Normalised multi-differential cross sections for top quark pair ($$\hbox {t}{\bar{\hbox {t}}}$$tt¯) production are measured in proton-proton collisions at a centre-of-mass energy of 13$$\,{\text {TeV}}$$TeV using events containing two oppositely charged leptons. The analysed data were recorded with the CMS detector in 2016 and correspond to an integrated luminosity of $$35.9{\,{\text {fb}}^{-1}} $$35.9fb-1. The double-differential $$\hbox {t}{\bar{\hbox {t}}}$$tt¯ cross section is measured as a function of the kinematic properties of the top quark and of the $$\hbox {t}{\bar{\hbox {t}}}$$tt¯ system at parton level in the full phase space. A triple-differential measurement is performed as a function of the invariant mass and rapidity of the $$\hbox {t}{\bar{\hbox {t}}}$$tt¯ system and the multiplicity of additional jets at particle level. The data are compared to predictions of Monte Carlo event generators that complement next-to-leading-order (NLO) quantum chromodynamics (QCD) calculations with parton showers. Together with a fixed-order NLO QCD calculation, the triple-differential measurement is used to extract values of the strong coupling strength $$\alpha _{S}$$αS and the top quark pole mass ($$m_{{\text {t}}}^{{\text {pole}}}$$mtpole) using several sets of parton distribution functions (PDFs). The measurement of $$m_{{\text {t}}}^{{\text {pole}}}$$mtpole exploits the sensitivity of the $$\hbox {t}{\bar{\hbox {t}}}$$tt¯ invariant mass distribution to $$m_{{\text {t}}}^{{\text {pole}}}$$mtpole near the production threshold. Furthermore, a simultaneous fit of the PDFs, $$\alpha _{S}$$αS, and $$m_{{\text {t}}}^{{\text {pole}}}$$mtpole is performed at NLO, demonstrating that the new data have significant impact on the gluon PDF, and at the same time allow an accurate determination of $$\alpha _{S}$$αS and $$m_{{\text {t}}}^{{\text {pole}}}$$mtpole. The values $$\alpha _{S}(m_{{\text {Z}}}) = 0.1135{}^{+0.0021}_{-0.0017}$$αS(mZ)=0.1135-0.0017+0.0021 and $$m_{{\text {t}}}^{{\text {pole}}} = 170.5 \pm 0.8 \,{\text {GeV}} $$mtpole=170.5±0.8GeV are extracted, which account for experimental and theoretical uncertainties, the latter being estimated from NLO scale variations. Possible effects from Coulomb and soft-gluon resummation near the $$\hbox {t}{\bar{\hbox {t}}}$$tt¯ production threshold are neglected in these parameter extractions. A rough estimate of these effects indicates an expected correction of $$m_{{\text {t}}}^{{\text {pole}}}$$mtpole of the order of $$+1 \,{\text {GeV}} $$+1GeV, which can be regarded as additional theoretical uncertainty in the current $$m_{{\text {t}}}^{{\text {pole}}}$$mtpole extraction.

L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.

We demonstrate ultrafast all-optical control of terahertz (THz) radiation through nanoresonators, slot antennas with a hundred micron length but submicron width in thin gold layers, fabricated on vanadium dioxide (VO2) thin films. Our THz nanoresonators show almost perfect transmission at resonance. By virtue of phase transition of VO2 from insulating to metallic state, induced in subpicosecond time scale by moderate optical pump, ultrafast control of THz transmission is enabled. This is compared to bare VO2 films where no switching dynamics are observed under similar conditions.

Background:Systemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma undergoing radical cystectomy.Methods:The study cohort consisted of 419 patients with a median follow-up of 37.7 months. The SIRs used for each described prognostic nomogram are consistent with previously published data: C-reactive protein, albumin, white cell count, neutrophil count, lymphocyte count, and platelet count. Primary end point was disease-specific survival (DSS) and overall survival (OS) after surgery. Cox regression models were used to determine the time to disease-specific and overall mortality. Multivariate regression coefficients of the predictors were used to develop nomograms for predicting 5-year DSS and OS probability.Results:Multivariate Cox regression analyses revealed that albumin, lymphocyte count, and platelet count were significantly associated with a significantly increased risk for death from bladder cancer. The nomograms including each index were developed to predict the probability of 5-year DSS and OS after radical cystectomy. The C statistics were 77.8% and 77.3%, respectively, and exceeded the 2002 AJCC (72.0% and 70.3%, respectively). In the decision curve analyses, the nomograms including SIR demonstrated higher net benefit gains compared with the models without SIR.Conclusions:Cellular components of SIR have better prognostic values compared with acute-phase protein in patients undergoing radical cystectomy for bladder cancer.

Since the installation of an ITER-like wall, the JET programme has focused on the consolidation of ITER design choices and the preparation for ITER operation, with a specific emphasis given to the bulk tungsten melt experiment, which has been crucial for the final decision on the material choice for the day-one tungsten divertor in ITER. Integrated scenarios have been progressed with the re-establishment of long-pulse, high-confinement H-modes by optimizing the magnetic configuration and the use of ICRH to avoid tungsten impurity accumulation. Stationary discharges with detached divertor conditions and small edge localized modes have been demonstrated by nitrogen seeding. The differences in confinement and pedestal behaviour before and after the ITER-like wall installation have been better characterized towards the development of high fusion yield scenarios in DT. Post-mortem analyses of the plasma-facing components have confirmed the previously reported low fuel retention obtained by gas balance and shown that the pattern of deposition within the divertor has changed significantly with respect to the JET carbon wall campaigns due to the absence of thermally activated chemical erosion of beryllium in contrast to carbon. Transport to remote areas is almost absent and two orders of magnitude less material is found in the divertor.