In vitro antibacterial and time kill evaluation of mononuclear phosphanegold(I) dithiocarbamates

Four compounds, R3PAu[S2CN(CH2CH2OH)2], R = Ph (1) and cyclohexyl (2), and Et3PAuS2CNRꞌ2, Rꞌ = Rꞌ = Et (3) and Rꞌ2 = (CH2)4 (4), have been evaluated for antibacterial activity against a panel of 24 Gram positive (8) and Gram negative (16) bacteria. Based on minimum inhibitory concentration (MIC) scores, compounds 1 and 2 were shown to be specifically potent against Gram positive bacteria whereas compounds 3 and, to a lesser extent, 4 exhibited broad range activity. All four compounds were active against methicillin resistant Staphylococcus aureus (MRSA). Time kill assays revealed the compounds to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Each compound was bactericidal against one or more bacteria with 3 being especially potent after 8 h exposure; compounds 1 and 3 were bactericidal against MRSA. Compound 3 was the most effective bactericide across the series especially toward B. subtilis, S. saprophyticus, A. hydrophila, P. vulgaris, and V. parahaemolyticus. This study demonstrates the potential of this class of compounds as antibacterial agents, either broad range or against specific bacteria

G2/M cell cycle arrest on HT-29 cancer cells and toxicity assessment of triphenylphosphanegold(I) carbonimidothioates, Ph3PAu[SC(OR) = NPh], R = Me, Et, and iPr, during zebrafish development

Phosphanegold(I) thiolates, Ph3PAu[SC(OR) = NPh], R = Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24 h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17–22% cf. untreated cells. LC50 values were determined in zebrafish (8.36, 8.17, and 7.64 μM for 1–3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625 μM, and 3 was tolerated at even higher doses of up to 1.25 μM

Three ammonium salts of sulfathiazole: crystallography and anti-microbial assay

The crystal and molecular structures of three ammonium salts derived from sulfathiazole are described. In each case, the anion is in the azanide form, features an intramolecular S←O interaction, and adopts a U-shape. The structures of two cations, [R(HOCH2CH2)NH2]+, namely for R = Me (1) and iPr (2), are unprecedented in the crystallographic literature. Extensive hydrogen bonding is observed in all crystal structures and leads to a two-dimensional array for 1, and three-dimensional architectures for each of 2 and 3 (R = CH2CH2OH). The salts exhibited anti-microbial activity against a range of Gram-positive and Gram-negative bacteria, and proved bactericidal toward Vibrio parahaemolyticus, but had no advantage over sulfathiazole itself

The influence of R substituents in triphenylphosphinegold(I) carbonimidothioates, Ph 3PAu[SC(OR) = NPh] (R = Me, Et and iPr), upon in vitro cytotoxicity against the HT-29 colon cancer cell line and upon apoptotic pathways

The Ph3PAu[SC(OR) = NPh], R = Me (1), Et (2) and iPr (3), compounds are significantly cytotoxic to the HT-29 cancer cell line with1 being the most active. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis is demonstrated and both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. Compound1 activates the p73 gene, whereas each of2 and3 activates the p53 gene. An additional apoptotic mechanism is exhibited by2, that is, via the JNK/MAP pathway

NP-hardness of Deciding Convexity of Quartic Polynomials and Related Problems

We show that unless P=NP, there exists no polynomial time (or even pseudo-polynomial time) algorithm that can decide whether a multivariate polynomial of degree four (or higher even degree) is globally convex. This solves a problem that has been open since 1992 when N. Z. Shor asked for the complexity of deciding convexity for quartic polynomials. We also prove that deciding strict convexity, strong convexity, quasiconvexity, and pseudoconvexity of polynomials of even degree four or higher is strongly NP-hard. By contrast, we show that quasiconvexity and pseudoconvexity of odd degree polynomials can be decided in polynomial time.Comment: 20 page

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters