RNA signatures allow rapid identification of pathogens and antibiotic susceptibilities

With rising rates of drug-resistant infections, there is a need for diagnostic methods that rapidly can detect the presence of pathogens and reveal their susceptibility to antibiotics. Here we propose an approach to diagnosing the presence and drug-susceptibility of infectious diseases based on direct detection of RNA from clinical samples. We demonstrate that species-specific RNA signatures can be used to identify a broad spectrum of infectious agents, including bacteria, viruses, yeast, and parasites. Moreover, we show that the behavior of a small set of bacterial transcripts after a brief antibiotic pulse can rapidly differentiate drug-susceptible and -resistant organisms and that these measurements can be made directly from clinical materials. Thus, transcriptional signatures could form the basis of a uniform diagnostic platform applicable across a broad range of infectious agents

Helicity Analysis of Semileptonic Hyperon Decays Including Lepton Mass Effects

Using the helicity method we derive complete formulas for the joint angular decay distributions occurring in semileptonic hyperon decays including lepton mass and polarization effects. Compared to the traditional covariant calculation the helicity method allows one to organize the calculation of the angular decay distributions in a very compact and efficient way. In the helicity method the angular analysis is of cascade type, i.e. each decay in the decay chain is analyzed in the respective rest system of that particle. Such an approach is ideally suited as input for a Monte Carlo event generation program. As a specific example we take the decay $\Xi^0 \to \Sigma^+ + l^- + \bar{\nu}_l$ ($l^-=e^-, \mu^-$) followed by the nonleptonic decay $\Sigma^+ \to p + \pi^0$ for which we show a few examples of decay distributions which are generated from a Monte Carlo program based on the formulas presented in this paper. All the results of this paper are also applicable to the semileptonic and nonleptonic decays of ground state charm and bottom baryons, and to the decays of the top quark.Comment: Published version. 40 pages, 11 figures included in the text. Typos corrected, comments added, references added and update

Branching Fractions of tau Leptons to Three Charged Hadrons

From electron-positron collision data collected with the CLEO detector operating at CESR near \sqrt{s}=10.6 GeV, improved measurements of the branching fractions for tau decays into three explicitly identified hadrons and a neutrino are presented as {\cal B}(\tau^-\to\pi^-\pi^+\pi^-\nu_\tau)=(9.13\pm0.05\pm0.46)%, {\cal B}(\tau^-\to K^-\pi^+\pi^-\nu_\tau)=(3.84\pm0.14\pm0.38)\times10^{-3}, {\cal B}(\tau^-\to K^-K^+\pi^-\nu_\tau)=(1.55\pm0.06\pm0.09)\times10^{-3}, and {\cal B}(\tau^-\to K^-K^+K^-\nu_\tau)<3.7\times10^{-5} at 90% C.L., where the uncertainties are statistical and systematic, respectively.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, to appear in Phys. Rev. Let

The Presence of the Iron-Sulfur Motif Is Important for the Conformational Stability of the Antiviral Protein, Viperin

Viperin, an antiviral protein, has been shown to contain a CX3CX2C motif, which is conserved in the radical S-adenosyl-methionine (SAM) enzyme family. A triple mutant which replaces these three cysteines with alanines has been shown to have severe deficiency in antiviral activity. Since the crystal structure of Viperin is not available, we have used a combination of computational methods including multi-template homology modeling and molecular dynamics simulation to develop a low-resolution predicted structure. The results show that Viperin is an α -β protein containing iron-sulfur cluster at the center pocket. The calculations suggest that the removal of iron-sulfur cluster would lead to collapse of the protein tertiary structure. To verify these predictions, we have prepared, expressed and purified four mutant proteins. In three mutants individual cysteine residues were replaced by alanine residues while in the fourth all the cysteines were replaced by alanines. Conformational analyses using circular dichroism and steady state fluorescence spectroscopy indicate that the mutant proteins are partially unfolded, conformationally unstable and aggregation prone. The lack of conformational stability of the mutant proteins may have direct relevance to the absence of their antiviral activity

Improved Measurement of the Form Factors in the Decay Lambda_c^+ --> Lambda e^+ nu_e

