8 research outputs found

    A Unified Model of the GABA(A) Receptor Comprising Agonist and Benzodiazepine Binding Sites

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    We present a full-length α(1)β(2)γ(2) GABA receptor model optimized for agonists and benzodiazepine (BZD) allosteric modulators. We propose binding hypotheses for the agonists GABA, muscimol and THIP and for the allosteric modulator diazepam (DZP). The receptor model is primarily based on the glutamate-gated chloride channel (GluCl) from C. elegans and includes additional structural information from the prokaryotic ligand-gated ion channel ELIC in a few regions. Available mutational data of the binding sites are well explained by the model and the proposed ligand binding poses. We suggest a GABA binding mode similar to the binding mode of glutamate in the GluCl X-ray structure. Key interactions are predicted with residues α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and the backbone of β(2)S156. Muscimol is predicted to bind similarly, however, with minor differences rationalized with quantum mechanical energy calculations. Muscimol key interactions are predicted to be α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and β(2)F200. Furthermore, we argue that a water molecule could mediate further interactions between muscimol and the backbone of β(2)S156 and β(2)Y157. DZP is predicted to bind with interactions comparable to those of the agonists in the orthosteric site. The carbonyl group of DZP is predicted to interact with two threonines α(1)T206 and γ(2)T142, similar to the acidic moiety of GABA. The chlorine atom of DZP is placed near the important α(1)H101 and the N-methyl group near α(1)Y159, α(1)T206, and α(1)Y209. We present a binding mode of DZP in which the pending phenyl moiety of DZP is buried in the binding pocket and thus shielded from solvent exposure. Our full length GABA(A) receptor is made available as Model S1

    Measurement of the Top Pair Production Cross Section in the Dilepton Decay Channel in ppbar Collisions at sqrt s = 1.96 TeV

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    Submitted to Phys. Rev. DA measurement of the \ttbar production cross section in \ppbar collisions at s\sqrt{{\rm s}} = 1.96 TeV using events with two leptons, missing transverse energy, and jets is reported. The data were collected with the CDF II Detector. The result in a data sample corresponding to an integrated luminosity 2.8 fb1^{-1} is: \sigma_{\ttbar} = 6.27 ±\pm 0.73(stat) ±\pm 0.63(syst) ±\pm 0.39(lum) pb. for an assumed top mass of 175 GeV/c2c^{2}.A measurement of the tt̅ production cross section in pp̅ collisions at √s=1.96  TeV using events with two leptons, missing transverse energy, and jets is reported. The data were collected with the CDF II detector. The result in a data sample corresponding to an integrated luminosity 2.8  fb-1 is σtt̅ =6.27±0.73(stat)±0.63(syst)±0.39(lum)  pb. for an assumed top mass of 175  GeV/c2.Peer reviewe

    Die Ileitis regionalis

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    Lasers in nonsurgical periodontal therapy

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    Search for the Higgs boson in the all-hadronic final state using the CDF II detector

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    We report on a search for the production of the Higgs boson decaying to two bottom quarks accompanied by two additional quarks. The data sample used corresponds to an integrated luminosity of approximately 4 fb(-1) of p (p) over bar collisions at root s = 1.96 TeV recorded by the CDF II experiment. This search includes twice the integrated luminosity of the previous published result, uses analysis techniques to distinguish jets originating from light flavor quarks and those from gluon radiation, and adds sensitivity to a Higgs boson produced by vector boson fusion. We find no evidence of the Higgs boson and place limits on the Higgs boson production cross section for Higgs boson masses between 100 GeV/c(2) and 150 GeV/c(2) at the 95% confidence level. For a Higgs boson mass of 120 GeV/c(2), the observed (expected) limit is 10.5 (20.0) times the predicted standard model cross section

    Search for a Higgs boson in the diphoton final state in pp collisions at sqrt[s]=1.96TeV.

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    A search for a narrow Higgs boson resonance in the diphoton mass spectrum is presented based on data corresponding to 7.0fb{-1} of integrated luminosity from pp collisions at sqrt[s]=1.96TeV collected by the CDF experiment. No evidence of such a resonance is observed, and upper limits are set on the cross section times branching ratio of the resonant state as a function of Higgs boson mass. The limits are interpreted in the context of the standard model and one fermiophobic benchmark model where the data exclude fermiophobic Higgs bosons with masses below 114GeV/c{2} at a 95% Bayesian credibility level
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