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Abstract BackgroundPathogenic infections pose a significant threat to global health, affecting millions of people every year and presenting substantial challenges to healthcare systems worldwide. Efficient and timely testing plays a critical role in disease control and transmission prevention. Group testing is a well-established method for reducing the number of tests needed to screen large populations when the disease prevalence is low. However, it does not fully utilize the quantitative information provided by qPCR methods, nor is it able to accommodate a wide range of pathogen loads. ResultsTo address these issues, we introduce a novel adaptive semi-quantitative group testing (SQGT) scheme to efficiently screen populations via two-stage qPCR testing. The SQGT method quantizes cycle threshold (Ct) values into multiple bins, leveraging the information from the first stage of screening to improve the detection sensitivity. DynamicCtthreshold adjustments mitigate dilution effects and enhance test accuracy. Comparisons with traditional binary outcome GT methods show that SQGT reduces the number of tests by 24% on the only complete real-world qPCR group testing dataset from Israel, while maintaining a negligible false negative rate. ConclusionIn conclusion, our adaptive SQGT approach, utilizing qPCR data and dynamic threshold adjustments, offers a promising solution for efficient population screening. With a reduction in the number of tests and minimal false negatives, SQGT holds potential to enhance disease control and testing strategies on a global scale. 

This study uses a combined research approach based on remote-sensing and numerical modeling to quantify the effects of burned areas on the surface climate in the two Brazilian biomes most affected by fires: the tropical savanna and the Amazon rainforest. Our estimates indicate that between 2007 and 2020, approximately 6% of the savanna and 2% of the rainforest were burned on average. Non-parametric regressions based on 14-year climate model simulations indicate that latent heat flux decreases on average by approximately 0.17 W m−2 in the savanna and 0.60 W m−2 in the rainforest per each 1 km2 burned, with most of the impacts registered during the onset of the wet season. Sensible and ground heat fluxes are also impacted but at less intensity. Surface air is also warmer and drier, especially over rainforest burned sites. On average, fire reduced gross primary production in the savanna and rainforest by 12% and 10%, respectively, in our experiments. 

Abstract Targeted protein degradation (TPD) is a promising approach in drug discovery for degrading proteins implicated in diseases. A key step in this process is the formation of a ternary complex where a heterobifunctional molecule induces proximity of an E3 ligase to a protein of interest (POI), thus facilitating ubiquitin transfer to the POI. In this work, we characterize 3 steps in the TPD process. (1) We simulate the ternary complex formation of SMARCA2 bromodomain and VHL E3 ligase by combining hydrogen-deuterium exchange mass spectrometry with weighted ensemble molecular dynamics (MD). (2) We characterize the conformational heterogeneity of the ternary complex using Hamiltonian replica exchange simulations and small-angle X-ray scattering. (3) We assess the ubiquitination of the POI in the context of the full Cullin-RING Ligase, confirming experimental ubiquitinomics results. Differences in degradation efficiency can be explained by the proximity of lysine residues on the POI relative to ubiquitin.