Bell's Theorem and Locally-Mediated Reformulations of Quantum Mechanics

Bell's Theorem rules out many potential reformulations of quantum mechanics, but within a generalized framework, it does not exclude all "locally-mediated" models. Such models describe the correlations between entangled particles as mediated by intermediate parameters which track the particle world-lines and respect Lorentz covariance. These locally-mediated models require the relaxation of an arrow-of-time assumption which is typically taken for granted. Specifically, some of the mediating parameters in these models must functionally depend on measurement settings in their future, i.e., on input parameters associated with later times. This option (often called "retrocausal") has been repeatedly pointed out in the literature, but the exploration of explicit locally-mediated toy-models capable of describing specific entanglement phenomena has begun only in the past decade. A brief survey of such models is included here. These models provide a continuous and consistent description of events associated with spacetime locations, with aspects that are solved "all-at-once" rather than unfolding from the past to the future. The tension between quantum mechanics and relativity which is usually associated with Bell's Theorem does not occur here. Unlike conventional quantum models, the number of parameters needed to specify the state of a system does not grow exponentially with the number of entangled particles. The promise of generalizing such models to account for all quantum phenomena is identified as a grand challenge.Comment: 61 pages, 2 figures; accepted for publication by Rev. Mod. Phy

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Dynamic and multi-pharmacophore modeling for designing polo-box domain inhibitors.

The polo-like kinase 1 (Plk1) is a critical regulator of cell division that is overexpressed in many types of tumors. Thus, a strategy in the treatment of cancer has been to target the kinase activity (ATPase domain) or substrate-binding domain (Polo-box Domain, PBD) of Plk1. However, only few synthetic small molecules have been identified that target the Plk1-PBD. Here, we have applied an integrative approach that combines pharmacophore modeling, molecular docking, virtual screening, and in vitro testing to discover novel Plk1-PBD inhibitors. Nine Plk1-PBD crystal structures were used to generate structure-based hypotheses. A common pharmacophore model (Hypo1) composed of five chemical features was selected from the 9 structure-based hypotheses and used for virtual screening of a drug-like database consisting of 159,757 compounds to identify novel Plk1-PBD inhibitors. The virtual screening technique revealed 9,327 compounds with a maximum fit value of 3 or greater, which were selected and subjected to molecular docking analyses. This approach yielded 93 compounds that made good interactions with critical residues within the Plk1-PBD active site. The testing of these 93 compounds in vitro for their ability to inhibit the Plk1-PBD, showed that many of these compounds had Plk1-PBD inhibitory activity and that compound Chemistry_28272 was the most potent Plk1-PBD inhibitor. Thus Chemistry_28272 and the other top compounds are novel Plk1-PBD inhibitors and could be used for the development of cancer therapeutics

Anatomy of the differential gluon structure function of the proton from the experimental data on F_2p

The use of the differential gluon structure function of the proton ${\cal F}(x,Q^{2})$ introduced by Fadin, Kuraev and Lipatov in 1975 is called upon in many applications of small-x QCD. We report here the first determination of ${\cal F}(x,Q^{2})$ from the experimental data on the small-x proton structure function $F_{2p}(x,Q^{2})$. We give convenient parameterizations for ${\cal F}(x,Q^{2})$ based partly on the available DGLAP evolution fits (GRV, CTEQ & MRS) to parton distribution functions and on realistic extrapolations into soft region. We discuss an impact of soft gluons on various observables. The x-dependence of the so-determined ${\cal F}(x,Q^{2})$ varies strongly with Q^2 and does not exhibit simple Regge properties. None the less the hard-to-soft diffusion is found to give rise to a viable approximation of the proton structure function F_{2p}(x,Q^2) by the soft and hard Regge components with intercepts \Delta_{soft}=0 and \Delta_{hard}\sim 0.4.Comment: 37 pages, 25 figure