The rockefeller university

Differential cross sections are measured for the standard model Higgs boson produced in association with vector bosons (W, Z) and decaying to a pair of b quarks. Measurements are performed within the framework of the simplified template cross sections. The analysis relies on the leptonic decays of theW and Z bosons, resulting in final states with 0, 1, or 2 electrons or muons. The Higgs boson candidates are either reconstructed from pairs of resolved b-tagged jets, or from single large-radius jets containing the particles arising from two b quarks. Proton-proton collision data at root s = 13 TeV, collected by the CMS experiment in 2016-2018 and corresponding to a total integrated luminosity of 138 fb(-1), are analyzed. The inclusive signal strength, defined as the product of the observed production cross section and branching fraction relative to the standard model expectation, combining all analysis categories, is found to be mu = 1.15(-0.20)(+0.22). This corresponds to an observed (expected) significance of 6.3 (5.6) standard deviations.

The brain's remarkable properties arise from the collective activity of millions of neurons. Widespread application of dimensionality reduction to multi-neuron recordings implies that neural dynamics can be approximated by low-dimensional "latent"signals reflecting neural computations. However, can such low-dimensional representations truly explain the vast range of brain activity, and if not, what is the appropriate resolution and scale of recording to capture them? Imaging neural activity at cellular resolution and nearsimultaneously across the mouse cortex, we demonstrate an unbounded scaling of dimensionality with neuron number in populations up to 1 million neurons. Although half of the neural variance is contained within sixteen dimensions correlated with behavior, our discovered scaling of dimensionality corresponds to an ever-increasing number of neuronal ensembles without immediate behavioral or sensory correlates. The activity patterns underlying these higher dimensions are fine grained and cortex wide, highlighting that largescale, cellular-resolution recording is required to uncover the full substrates of neuronal computations.

CD4 T helper cells use the SNARE protein SYNTAXIN-11 to promote B cell differentiation, germinal center formation, and class switching by facilitating CD40L mobilization and IL-2 and IL-10 secretion. Variable hypogammaglobulinemia is a novel phenotype of human STX11 deficiency. SYNTAXIN-11 (STX11) is a SNARE protein that mediates the fusion of cytotoxic granules with the plasma membrane at the immunological synapses of CD8 T or NK cells. Autosomal recessive inheritance of deleterious STX11 variants impairs cytotoxic granule exocytosis, causing familial hemophagocytic lymphohistiocytosis type 4 (FHL-4). In several FHL-4 patients, we also observed hypogammaglobulinemia, elevated frequencies of naive B cells, and increased double-negative DN2:DN1 B cell ratios, indicating a hitherto unrecognized role of STX11 in humoral immunity. Detailed analysis of Stx11-deficient mice revealed impaired CD4 T cell help for B cells, associated with disrupted germinal center formation, reduced isotype class switching, and low antibody avidity. Mechanistically, Stx11-/- CD4 T cells exhibit impaired membrane fusion leading to reduced CD107a and CD40L surface mobilization and diminished IL-2 and IL-10 secretion. Our findings highlight a critical role of STX11 in SNARE-mediated membrane trafficking and vesicle exocytosis in CD4 T cells, important for successful CD4 T cell-B cell interactions. Deficiency in STX11 impairs CD4 T cell-dependent B cell differentiation and humoral responses.

Since 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.

A search for W' bosons decaying to a top and a bottom quark in final states including an electron or a muon is performed with the CMS detector at the LHC. The analyzed data correspond to an integrated luminosity of 138 fb(-1) of proton-proton collisions at a center-of-mass energy of 13TeV. Good agreement with the standard model expectation is observed and no evidence for the existence of the W' boson is found over the mass range examined. The largest observed deviation from the standard model expectation is found for a W' boson mass (m(W)') hypothesis of 3.8TeV with a relative decay width of 1%, with a local (global) significance of 2.6 (2.0) standard deviations. Upper limits on the production cross sections of W' bosons decaying to a top and a bottom quark are set. Left- and right-handed W' bosons with m(W)' below 3.9 and 4.3TeV, respectively, are excluded at the 95% confidence level, under the assumption that the new particle has a narrow decay width. Limits are also set for relative decay widths up to 30%.

In this issue of Molecular Cell, Yang et al.(1) find that arginine-to-cysteine substitutants are enriched in a subset of lung cancer proteomes, potentiated by arginine deprivation, and promote resistance to chemotherapy.

