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  1. Abstract

    Artemisinins have revolutionized the treatment ofPlasmodium falciparummalaria; however, resistance threatens to undermine global control efforts. To broadly explore artemisinin susceptibility in apicomplexan parasites, we employ genome-scale CRISPR screens recently developed forToxoplasma gondiito discover sensitizing and desensitizing mutations. Using a sublethal concentration of dihydroartemisinin (DHA), we uncover the putative transporter Tmem14c whose disruption increases DHA susceptibility. Screens performed under high doses of DHA provide evidence that mitochondrial metabolism can modulate resistance. We show that disrupting a top candidate from the screens, the mitochondrial protease DegP2, lowers porphyrin levels and decreases DHA susceptibility, without significantly altering parasite fitness in culture. Deleting the homologous gene inP. falciparum, PfDegP, similarly lowers heme levels and DHA susceptibility. These results expose the vulnerability of heme metabolism to genetic perturbations that can lead to increased survival in the presence of DHA.

     
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  2. A<sc>bstract</sc>

    A search for new physics in top quark production with additional final-state leptons is performed using data collected by the CMS experiment in proton-proton collisions at$$ \sqrt{s} $$s= 13 TeV at the LHC during 2016–2018. The data set corresponds to an integrated luminosity of 138 fb1. Using the framework of effective field theory (EFT), potential new physics effects are parametrized in terms of 26 dimension-six EFT operators. The impacts of EFT operators are incorporated through the event-level reweighting of Monte Carlo simulations, which allows for detector-level predictions. The events are divided into several categories based on lepton multiplicity, total lepton charge, jet multiplicity, and b-tagged jet multiplicity. Kinematic variables corresponding to the transverse momentum (pT) of the leading pair of leptons and/or jets as well as thepTof on-shell Z bosons are used to extract the 95% confidence intervals of the 26 Wilson coefficients corresponding to these EFT operators. No significant deviation with respect to the standard model prediction is found.

     
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    Free, publicly-accessible full text available December 1, 2024
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  6. Abstract

    A description is presented of the algorithms used to reconstruct energy deposited in the CMS hadron calorimeter during Run 2 (2015–2018) of the LHC. During Run 2, the characteristic bunch-crossing spacing for proton-proton collisions was 25 ns, which resulted in overlapping signals from adjacent crossings. The energy corresponding to a particular bunch crossing of interest is estimated using the known pulse shapes of energy depositions in the calorimeter, which are measured as functions of both energy and time. A variety of algorithms were developed to mitigate the effects of adjacent bunch crossings on local energy reconstruction in the hadron calorimeter in Run 2, and their performance is compared.

     
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    Free, publicly-accessible full text available November 1, 2024
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