On optimal modularity for system construction

Modularity is a natural instrument and a ubiquitous practice for the engineering of human‐made systems. However, modularization remains more of an art than a science; to the extent that the notion of optimal modularity is rarely used in engineering design. We prove that optimal modularity exists (at least for construction)—and is achieved through balanced modularization as structural symmetry in the distribution of the sizes of modules. We show that system construction cost is highly sensitive to both the number of modules and the modularization structure. However, this sensitivity has an inverse relationship with process capability and is minimal for highly capable construction processes with small process uncertainties. Conclusions are reached by a Bayesian estimation technique for a relatively simple construction model originally introduced by Herbert Simon for the hypothetical production of a linear structure, taking into account errors that may occur in the work associated with the production of the links between the nodes in the structure for varied numbers of modules. © 2015 Wiley Periodicals, Inc. Complexity 21: 176–189, 2016     

Wisdom: Understanding and the Good Life

I argue that a necessary condition for being wise is: understanding how to live well. The condition, by requiring understanding rather than a wide variety of justified beliefs or knowledge, as Ryan and Whitcomb respectively require, yields the desirable result that being wise is compatible with having some false beliefs but not just any false beliefs about how to live well—regardless of whether those beliefs are justified or not. In arguing for understanding how to live well as a necessary condition for wisdom, I reject the view, proposed by both Ryan and Whitcomb, that subjects such as chemistry lies within the domain of wisdom. I show that the argued for condition yields the desirable result that being wise is not a common achievement, but that it is not something that can only plausibly be achieved in the modern era.     

Lossless compression of chemical fingerprints using integer entropy codes improves storage and retrieval

Many modern chemoinformatics systems for small molecules rely on large fingerprint vector representations, where the components of the vector record the presence or number of occurrences in the molecular graphs of particular combinatorial features, such as labeled paths or labeled trees. These large fingerprint vectors are often compressed to much shorter fingerprint vectors using a lossy compression scheme based on a simple modulo procedure. Here, we combine statistical models of fingerprints with integer entropy codes, such as Golomb and Elias codes, to encode the indices or the run lengths of the fingerprints. After reordering the fingerprint components by decreasing frequency order, the indices are monotone-increasing and the run lengths are quasi-monotone-increasing, and both exhibit power-law distribution trends. We take advantage of these statistical properties to derive new efficient, lossless, compression algorithms for monotone integer sequences: monotone value (MOV) coding and monotone length (MOL) coding. In contrast to lossy systems that use 1024 or more bits of storage per molecule, we can achieve lossless compression of long chemical fingerprints based on circular substructures in slightly over 300 bits per molecule, close to the Shannon entropy limit, using a MOL Elias Gamma code for run lengths. The improvement in storage comes at a modest computational cost. Furthermore, because the compression is lossless, uncompressed similarity (e.g., Tanimoto) between molecules can be computed exactly from their compressed representations, leading to significant improvements in retrival performance, as shown on six benchmark data sets of druglike molecules.     

Quantitative determination of BMS-378806 in human plasma and urine by high-performance liquid chromatography/tandem mass spectrometry

BMS-378806 is a human immunodeficiency virus (HIV) entry inhibitor that is being developed for the oral treatment of HIV infection. Human plasma and urine LC/MS/ MS methods have been developed and validated for the quantitation of BMS-378806. For human plasma method, methyl t-butyl ether was used to extract BMS-378806 from plasma in a 96-well format, and the organic layers were dried down and then reconstituted for the injection, while a dilute-and-shoot approach was used for human urine method in a 96-well format. Chromatographic separation was achieved isocratically on a Phenomenex C18 (2) Luna column (2 x 50 mm2, 5 microm). The mobile phase contained 60:40 v/v of 0.1% formic acid in water and ACN. Detection was by positive ion electrospray MS/MS. The standard curves ranged from 1.25 to 1000 ng/mL for the plasma assay and from 10 to 5000 ng/mL for the urine assay. The curves were fitted to a 1/x2 weighted quadratic regression model for both methods. The validation results demonstrated that both methods had satisfactory precision and accuracy across the calibration ranges. The methods were applied to the analysis of human plasma and urine samples from a single ascending dose clinical study to assess the pharmacokinetics of the drug. The pharmacokinetic analysis results indicated the absorption and disposition of the drug was rapid. The systemic exposure of BMS-378806 was generally dose proportional among the doses from 100 to 1200 mg, but not dose proportional to 1600 mg. There were modest increases in the systemic exposure when the drug was given with food or given as a solution formulation. Renal excretion was not a substantial elimination pathway of the drug. BMS378806 was safe and well tolerated over a dose range of 100-1600 mg administered as a single oral dose.     

Enantioselective hydrogenation of ethyl pyruvate over diop modified Pt nanoclusters. Determination of geometry of the ligand adsorption mode via DRIFTS

Immobilization of chiral ligands on the surface of metal nanoparticles is one concept for heterogenation of enantioselective catalysts. Diop modified Pt nanoclusters were found to be able to induce enantioselectivity and enhancement of the reaction rate in hydrogenation of ethyl pyruvate. The model of geometry of the diop adsorption has been proposed based on DRIFTS and molecular modelling investigations. The ability of diop to induce enantioselectivity and enhanced reaction rate was explained through the adsorption geometry and comparison with known models of enantioselectivity established for the cinchonidine on Pt system.     

Synthesis, structure, redox properties and azide binding for a series of biphenyl-based Cu(II) complexes

A series of biphenyl-based N(3)O ligands, 2, 4, 6, and 8 were synthesized and their Cu(II) complexes prepared. These complexes were characterized by a combination of elemental analysis, FAB-MS, UV-vis spectroscopy and electrochemistry. The structure of [Cu(N(3)O-mpy-NO2)Cl2], 12 [N(3)O-mpy = 2-(3-pyridylmethylimino)-2'-(2-methylaminophenol)biphenyl], was solved and showed that the ligand coordinates through the three nitrogens with the phenol oxygen uncoordinated. Titration of azide anion into solutions of the complexes in methanol resulted in the appearance of a new band between 485-495 nm at the expense of the starting peak at 380 nm. Cyclic voltammetry studies indicated that the complexes undergo quasi-reversible one-electron reductions in acetonitrile at potentials between 0.13-0.58 V vs. Ag/AgCl. The complexes were found to be weakly active for the oxidation of di-tert-butyl catechol (DTBC).