One site fits both: A model for the ternary complex of folate + NADPH in R67 dihydrofolate reductase, a D2 symmetric enzyme

R67 dihydrofolate reductase (DHFR) is a novel enzyme that confers resistance to the antibiotic trimethoprim. The crystal structure of R67 DHFR displays a toroidal structure with a central active-site pore. This homotetrameric protein exhibits 222 symmetry, with only a few residues from each chain contributing to the active site, so related sites must be used to bind both substrate (dihydrofolate) and cofactor (NADPH) in the productive R67 DHFR?NADPH?dihydrofolate complex. Whereas the site of folate binding has been partially resolved crystallographically, an interesting question remains: how can the highly symmetrical active site also bind and orient NADPH for catalysis? To model this ternary complex, we employed DOCK and SLIDE, two methods for docking flexible ligands into proteins using quite different algorithms. The bound pteridine ring of folate (Fol I) from the crystal structure of R67 DHFR was used as the basis for docking the nicotinamide-ribose-P_i (NMN) moiety of NADPH. NMN was positioned by both DOCK and SLIDE on the opposite side of the pore from Fol I, where it interacts with Fol I at the pore's center. Numerous residues serve dual roles in binding. For example, Gln 67 from both the B and D subunits has several contacts with the pteridine ring, while the same residue from the A and C subunits has several contacts with the nicotinamide ring. The residues involved in dual roles are generally amphipathic, allowing them to make both hydrophobic and hydrophilic contacts with the ligands. The result is a `hot spot' binding surface allowing the same residues to co-optimize the binding of two ligands, and orient them for catalysis.     

Phase-field modeling of void evolution and swelling in materials under irradiation

Void swelling is an important phenomenon observed in both nuclear fuels and cladding materials in operating nuclear reactors. In this work we develop a phase-field model to simulate void evolution and void volume change in irradiated materials. Important material processes, including the generation of defects such as vacancies and self-interstitials, their diffusion and annihilation, and void nucleation and evolution, have been taken into account in this model. The thermodynamic and kinetic properties, such...     

Development of a prototype high-current low-energy ion implanter

A high current-low energy implant system for the processing of semiconductor devices at medium-high dopant levels is described. Criteria for selection and design of ion beam components such as ion beam optics, vacuum requirements and reliability are discussed. Variations in wafer uniformities for within wafer, wafer-to-wafer and run-to-run are presented.     

Generators and normal forms of Richard Thompson’s group F and the four-color theorem

We use a result of Kauffman to explore the connection between Richard Thompson’s Group F and the four-color theorem.     

Distinguishing Ontario ginseng landraces and ginseng species using NMR-based metabolomics

The use of ¹H-NMR-based metabolomics to distinguish and identify unique markers of five Ontario ginseng (Panax quinquefolius L.) landraces and two ginseng species (P. quinquefolius and P. ginseng) was evaluated. Three landraces (2, 3, and 5) were distinguished from one another in the principal component analysis (PCA) scores plot. Further analysis was conducted and specific discriminating metabolites from the PCA loadings were determined. Landraces 3 and 5 were distinguishable on the basis of a decreased NMR intensity in the methyl ginsenoside region, indicating decreased overall ginsenoside levels. In addition, landrace 5 was separated by an increased amount of sucrose relative to the rest of the landraces. Landrace 2 was separated from the rest of the landraces by the increased level of ginsenoside R_b1. The Ontario P. quinquefolius was also compared with Asian P. ginseng by PCA, and clear separation between the two groups was detected in the PCA scores plot. The PCA loadings plot and a t-test NMR difference plot were able to identify an increased level of maltose and a decreased level of sucrose in the Asian ginseng compared with the Ontario ginseng. An overall decrease of ginsenoside content, especially ginsenoside R_b1, was also detected in the Asian ginseng’s metabolic profile. This study demonstrates the potential of NMR-based metabolomics as a powerful high-throughput technique in distinguishing various closely related ginseng landraces and its ability to identify metabolic differences from Ontario and Asian ginseng. The results from this study will allow better understanding for quality assessment, species authentication, and the potential for developing a fully automated method for quality control.

Programmable imaging with two-axis micromirrors

We demonstrate a means of creating a digital image by using a two-axis tilt micromirror to scan a scene. For each different orientation we extract a single gray scale value from the mirror and combine them to form a single composite image. This allows one to choose the distribution of the samples, and so in principle a variable resolution image could be created. We demonstrate this ability to control resolution and projection by constructing a voltage table that compensates for the nonlinear response of the mirrors to the applied voltage.     

Arene C−H Activation at Aluminium(I): meta Selectivity Driven by the Electronics of SNAr Chemistry

The reactivity of the electron-rich anionic Al^I aluminyl compound K₂[(NON)Al]₂ (NON=4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethylxanthene) towards mono- and disubstituted arenes is reported. C−H activation chemistry with n-butylbenzene gives exclusively the product of activation at the arene meta position. Mechanistically, this transformation proceeds in a single step via a concerted Meisenheimer-type transition state. Selectivity is therefore based on similar electronic factors to classical S_NAr chemistry, which implies the destabilisation of transition states featuring electron-donating groups in either ortho or para positions. In the cases of toluene and the three isomers of xylene, benzylic C−H activation is also possible, with the product(s) formed reflecting the feasibility (or otherwise) of competing arene C−H activation at a site which is neither ortho nor para to a methyl substituent.     

Effect of Shear Displacement and Stress Changes on Fracture Hydraulic Aperture and Flow Anisotropy

Transport in Porous Media - Fluid flow in fractures has the potential to drastically change the economic, environmental, and safety risks associated with a subsurface operation. This work focuses...     

Synthesis and coordination chemistry of a water-soluble verdazyl radical. structures and magnetic properties of M(H2O)2(vdCO2)(2).2H2O (M = Co,Ni; vdCO2 = 1,5-dimethyl-6-oxo-verdazyl-3-carboxylate)

The synthesis of a verdazyl radical with a carboxylate substituent renders the radical highly soluble in water, thereby permitting the aqueous synthesis of Ni(II) and Co(II) verdazyl complexes which have been structurally and magnetically characterized.     

A measurement of the 50Ti(γ, n) and 50Ti(γ, n0) cross sections

Measurements of the ⁵⁰Ti(γ, n) and ⁵⁰Ti(γ, n₀) cross sections have been made in the energy range of the giant dipole resonance (GDR). Assuming the GDR is split into two isospin components, approximated as Lorentzians, a calculation based on statistical decay of the GDR states is consistent with the experimental results.