Artemisinins have revolutionized the treatment of
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Abstract Plasmodium falciparum malaria; 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 gondii to 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. Deletingmore » -
Free, publicly-accessible full text available March 1, 2023
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Free, publicly-accessible full text available January 1, 2023
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A bstract A search is presented for new particles produced at the LHC in proton-proton collisions at $$ \sqrt{s} $$ s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb − 1 , collected in 2017–2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with anmore »Free, publicly-accessible full text available November 1, 2022
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Free, publicly-accessible full text available September 1, 2022
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Free, publicly-accessible full text available September 1, 2022
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Free, publicly-accessible full text available August 1, 2022
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Free, publicly-accessible full text available August 1, 2022
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Abstract Production cross sections of the Higgs boson are measured in the $${\mathrm{H}} \rightarrow {\mathrm{Z}} {\mathrm{Z}} \rightarrow 4\ell $$ H → Z Z → 4 ℓ ( $$\ell ={\mathrm{e}},{{{\upmu }}_{\mathrm{}}^{\mathrm{}}} $$ ℓ = e , μ ) decay channel. A data sample of proton–proton collisions at a center-of-mass energy of 13 $$\,\text {Te}\text {V}$$ Te , collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137 $$\,\text {fb}^{-1}$$ fb - 1 is used. The signal strength modifier $$\mu $$ μ , defined as the ratio of the Higgs boson production rate in the $$4\ellmore »Free, publicly-accessible full text available June 1, 2022
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A bstract Jet production in lead-lead (PbPb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV is studied with the CMS detector at the LHC, using PbPb and pp data samples corresponding to integrated luminosities of 404 μ b − 1 and 27.4 pb − 1 , respectively. Jets with different areas are reconstructed using the anti- k T algorithm by varying the distance parameter R . The measurements are performed using jets with transverse momenta ( p T ) greater than 200 GeV and in a pseudorapidity range of |η| < 2. To reveal the mediummore »