Measurements of inclusive and normalized differential cross sections of the associated production of top quark-antiquark and bottom quark-antiquark pairs, t (t) over barb (b) over bar, are presented. The results are based on data from proton-proton collisions collected by the CMS detector at a centre-of-mass energy of 13TeV, corresponding to an integrated luminosity of 138 fb(-1). The cross sections are measured in the lepton+jets decay channel of the top quark pair, using events containing exactly one isolated electron or muon and at least five jets. Measurements are made in four fiducial phase space regions, targeting different aspects of the t (t) over barb (b) over bar process. Distributions are unfolded to the particle level through maximum likelihood fits, and compared with predictions from several event generators. The inclusive cross section measurements of this process in the fiducial phase space regions are the most precise to date. In most cases, the measured inclusive cross sections exceed the predictions with the chosen generator settings. The only exception is when using a particular choice of dynamic renormalization scale, mu(R) = 1/2 Pi(i=t), (t) over bar ,b (b) over bar m(T, i)(,)(1/4) where m(T), (2)(i) = m(i)(2) + p(T,i)(2) are the transverse masses of top and bottom quarks. The differential cross sections show varying degrees of compatibility with the theoretical predictions, and none of the tested generators with the chosen settings simultaneously describe all the measured distributions.

Synovial tissue inflammation is a hallmark of rheumatoid arthritis (RA). Recent work has identified prominent pathogenic cell states in inflamed RA synovial tissue, such as T peripheral helper cells; however, the epigenetic regulation of these states has yet to be defined. Here, we examine genome-wide open chromatin at single-cell resolution in 30 synovial tissue samples, including 12 samples with transcriptional data in multimodal experiments. We identify 24 chromatin classes and predict their associated transcription factors, including a CD8 + GZMK+ class associated with EOMES and a lining fibroblast class associated with AP-1. By integrating with an RA tissue transcriptional atlas, we propose that these chromatin classes represent 'superstates' corresponding to multiple transcriptional cell states. Finally, we demonstrate the utility of this RA tissue chromatin atlas through the associations between disease phenotypes and chromatin class abundance, as well as the nomination of classes mediating the effects of putatively causal RA genetic variants. The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define 'chromatin superstates' in patients with RA, which associate with distinct transcription factors and disease phenotypes.

Recombinant expression of proteins, propelled by therapeutic antibodies, has evolved into a multibillion dollar industry. Essential here is the quality control assessment of critical attributes, such as sequence fidelity, proper folding, and posttranslational modifications. Errors can lead to diminished bioactivity and, in the context of therapeutic proteins, an elevated risk for immunogenicity. Over the years, many techniques were developed and applied to validate proteins in a standardized and high- throughput fashion. One parameter has, however, so far been challenging to assess. Disulfide bridges, covalent bonds linking two cysteine residues, assist in the correct folding and stability of proteins and thus have a major influence on their efficacy. Mass spectrometry promises to be an optimal technique to uncover them in a fast and accurate fashion. In this work, we present a unique combination of sample preparation, data acquisition, and analysis facilitating the rapid and accurate assessment of disulfide bridges in purified proteins. Through microwave- assisted acid hydrolysis, the proteins are digested rapidly and artifact-free into peptides, with a substantial degree of overlap over the sequence. The nonspecific nature of this procedure, however, introduces chemical background, which is efficiently removed by integrating ion mobility preceding the mass spectrometric measurement. The nonspecific nature of the digestion step additionally necessitates new developments in data analysis, for which we extended the XlinkX node in Proteome Discoverer to efficiently process the data and ensure correctness through effective false discovery rate correction. The entire workflow can be completed within 1 h, allowing for high-throughput, high-accuracy disulfide mapping.

In this review, we provide an overview of the intricate host-virus interactions that have emerged from the study of SARS-CoV-2 infection. We focus on the antiviral mechanisms of interferonstimulated genes (ISGs) and their modulation of viral entry, replication, and release. We explore the role of a selection ISGs, restricting SARS-CoV-2 infection and discuss the virus's countermeasures. By synthesizing the latest research on SARSCoV-2 and host antiviral responses, this review aims to provide a deeper understanding of the antiviral state of the cell under SARS-CoV-2 and other viral infections, offering insights for the development of novel antiviral strategies and therapeutics.