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The human ether-à-go-go channel (hEag1 or KV10.1) is a cancer-relevant voltage-gated potassium channel that is overexpressed in a majority of human tumors. Peptides that are able to selectively inhibit this channel can be lead compounds in the search for new anticancer drugs. Here, we report the activity-guided purification and electrophysiological characterization of a novel KV10.1 inhibitor from the sea anemone Anthopleura elegantissima. Purified sea anemone fractions were screened for inhibitory activity on KV10.1 by measuring whole-cell currents as expressed in Xenopus laevis oocytes using the two-microelectrode voltage clamp technique. Fractions that showed activity on Kv10.1 were further purified by RP-HPLC. The amino acid sequence of the peptide was determined by a combination of MALDI- LIFT-TOF/TOF MS/MS and CID-ESI-FT-ICR MS/MS and showed a high similarity with APETx1 and APETx3 and was therefore named APETx4. Subsequently, the peptide was electrophysiologically characterized on KV10.1. The selectivity of the toxin was investigated on an array of voltage-gated ion channels, including the cardiac human ether-à-go-go-related gene potassium channel (hERG or Kv11.1). The toxin inhibits KV10.1 with an IC50 value of 1.1 μM. In the presence of a similar toxin concentration, a shift of the activation curve towards more positive potentials was observed. Similar to the effect of the gating modifier toxin APETx1 on hERG, the inhibition of Kv10.1 by the isolated toxin is reduced at more positive voltages and the peptide seems to keep the channel in a closed state. Although the peptide also induces inhibitory effects on other KV and NaV channels, it exhibits no significant effect on hERG. Moreover, APETx4 induces a concentration-dependent cytotoxic and proapoptotic effect in various cancerous and noncancerous cell lines. This newly identified KV10.1 inhibitor can be used as a tool to further characterize the oncogenic channel KV10.1 or as a scaffold for the design and synthesis of more potent and safer anticancer drugs.

An analysis of dijet events in PbPb and pp collisions is performed to explore the properties of energy loss by partons traveling in a quark-gluon plasma. Data are collected at a nucleon-nucleon center-of-mass energy of 2.76 TeV at the LHC. The distribution of transverse momentum (p sub(T)) surrounding dijet systems is measured by selecting charged particles in different ranges of p sub(T) and at different angular cones of pseudorapidity and azimuth. The measurement is performed as a function of centrality of the PbPb collisions, the p sub(T) asymmetry of the jets in the dijet pair, and the distance parameter R used in the anti-k sub(T) jet clustering algorithm. In events with unbalanced dijets, PbPb collisions show an enhanced multiplicity in the hemisphere of the subleading jet, with the p sub(T) imbalance compensated by an excess of low-p sub(T) particles at large angles from the jet axes. [Figure not available: see fulltext.]

(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image).A search for a light charged Higgs boson, originating from the decay of a top quark and subsequently decaying into a charm quark and a strange antiquark, is presented. The data used in the analysis correspond to an integrated luminosity of 19.7 fb super(-1) recorded in proton-proton collisions at ... TeV by the CMS experiment at the LHC. The search is performed in the process ..., where the W boson decays to a lepton (electron or muon) and a neutrino. The decays lead to a final state comprising an isolated lepton, at least four jets and large missing transverse energy. No significant deviation is observed in the data with respect to the standard model predictions, and model-independent upper limits are set on the branching fraction ..., ranging from 1.2 to 6.5% for a charged Higgs boson with mass between 90 and 160 GeV, under the assumption that ... [Figure not available: see fulltext.]

Here, results are reported from a search for the pair production of top squarks, the supersymmetric partners of top quarks, in final states with jets and missing transverse momentum. The data sample used in this search was collected by the CMS detector and corresponds to an integrated luminosity of 18.9 fb–1 of proton-proton collisions at a centre-of-mass energy of 8 TeV produced by the LHC. The search features novel background suppression and prediction methods, including a dedicated top quark pair reconstruction algorithm. The data are found to be in agreement with the predicted backgrounds. Exclusion limits are set in simplified supersymmetry models with the top squark decaying to jets and an undetected neutralino, either via a top quark or through a bottom quark and chargino. Models with the top squark decaying via a top quark are excluded for top squark masses up to 755 GeV in the case of neutralino masses below 200 GeV. For decays via a chargino, top squark masses up to 620 GeV are excluded, depending on the masses of the chargino and neutralino.

(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image).A search is presented for a singly produced excited bottom quark (b super(*)) decaying to a top quark and a W boson in the all-hadronic, lepton+jets, and dilepton final states in proton-proton collisions at ... TeV recorded by the CMS experiment at the CERN LHC. Data corresponding to an integrated luminosity of 19.7 fb super(-1) are used. No significant excess of events is observed with respect to standard model expectations. We set limits at 95% confidence on the product of the b super(*) quark production cross section and its branching fraction to tW. The cross section limits are interpreted for scenarios including left-handed, right-handed, and vector-like couplings of the b super(*) quark and are presented in the two-dimensional coupling plane based on the production and decay coupling constants. The masses of the left-handed, right-handed, and vector-like b super(*) quark states are excluded at 95% confidence below 1390, 1430, and 1530 GeV, respectively, for benchmark couplings. This analysis gives the most stringent limits on the mass of the b super() quark to date. [Figure not available: see fulltext.]

