Combined HERA data on charm production in deep-inelastic scattering have previously been used to determine the charm-quark running mass mc(mc) in the MS‾ renormalisation scheme. Here, the same data ...are used as a function of the photon virtuality Q2 to evaluate the charm-quark running mass at different scales to one-loop order, in the context of a next-to-leading order QCD analysis. The scale dependence of the mass is found to be consistent with QCD expectations.
A
bstract
The exclusive photoproduction reactions
γp
→
J/ψ
(1
S
)
p
and
γp
→
ψ
(2
S
)
p
have been measured at an
ep
centre-of-mass energy of 318 GeV with the ZEUS detector at HERA using an integrated ...luminosity of 373 pb
−
1
. The measurement was made in the kinematic range 30
< W <
180 GeV,
Q
2
<
1 GeV
2
and |
t
|
<
1 GeV
2
, where
W
is the photon-proton centre-of-mass energy,
Q
2
is the photon virtuality and
t
is the squared four-momentum transfer at the proton vertex. The decay channels used were
J/ψ
(1
S
)
→ μ
+
μ
−
,
ψ
(2
S
)
→ μ
+
μ
−
and
ψ
(2
S
)
→ J/ψ
(1
S
)
π
+
π
−
with subsequent decay
J/ψ
(1
S
)
→ μ
+
μ
−
. The ratio of the production cross sections,
R
=
σ
ψ
(2
S
)
/σ
J/ψ
(1
S
)
, has been measured as a function of
W
and |
t
| and compared to previous data in photoproduction and deep inelastic scattering and with predictions of QCD-inspired models of exclusive vector-meson production, which are in reasonable agreement with the data.
High-affinity MHC I-peptide interactions are considered essential for immunogenicity. However, some neo-epitopes with low affinity for MHC I have been reported to elicit CD8 T cell dependent tumor ...rejection in immunization-challenge studies. Here we show in a mouse model that a neo-epitope that poorly binds to MHC I is able to enhance the immunogenicity of a tumor in the absence of immunization. Fibrosarcoma cells with a naturally occurring mutation are edited to their wild type counterpart; the mutation is then re-introduced in order to obtain a cell line that is genetically identical to the wild type except for the neo-epitope-encoding mutation. Upon transplantation into syngeneic mice, all three cell lines form tumors that are infiltrated with activated T cells. However, lymphocytes from the two tumors that harbor the mutation show significantly stronger transcriptional signatures of cytotoxicity and TCR engagement, and induce greater breadth of TCR reactivity than those of the wild type tumors. Structural modeling of the neo-epitope peptide/MHC I pairs suggests increased hydrophobicity of the neo-epitope surface, consistent with higher TCR reactivity. These results confirm the in vivo immunogenicity of low affinity or 'non-binding' epitopes that do not follow the canonical concept of MHC I-peptide recognition.
Abstract The exclusive photoproduction reactions γp → J/ψ(1S)p and γp → ψ(2S)p have been measured at an ep centre-of-mass energy of 318 GeV with the ZEUS detector at HERA using an integrated ...luminosity of 373 pb −1. The measurement was made in the kinematic range 30 < W < 180 GeV, Q 2 < 1 GeV2 and |t| < 1 GeV2, where W is the photon-proton centre-of-mass energy, Q 2 is the photon virtuality and t is the squared four-momentum transfer at the proton vertex. The decay channels used were J/ψ(1S) → μ + μ − , ψ(2S) → μ + μ − and ψ(2S) → J/ψ(1S)π + π − with subsequent decay J/ψ(1S) → μ + μ − . The ratio of the production cross sections, R = σ ψ(2S) /σ J/ψ(1S), has been measured as a function of W and |t| and compared to previous data in photoproduction and deep inelastic scattering and with predictions of QCD-inspired models of exclusive vector-meson production, which are in reasonable agreement with the data.
Identification of neoepitopes that can control tumor growth in vivo remains a challenge even 10 y after the first genomics-defined cancer neoepitopes were identified. In this study, we identify a ...neoepitope, resulting from a mutation in the junction plakoglobin (Jup) gene (chromosome 11), from the mouse colon cancer line MC38-FABF (C57BL/6). This neoepitope, Jup mutant (JupMUT), was detected during mass spectrometry of MHC class I-eluted peptides from the tumor. JupMUT has a predicted binding affinity of 564 nM for the Kb molecule and a higher predicted affinity of 82 nM for Db. However, whereas structural modeling of JupMUT and its unmutated counterpart Jup wild-type indicates that there are little conformational differences between the two epitopes bound to Db, large structural divergences are predicted between the two epitopes bound to Kb. Together with in vitro binding data with RMA-S cells, these data suggest that Kb rather than Db is the relevant MHC class I molecule of JupMUT. Immunization of naive C57BL/6 mice with JupMUT elicits CD8-dependent tumor control of a MC38-FABF challenge. Despite the CD8 dependence of JupMUT-mediated tumor control in vivo, CD8+ T cells from JupMUT-immunized mice do not produce higher levels of IFN-γ than do naive mice. The structural and immunological characteristics of JupMUT are substantially different from those of many other neoepitopes that have been shown to mediate tumor control.
