Results are presented from searches for the standard model Higgs boson in proton-proton collisions at root s = 7 and 8 TeV in the Compact Muon Solenoid experiment at the LHC, using data samples corresponding to integrated luminosities of up to 5.1 fb(-1) at 7 TeV and 5.3 fb(-1) at 8 TeV. The search is performed in five decay modes: gamma gamma, ZZ, W+W-, tau(+)tau(-), and b (b) over bar. An excess of events is observed above the expected background, with a local significance of 5.0 standard deviations, at a mass near 125 GeV, signalling the production of a new particle. The expected significance for a standard model Higgs boson of that mass is 5.8 standard deviations. The excess is most significant in the two decay modes with the best mass resolution, gamma gamma and ZZ; a fit to these signals gives a mass of 125.3 +/- 0.4(stat.) +/- 0.5(syst.) GeV. The decay to two photons indicates that the new particle is a boson with spin different from one. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved

Endothelium-derived relaing factor (EDRF) activity has been attributed to the highly labile nitric oxide radical (NO). In view of the fact that the plasma and cellular mifleux contain reactive species that can rapidly inactivate NO, it has been postulated that NO is stabilized by a carrier molecule that preserves its biological activity. Reduced thiol species are candidates for this role, reacting readily in the presence of NO to yield biologically active S-nitrosothiols that are more stable than NO itself. Because sulfhydryl groups in proteins represent an abundant source of reduced thiol in biologic systems, we examined the reaction of several sulfhy--I dryl-containing proteins of diverse nature and function upon exposure to authentic NO and EDRF. We demonstrate that S-nitroso proteins form readily under physiologic conditions and possess EDRF-like effects of vasodilation and platelet inhibition. These observations suggest that S-nitrosothiol groups in proteins may serve as intermediates in the cellular metabolism ofNO and raise the possibility ofan additional type of cellular regulatory mechanism.The richest source of reduced thiol in plasma (and a particularly prevalent source in cellular cytosol) is protein sulflydryl groups (19). The reaction ofNO with protein thiols has not been previously studied, and the potential biological significance ofthis reaction has been neglected because ofthe exclusion of proteins from (bio)assays of the functional activity and half-life of EDRF and from analyses of its chemical characteristics. We therefore investigated the reaction of protein thiols exposed to NO, and we present data showing that a variety of proteins of biological significance and relative abundance can be S-nitrosylated. S-Nitrosylation of proteins endows these molecules with potent and long-lasting EDRF-like effects of vasodilation and platelet inhibition that are mediated by guanylate cyclase activation. These observations raise the possibility that S-nitrosothiol groups in proteins may serve as intermediates in the cellular metabolism or bioactivity ofNO and that their formation may represent an important cellular regulatory mechanism.The endothelium-dependent relaxation of vascular smooth muscle first observed by Furchgott and Zawadski (1) has been largely attributed to nitric oxide (NO) derived from L-arginine through the action of NO synthase (2)(3)(4). This free radical ultimately stimulates guanylate cyclase by the formation of a nitrosyl-heme complex at the activator site of the enzyme (5, 6); however, the molecular mechanism(s) by which NO is transferred from synthase to cyclase remains poorly understood. The rapidity of the reaction of NO with molecular oxygen (7), superoxide anion (8), and heme (2) as well as nonheme iron (9) and the ready availability of these inactivating reactants in the plasma and cellular milieux militate against simple diffusion-limited transport of free NO in this medium. That endothelium-derived relaxing factor (EDRE) has the relatively long half-life of the ord...

We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endotheliumderived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for -0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S-NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosodiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains =7 pIM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-erum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at -1 #M; 60 min after administration of NG-monomethyl-Larginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by "40% (>95% of which were accounted for by S-nitrosoproteins, and ""80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be regulated for the maintenance of vascular tone.Endothelium-derived relaxing factor (EDRF), first described by Furchgott and Zawadzki (1), is a product of the normal endothelial cell having both vasodilatory (2) and antiplatelet (3,4) properties. Pharmacologic studies suggest that disease states as varied as septic shock (5), atherosclerosis (6), and hypoxia-induced pulmonary hypertension (7) may be associated with abnormal concentrations of EDRF in the vascular milieu. As a result of the seminal work of two groups (8, 9), this bioactive substance is believed to be equivalent to nitric oxide or a chemical congener or adduct thereof. Among the species thought of potential importance as adducts of nitric oxide are S-nitrosothiols-adducts with the sulfhydryl groups of amino acids, peptides, and proteins. We have recently shown that nitric oxide and authentic EDRF react with free thiol groups of proteins under physiologic conditions in vitro to form S-nitrosoproteins (10)-nitric oxide adducts with bioactivities comparable to EDRF but with half-lives of the order of hours. Although the facile formation of such species is intrinsically interest...

Abstract:The discovery by the ATLAS and CMS experiments of a new boson with mass around 125 GeV and with measured properties compatible with those of a Standard-Model Higgs boson, coupled with the absence of discoveries of phenomena beyond the Standard Model at the TeV scale, has triggered interest in ideas for future Higgs factories. A new circular e + e − collider hosted in a 80 to 100 km tunnel, TLEP, is among the most attractive solutions proposed so far. It has a clean experimental environment, produces high luminosity for top-quark, Higgs boson, W and Z studies, accommodates multiple detectors, and can reach energies up to the tt threshold and beyond. It will enable measurements of the Higgs boson properties and of Electroweak Symmetry-Breaking (EWSB) parameters with unequalled precision, offering exploration of physics beyond the Standard Model in the multi-TeV range. Moreover, being the natural precursor of the VHE-LHC, a 100 TeV hadron machine in the same tunnel, it builds up a long-term vision for particle physics. Altogether, the combination of TLEP and the VHE-LHC offers, for a great cost effectiveness, the best precision and the best search reach of all options presently on the market. This paper presents a first appraisal of the salient features of the TLEP physics potential, to serve as a baseline for a more extensive design study.

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