Modular peptide binders - development of a predictive technology as alternative for reagent antibodies

Current biomedical research and diagnostics critically depend on detection agents for specific recognition and quantification of protein molecules. Monoclonal antibodies have been used for this purpose over decades and facilitated numerous biological and biomedical investigations. Recently, however, it has become apparent that many commercial reagent antibodies lack specificity or do not recognize their target at all. Thus, synthetic alternatives are needed whose complex designs are facilitated by multidisciplinary approaches incorporating experimental protein engineering with computational modeling. Here, we review the status of such an engineering endeavor based on the modular armadillo repeat protein scaffold and discuss challenges in its implementation. Keywords: affinity reagent; armadillo repeat proteins; computational design; directed evolution; library generation; protein-peptide interfac

Charmless two-body B decays: A global analysis with QCD factorization

In this paper, we perform a global analysis of $B \to PP$ and $PV$ decays with the QCD factorization approach. It is encouraging to observe that the predictions of QCD factorization are in good agreement with experiment. The best fit $\gamma$ is around $79^\circ$. The penguin-to-tree ratio $|P_{\pi \pi}/T_{\pi \pi}|$ of $\pi^+ \pi^-$ decays is preferred to be larger than 0.3. We also show the confidence levels for some interesting channels: $B^0 \to \pi^0 \pi^0$, $K^+ K^-$ and $B^+ \to \omega \pi^+$, $\omega K^+$. For $B \to \pi K^\ast$ decays, they are expected to have smaller branching ratios with more precise measurements.Comment: 20 pages, 4 figures, version to appear in Phys. Rev.

What can we learn from a measurement of sin(2 beta + gamma)?

The constraints on the value of the CKM phase gamma that may be achieved by prospective measurements of sin(2 beta) and sin(2 beta + gamma) are discussed. Significant constraints require quite small errors, and may depend on assumptions about strong phases. The measurement of sin(2 beta + gamma) combined with other experiments could provide valuable limits on new physics in Bd-Bdbar mixing.Comment: 10 pages, 7 figures, RevTex 4, uses amsmath and graphic

Elastic and inelastic SU(3)-breaking final-state interactions in B decays to pseudoscalar mesons

We discuss all contributions from Zweig-rule-satisfying SU(3)-breaking final state interactions (FSIs)in the B -> PP decays (neglecting charmed intermediate states), where PP=pi pi, pi K, KK, pi eta (eta'), and K eta (eta'). First, effects of SU(3) breaking in rescattering through Pomeron exchange are studied. Then, after making a plausible assumption concerning the pattern of SU(3) breaking in non-Pomeron FSIs, we give general formulas for how the latter modify short-distance (SD) amplitudes. In the SU(3) limit, these formulas depend on three effective parameters characterizing the strength of all non-Pomeron rescattering effects. We point out that the experimental bounds on the B -> K^+K^- branching ratio may limit the value of only one of these FSI parameters. Thus, the smallness of the B -> K^+K^- decay rate does not imply negligible rescattering effects in other decays. Assuming a vanishing value of this parameter, we perform various fits to the available B -> PP branching ratios. The fits determine the quark-diagram SD amplitudes, the two remaining FSI parameters and the weak angle gamma. While the set of all B -> PP branching ratios is well described with gamma around its expected SM value, the fits permit other values of gamma as well. For a couple of such good fits, we predict asymmetries for the B -> K pi, pi^+ eta (eta'), K^+ eta (eta') decays as well as the values of the CP-violating parameters S_{pi pi} and C_{pi pi} for the time-dependent rate of B^0(t) -> pi^+ pi^-. Apart from a problem with the recent B^+ -> pi^+ eta asymmetry measurement, comparison with the data seems to favour the values of gamma in accordance with SM expectations.Comment: 27 pages, 5 figure

The Configuration System of the ATLAS Trigger

The ATLAS detector at CERN’s LHC will be exposed to proton-proton collisions at a rate of 40 MHz. To reduce the data rate to a manageable final output rate of 200Hz, only potentially interesting events are selected by a three-level trigger system. A system has been designed and implemented that enables the configuration of all three trigger levels from a centrally maintained relational database, for the purpose of both online data taking and offline trigger simulation. We present the current status of this trigger configuration system, covering the database design, client software and user interface tools, and putting emphasis on its multiple uses for data-taking, Monte-Carlo simulation, and trigger validation on express-stream data

