170 research outputs found

    SARS-CoV-2 structural features may explain limited neutralizing-antibody responses.

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    Neutralizing antibody responses of SARS-CoV-2-infected patients may be low and of short duration. We propose here that coronaviruses employ a structural strategy to avoid strong and enduring antibody responses. Other viruses induce optimal and long-lived neutralizing antibody responses, thanks to 20 or more repetitive, rigid antigenic epitopes, spaced by 5–10 nm, present on the viral surface. Such arrays of repetitive and highly organized structures are recognized by the immune system as pathogen-associated structural patterns (PASPs), which are characteristic for pathogen surfaces. In contrast, coronaviruses are large particles with long spikes (S protein) embedded in a fluid membrane. Therefore, the neutralizing epitopes (which are on the S protein) are loosely “floating” and widely spaced by an average of about 25 nm. Consequently, recruitment of complement is poor and stimulation of B cells remains suboptimal, offering an explanation for the inefficient and short-lived neutralizing antibody responses

    Vaccination with nanoparticles combined with micro-adjuvants protects against cancer.

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    Induction of strong T cell responses, in particular cytotoxic T cells, is a key for the generation of efficacious therapeutic cancer vaccines which yet, remains a major challenge for the vaccine developing world. Here we demonstrate that it is possible to harness the physiological properties of the lymphatic system to optimize the induction of a protective T cell response. Indeed, the lymphatic system sharply distinguishes between nanoscale and microscale particles. The former reaches the fenestrated lymphatic system via diffusion, while the latter either need to be transported by dendritic cells or form a local depot. Our previously developed cucumber-mosaic virus-derived nanoparticles termed (CuMV <sub>TT</sub> -VLPs) incorporating a universal Tetanus toxoid epitope TT830-843 were assessed for their draining kinetics using stereomicroscopic imaging. A nano-vaccine has been generated by coupling p33 epitope as a model antigen to CuMV <sub>TT</sub> -VLPs using bio-orthogonal Cu-free click chemistry. The CuMV <sub>TT</sub> -p33 nano-sized vaccine has been next formulated with the micron-sized microcrystalline tyrosine (MCT) adjuvant and the formed depot effect was studied using confocal microscopy and trafficking experiments. The immunogenicity of the nanoparticles combined with the micron-sized adjuvant was next assessed in an aggressive transplanted murine melanoma model. The obtained results were compared to other commonly used adjuvants such as B type CpGs and Alum. Our results showed that CuMV <sub>TT</sub> -VLPs can efficiently and rapidly drain into the lymphatic system due to their nano-size of ~ 30 nm. However, formulating the nanoparticles with the micron-sized MCT adjuvant of ~ 5 ΌM resulted in a local depot for the nanoparticles and a longer exposure time for the immune system. The preclinical nano-vaccine CuMV <sub>TT</sub> -p33 formulated with the micron-sized MCT adjuvant has enhanced the specific T cell response in the stringent B16F10p33 murine melanoma model. Furthermore, the micron-sized MCT adjuvant was as potent as B type CpGs and clearly superior to the commonly used Alum adjuvant when total CD8 <sup>+</sup> , specific p33 T cell response or tumour protection were assessed. The combination of nano- and micro-particles may optimally harness the physiological properties of the lymphatic system. Since the nanoparticles are well defined virus-like particles and the micron-sized adjuvant MCT has been used for decades in allergen-specific desensitization, this approach may readily be translated to the clinic

    On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

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    A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

    Search for the doubly heavy baryon Ξbc+\it{\Xi}_{bc}^{+} decaying to J/ψΞc+J/\it{\psi} \it{\Xi}_{c}^{+}

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    A first search for the Ξbc+→J/ψΞc+\it{\Xi}_{bc}^{+}\to J/\it{\psi}\it{\Xi}_{c}^{+} decay is performed by the LHCb experiment with a data sample of proton-proton collisions, corresponding to an integrated luminosity of 9 fb−19\,\mathrm{fb}^{-1} recorded at centre-of-mass energies of 7, 8, and 13 TeV13\mathrm{\,Te\kern -0.1em V}. Two peaking structures are seen with a local (global) significance of 4.3 (2.8)4.3\,(2.8) and 4.1 (2.4)4.1\,(2.4) standard deviations at masses of 6571 MeV ⁣/c26571\,\mathrm{Me\kern -0.1em V\!/}c^2 and 6694 MeV ⁣/c26694\,\mathrm{Me\kern -0.1em V\!/}c^2, respectively. Upper limits are set on the Ξbc+\it{\Xi}_{bc}^{+} baryon production cross-section times the branching fraction relative to that of the Bc+→J/ψDs+B_{c}^{+}\to J/\it{\psi} D_{s}^{+} decay at centre-of-mass energies of 8 and 13 TeV13\mathrm{\,Te\kern -0.1em V}, in the Ξbc+\it{\Xi}_{bc}^{+} and in the Bc+B_{c}^{+} rapidity and transverse-momentum ranges from 2.0 to 4.5 and 0 to 20 GeV ⁣/c20\,\mathrm{Ge\kern -0.1em V\!/}c, respectively. Upper limits are presented as a function of the Ξbc+\it{\Xi}_{bc}^{+} mass and lifetime.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-005.html (LHCb public pages

