Note: Scalable Multiphoton Coincidence-counting Electronics

We present a multichannel coincidence-counting module for use in quantum optics experiments. The circuit takes up to four transistor–transistor logic pulse inputs and counts either twofold, threefold, or fourfold coincidences, within a user-selected coincidence-time window as short as 12 ns. The module can accurately count eight sets of multichannel coincidences, for input rates of up to 84 MHz. Due to their low cost and small size, multiple modules can easily be combined to count arbitrary M-order coincidences among N inputs

First measurement of Xi(-) polarization in photoproduction

Despite decades of studies of the photoproduction of hyperons, both their production mechanisms and their spectra of excited states are still largely unknown. While the parity-violating weak decay of hyperons offers a means of measuring their polarization, which could help discern their production mechanisms and identify their excitation spectra, no such study has been possible for doubly strange baryons in photoproduction, due to low production cross sections. However, by making use of the reaction γp→K+K+Ξ−, we have measured, for the first time, the induced polarization, P, and the transferred polarization from circularly polarized real photons, characterized by Cx and Cz, to recoiling Ξ−s. The data were obtained using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab for photon energies from just over threshold (2.4 GeV) to 5.45 GeV. These first-time measurements are compared, and are shown to broadly agree, with model predictions in which cascade photoproduction proceeds through the decay of intermediate hyperon resonances that are produced via relativistic meson exchange, offering a new step forward in the understanding of the production and polarization of doubly-strange baryons

Measurement of unpolarized and polarized cross sections for deeply virtual Compton scattering on the proton at Jefferson Laboratory with CLAS

This paper reports the measurement of polarized and unpolarized cross sections for the ep→e′p′γ reaction, which is composed of deeply virtual Compton scattering (DVCS) and Bethe-Heitler (BH) processes, at an electron beam energy of 5.88 GeV at the Thomas Jefferson National Accelerator Facility using the Large Acceptance Spectrometer CLAS. The unpolarized cross sections and polarized cross section differences have been measured over broad kinematics, 0.10<xB<0.58, 1.0<Q2<4.8GeV2, and 0.09<-t<2.00GeV2. The results are found to be consistent with previous CLAS data, and these new data are discussed in the framework of the generalized parton distribution approach. Calculations with two widely used phenomenological models are approximately compatible with the experimental results over a large portion of the kinematic range of the data

Differential cross section for γd → ωd using CLAS at Jefferson Lab

The cross section for coherent $\omega$-meson photoproduction off the deuteron has been measured for the first time as a function of the momentum transfer $t = (P_{\gamma}-P_{\omega})^2$ and photon energy $E_{\gamma}$ using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The cross sections are measured in the energy range $1.4 < E_{\gamma} < 3.4$ GeV. A model based on $\omega-N$ rescattering is consistent with the data at low and intermediate momentum transfer, $|t|$. For $2.8 < E_{\gamma} < 3.4$ GeV, the total cross-section of $\omega-N$ scattering, based on fits within the framework of the Vector Meson Dominance model, is in the range of 30-40 mb.Comment: 8 pages, 5 figure

Measurements of the γvp→p′π+π- cross section with the CLAS detector for 0.4 GeV2<Q2<1.0 GeV2 and 1.3 GeV<W<1.825 GeV

New results on the single-differential and fully integrated cross sections for the process γvp→p′π+π- are presented. The experimental data were collected with the CLAS detector at Jefferson Laboratory. Measurements were carried out in the kinematic region of the reaction invariant mass W from 1.3 to 1.825 GeV and the photon virtuality Q2 from 0.4 to 1.0 GeV2. The cross sections were obtained in narrow Q2 bins (0.05 GeV2) with the smallest statistical uncertainties achieved in double-pion electroproduction experiments to date. The results were found to be in agreement with previously available data where they overlap. A preliminary interpretation of the extracted cross sections, which was based on a phenomenological meson-baryon reaction model, revealed substantial relative contributions from nucleon resonances. The data offer promising prospects to improve knowledge on the Q2 evolution of the electrocouplings of most resonances with masses up to ∼1.8 GeV

Cycling cancer persister cells arise from lineages with distinct programs

Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure1, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment2. Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell's clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation are associated with persister proliferative capacity across multiple cancer types. Impeding oxidative stress or metabolic reprogramming alters the fraction of cycling persisters. In human tumours, programs associated with cycling persisters are induced in minimal residual disease in response to multiple targeted therapies. The Watermelon system enabled the identification of rare persister lineages that are preferentially poised to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence

Cycling cancer persister cells arise from lineages with distinct programs

Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure1, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment2. Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell's clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation are associated with persister proliferative capacity across multiple cancer types. Impeding oxidative stress or metabolic reprogramming alters the fraction of cycling persisters. In human tumours, programs associated with cycling persisters are induced in minimal residual disease in response to multiple targeted therapies. The Watermelon system enabled the identification of rare persister lineages that are preferentially poised to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence

Metabolic modeling of single Th17 cells reveals regulators of autoimmunity

Metabolism is a major regulator of immune cell function, but it remains difficult to study the metabolic status of individual cells. Here, we present Compass, an algorithm to characterize cellular metabolic states based on single-cell RNA sequencing and flux balance analysis. We applied Compass to associate metabolic states with T helper 17 (Th17) functional variability (pathogenic potential) and recovered a metabolic switch between glycolysis and fatty acid oxidation, akin to known Th17/regulatory T&nbsp;cell (Treg) differences, which we validated by metabolic assays. Compass also predicted that Th17 pathogenicity was associated with arginine and downstream polyamine metabolism. Indeed, polyamine-related enzyme expression was enhanced in pathogenic Th17 and suppressed in Treg cells. Chemical and genetic perturbation of polyamine metabolism inhibited Th17 cytokines, promoted Foxp3 expression, and remodeled the transcriptome and epigenome of Th17 cells toward a Treg-like state. In&nbsp;vivo perturbations of the polyamine pathway altered the phenotype of encephalitogenic T&nbsp;cells and attenuated tissue inflammation in CNS autoimmunity