Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron

The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of $\sqrt s =1.96$ TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is $A_{\mathrm{FB}}^{t\bar{t}} = 0.128 \pm 0.025$. The combined inclusive and differential asymmetries are consistent with recent standard model predictions

Dendritic Cells in Anticancer Vaccination: Rationale for Ex Vivo Loading or In Vivo Targeting

Dendritic cells (DCs) have shown great potential as a component or target in the landscape of cancer immunotherapy. Different in vivo and ex vivo strategies of DC vaccine generation with different outcomes have been proposed. Numerous clinical trials have demonstrated their efficacy and safety in cancer patients. However, there is no consensus regarding which DC-based vaccine generation method is preferable. A problem of result comparison between trials in which different DC-loading or -targeting approaches have been applied remains. The employment of different DC generation and maturation methods, antigens and administration routes from trial to trial also limits the objective comparison of DC vaccines. In the present review, we discuss different methods of DC vaccine generation. We conclude that standardized trial designs, treatment settings and outcome assessment criteria will help to determine which DC vaccine generation approach should be applied in certain cancer cases. This will result in a reduction in alternatives in the selection of preferable DC-based vaccine tactics in patient. Moreover, it has become clear that the application of a DC vaccine alone is not sufficient and combination immunotherapy with recent advances, such as immune checkpoint inhibitors, should be employed to achieve a better clinical response and outcome

Cancer Vaccines: Antigen Selection Strategy

Unlike traditional cancer therapies, cancer vaccines (CVs) harness a high specificity of the host’s immunity to kill tumor cells. CVs can train and bolster the patient’s immune system to recognize and eliminate malignant cells by enhancing immune cells’ identification of antigens expressed on cancer cells. Various features of antigens like immunogenicity and avidity influence the efficacy of CVs. Therefore, the choice and application of antigens play a critical role in establishing and developing CVs. Tumor-associated antigens (TAAs), a group of proteins expressed at elevated levels in tumor cells but lower levels in healthy normal cells, have been well-studied and developed in CVs. However, immunological tolerance, HLA restriction, and adverse events are major obstacles that threaten TAA-based CVs’ efficacy due to the “self-protein” characteristic of TAAs. As “abnormal proteins” that are completely absent from normal cells, tumor-specific antigens (TSAs) can trigger a robust immune response against tumor cells with high specificity and without going through central tolerance, contributing to cancer vaccine development feasibility. In this review, we focus on the unique features of TAAs and TSAs and their application in vaccines, summarizing their performance in preclinical and clinical trials

Cancer Vaccines: Antigen Selection Strategy

Unlike traditional cancer therapies, cancer vaccines (CVs) harness a high specificity of the host’s immunity to kill tumor cells. CVs can train and bolster the patient’s immune system to recognize and eliminate malignant cells by enhancing immune cells’ identification of antigens expressed on cancer cells. Various features of antigens like immunogenicity and avidity influence the efficacy of CVs. Therefore, the choice and application of antigens play a critical role in establishing and developing CVs. Tumor-associated antigens (TAAs), a group of proteins expressed at elevated levels in tumor cells but lower levels in healthy normal cells, have been well-studied and developed in CVs. However, immunological tolerance, HLA restriction, and adverse events are major obstacles that threaten TAA-based CVs’ efficacy due to the “self-protein” characteristic of TAAs. As “abnormal proteins” that are completely absent from normal cells, tumor-specific antigens (TSAs) can trigger a robust immune response against tumor cells with high specificity and without going through central tolerance, contributing to cancer vaccine development feasibility. In this review, we focus on the unique features of TAAs and TSAs and their application in vaccines, summarizing their performance in preclinical and clinical trials

Redox Regulation of Signaling Complex between Caveolin-1 and Neuronal Calcium Sensor Recoverin