    Study of the lineshape of the chi(c1) (3872) state

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    A study of the lineshape of the chi(c1) (3872) state is made using a data sample corresponding to an integrated luminosity of 3 fb(-1) collected in pp collisions at center-of-mass energies of 7 and 8 TeV with the LHCb detector. Candidate chi(c1)(3872) and psi(2S) mesons from b-hadron decays are selected in the J/psi pi(+)pi(-) decay mode. Describing the lineshape with a Breit-Wigner function, the mass splitting between the chi(c1 )(3872) and psi(2S) states, Delta m, and the width of the chi(c1 )(3872) state, Gamma(Bw), are determined to be (Delta m=185.598 +/- 0.067 +/- 0.068 Mev,)(Gamma BW=1.39 +/- 0.24 +/- 0.10 Mev,) where the first uncertainty is statistical and the second systematic. Using a Flatte-inspired model, the mode and full width at half maximum of the lineshape are determined to be (mode=3871.69+0.00+0.05 MeV.)(FWHM=0.22-0.04+0.13+0.07+0.11-0.06-0.13 MeV, ) An investigation of the analytic structure of the Flatte amplitude reveals a pole structure, which is compatible with a quasibound D-0(D) over bar*(0) state but a quasivirtual state is still allowed at the level of 2 standard deviations

    Measurement of the CKM angle γγ in B±→DK±B^\pm\to D K^\pm and B±→Dπ±B^\pm \to D π^\pm decays with D→KS0h+h−D \to K_\mathrm S^0 h^+ h^-

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    A measurement of CPCP-violating observables is performed using the decays B±→DK±B^\pm\to D K^\pm and B±→Dπ±B^\pm\to D \pi^\pm, where the DD meson is reconstructed in one of the self-conjugate three-body final states KSπ+π−K_{\mathrm S}\pi^+\pi^- and KSK+K−K_{\mathrm S}K^+K^- (commonly denoted KSh+h−K_{\mathrm S} h^+h^-). The decays are analysed in bins of the DD-decay phase space, leading to a measurement that is independent of the modelling of the DD-decay amplitude. The observables are interpreted in terms of the CKM angle Îł\gamma. Using a data sample corresponding to an integrated luminosity of 9 fb−19\,\text{fb}^{-1} collected in proton-proton collisions at centre-of-mass energies of 77, 88, and 13 TeV13\,\text{TeV} with the LHCb experiment, Îł\gamma is measured to be (68.7−5.1+5.2)∘\left(68.7^{+5.2}_{-5.1}\right)^\circ. The hadronic parameters rBDKr_B^{DK}, rBDπr_B^{D\pi}, ÎŽBDK\delta_B^{DK}, and ÎŽBDπ\delta_B^{D\pi}, which are the ratios and strong-phase differences of the suppressed and favoured B±B^\pm decays, are also reported

    Measurement of CP asymmetries and branching fraction ratios of B− decays to two charm mesons

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    The CPCP asymmetries of seven B−B^- decays to two charm mesons are measured using data corresponding to an integrated luminosity of 9fb−19\text{fb}^{-1} of proton-proton collisions collected by the LHCb experiment. Decays involving a D∗0D^{*0} or Ds∗−D^{*-}_s meson are analysed by reconstructing only the D0D^0 or Ds−D^-_s decay products. This paper presents the first measurement of ACP(B−→Ds∗−D0)\mathcal{A}^{CP}(B^- \rightarrow D^{*-}_s D^0) and ACP(B−→Ds−D∗0)\mathcal{A}^{CP}(B^- \rightarrow D^{-}_s D^{*0}), and the most precise measurement of the other five CPCP asymmetries. There is no evidence of CPCP violation in any of the analysed decays. Additionally, two ratios between branching fractions of selected decays are measured.The CP asymmetries of seven B−^{−} decays to two charm mesons are measured using data corresponding to an integrated luminosity of 9 fb−1^{−1} of proton-proton collisions collected by the LHCb experiment. Decays involving a D∗0^{*0} or Ds∗− {D}_s^{\ast -} meson are analysed by reconstructing only the D0^{0} or Ds− {D}_s^{-} decay products. This paper presents the first measurement of ACP \mathcal{A} ^{CP}(B−^{−}→Ds∗− {D}_s^{\ast -} D0^{0}) and ACP \mathcal{A} ^{CP}(B−^{−}→Ds− {D}_s^{-} D∗0^{∗0}), and the most precise measurement of the other five CP asymmetries. There is no evidence of CP violation in any of the analysed decays. Additionally, two ratios between branching fractions of selected decays are measured.[graphic not available: see fulltext]The CPCP asymmetries of seven B−B^- decays to two charm mesons are measured using data corresponding to an integrated luminosity of 9 fb−19\text{ fb}^{-1} of proton-proton collisions collected by the LHCb experiment. Decays involving a D∗0D^{*0} or Ds∗−D^{*-}_s meson are analysed by reconstructing only the D0D^0 or Ds−D^-_s decay products. This paper presents the first measurement of ACP(B−→Ds∗−D0)\mathcal{A}^{CP}(B^- \rightarrow D^{*-}_s D^0) and ACP(B−→Ds−D∗0)\mathcal{A}^{CP}(B^- \rightarrow D^{-}_s D^{*0}), and the most precise measurement of the other five CPCP asymmetries. There is no evidence of CPCP violation in any of the analysed decays. Additionally, two ratios between branching fractions of selected decays are measured
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