75 research outputs found

    Time for T? Immunoinformatics addresses the challenges of vaccine design for neglected tropical and emerging infectious diseases

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    Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere

    GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination

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    The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a “T cell–driven” methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens

    Observation of Two New Excited Ξb0 States Decaying to Λb0 K-π+

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    Two narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]<2.20(2.56) and Γ[Ξb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances

    Measurement of antiproton production from antihyperon decays in p He collisions at √sNN = 110 GeV

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    The interpretation of cosmic antiproton flux measurements from space-borne experiments is currently limited by the knowledge of the antiproton production cross-section in collisions between primary cosmic rays and the interstellar medium. Using collisions of protons with an energy of 6.5TeV incident on helium nuclei at rest in the proximity of the interaction region of the LHCb experiment, the ratio of antiprotons originating from antihyperon decays to prompt production is measured for antiproton momenta between 12 and 110GeV. The dominant antihyperon contribution, namely Λ¯→p¯π+ decays from promptly produced Λ¯ particles, is also exclusively measured. The results complement the measurement of prompt antiproton production obtained from the same data sample. At the energy scale of this measurement, the antihyperon contributions to antiproton production are observed to be significantly larger than predictions of commonly used hadronic production models

    Direct CP violation in charmless three-body decays of B± mesons

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    Measurements of C P asymmetries in charmless three-body decays of B ± mesons are reported using proton-proton collision data collected by the LHCb detector, corresponding to an integrated luminosity of 5.9     fb − 1 . The previously observed C P asymmetry in B ± → π ± K + K − decays is confirmed, and C P asymmetries are observed with a significance of more than five standard deviations in the B ± → π ± π + π − and B ± → K ± K + K − decays, while the C P asymmetry of B ± → K ± π + π − decays is confirmed to be compatible with zero. The distributions of these asymmetries are also studied as a function of the three-body phase space and suggest contributions from rescattering and resonance interference processes. An indication of the presence of the decays B ± → π ± χ c 0 ( 1 P ) in both B ± → π ± π + π − and B ± → π ± K + K − decays is observed, as is C P violation involving these amplitudes

    Measurement of J/ψ -pair production in pp collisions at √s = 13 TeV and study of gluon transverse-momentum dependent PDFs

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    The production cross-section of J/ψ pairs in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV is measured using a data sample corresponding to an integrated luminosity of 4.2 fb−1 collected by the LHCb experiment. The measurement is performed with both J/ψ mesons in the transverse momentum range 0 < pT< 14 GeV/c and rapidity range 2.0 < y < 4.5. The cross-section of this process is measured to be 16.36 ± 0.28 (stat) ± 0.88 (syst) nb. The contributions from single-parton scattering and double-parton scattering are separated based on the dependence of the cross-section on the absolute rapidity difference ∆y between the two J/ψ mesons. The effective cross-section of double-parton scattering is measured to be σeff = 13.1 ± 1.8 (stat) ± 2.3 (syst) mb. The distribution of the azimuthal angle ϕCS of one of the J/ψ mesons in the Collins-Soper frame and the pT-spectrum of the J/ψ pairs are also measured for the study of the gluon transverse-momentum dependent distributions inside protons. The extracted values of ⟨cos 2ϕCS⟩ and ⟨cos 4ϕCS⟩ are consistent with zero, but the presence of azimuthal asymmetry at a few percent level is allowed

    Designing Better Radiology Workstations: Impact of Two User Interfaces on Interpretation Errors and User Satisfaction

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    This paper presents our solution for supporting radiologists’ interpretation of digital images by automating image presentation during sequential interpretation steps. We extended current hanging protocols with support for “stages” which reflect the presentation of digital information required to complete a single step within a complex task. We demonstrated the benefits of staging in a user experiment with 20 lay subjects involved in a comparative visual search for targets, similar to a radiology task of identifying anatomical abnormalities. We designed a task and a set of stimuli that allowed us to simulate the interpretation workflow from a typical radiology scenario—reading a chest radiography exam when a prior study is also available. The simulation was enabled by abstracting both the radiologist’s task and the basic workstation navigation functionality. The staged interface was significantly faster than the traditional user interface, provided a 37% reduction in the interpretation errors, and improved user satisfaction
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