Differential Gene Expression Changes in Children with Severe Dengue Virus Infections

Dengue virus infection is an impressively emerging disease that can be fatal in severe cases. It is not precisely clear why some patients progress to severe disease whereas most patients only suffer from a mild infection. In severe disease, a “cytokine storm” is induced, which indicates the release of a great number of inflammatory mediators (“cytokines”). Evidence suggested that a balance could be involved between protective and pathologic cytokine release patterns. We studied this concept in a cohort of Indonesian children with severe dengue disease using a gene expression profiling method

Decreased Dengue Replication and an Increased Anti-viral Humoral Response with the use of Combined Toll-Like Receptor 3 and 7/8 Agonists in Macaques

Pathogenic versus protective outcomes to Dengue virus (DENV) infection are associated with innate immune function. This study aimed to determine the role of increased TLR3- and TLR7/8-mediated innate signaling after Dengue infection of rhesus macaques in vivo to evaluate its impact on disease and anti-DENV immune responses.TLR3 and TLR7/8 agonists (emulsified in Montanide) were administered subcutaneously to rhesus macaques at 48 hours and 7 days after DENV infection. The Frequency and activation of myeloid dendritic cells, plasmacytoid dendritic cells, and B cells were measured by flow cytometry while the serum levels of 14 different cytokines and chemokines were quantified. Adaptive immune responses were measured by DENV-specific antibody subtype measurements. Results showed that the combined TLR agonists reduced viral replication and induced the development of a proinflammatory reaction, otherwise absent in Dengue infection alone, without any clear signs of exacerbated disease. Specifically, the TLR-induced response was characterized by activation changes in mDC subsets concurrent with higher serum levels of CXCL-10 and IL-1Ra. TLR stimulation also induced higher titers of anti-DENV antibodies and acted to increase the IgG2/IgG1 ratio of anti-DENV to favor the subtype associated with DENV control. We also observed an effect of DENV-mediated suppression of mDC activation consistent with prior in vitro studies.These data show that concurrent TLR3/7/8 activation of the innate immune response after DENV infection in vivo acts to increase antiviral mechanisms via increased inflammatory and humoral responses in rhesus macaques, resulting in decreased viremia and melioration of the infection. These findings underscore an in vivo protective rather than a pathogenic role for combined TLR3/7/8-mediated activation in Dengue infection of rhesus macaques. Our study provides definitive proof-of-concept into the mechanism by which DENV evades immune recognition and activation in vivo

Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

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 = 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 κT = 0.25 and a relative decay width Γ/MT′ < 5%

Combined searches for the production of supersymmetric top quark partners in proton–proton collisions at √s=13Te

A combination of searches for top squark pair production using proton–proton collision data at a center-of-mass energy of 13TeV at the CERN LHC, corresponding to an integrated luminosity of 137fb$^{-1}$ collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on the model, the combined result excludes a top squark mass up to 1325GeV for a massless neutralino, and a neutralino mass up to 700GeV for a top squark mass of 1150GeV. Top squarks with masses from 145 to 295GeV, for neutralino masses from 0 to 100GeV, with a mass difference between the top squark and the neutralino in a window of 30GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420GeV

Search for flavor-changing neutral current interactions of the top quark and the Higgs boson decaying to a bottom quark-antiquark pair at s√ = 13 TeV

A search for flavor-changing neutral current interactions of the top quark (t) and the Higgs boson (H) is presented. The search is based on a data sample corresponding to an integrated luminosity of 137 fb−1 recorded by the CMS experiment at the LHC in proton-proton collisions at s√ = 13 TeV. Events containing exactly one lepton (muon or electron) and at least three jets, among which at least two are identified as originating from the hadronization of a bottom quark, are analyzed. A set of deep neural networks is used for kinematic event reconstruction, while boosted decision trees distinguish the signal from the background events. No significant excess over the background predictions is observed, and upper limits on the signal production cross sections are extracted. These limits are interpreted in terms of top quark decay branching fractions (B ) to the Higgs boson and an up (u) or a charm quark (c). Assuming one nonvanishing extra coupling at a time, the observed (expected) upper limits at 95% confidence level are B (t → Hu) &lt; 0.079 (0.11)% and B (t → Hc) &lt; 0.094 (0.086)%

Studies of charm and beauty hadron long-range correlations in pp and pPb collisions at LHC energies

Measurements of the second Fourier harmonic coefficient (v(2)) of the azimuthal distributions of prompt and nonprompt D-0 mesons produced in pp and pPb collisions are presented. Nonprompt D-0 mesons come from beauty hadron decays. The data samples are collected by the CMS experiment at nucleon-nucleon center-of-mass energies of 13 and 8.16 TeV, respectively. In high multiplicity pp collisions, v(2) signals for prompt charm hadrons are reported for the first time, and are found to be comparable to those for light-flavor hadron species over a transverse momentum (pT) range of 2-6 GeV. Compared at similar event multiplicities, the prompt D-0 meson v(2) values in pp and pPb collisions are similar in magnitude. The v(2) values for open beauty hadrons are extracted for the first time via nonprompt D-0 mesons in pPb collisions. For pT in the range of 2-5 GeV, the results suggest that v(2) for nonprompt D-0 mesons is smaller than that for prompt D-0 mesons. These new measurements indicate a positive charm hadron v(2) in pp collisions and suggest a mass dependence in v(2) between charm and beauty hadrons in the pPb system. These results provide insights into the origin of heavy-flavor quark collectivity in small systems. (C) 2020 The Author(s). Published by Elsevier B.V.Peer reviewe