Single-Cell FISH Analysis Reveals Distinct Shifts in PKM Isoform Populations during Drug Resistance Acquisition

The Warburg effect, i.e., the utilization of glycolysis under aerobic conditions, is recognized as a survival advantage of cancer cells. However, how the glycolytic activity is affected during drug resistance acquisition has not been explored at single-cell resolution. Because the relative ratio of the splicing isoform of pyruvate kinase M (PKM), PKM2/PKM1, can be used to estimate glycolytic activity, we utilized a single-molecule fluorescence in situ hybridization (SM-FISH) method to simultaneously quantify the mRNA levels of PKM1 and PKM2. Treatment of HCT116 cells with gefitinib (GE) resulted in two distinct populations of cells. However, as cells developed GE resistance, the GE-sensitive population with reduced PKM2 expression disappeared, and GE-resistant cells (Res) demonstrated enhanced PKM1 expression and a tightly regulated PKM2/PKM1 ratio. Our data suggest that maintaining an appropriate PKM2 level is important for cell survival upon GE treatment, whereas increased PKM1 expression becomes crucial in GE Res. This approach demonstrates the importance of single-cell-based analysis for our understanding of cancer cell metabolic responses to drugs, which could aid in the design of treatment strategies for drug-resistant cancers

Development of the CMS detector for the CERN LHC Run 3

International audienceSince the initial data taking of the CERN LHC, the CMS experiment has undergone substantial upgrades and improvements. This paper discusses the CMS detector as it is configured for the third data-taking period of the CERN LHC, Run 3, which started in 2022. The entire silicon pixel tracking detector was replaced. A new powering system for the superconducting solenoid was installed. The electronics of the hadron calorimeter was upgraded. All the muon electronic systems were upgraded, and new muon detector stations were added, including a gas electron multiplier detector. The precision proton spectrometer was upgraded. The dedicated luminosity detectors and the beam loss monitor were refurbished. Substantial improvements to the trigger, data acquisition, software, and computing systems were also implemented, including a new hybrid CPU/GPU farm for the high-level trigger

Measurement of the τ\tau lepton polarization in Z boson decays in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe polarization of $\tau$ leptons is measured using leptonic and hadronic $\tau$ lepton decays in Z $\to\tau^+\tau^-$ events in proton-proton collisions at $\sqrt{s}$ = 13 TeV recorded by CMS at the CERN LHC with an integrated luminosity of 36.3 fb$^{-1}$. The measured $\tau^-$ polarization at the Z boson mass pole is $\mathcal{P}_{\tau}$(Z) = $-$0.144$\pm$0.006 (stat) $\pm$ 0.014 (syst) = $-$0.144$\pm$0.015, in good agreement with the measurement of the $\tau$ lepton asymmetry parameter of $A_{\tau}$ = 0.1439$\pm$0.0043 = $-\mathcal{P}_{\tau}$(Z) at LEP. The $\tau$ polarization depends on the ratio of the vector to axial-vector couplings of the $\tau$ leptons in the neutral current expression, and thus on the effective weak mixing angle $\sin^{2}\theta_\mathrm{W}^{\text{eff}}$, independently of the Z boson production mechanism. The obtained value $\sin^{2}\theta_\mathrm{W}^{\text{eff}}$ = 0.2319$\pm$0.0008 (stat) $\pm$ 0.0018 (syst) = 0.2319$\pm$0.0019 is in good agreement with measurements at e$^+$e$^-$ colliders

Search for stealth supersymmetry in final states with two photons, jets, and low missing transverse momentum in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe results of a search for stealth supersymmetry in final states with two photons and jets, targeting a phase space region with low missing transverse momentum ($p_\text{T}^\text{miss}$), are reported. The study is based on a sample of proton-proton collisions at $\sqrt{s}$ =13 TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138 fb$^{-1}$. As LHC results continue to constrain the parameter space of the minimal supersymmetric standard model, the low $p_\text{T}^\text{miss}$ regime is increasingly valuable to explore. To estimate the backgrounds due to standard model processes in such events, we apply corrections derived from simulation to an estimate based on a control selection in data. The results are interpreted in the context of simplified stealth supersymmetry models with gluino and squark pair production. The observed data are consistent with the standard model predictions, and gluino (squark) masses of up to 2150 (1850) GeV are excluded at the 95% confidence level

Search for long-lived particles decaying in the CMS muon detectors in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for long-lived particles (LLPs) decaying in the CMS muon detectors is presented. A data sample of proton-proton collisions at $\sqrt{s}$ = 13 TeV corresponding to an integrated luminosity of 138 fb$^{-1}$ recorded at the LHC in 2016-2018, is used. The decays of LLPs are reconstructed as high multiplicity clusters of hits in the muon detectors. In the context of twin Higgs models, the search is sensitive to LLP masses from 0.4 to 55 GeV and a broad range of LLP decay modes, including decays to hadrons, $\tau$ leptons, electrons, or photons. No excess of events above the standard model background is observed. The most stringent limits to date from LHC data are set on the branching fraction of the Higgs boson decay to a pair of LLPs with masses below 10 GeV. This search also provides the best limits for various intervals of LLP proper decay length and mass. Finally, this search sets the first limits at the LHC on a dark quantum chromodynamic sector whose particles couple to the Higgs boson through gluon, Higgs boson, photon, vector, and dark-photon portals, and is sensitive to branching fractions of the Higgs boson to dark quarks as low as 2$\times$10$^{-3}$