The first measurement of the jet mass [Formula: see text] of top quark jets produced in [Formula: see text] events from pp collisions at [Formula: see text] [Formula: see text] is reported for the jet with the largest transverse momentum [Formula: see text] in highly boosted hadronic top quark decays. The data sample, collected with the CMS detector, corresponds to an integrated luminosity of 19.7[Formula: see text]. The measurement is performed in the lepton+jets channel in which the products of the semileptonic decay [Formula: see text] with [Formula: see text] where [Formula: see text] is an electron or muon, are used to select [Formula: see text] events with large Lorentz boosts. The products of the fully hadronic decay [Formula: see text] with [Formula: see text] are reconstructed using a single Cambridge-Aachen jet with distance parameter [Formula: see text], and [Formula: see text] [Formula: see text]. The [Formula: see text] cross section as a function of [Formula: see text] is unfolded at the particle level and is used to test the modelling of highly boosted top quark production. The peak position of the [Formula: see text] distribution is sensitive to the top quark mass [Formula: see text], and the data are used to extract a value of [Formula: see text] to assess this sensitivity.

Normalized double-differential cross sections for top quark pair ([Formula: see text]) production are measured in pp collisions at a centre-of-mass energy of 8[Formula: see text] with the CMS experiment at the LHC. The analyzed data correspond to an integrated luminosity of 19.7[Formula: see text]. The measurement is performed in the dilepton [Formula: see text] final state. The [Formula: see text] cross section is determined as a function of various pairs of observables characterizing the kinematics of the top quark and [Formula: see text] system. The data are compared to calculations using perturbative quantum chromodynamics at next-to-leading and approximate next-to-next-to-leading orders. They are also compared to predictions of Monte Carlo event generators that complement fixed-order computations with parton showers, hadronization, and multiple-parton interactions. Overall agreement is observed with the predictions, which is improved when the latest global sets of proton parton distribution functions are used. The inclusion of the measured [Formula: see text] cross sections in a fit of parametrized parton distribution functions is shown to have significant impact on the gluon distribution.

A measurement of the top quark mass is reported in events containing a single top quark produced via the electroweak channel. The analysis is performed using data from proton-proton collisions collected with the CMS detector at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 fb[Formula: see text]. Top quark candidates are reconstructed from their decay to a [Formula: see text] boson and a b quark, with the [Formula: see text] boson decaying leptonically to a muon and a neutrino. The final state signature and kinematic properties of single top quark events in the channel are used to enhance the purity of the sample, suppressing the contribution from top quark pair production. A fit to the invariant mass distribution of reconstructed top quark candidates yields a value of the top quark mass of [Formula: see text]. This result is in agreement with the current world average, and represents the first measurement of the top quark mass in event topologies not dominated by top quark pair production, therefore contributing to future averages with partially uncorrelated systematic uncertainties and a largely uncorrelated statistical uncertainty.

A measurement of the top quark pair production ( $$\\mathrm{t}\\overline{\\mathrm{t}} $$ tt¯) cross section in proton–proton collisions at the centre-of-mass energy of 8 $$\\,\\text {TeV}$$ TeV is presented using data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 19.6 $$\\,\\text {fb}^{-\\text {1}}$$ fb-1. This analysis is performed in the $$\\mathrm{t}\\overline{\\mathrm{t}} $$ tt¯ decay channels with one isolated, high transverse momentum electron or muon and at least four jets, at least one of which is required to be identified as originating from hadronization of a b quark. The calibration of the jet energy scale and the efficiency of b jet identification are determined from data. The measured $$\\mathrm{t}\\overline{\\mathrm{t}} $$ tt¯ cross section is $$228.5 \\pm 3.8\\,\\text {(stat)} \\pm 13.7\\,\\text {(syst)} \\pm 6.0\\,\\text {(lumi)} \\text { pb} $$ 228.5±3.8(stat)±13.7(syst)±6.0(lumi) pb. This measurement is compared with an analysis of 7 $$\\,\\text {TeV}$$ TeV data, corresponding to an integrated luminosity of 5.0 $$\\,\\text {fb}^{-\\text {1}}$$ fb-1, to determine the ratio of 8 $$\\,\\text {TeV}$$ TeV to 7 $$\\,\\text {TeV}$$ TeV cross sections, which is found to be $$1.43 \\pm 0.04\\,\\text {(stat)} \\pm 0.07\\,\\text {(syst)} \\pm 0.05\\,\\text {(lumi)} $$ 1.43±0.04(stat)±0.07(syst)±0.05(lumi). The measurements are in agreement with QCD predictions up to next-to-next-to-leading order.

Searches are presented for direct production of top or bottom squark pairs in proton-proton collisions at the CERN LHC. Two searches, based on complementary techniques, are performed in all-jet final states that are characterized by a significant imbalance in transverse momentum. An additional search requires the presence of a charged lepton isolated from other activity in the event. The data were collected in 2015 at a centre-of-mass energy of 13[Formula: see text] with the CMS detector and correspond to an integrated luminosity of 2.3[Formula: see text]. No statistically significant excess of events is found beyond the expected contribution from standard model processes. Exclusion limits are set in the context of simplified models of top or bottom squark pair production. Models with top and bottom squark masses up to 830 and 890[Formula: see text], respectively, are probed for light neutralinos. For models with top squark masses of 675[Formula: see text], neutralino masses up to 260[Formula: see text] are excluded at 95% confidence level.