Using the CLEO detector at the Cornell Electron Storage Ring, we have studied the distribution of kinematic variables in the decay Lambda_c^+ -> Lambda e^+ nu_e. By performing a four-dimensional maximum likelihood fit, we determine the form factor ratio, R = f_2/f_1 = -0.31 +/- 0.05(stat) +/- 0.04(syst), the pole mass, M_{pole} = (2.21 +/- 0.08(stat) +/- 0.14(syst)) GeV/c^2, and the decay asymmetry parameter of the Lambda_c, alpha_{Lambda_c} = -0.86 +/- 0.03(stat) +/- 0.02(syst), for = 0.67 (GeV/c^2)^2. We compare the angular distributions of the Lambda_c^+ and Lambda_c^- and find no evidence for CP-violation: A_{Lambda_c} = (alpha_{Lambda_c^+} + alpha_{Lambda_c^-})/ (alpha_{Lambda_c^+} - alpha_{Lambda_c^-}) = 0.00 +/- 0.03(stat) +/- 0.01(syst) +/- 0.02, where the third error is from the uncertainty in the world average of the CP-violating parameter, A_{Lambda}, for Lambda -> p pi^-.Comment: 8 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2004/, submitted to PR

Measurement of Inclusive B --> psi Production

Using the combined CLEO II and CLEO II.V data sets of 9.1 fb^{-1} at the Upsilon(4S), we measure properties of Psi mesons produced directly from decays of the B meson, where ``B'' denotes an admixture of B+, B-, B0, and B0bar, and ``Psi'' denotes either J/Psi or Psi(2S). We report first measurements of Psi polarization in B -> Psi(direct) X: alpha(J/Psi) = -0.30 {+0.07 -0.06 stat} {+-0.04 syst} and alpha(Psi(2S)) = -0.45 {+0.22 -0.19 stat} {+-0.04 syst}. We also report improved measurements of the momentum distributions of Psi produced directly from B decays, correcting for measurement smearing. Finally, we report measurements of the inclusive branching fraction for B -> Psi X and B -> Chi_c1 X.Comment: 8 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Search for Lepton-Flavor-Violating Decays of B Mesons

We have searched a sample of 9.6 million BB-bar events for the lepton-flavor-violating decays B --> h e^{+-} mu^{-+}, B^+ --> h^- e^+ e^+, B^+ --> h^- e^+ mu^+, and B^+ --> h^- mu^+ mu^+, where h is pi, K, rho, and K*(892), a total of sixteen modes. We find no evidence for these decays, and place 90% confidence level upper limits on their branching fractions that range from 1.0 to 8.3 X 10^{-6}.Comment: 8 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, PRD R

Study of the q^2-Dependence of B --> pi ell nu and B --> rho(omega)ell nu Decay and Extraction of |V_ub|

We report on determinations of |Vub| resulting from studies of the branching fraction and q^2 distributions in exclusive semileptonic B decays that proceed via the b->u transition. Our data set consists of the 9.7x10^6 BBbar meson pairs collected at the Y(4S) resonance with the CLEO II detector. We measure B(B0 -> pi- l+ nu) = (1.33 +- 0.18 +- 0.11 +- 0.01 +- 0.07)x10^{-4} and B(B0 -> rho- l+ nu) = (2.17 +- 0.34 +0.47/-0.54 +- 0.41 +- 0.01)x10^{-4}, where the errors are statistical, experimental systematic, systematic due to residual form-factor uncertainties in the signal, and systematic due to residual form-factor uncertainties in the cross-feed modes, respectively. We also find B(B+ -> eta l+ nu) = (0.84 +- 0.31 +- 0.16 +- 0.09)x10^{-4}, consistent with what is expected from the B -> pi l nu mode and quark model symmetries. We extract |Vub| using Light-Cone Sum Rules (LCSR) for 0<= q^2<16 GeV^2 and Lattice QCD (LQCD) for 16 GeV^2 <= q^2 < q^2_max. Combining both intervals yields |Vub| = (3.24 +- 0.22 +- 0.13 +0.55/-0.39 +- 0.09)x10^{-3}$ for pi l nu, and |Vub| = (3.00 +- 0.21 +0.29/-0.35 +0.49/-0.38 +-0.28)x10^{-3} for rho l nu, where the errors are statistical, experimental systematic, theoretical, and signal form-factor shape, respectively. Our combined value from both decay modes is |Vub| = (3.17 +- 0.17 +0.16/-0.17 +0.53/-0.39 +-0.03)x10^{-3}.Comment: 45 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR