains tested. Brewing trials demonstrated that adding killer yeast during a simulated diastatic contamination event could prevent hyperattenuation. Currently, most craft breweries can only safeguard against diastatic yeast contamination by good hygiene and monitoring for the presence of diastatic yeasts. The detection of diastatic yeasts will often lead to the destruction of contaminated products and the aggressive decontamination of brewing facilities. Using killer yeasts in brewing offers an approach to safeguard against product loss and potentially remediate contaminated beer.IMPORTANCEThe rise of craft brewing means that more domestic beer in the marketplace is being produced in facilities lacking the means for pasteurization, which increases the risk of microbial spoilage. The most damaging spoilage yeasts are “diastatic” strains ofSaccharomyces cerevisiaethat cause increased fermentation (hyperattenuation), resulting in unpalatable flavors such as phenolic off-flavor, as well as over-carbonation that can cause exploding packaging. In the absence of a pasteurizer, there are no methods available that would avert the loss of beer due to contamination by diastatic yeasts. This manuscript has found that diastatic yeasts are sensitive to antifungal proteins named “killer toxins” produced bySaccharomycesyeasts, and in industrial-scale fermentation trials, killer yeasts can remediate diastatic yeast contamination. Using killer toxins to prevent diastatic contamination is a unique and innovative approach that could prevent lost revenue to yeast spoilage and save many breweries the time and cost of purchasing and installing a pasteurizer. 

Small area estimation models are critical for dissemination and understanding of important population characteristics within sub-domains that often have limited sample size. The classic Fay-Herriot model is perhaps the most widely used approach to generate such estimates. However, a limiting assumption of this approach is that the latent true population quantity has a linear relationship with the given covariates. Through the use of random weight neural networks, we develop a Bayesian hierarchical extension of this framework that allows for estimation of nonlinear relationships between the true population quantity and the covariates. We illustrate our approach through an empirical simulation study as well as an analysis of median household income for census tracts in the state of California. 

The cytoskeleton is a complex network of interconnected biopolymers consisting of actin filaments, microtubules, and intermediate filaments. These biopolymers work in concert to transmit cell-generated forces to the extracellular matrix required for cell motility, wound healing, and tissue maintenance. While we know cell-generated forces are driven by actomyosin contractility and balanced by microtubule network resistance, the effect of intermediate filaments on cellular forces is unclear. Using a combination of theoretical modeling and experiments, we show that vimentin intermediate filaments tune cell stress by assisting in both actomyosin-based force transmission and reinforcement of microtubule networks under compression. We show that the competition between these two opposing effects of vimentin is regulated by the microenvironment stiffness. These results reconcile seemingly contradictory results in the literature and provide a unified description of vimentin’s effects on the transmission of cell contractile forces to the extracellular matrix.