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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 bstract The first measurement of the top quark pair ( $$ \textrm{t}\overline{\textrm{t}} $$ t t ¯ ) production cross section in proton-proton collisions at $$ \sqrt{s} $$ s = 13 . 6 TeV is presented. Data recorded with the CMS detector at the CERN LHC in Summer 2022, corresponding to an integrated luminosity of 1 . 21 fb − 1 , are analyzed. Events are selected with one or two charged leptons (electrons or muons) and additional jets. A maximum likelihood fit is performed in event categories defined by the number and flavors of the leptons, the number of jets, and the number of jets identified as originating from b quarks. An inclusive $$ \textrm{t}\overline{\textrm{t}} $$ t t ¯ production cross section of 881 ± 23 (stat + syst) ± 20 (lumi) pb is measured, in agreement with the standard model prediction of $$ {924}_{-40}^{+32} $$ 924 − 40 + 32 pb.

A bstract A search for physics beyond the standard model (SM) in the final state with a hadronically decaying tau lepton and a neutrino is presented. This analysis is based on data recorded by the CMS experiment from proton-proton collisions at a center-of-mass energy of 13 TeV at the LHC, corresponding to a total integrated luminosity of 138 fb − 1 . The transverse mass spectrum is analyzed for the presence of new physics. No significant deviation from the SM prediction is observed. Limits are set on the production cross section of a W′ boson decaying into a tau lepton and a neutrino. Lower limits are set on the mass of the sequential SM-like heavy charged vector boson and the mass of a quantum black hole. Upper limits are placed on the couplings of a new boson to the SM fermions. Constraints are put on a nonuniversal gauge interaction model and an effective field theory model. For the first time, upper limits on the cross section of t -channel leptoquark (LQ) exchange are presented. These limits are translated into exclusion limits on the LQ mass and on its coupling in the t -channel. The sensitivity of this analysis extends intomore »the parameter space of LQ models that attempt to explain the anomalies observed in B meson decays. The limits presented for the various interpretations are the most stringent to date. Additionally, a model-independent limit is provided.« less

Abstract The Precision Proton Spectrometer (PPS) of the CMS and TOTEM experiments collected 107.7 fb -1 in proton-proton (pp) collisions at the LHC at 13 TeV (Run 2). This paper describes the key features of the PPS alignment and optics calibrations, the proton reconstruction procedure, as well as the detector efficiency and the performance of the PPS simulation. The reconstruction and simulation are validated using a sample of (semi)exclusive dilepton events. The performance of PPS has proven the feasibility of continuously operating a near-beam proton spectrometer at a high luminosity hadron collider.

A bstract A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at $$ \sqrt{s} $$ s = 13 TeV, corresponding to an integrated luminosity of 138 fb − 1 . This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κ T = 0 . 25 and a relative decay width Γ /M T′ < 5%.

Abstract The production of Z bosons associated with jets is measured in $$\text {p}\text {p}$$ pp collisions at $$\sqrt{s}=13\,\text {Te}\hspace{-.08em}\text {V} $$ s = 13 Te V with data recorded with the CMS experiment at the LHC corresponding to an integrated luminosity of 36.3 $$\,\text {fb}^{-1}$$ fb - 1 . The multiplicity of jets with transverse momentum $$p_{\textrm{T}} > 30\,\text {Ge}\hspace{-.08em}\text {V} $$ p T > 30 Ge V is measured for different regions of the Z boson’s $$p_{\textrm{T}} (\text {Z })$$ p T ( Z ) , from lower than 10 $$\,\text {Ge}\hspace{-.08em}\text {V}$$ Ge V to higher than 100 $$\,\text {Ge}\hspace{-.08em}\text {V}$$ Ge V . The azimuthal correlation $$\varDelta \phi $$ Δ ϕ between the Z boson and the leading jet, as well as the correlations between the two leading jets are measured in three regions of $$p_{\textrm{T}} (\text {Z })$$ p T ( Z ) . The measurements are compared with several predictions at leading and next-to-leading orders, interfaced with parton showers. Predictions based on transverse-momentum dependent parton distributions and corresponding parton showers give a good description of the measurement in the regions where multiple parton interactions and higher jet multiplicities are not important. The effects ofmore »multiple parton interactions are shown to be important to correctly describe the measured spectra in the low $$p_{\textrm{T}} (\text {Z })$$ p T ( Z ) regions.« less