George B. Dantzig and systems optimization

We pay homage to George B. Dantzig by describing a less well-known part of his legacy–his early and dedicated championship of the importance of systems optimization in solving complex real-world problems.     

Measurement of branching fractions and mass spectra of B-->Kpipigamma

We present a measurement of the partial branching fractions and mass spectra of the exclusive radiative penguin processes B-->Kpipigamma in the range m(Kpipi)<1.8 GeV/c(2). We reconstruct four final states: K(+)pi(-)pi(+)gamma, K(+)pi(-)pi(0)gamma, K(S)(0)pi(-)pi(+)gamma, and K(S)(0)pi(+)pi(0)gamma, where K(S)(0)-->pi(+)pi(-). Using 232 x 10(6) e(+)e(-)-->BB events recorded by the BABAR experiment at the SLAC PEP-II asymmetric-energy storage ring, we measure the branching fractions B(B(+)-->K(+)pi(-)pi(+)gamma)=[2.95+/-0.13(stat)+/-0.20(syst)] x 10(-5), B(B(0)-->K(+)pi(-)pi(0)gamma)=[4.07+/-0.22(stat)+/-0.31(syst)] x 10(-5), B(B(0)-->K(0)pi(+)pi(-)gamma)=[1.85+/-0.21(stat)+/-0.12(syst)] x 10(-5), and B(B(+)-->K(0)pi(+)pi(0)gamma)=[4.56+/-0.42(stat)+/-0.31(syst)] x 10(-5).     

Expanding Lipidome Coverage Using LC-MS/MS Data-Dependent Acquisition with Automated Exclusion List Generation

Untargeted omics analyses aim to comprehensively characterize biomolecules within a biological system. Changes in the presence or quantity of these biomolecules can indicate important biological perturbations, such as those caused by disease. With current technological advancements, the entire genome can now be sequenced; however, in the burgeoning fields of lipidomics, only a subset of lipids can be identified. The recent emergence of high resolution tandem mass spectrometry (HR-MS/MS), in combination with ultra-high performance liquid chromatography, has resulted in an increased coverage of the lipidome. Nevertheless, identifications from MS/MS are generally limited by the number of precursors that can be selected for fragmentation during chromatographic elution. Therefore, we developed the software IE-Omics to automate iterative exclusion (IE), where selected precursors using data-dependent topN analyses are excluded in sequential injections. In each sequential injection, unique precursors are fragmented until HR-MS/MS spectra of all ions above a user-defined intensity threshold are acquired. IE-Omics was applied to lipidomic analyses in Red Cross plasma and substantia nigra tissue. Coverage of the lipidome was drastically improved using IE. When applying IE-Omics to Red Cross plasma and substantia nigra lipid extracts in positive ion mode, 69% and 40% more molecular identifications were obtained, respectively. In addition, applying IE-Omics to a lipidomics workflow increased the coverage of trace species, including odd-chained and short-chained diacylglycerides and oxidized lipid species. By increasing the coverage of the lipidome, applying IE to a lipidomics workflow increases the probability of finding biomarkers and provides additional information for determining etiology of disease.

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Photoactive Ru(II) -polypyridyl complexes that display sequence selectivity and high-affinity binding to duplex DNA through groove binding

The duplex-DNA binding properties of a nonintercalating polypyridyl ruthenium(II) complex that incorporates a linear extended ligand with a catechol moiety has been probed with a variety of photo- and biophysical techniques. These studies reveal that the complex groove binds to DNA sequences biphasically, and displays binding constants equivalent to those of high-affinity metallointercalators. The complex also displays preferential binding to AT-rich sequences. Changes in the structure of the coordinated catechol ligand and the incorporation of intercalating ancillary ligands into the complex were found to modulate both the optical-binding response and binding parameters of the system, which indicates that the catechol moiety plays a crucial role in the observed enhancement to binding affinities.     

Deciphering the molecular details for the binding of the prion protein to main ganglioside GM1 of neuronal membranes

The prion protein (PrP) resides in lipid rafts in?vivo, and lipids modulate misfolding of the protein to infectious isoforms. Here we demonstrate that binding of recombinant PrP to model raft membranes requires the presence of ganglioside GM1. A combination of liquid- and solid-state NMR revealed the binding sites of PrP to the saccharide head group of GM1. The binding epitope for GM1 was mapped to the folded C-terminal domain of PrP, and docking simulations identified key residues in the C-terminal region of helix C and the loop between strand S2 and helix B. Crucially, this region of PrP is linked to prion resistance in?vivo, and structural changes caused by lipid binding in this region may explain the requirement for lipids in the generation of infectious prions in?vitro.     

Simultaneous testing for the successive differences of exponential location parameters under heteroscedasticity

In this paper, the design-oriented two-stage and data-analysis one-stage multiple comparison procedures for successive comparisons of exponential location parameters under heteroscedasticity are proposed. One-sided and two-sided simultaneous confidence intervals are also given. We also extend these simultaneous confidence intervals for successive differences to a larger class of contrasts of the location parameters. Upper limits of critical values are obtained using the recent techniques given in Lam [Lam, K., 1987. Subset selection of normal populations under heteroscedasticity. In: Proceedings of the Second International Advanced Seminar/Workshop on Inference Procedures Associated with Statistical Ranking and Selection, Sydney, Australia; Lam, K., 1988. An improved two-stage selection procedure. Communications in Statistics Simulation and Computation. 17 (3), 995-1006]. These approximate critical values are shown to have better results than the approximate critical values using the Bonferroni inequality developed in this paper. Finally, the application of the proposed procedures is illustrated with an example.     

Communication: A new approach to dual-basis second-order Møller-Plesset calculations

We describe a hierarchy of approximations (MP2[x]) that allow one to estimate second-order M?ller-Plesset (MP2) energies in a large basis set from small-basis calculations. The most cost-effective approximation, MP2[K], is significantly cheaper than full MP2 but numerical tests on small atoms and molecules indicate that it is nonetheless accurate. We conclude that MP2[K] is an attractive level of theory for large systems.     

Proper-Time Classical Electrodynamics

We construct a generalization of Maxwell's equations associated with the proper-time of the source which accounts for radiation reaction without any assumptions concerning the nature of the source. The theory leads to a new invariance group, related to the Lorentz group, which leaves the proper-time of the source fixed for all observers.