Search for flavor changing neutral current interactions of the top quark in final states with a photon and additional jets in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for the production of a top quark in association with a photon and additional jets via flavor changing neutral current interactions is presented. The analysis uses proton-proton collision data recorded by the CMS detector at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb$^{-1}$. The search is performed by looking for processes where a single top quark is produced in association with a photon, or a pair of top quarks where one of the top quarks decays into a photon and an up or charm quark. Events with an electron or a muon, a photon, one or more jets, and missing transverse momentum are selected. Multivariate analysis techniques are used to discriminate signal and standard model background processes. No significant deviation is observed over the predicted background. Observed (expected) upper limits are set on the branching fractions of top quark decays: $\mathcal{B}$(t$\to$u$\gamma$) $\lt$ 0.95$\times$10$^{-5}$ (1.20$\times$10$^{-5}$) and $\mathcal{B}$(t$\to$c$\gamma$) $\lt$ 1.51$\times$10$^{-5}$ (1.54$\times$10$^{-5}$) at 95% confidence level, assuming a single nonzero coupling at a time. The obtained limit for $\mathcal{B}$(t$\to$u$\gamma$) is similar to the current best limit, while the limit for $\mathcal{B}$(t$\to$c$\gamma$) is significantly tighter than previous results

Search for the lepton flavor violating τ→\tau \to 3μ\mu decay in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for the lepton flavor violating $\tau \to$ 3$\mu$ decay is performed using proton-proton collision events at a center-of-mass energy of 13 TeV collected by the CMS experiment at the LHC in 2017-2018, corresponding to an integrated luminosity of 97.7 fb$^{-1}$. Tau leptons produced in both heavy-flavor hadron and W boson decays are exploited in the analysis. No evidence for the decay is observed. The results of this search are combined with an earlier null result based on data collected in 2016 to obtain a total integrated luminosity of 131 fb$^{-1}$. The observed (expected) upper limits on the branching fraction $\mathcal{B}$($\tau \to$ 3$\mu$) at confidence levels of 90 and 95% are 2.9$\times$10$^{-8}$ (2.4$\times$10$^{-8}$) and 3.6$\times$10$^{-8}$ (3.0$\times$10$^{-8}$), respectively

Measurement of multidifferential cross sections for dijet production in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA measurement of the dijet production cross section is reported based on proton-proton collision data collected in 2016 at $\sqrt{s}$ = 13 TeV by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of up to 36.3 fb$^{-1}$. Jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm for distance parameters of $R$ = 0.4 and 0.8. Cross sections are measured double-differentially (2D) as a function of the largest absolute rapidity $\lvert y_\text{max}\rvert$ of the two jets with the highest transverse momenta $p_\mathrm{T}$ and their invariant mass $m_{1,2}$, and triple-differentially (3D) as a function of the rapidity separation $y^*$, the total boost $y_\mathrm{b}$, and either $m_{1,2}$ or the average $p_\mathrm{T}$ of the two jets. The cross sections are unfolded to correct for detector effects and are compared with fixed-order calculations derived at next-to-next-to-leading order in perturbative quantum chromodynamics. The impact of the measurements on the parton distribution functions and the strong coupling constant at the mass of the Z boson is investigated, yielding a value of $\alpha_\mathrm{S}$ = 0.1179 $\pm$ 0.0019

Search for charged-lepton flavor violation in the production and decay of top quarks using trilepton final states in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search is performed for charged-lepton flavor violating processes in top quark (t) production and decay. The data were collected by the CMS experiment from proton-proton collisions at a center-of-mass energy of 13 TeV and correspond to an integrated luminosity of 138 fb$^{-1}$. The selected events are required to contain one opposite-sign electron-muon pair, a third charged lepton (electron or muon), and at least one jet of which no more than one is associated with a bottom quark. Boosted decision trees are used to distinguish signal from background, exploiting differences in the kinematics of the final states particles. The data are consistent with the standard model expectation. Upper limits at 95% confidence level are placed in the context of effective field theory on the Wilson coefficients, which range between 0.024-0.424 TeV$^{-2}$ depending on the flavor of the associated light quark and the Lorentz structure of the interaction. These limits are converted to upper limits on branching fractions involving up (charm) quarks, t$\to$e$\mu$u (t$\to$e$\mu$c), of 0.032 (0.498)$\times$10$^{-6}$, 0.022 (0.369)$\times$10$^{-6}$, and 0.012 (0.216)$\times$10$^{-6}$ for tensor-like, vector-like, and scalar-like interactions, respectively