Modular peptide binders – development of a predictive technology as alternative for reagent antibodies

Current biomedical research and diagnostics critically depend on detection agents for specific recognition and quantification of protein molecules. Monoclonal antibodies have been used for this purpose over decades and facilitated numerous biological and biomedical investigations. Recently, however, it has become apparent that many commercial reagent antibodies lack specificity or do not recognize their target at all. Thus, synthetic alternatives are needed whose complex designs are facilitated by multidisciplinary approaches incorporating experimental protein engineering with computational modeling. Here, we review the status of such an engineering endeavor based on the modular armadillo repeat protein scaffold and discuss challenges in its implementation

Radiative tau decay and the magnetic moment of the muon

We discuss the decay tau^- -> nu_tau pi^- pi^0 gamma in terms of a model with the correct low-energy structure and with the relevant resonance degress of freedom. The nontrivial radiative dynamics becomes visible for large photon momenta only. We use the model to calculate electromagnetic corrections for the two-pion contribution to hadronic vacuum polarization extracted from photon-inclusive two-pion decays. The corrections are insensitive to the details of the model and depend on the pion form factor only. Putting all relevant isospin violating corrections together, we obtain a shift Delta a_mu = (- 120 +/- 26 +/- 3) x 10^-11 to be applied to determinations of the anomalous magnetic moment of the muon from photon-inclusive tau data.Comment: 24 pages, 6 figure

The TriggerTool Graphical User Interface to the ATLAS Trigger Configuration Database

A system has been designed and implemented to configure all three levels of the ATLAS trigger system from a centrally provided relational database, in which an archive of all trigger configurations used in data taking is also maintained. The user interaction with this database is via a Java-based graphical user interface known as the TriggerTool. We describe here how the TriggerTool has been designed to fulfill several different roles for users of varying expertise, from being a browser of the database to a tool for creating and modifying configuration

The Physics of Hadronic Tau Decays

Hadronic tau decays represent a clean laboratory for the precise study of quantum chromodynamics (QCD). Observables (sum rules) based on the spectral functions of hadronic tau decays can be related to QCD quark-level calculations to determine fundamental quantities like the strong coupling constant, parameters of the chiral Lagrangian, |V_us|, the mass of the strange quark, and to simultaneously test the concept of quark-hadron duality. Using the best available measurements and a revisited analysis of the theoretical framework, the value alpha_s(m_tau) = 0.345 +- 0.004[exp] +- 0.009[theo] is obtained. Taken together with the determination of alpha_s(m_Z) from the global electroweak fit, this result leads to the most accurate test of asymptotic freedom: the value of the logarithmic slope of 1/alpha_s(s) is found to agree with QCD at a precision of 4%. In another approach, the tau spectral functions can be used to determine hadronic quantities that, due to the nonperturbative nature of long-distance QCD, cannot be computed from first principles. An example for this is the contribution from hadronic vacuum polarization to loop-dominated processes like the anomalous magnetic moment of the muon. This article reviews the measurements of nonstrange and strange tau spectral functions and their phenomenological applications.Comment: 89 pages, 32 figures; final version accepted for publication by Reviews of Modern Physic

Simultaneous Extraction of the Fermi constant and PMNS matrix elements in the presence of a fourth generation

Several recent studies performed on constraints of a fourth generation of quarks and leptons suffer from the ad-hoc assumption that 3 x 3 unitarity holds for the first three generations in the neutrino sector. Only under this assumption one is able to determine the Fermi constant G_F from the muon lifetime measurement with the claimed precision of G_F = 1.16637 (1) x 10^-5 GeV^-2. We study how well G_F can be extracted within the framework of four generations from leptonic and radiative mu and tau decays, as well as from K_l3 decays and leptonic decays of charged pions, and we discuss the role of lepton universality tests in this context. We emphasize that constraints on a fourth generation from quark and lepton flavour observables and from electroweak precision observables can only be obtained in a consistent way if these three sectors are considered simultaneously. In the combined fit to leptonic and radiative mu and tau decays, K_l3 decays and leptonic decays of charged pions we find a p-value of 2.6% for the fourth generation matrix element |U_{e 4}|=0 of the neutrino mixing matrix.Comment: 19 pages, 3 figures with 16 subfigures, references and text added refering to earlier related work, figures and text in discussion section added, results and conclusions unchange