Identification of neoepitopes that are effective in cancer therapy is a major challenge in creating cancer vaccines. Here, using an entirely unbiased approach, we queried all possible neoepitopes in ...a mouse cancer model and asked which of those are effective in mediating tumor rejection and, independently, in eliciting a measurable CD8 response. This analysis uncovered a large trove of effective anticancer neoepitopes that have strikingly different properties from conventional epitopes and suggested an algorithm to predict them. It also revealed that our current methods of prediction discard the overwhelming majority of true anticancer neoepitopes. These results from a single mouse model were validated in another antigenically distinct mouse cancer model and are consistent with data reported in human studies. Structural modeling showed how the MHC I-presented neoepitopes had an altered conformation, higher stability, or increased exposure to T cell receptors as compared with the unmutated counterparts. T cells elicited by the active neoepitopes identified here demonstrated a stem-like early dysfunctional phenotype associated with effective responses against viruses and tumors of transgenic mice. These abundant anticancer neoepitopes, which have not been tested in human studies thus far, can be exploited for generation of personalized human cancer vaccines.
The porous 3D scaffolds with three types of pore structure A, B and C were created by the direct metal laser sintering (DMLS) technology from the powders of titanium Ti-6Al-4V alloy. Calcium ...phosphate (CPC) and Zn‑calcium phosphate (Zn-CPC) coatings were formed on the 3D scaffolds by the micro-arc oxidation (MAO) method in the acidic electrolyte. As well as another calcium phosphate (CPL) and Ag‑calcium phosphate (Ag-CPL) coatings, that were synthesized in the alkaline electrolyte. Preliminary studies of the surface morphology, elemental and phase composition, and strength properties of the coatings were carried out on the plate samples from titanium Ti-6Al-4V alloy using scanning electron microscopy (SEM), X-ray diffraction, and scratch testing. The surface morphology of the coatings on the 3D scaffolds was also investigated via SEM method. The internal pore structure of both the coated and uncoated samples was examined by the Micro-CT analysis. It was found that the coatings were evenly distributed over the surface and in the inner pore structure of the all types of the 3D scaffolds. The biological studies carried out on both the plate samples and the 3D samples have shown that the coatings demonstrated no cytotoxic effect on cell culture of human fibroblast pFb. All the coatings, excluding CPL, exhibited high antibacterial activity against bacteria MRSA ATCC 43300 and Escherichia coli ATCC 25922.
•The porous 3D scaffolds with various types of pore structure were created by DMLS technology from the Ti-6Al-4V alloy.•Ag- and Zn‑calcium phosphate coatings were evenly distributed in the inner pore structure of the 3D scaffolds.•The coatings demonstrated no cytotoxic effect on cell culture of human fibroblast and high antibacterial activity.
A combination is presented of all inclusive deep inelastic cross sections previously published by the H1 and ZEUS collaborations at HERA for neutral and charged current $e^{\pm}p$ scattering for zero ...beam polarisation. The data were taken at proton beam energies of 920, 820, 575 and 460 GeV and an electron beam energy of 27.5 GeV. The data correspond to an integrated luminosity of about 1 fb$^{-1}$ and span six orders of magnitude in negative four-momentum-transfer squared, $Q^2$, and Bjorken $x$. The correlations of the systematic uncertainties were evaluated and taken into account for the combination. The combined cross sections were input to QCD analyses at leading order, next-to-leading order and at next-to-next-to-leading order, providing a new set of parton distribution functions, called HERAPDF2.0. In addition to the experimental uncertainties, model and parameterisation uncertainties were assessed for these parton distribution functions. Variants of HERAPDF2.0 with an alternative gluon parameterisation, HERAPDF2.0AG, and using fixed-flavour-number schemes, HERAPDF2.0FF, are presented. The analysis was extended by including HERA data on charm and jet production, resulting in the variant HERAPDF2.0Jets. The inclusion of jet-production cross sections made a simultaneous determination of these parton distributions and the strong coupling constant possible, resulting in $\alpha_s(M_Z)=0.1183 \pm 0.0009 {\rm(exp)} \pm 0.0005{\rm (model/parameterisation)} \pm 0.0012{\rm (hadronisation)} ^{+0.0037}_{-0.0030}{\rm (scale)}$. An extraction of $xF_3^{\gamma Z}$ and results on electroweak unification and scaling violations are also presented.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neoepitopes are the only truly tumor-specific antigens. Although potential neoepitopes can be readily identified using genomics, the neoepitopes that mediate tumor rejection constitute a small ...minority, and there is little consensus on how to identify them. Here, for the first time, we use a combination of genomics, unbiased discovery MS immunopeptidomics and targeted MS to directly identify neoepitopes that elicit actual tumor rejection in mice. We report that MS-identified neoepitopes are an astonishingly rich source of tumor rejection mediating neoepitopes. MS has also demonstrated unambiguously the presentation by MHC I, of confirmed tumor rejection neoepitopes which bind weakly to MHC I; this was done using DCs exogenously loaded with long peptides containing the weakly binding neoepitopes. Such weakly MHC I-binding neoepitopes are routinely excluded from analysis, and our demonstration of their presentation, and their activity in tumor rejection, reveals a broader universe of tumor-rejection neoepitopes than presently imagined. Modeling studies show that a mutation in the active neoepitope alters its conformation such that its T cell receptor-facing surface is significantly altered, increasing its exposed hydrophobicity. No such changes are observed in the inactive neoepitope. These results broaden our understanding of antigen presentation and help prioritize neoepitopes for personalized cancer immunotherapy.
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