Plate-based diversity subset screening: an efficient paradigm for high throughput screening of a large screening file

The screening files of many large companies, including Pfizer, have grown considerably due to internal chemistry efforts, company mergers and acquisitions, external contracted synthesis, or compound purchase schemes. In order to screen the targets of interest in a cost-effective fashion, we devised an easy-to-assemble, plate-based diversity subset (PBDS) that represents almost the entire computed chemical space of the screening file whilst comprising only a fraction of the plates in the collection. In order to create this file, we developed new design principles for the quality assessment of screening plates: the Rule of 40 (Ro40) and a plate selection process that insured excellent coverage of both library chemistry and legacy chemistry space. This paper describes the rationale, design, construction, and performance of the PBDS, that has evolved into the standard paradigm for singleton (one compound per well) high-throughput screening in Pfizer since its introduction in 2006.     

Preparative isolation of (+)-beta-eudesmol fromAmyris balsamifera

Summary Optically pure (+)-beta-eudesmol is a possible starting material for the synthesis of several termite defense compounds. A two step procedure for the isolation of gram quantities of (+)-beta-eudesmol from commercially availableAmyris balsamifera oil (syn. West Indian sandalwood oil), containing 8% beta-eudesmol, was developed. Step one consisted of an efficient vacuum distillation of the total oil. Step two was a medium pressure LC separation with an AgNO₃ impregnated silica gel stationary phase. Several other separation procedures failed due to the presence of many closely related sesquiterpene alcohols (75% of the oil).     

Concentrated diffusing colloidal probes of Ca2+-dependent cadherin interactions

We report video microscopy measurements and inverse simulation analyses of specific Ca(2+)-dependent interactions between N-cadherin fragments attached to supported lipid bilayer-coated silica colloids in quasi-2D concentrated configurations. Our results include characterization of the bilayer formation and fluidity and the attachment of active extracellular cadherin fragments on bilayers. Direct measurements of interaction potentials show nonspecific macromolecular repulsion between cadherin fragments in the absence of Ca(2+) and irreversible bilayer fusion via cadherin-mediated attraction at >100 μM Ca(2+). Analysis of Ca(2+)-dependent N-cadherin bond formation in quasi-2D concentrated configurations using inverse Monte Carlo and Brownian Dynamics simulations show measurable attraction starting at 0.1 μM Ca(2+), a concentration significantly below previously reported values.     

Extension of the riesz representation theorem and solution of the Maxwell-Boltzmann functional equation

Aequationes mathematicae -     

A test of factorisation predictions for the fragmentation processes pp→π± at p momenta of 9.1 and 4.6 GeV/c

Relations have been derived between the invariant cross sections for various inclusive processes by assuming factorisation of the leading (pomeron) and non-leading (meson) trajectories. In this paper predictions for the invariant cross sections $\text{f(}\text{p}\text{p}\text{→π}{}^{\mathrm{\pm }}\text{)(2E}{}^1\text{/π√s)}\text{d}{}^2\text{σ/}\text{d}\text{x}\text{d}\text{p}{}^2{}_{\mathrm{\perp }}{}^2$ have been tested using data from $\text{p}\text{p}$interactions at 4.6 and 9.1 GeV/c.A large discrepancy between experiment and theory is apparent for the π^? data: in the π⁺ case the discrepancy is less marked but still present.     

Deflected mirage mediation: a phenomenological framework for generalized supersymmetry breaking

We present a general phenomenological framework for dialing between gravity mediation, gauge mediation, and anomaly mediation. The approach is motivated from recent developments in moduli stabilization, which suggest that gravity mediated terms can be effectively loop suppressed and thus comparable to gauge and anomaly mediated terms. The gauginos exhibit a mirage unification behavior at a "deflected" scale, and gluinos are often the lightest colored sparticles. The approach provides a rich setting in which to explore generalized supersymmetry breaking at the CERN Large Hadron Collider.