Functional genomics and NMR spectroscopy

The recent success of the human genome project and the continued accomplishment in obtaining DNA sequences for a vast array of organisms is providing an unprecedented wealth of information. Nevertheless, an abundance of the proteome contains hypothetical proteins or proteins of unknown function, where high throughput approaches for genome-wide functional annotation (functional genomics) has evolved as the necessary next step. Nuclear magnetic resonance spectroscopy is playing an important role in functional genomics by providing information on the structure of protein and protein-ligand complexes, from metabolite fingerprinting and profiling, from the analysis of the metabolome, and from ligand affinity screens to identify chemical probes.     

An efficient and scalable one-pot double Michael addition-Dieckmann condensation for the synthesis of 4,4-disubstituted cyclohexane beta-keto esters

A simple, scalable, and efficient one-pot methodology for the synthesis of 4,4-disubstituted cyclohexane beta-keto esters from benzylic nitriles or esters and methyl acrylate promoted by potassium tert-butoxide is described. The process relies on a tandem double Michael addition-Dieckmann condensation reaction, which results in the formation of three discrete carbon-carbon bonds in a single pot, including a quaternary center. The method allows for the convenient and rapid synthesis of a variety of 4-aryl-4-cyano-2-carbomethoxycyclohexanone and 4-aryl-2,4-biscarbomethoxycyclohexanone building blocks for use in natural products synthesis and medicinal chemistry.     

A non-linear viscoelastic model for ceramics at high temperatures

High-temperature mechanical behavior of ceramics is characterized by non-linear rate dependent responses, asymmetric behavior in tension and compression, and nucleation and coalescence of voids leading to rupture. Moreover, rupture experiments show considerable scatter or randomness in fatigue lives of nominally equal specimens. To capture the non-linear, asymmetric time-dependent behavior, a new non-linear viscoelastic model is proposed. Non-linearity and asymmetry are introduced in the volumetric component. To model the random formation and coalescence of voids, each element is assigned a failure strain sampled from a lognormal distribution. An element is deleted when its volumetric strain exceeds its failure strain. Temporal increases in strains produce a sequential loss of elements (a model for void nucleation and growth), which in turn leads to failure. Non-linear viscoelastic model parameters are determined from uniaxial tensile and compressive creep experiments on silicon nitride. The model is then used to predict the deformation of four-point bending and ball-on-ring specimens. Simulation is used to predict statistical moments of rupture lives. Numerical simulation results compare well with results of four-point bending experiments.     

Measurement of the local wavenumber and frequency spectrum in a plane wake

A digital technique is presented for experimentally measuring the local wavenumber-frequency spectrum S _L(k, f) of a fluctuating velocity field using two probes. From S _L(k, f), the local wavenumber spectrum S _L(k), the averaged dispersion relation, and the broadening of the wavenumber spectrum for a given frequency can be determined. The technique is demonstrated by applying it to the velocity field of a plane wake which is undergoing transition from laminar to turbulent flow. A specially designed two sensor hotwire probe is used to obtain simultaneous records of streamwise velocity fluctuations at two locations having a fixed streamwise separation. New information is obtained concerning: the spatial characteristics of instability waves in the wake; the importance of local wavenumber matching in nonlinear coupling among waves; and broadening of the dispersion relation associated with the transition to turbulence. The usefulness of the S _L(k, f) approach when Taylor's hypothesis is not valid is also discussed.     

Synthesis of methyl-, fluoro-, and chloro-substituted 6-hydroxyisoindolin-1-ones

The synthesis of a series of methyl-, fluoro-, and chloro-substituted 6-hydroxyisoindolin-1-ones is described.     

Mutually-antagonistic interactions in baseball networks

We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit structural changes over time. We find interesting structure in the networks and examine their sensitivity to baseball’s rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to (1) compare the performance of players who competed under different conditions and (2) include information about which particular players a given player has faced. We find that a player’s position in the network does not correlate with his placement in the random walker ranking. However, network position does have a substantial effect on the robustness of ranking placement to changes in head-to-head matchups.