Genetically Engineered Microvesicles Carrying Suicide mRNA/Protein Inhibit Schwannoma Tumor Growth

Microvesicles (MVs) play an important role in intercellular communication by carrying mRNAs, microRNAs (miRNAs), non-coding RNAs, proteins, and DNA from cell to cell. To our knowledge, this is the first report of delivery of a therapeutic mRNA/protein via MVs for treatment of cancer. We first generated genetically engineered MVs by expressing high levels of the suicide gene mRNA and protein–cytosine deaminase (CD) fused to uracil phosphoribosyltransferase (UPRT) in MV donor cells. MVs were isolated from these cells and used to treat pre-established nerve sheath tumors (schwannomas) in an orthotopic mouse model. We demonstrated that MV-mediated delivery of CD-UPRT mRNA/protein by direct injection into schwannomas led to regression of these tumors upon systemic treatment with the prodrug (5-fluorocytosine (5-FC)), which is converted within tumor cells to 5-fluorouracil (5-FU)–an anticancer agent. Taken together, these studies suggest that MVs can serve as novel cell-derived “liposomes” to effectively deliver therapeutic mRNA/proteins to treatment of diseases

From prompt to direct J/ψ\psi production: new insights on the χc1\chi_{c1} and χc2\chi_{c2} polarizations and feed-down contributions from a global-fit analysis of mid-rapidity LHC data

While the prompt J/$\psi$ cross section and polarization have been measured with good precision as a function of transverse momentum, $p_{\rm T}$, those of the directly produced J/$\psi$ are practically unknown, given that the cross sections and polarizations of the $\chi_{c1}$ and $\chi_{c2}$ mesons, large indirect contributors to J/$\psi$ production, are only known with rather poor accuracy. The lack of precise measurements of the $\chi_{cJ}$ polarizations induces large uncertainties in the level of their feed-down contributions to the prompt J/$\psi$ yield, because of the polarization-dependent acceptance corrections. The experimental panorama of charmonium production can be significantly improved through a consistent and model-independent global analysis of existing measurements of J/$\psi$, $\psi$(2S) and $\chi_{c}$ cross sections and polarizations, faithfully respecting all the correlations and uncertainties. In particular, it is seen that the $\chi_{cJ}$ polarizations and feed-down fractions to J/$\psi$ production have a negligible dependence on the J/$\psi$ $p_{\rm T}$, with average values $\lambda_\vartheta^{\chi_{c1}} = 0.55 \pm 0.23$, $\lambda_\vartheta^{\chi_{c2}} = -0.39 \pm 0.22$, $R^{\chi_{c1}} = (18.8 \pm 1.4)\%$ and $R^{\chi_{c2}} = (6.5 \pm 0.5)\%$. The analysis also shows that $(67.2 \pm 1.9)\%$ of the prompt J/$\psi$ yield is due to directly-produced mesons, of polarization constrained to remarkably small values, $\lambda_\vartheta^{{\rm J}/\psi} = 0.04 \pm 0.06$.Comment: Submitted to Eur. Phys. J.

Study of the B +→ J / ψ Λ ¯ p decay in proton-proton collisions at √s = 8 TeV

A study of the B +→ J / ψ Λ ¯ p decay using proton-proton collision data collected at s = 8 TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 19.6 fb−1, is presented. The ratio of branching fractions B(B+→J/ψΛ¯p)/B(B+→J/ψK∗(892)+) is measured to be (1.054 ± 0.057(stat) ± 0.035(syst) ± 0.011(B))%, where the last uncertainty reflects the uncertainties in the world-average branching fractions of Λ ¯ and K*(892) + decays to reconstructed final states. The invariant mass distributions of the J / ψ Λ ¯ , J/ψp, and Λ ¯ p systems produced in the B +→ J / ψ Λ¯ p decay are investigated and found to be inconsistent with the pure phase space hypothesis. The analysis is extended by using a model-independent angular amplitude analysis, which shows that the observed invariant mass distributions are consistent with the contributions from excited kaons decaying to the Λ ¯ p system. [Figure not available: see fulltext.

Measurement of the top quark Yukawa coupling from t t kinematic distributions in the lepton+jets final state in proton-proton collisions at s =13 TeV MEASUREMENT of the TOP QUARK YUKAWA COUPLING from ... SIRUNYAN et al.

Results are presented for an extraction of the top quark Yukawa coupling from top quark-antiquark (tt) kinematic distributions in the lepton plus jets final state in proton-proton collisions, based on data collected by the CMS experiment at the LHC at s=13 TeV, corresponding to an integrated luminosity of 35.8 fb-1. Corrections from weak boson exchange, including Higgs bosons, between the top quarks can produce large distortions of differential distributions near the energy threshold of tt production. Therefore, precise measurements of these distributions are sensitive to the Yukawa coupling. Top quark events are reconstructed with at least three jets in the final state, and a novel technique is introduced to reconstruct the tt system for events with one missing jet. This technique enhances the experimental sensitivity in the low invariant mass region, Mtt. The data yields in Mtt, the rapidity difference |yt-yt|, and the number of reconstructed jets are compared with distributions representing different Yukawa couplings. These comparisons are used to measure the ratio of the top quark Yukawa coupling to its standard model predicted value to be 1.07-0.43+0.34 with an upper limit of 1.67 at the 95% confidence level

Search for new neutral Higgs bosons through the H → ZA→ ℓ+ℓ−b b ¯ process in pp collisions at √s = 13 TeV

This paper reports on a search for an extension to the scalar sector of the standard model, where a new CP-even (odd) boson decays to a Z boson and a lighter CP-odd (even) boson, and the latter further decays to a b quark pair. The Z boson is reconstructed via its decays to electron or muon pairs. The analysed data were recorded in proton-proton collisions at a center-of-mass energy s = 13 TeV, collected by the CMS experiment at the LHC during 2016, corresponding to an integrated luminosity of 35.9 fb−1. Data and predictions from the standard model are in agreement within the uncertainties. Upper limits at 95% confidence level are set on the production cross section times branching fraction, with masses of the new bosons up to 1000 GeV. The results are interpreted in the context of the two-Higgs-doublet model. [Figure not available: see fulltext.]

Search for a heavy Higgs boson decaying to a pair of W bosons in proton-proton collisions at √s = 13 TeV

A search for a heavy Higgs boson in the mass range from 0.2 to 3.0 TeV, decaying to a pair of W bosons, is presented. The analysis is based on proton-proton collisions at s = 13 TeV recorded by the CMS experiment at the LHC in 2016, corresponding to an integrated luminosity of 35.9 fb−1. The W boson pair decays are reconstructed in the 2ℓ2ν and ℓν2q final states (with ℓ = e or μ). Both gluon fusion and vector boson fusion production of the signal are considered. Interference effects between the signal and background are also taken into account. The observed data are consistent with the standard model (SM) expectation. Combined upper limits at 95% confidence level on the product of the cross section and branching fraction exclude a heavy Higgs boson with SM-like couplings and decays up to 1870 GeV. Exclusion limits are also set in the context of a number of two-Higgs-doublet model formulations, further reducing the allowed parameter space for SM extensions. [Figure not available: see fulltext.