Numerical block diagonalization of matrix *-algebras with application to semidefinite programming

Semidefinite programming (SDP) is one of the most active areas in mathematical programming, due to varied applications and the availability of interior point algorithms. In this paper we propose a new pre-processing technique for SDP instances that exhibit algebraic symmetry. We present computational results to show that the solution times of certain SDP instances may be greatly reduced via the new approach.     

Halogen bonds as stabilizing interactions in a chiral self-assembled molecular monolayer

We report the formation of highly-ordered self-assembled monolayers of an achiral organic semiconductor molecule. STM results show spontaneous formation of very large single domains of ordered chiral monolayers. DFT calculations support the identification of halogen bonds as the primary interactions that steer molecular self-assembly, leading to organizational chirality.     

Library enhancement through the wisdom of crowds

We present a novel approach for enhancing the diversity of a chemical library rooted on the theory of the wisdom of crowds. Our approach was motivated by a desire to tap into the collective experience of our global medicinal chemistry community and involved four basic steps: (1) Candidate compounds for acquisition were screened using various structural and property filters in order to eliminate clearly nondrug-like matter. (2) The remaining compounds were clustered together with our in-house collection using a novel fingerprint-based clustering algorithm that emphasizes common substructures and works with millions of molecules. (3) Clusters populated exclusively by external compounds were identified as "diversity holes," and representative members of these clusters were presented to our global medicinal chemistry community, who were asked to specify which ones they liked, disliked, or were indifferent to using a simple point-and-click interface. (4) The resulting votes were used to rank the clusters from most to least desirable, and to prioritize which ones should be targeted for acquisition. Analysis of the voting results reveals interesting voter behaviors and distinct preferences for certain molecular property ranges that are fully consistent with lead-like profiles established through systematic analysis of large historical databases.     

Efficient substructure searching of large chemical libraries: the ABCD chemical cartridge

Efficient substructure searching is a key requirement for any chemical information management system. In this paper, we describe the substructure search capabilities of ABCD, an integrated drug discovery informatics platform developed at Johnson & Johnson Pharmaceutical Research & Development, L.L.C. The solution consists of several algorithmic components: 1) a pattern mapping algorithm for solving the subgraph isomorphism problem, 2) an indexing scheme that enables very fast substructure searches on large structure files, 3) the incorporation of that indexing scheme into an Oracle cartridge to enable querying large relational databases through SQL, and 4) a cost estimation scheme that allows the Oracle cost-based optimizer to generate a good execution plan when a substructure search is combined with additional constraints in a single SQL query. The algorithm was tested on a public database comprising nearly 1 million molecules using 4,629 substructure queries, the vast majority of which were submitted by discovery scientists over the last 2.5 years of user acceptance testing of ABCD. 80.7% of these queries were completed in less than a second and 96.8% in less than ten seconds on a single CPU, while on eight processing cores these numbers increased to 93.2% and 99.7%, respectively. The slower queries involved extremely generic patterns that returned the entire database as screening hits and required extensive atom-by-atom verification.     

Asymptotic Expansions for Stationary Distributions of Nonlinearly Perturbed Semi-Markov Processes. 1

Methodology and Computing in Applied Probability - New algorithms for construction of asymptotic expansions for stationary distributions of nonlinearly perturbed semi-Markov processes with finite...     

An improved synthesis and some reactions of diethyl 4-oxo-4H-pyran-2,5-dicarboxylate

The reaction of ethyl 2-(dimethylamino)methylene-3-oxobutanoate with diethyl oxalate in the presence of sodium hydride in THF gave diethyl 4-oxo-4H-pyran-2,5-dicarboxylate, from which 4-oxo-4H-pyran-2,5-dicarboxylic and 4-oxo-1-phenyl-1,4-dihydropyridine-2,5-dicarboxylic acids and their derivatives were obtained in good yields.     

<Emphasis Type="Italic">K</Emphasis><Subscript><Emphasis Type="Italic">e</Emphasis>3</Subscript> Decay Studies in the OKA Experiment

Recent results from OKA setup concerning form factor studies in K_e3 decay are presented. About 5.25 M events obtained for decays of 17.7 GeV/cK⁺ are selected for the analysis. The linear and quadratic slopes for the decay form factor f₊(t) are measured: λ'₊ = 2.95 ± 0.022 ± 0.018 × 10 ^-2 for the linear slope fit and λ₊ = 2.611 ± 0.035 ± 0.028 × 10 ^-2, λ"₊ = 1.91 ± 0.19 ± 0.14 × 10 ^-3 for the quadratic one. The scalar and tensor contributions are compatible with zero. Several alternative parametrizations are tried: the Pole fit parameter is found to be M _V = 891 ± 3 MeV; the parameter of the dispersive parametrization is measured to be Λ₊ = 2.458 ± 0.018 × 10^-2.     

One-Pot Synthesis of (E)-2-(3-Oxoindolin-2-ylidene)-2-arylacetonitriles

A highly efficient and expeditious one-pot approach towards 2-(3-oxoindolin-2-yl)acetonitriles was designed, which involves a base-assisted aldol reaction of ortho-nitroacetophenones, followed by hydrocyanation, triggering an unusual reductive cyclization reaction.