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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.

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.

A search for decays to invisible particles of Higgs bosons produced in association with a top-antitop quark pair or a vector boson, which both decay to a fully hadronic final state, has been performed using proton-proton collision data collected at$${\sqrt{s}=13\,\text {Te}\hspace{-.08em}\text {V}}$$$\sqrt{s}=13\text{Te}\text{V}$by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138$$\,\text {fb}^{-1}$$${\text{fb}}^{-1}$. The 95% confidence level upper limit set on the branching fraction of the 125$$\,\text {Ge}\hspace{-.08em}\text {V}$$$\text{Ge}\text{V}$Higgs boson to invisible particles,$${\mathcal {B}({\textrm{H}} \rightarrow \text {inv})}$$$B(\text{H}\to \text{inv})$, is 0.54 (0.39 expected), assuming standard model production cross sections. The results of this analysis are combined with previous$${\mathcal {B}({\textrm{H}} \rightarrow \text {inv})}$$$B(\text{H}\to \text{inv})$searches carried out at$${\sqrt{s}=7}$$$\sqrt{s}=7$, 8, and 13$$\,\text {Te}\hspace{-.08em}\text {V}$$$\text{Te}\text{V}$in complementary production modes. The combined upper limit at 95% confidence level on$${\mathcal {B}({\textrm{H}} \rightarrow \text {inv})}$$$B(\text{H}\to \text{inv})$is 0.15 (0.08 expected).