Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs

Measurements of the Ratios B(Ds+→ηℓ+ν)/B(Ds+→ϕℓ+ν){\cal B}(D_s^+\to \eta\ell^+\nu)/{\cal B}(D_s^+\to \phi\ell^+\nu) and B(Ds+→η′ℓ+ν)/B(Ds+→ϕℓ+ν){\cal B}(D_s^+\to \eta'\ell^+\nu)/{\cal B}(D_s^+\to \phi\ell^+\nu)

Using the CLEO~II detector we measure ${\cal B}(D_s^+\to \eta e^+\nu)/{\cal B}(D_s^+\to \phi e^+\nu) =1.24\pm0.12\pm0.15$, ${\cal B}(D_s^+\to \eta' e^+\nu)/{\cal B}(D_s^+\to \phi e^+\nu) =0.43\pm0.11\pm0.07$ and ${\cal B}(D_s^+\to \eta' e^+\nu)/{\cal B}(D_s^+\to \eta e^+\nu) =0.35\pm0.09\pm0.07$. We find the vector to pseudoscalar ratio, ${\cal B}(D_s^+\to \phi e^+\nu)/{\cal B}(D_s^+\to (\eta+\eta') e^+\nu) =0.60\pm0.06\pm0.06$, which is similar to the ratio found in non strange $D$ decays.Comment: 11 page uuencoded postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Measurement of the Branching Ratios for the Decays of Ds+→ηπ+,η′π+,ηρ+D_{s}^{+}\to \eta\pi^{+}, \eta^{'}\pi^{+}, \eta\rho^{+}, and eta′ρ+eta^{'}\rho^{+}

Using a data sample with integrated luminosity of about 3.9 fb^{-1} collected in e+ e- annihilation with the CLEO-II detector at the Cornell Electron Storage Ring, we have measured the branching ratios for the decay modes Ds -> (eta, eta') pi and Ds -> (eta, eta') rho relative to Ds -> phi pi. These decay modes are among the most common hadronic decays of the Ds's and can be related by factorization to the semileptonic decays Ds -> (eta,eta') l nu. The results obtained are compared with previous CLEO results and with the branching ratios measured for the related semileptonic decays. We also report results on the Cabibbo-suppressed decays of the D+ to the same final states.Comment: 18 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Determination of the Michel Parameters and the tau Neutrino Helicity in tau Decay

Using the CLEO II detector at the $e^+e^-$ storage ring CESR, we have determined the Michel parameters $\rho$, $\xi$, and $\delta$ in $\tau^\mp \to l^\mp\nu\bar{\nu}$ decay as well as the tau neutrino helicity parameter $h_{\nu_\tau}$ in $\tau^\mp \to \pi^\mp\pi^0\nu$ decay. From a data sample of $3.02\times 10^6$ tau pairs produced at $\sqrt{s}=10.6 GeV$, using events of the topology $e^+e^- \to \tau^+\tau^- \to (l^\pm\nu\bar{\nu}) (\pi^\mp\pi^0\nu)$ and $e^+e^- \to \tau^+\tau^- \to (\pi^\pm\pi^0\bar{\nu}) (\pi^\mp\pi^0\nu)$, and the determined sign of $h_{\nu_\tau}$, the combined result of the three samples is: $\rho = 0.747\pm 0.010\pm 0.006$, $\xi = 1.007\pm 0.040\pm 0.015$, $\xi\delta = 0.745\pm 0.026\pm 0.009$, and $h_{\nu_\tau} = -0.995\pm 0.010\pm 0.003$. The results are in agreement with the Standard Model V-A interaction.Comment: 18 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Measurement of the Inclusive Semi-electronic D0D^0 Branching Fraction

Using the angular correlation between the $\pi^+$ emitted in a $D^{*+} \rightarrow D^0 \pi^+$ decay and the $e^+$ emitted in the subsequent $D^0 \rightarrow Xe^+\nu$ decay, we have measured the branching fraction for the inclusive semi-electronic decay of the $D^0$ meson to be: {\cal B}(D^0 \rightarrow X e^+ \nu) = [6.64 \pm 0.18 (stat.) \pm 0.29 (syst.)] \%. The result is based on 1.7 fb$^{-1}$ of $e^+e^-$ collisions recorded by the CLEO II detector located at the Cornell Electron Storage Ring (CESR). Combining the analysis presented in this paper with previous CLEO results we find, \frac{{\cal B} (D^0 \rightarrow X e^+ \nu)} {{\cal B} (D^0 \rightarrow K^- \pi^+)} = 1.684 \pm 0.056 (stat.) \pm 0.093(syst.) and \frac{{\cal B}(D\rightarrow K^-e^+\nu)} {{\cal B}(D\rightarrow Xe^+\nu)} = 0.581 \pm 0.023 (stat.) \pm 0.028(syst.). The difference between the inclusive rate and the sum of the measured exclusive branching fractions (measured at CLEO and other experiments) is $(3.3 \pm 7.2) \%$ of the inclusive rate.Comment: Latex file, 33pages, 4 figures Submitted to PR

Study of Gluon versus Quark Fragmentation in Υ→ggγ\Upsilon\to gg\gamma and e+e−→qqˉγe^{+}e^{-}\to q\bar{q}\gamma Events at \sqrt{s}=10 GeV

Using data collected with the CLEO II detector at the Cornell Electron Storage Ring, we determine the ratio R(chrg) for the mean charged multiplicity observed in Upsilon(1S)->gggamma events, to the mean charged multiplicity observed in e+e- -> qqbar gamma events. We find R(chrg)=1.04+/-0.02+/-0.05 for jet-jet masses less than 7 GeV.Comment: 15 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Search for Exclusive Charmless Hadronic B Decays

We have searched for two-body charmless hadronic decays of $B$ mesons. Final states include $\pi\pi$, $K \pi$, and $KK$ with both charged and neutral kaons and pions; $\pi\rho$, $K \rho$, and $K^*\pi$; and $K\phi$, $K^*\phi$, and $\phi\phi$. The data used in this analysis consist of 2.6~million $B\bar{B}$~pairs produced at the $\Upsilon(4S)$ taken with the CLEO-II detector at the Cornell Electron Storage Ring (CESR). We measure the branching fraction of the sum of $B^0 \rightarrow \pi^+\pi^-$ and $B^0 \rightarrow K^+\pi^-$ to be $(1.8^{+0.6+0.2}_{-0.5-0.3}\pm0.2) \times 10^{-5}$. In addition, we place upper limits on individual branching fractions in the range from $10^{-4}$ to $10^{-6}$.Comment: 33 page LATEX file, uses REVTEX and psfig, 14 figures in a separate uuencoded postscript file, postscript version also available through http://w4.lns.cornell.edu/public/CLN

Semileptonic Branching Fraction of Charged and Neutral B Mesons

An examination of leptons in ${\Upsilon (4S)}$ events tagged by reconstructed $B$ decays yields semileptonic branching fractions of $b_-=(10.1 \pm 1.8\pm 1.4)\%$ for charged and $b_0=(10.9 \pm 0.7\pm 1.1)\%$ for neutral $B$ mesons. This is the first measurement for charged $B$. Assuming equality of the charged and neutral semileptonic widths, the ratio $b_-/b_0=0.93 \pm 0.18 \pm 0.12$ is equivalent to the ratio of lifetimes. A postscript version is available through World-Wide-Web in http://w4.lns.cornell.edu/public/CLNS/1994Comment: 9 pages (in REVTEX format) Preprint CLNS94-1286, CLEO 94-1