Caveolin-1 is a cholesterol-binding scaffold protein, which is localized in detergent-resistant membrane (DRM) rafts and interacts with components of signal transduction systems, including visual cascade. Among these components are neuronal calcium sensors (NCSs), some of which are redox-sensitive proteins that respond to calcium signals by modulating the activity of multiple intracellular targets. Here, we report that the formation of the caveolin-1 complex with recoverin, a photoreceptor NCS serving as the membrane-binding regulator of rhodopsin kinase (GRK1), is a redox-dependent process. Biochemical and biophysical in vitro experiments revealed a two-fold decreased affinity of recoverin to caveolin-1 mutant Y14E mimicking its oxidative stress-induced phosphorylation of the scaffold protein. At the same time, wild-type caveolin-1 demonstrated a 5–10-fold increased affinity to disulfide dimer of recoverin (dRec) or its thiol oxidation mimicking the C39D mutant. The formation of dRec in vitro was not affected by caveolin-1 but was significantly potentiated by zinc, the well-known mediator of redox homeostasis. In the MDCK cell model, oxidative stress indeed triggered Y14 phosphorylation of caveolin-1 and disulfide dimerization of recoverin. Notably, oxidative conditions promoted the accumulation of phosphorylated caveolin-1 in the plasma membrane and the recruitment of recoverin to the same sites. Co-localization of these proteins was preserved upon depletion of intracellular calcium, i.e., under conditions reducing membrane affinity of recoverin but favoring its interaction with caveolin-1. Taken together, these data suggest redox regulation of the signaling complex between recoverin and caveolin-1. During oxidative stress, the high-affinity interaction of thiol-oxidized recoverin with caveolin-1/DRMs may disturb the light-induced translocation of the former within photoreceptors and affect rhodopsin desensitization

Study of the normalized transverse momentum distribution of WW bosons produced in ppˉp \bar p collisions at s\sqrt {s} = 1.96 TeV

International audienceWe present a study of the normalized transverse momentum distribution of W bosons produced in pp¯ collisions, using data corresponding to an integrated luminosity of 4.35  fb-1 collected with the D0 detector at the Fermilab Tevatron collider at s=1.96  TeV. The measurement focuses on the transverse momentum region below 15 GeV, which is of special interest for electroweak precision measurements; it relies on the same detector calibration methods which were used for the precision measurement of the W boson mass. The measured distribution is compared to different QCD predictions and a procedure is given to allow the comparison of any further theoretical models to the D0 data

Studies of X(3872)X(3872) and ψ(2S)\psi(2S) production in ppˉp\bar{p} collisions at 1.96 TeV

International audienceWe present various properties of the production of the X(3872) and ψ(2S) states based on 10.4  fb-1 collected by the D0 experiment in Tevatron pp¯ collisions at s=1.96  TeV. For both states, we measure the nonprompt fraction fNP of the inclusive production rate due to decays of b-flavored hadrons. We find the fNP values systematically below those obtained at the LHC. The fNP fraction for ψ(2S) increases with transverse momentum, whereas for the X(3872) it is constant within large uncertainties, in agreement with the LHC results. The ratio of prompt to nonprompt ψ(2S) production, (1-fNP)/fNP, decreases only slightly going from the Tevatron to the LHC, but for the X(3872), this ratio decreases by a factor of about 3. We test the soft-pion signature of the X(3872) modeled as a weakly bound charm-meson pair by studying the production of the X(3872) as a function of the kinetic energy of the X(3872) and the pion in the X(3872)π center-of-mass frame. For a subsample consistent with prompt production, the results are incompatible with a strong enhancement in the production of the X(3872) at the small kinetic energy of the X(3872) and the π in the X(3872)π center-of-mass frame expected for the X+soft-pion production mechanism. For events consistent with being due to decays of b hadrons, there is no significant evidence for the soft-pion effect, but its presence at the level expected for the binding energy of 0.17 MeV and the momentum scale Λ=M(π) is not ruled out

Properties of Zc±(3900)Z_c^{\pm}(3900) Produced in ppˉp \bar p Collision

International audienceWe study the production of the exotic charged charmonium-like state $Z_c^{\pm}(3900)$ in $p \bar p$ collisions through the sequential process $\psi(4260) \rightarrow Z_c^{\pm}(3900) \pi^{\mp}$, $Z_c^{\pm}(3900) \rightarrow J/\psi \pi^{\pm}$. Using the subsample of candidates originating from semi-inclusive weak decays of $b$-flavored hadrons, we measure the invariant mass and natural width to be $M=3902.6^{+5.2}_{-5.0}{\rm \thinspace (stat)}^{+3.3}_{-1.4}{\rm \thinspace (syst)}$ MeV and $\Gamma=32 ^{+28}_{-21}{\rm \thinspace (stat)} ^{+26}_{-7}{\rm \thinspace (syst)}$ MeV, respectively. We search for prompt production of the $Z_c^{\pm}(3900)$ through the same sequential process. No significant signal is observed, and we set an upper limit of 0.66 at the 95\% credibility level on the ratio of prompt production to the production via $b$-hadron decays. The study is based on $10.4~\rm{fb^{-1}}$ of $p \overline p$ collision data collected by the D0 experiment at the Fermilab Tevatron collider