Late-Stage Functionalization by Chan–Lam Amination: Rapid Access to Potent and Selective Integrin Inhibitors

A late-stage functionalization of the aromatic ring in amino acid derivatives is described. The key step is a copper-catalysed diversification of a boronate ester by amination (Chan–Lam reaction) that can be carried out on a complex β-aryl-β-amino acid scaffold. This not only considerably extends the substrate scope of amination partners, but also delivers an array of potent and selective integrin inhibitors as potential treatment agents of idiopathic pulmonary fibrosis (IPF). This versatile chemical strategy, which is amenable to high-throughput-array protocols, allows the installation of pharmaceutically valuable heteroaromatic fragments at a late stage by direct coupling to NH heterocycles, leading to compounds with drug-like attributes. It thus constitutes a useful addition to the medicinal chemist's repertoire.     

Characterization and Monitoring of Porous Media with Electrical Imaging: A Review

Transport in Porous Media - Electrical geophysical imaging is a widely used noninvasive technology for visualizing porous media at scales larger than individual pores. Originally developed for...     

Investigating undergraduate mathematics learners’ cognitive engagement with recorded lecture videos

The use of recorded lecture videos (RLVs) in mathematics instruction continues to advance. Prior research at the post-secondary level has indicated a tendency for RLV use in mathematics to be negatively correlated with academic performance, although it is unclear whether this is because regular users are generally weaker mathematics students or because RLV use is somehow depressing student learning. Through the lens of cognitive engagement, a quasi-experimental pre- and post-test design study was conducted to investigate the latter possibility.

Cognitive engagement was operationalized using the Revised Two-Factor Study Process Questionnaire (R-SPQ-2F), which measures learning approaches on two major scales: surface and deep. In two mathematics courses at two universities, in Australia and the UK, participants were administered the questionnaire near the course start and finish. Overall findings were similar in both contexts: a reduction in live lecture attendance coupled with a dependence on RLVs was associated with an increase in surface approaches to learning.

This study has important implications for future pedagogical development and adds to the sense of urgency regarding research into best practices using RLVs in mathematics.     

An interior-point trust-funnel algorithm for nonlinear optimization

We present an interior-point trust-funnel algorithm for solving large-scale nonlinear optimization problems. The method is based on an approach proposed by Gould and Toint (Math Prog 122(1):155–196, 2010) that focused on solving equality constrained problems. Our method is similar in that it achieves global convergence guarantees by combining a trust-region methodology with a funnel mechanism, but has the additional capability of being able to solve problems with both equality and inequality constraints. The prominent features of our algorithm are that (i) the subproblems that define each search direction may be solved with matrix-free methods so that derivative matrices need not be formed or factorized so long as matrix-vector products with them can be performed; (ii) the subproblems may be solved approximately in all iterations; (iii) in certain situations, the computed search directions represent inexact sequential quadratic optimization steps, which may be desirable for fast local convergence; (iv) criticality measures for feasibility and optimality aid in determining whether only a subset of computations need to be performed during a given iteration; and (v) no merit function or filter is needed to ensure global convergence.     

The impact of comet Shoemaker-Levy 9 on Jupiter

We have performed computational shock-physics simulations of the hypervelocity (60 km/s) impact of 1–3 km, water-ice spheres entering a hydrogen-helium Jovian atmosphere. These conditions simulate the best current estimates for the collision of fragments of periodic comet Shoemaker-Levy 9 with Jupiter in July, 1994. We used the Eulerian shock-physics code CTH, and its parallel version PCTH to perform 2-D analyses of penetration and breakup, and 3-D analyses of the growth of the resulting fireball during the first 100 seconds after fragment entry. We can use our simulations to make specific predictions of the time interval between fragment entry and fireball arrival into line-of-sight from the earth. For a fragment larger than about 1 km, we believe that the time of fireball arrival above Jupiter's limb will be directly observable from earth. Measurements of this time by observers, in conjunction with our simulations, may allow mass of cometary fragments to be determined.This article was processed using Springer-Verlag T_EX Shock Waves macro package 1.0 and the AMS fonts, developed by the American Mathematical Society.     

Laser-scanning particle image velocimetry applied to a delta wing in transient maneuver

A laser scanning technique, which utilizes a galvanometer scanner to produce particle-image photographs, is employed to investigate the flow over a delta wing undergoing pitching maneuvers at a high angle of attack. Use of a unique forcing system and a large-scale prism arrangement allow characterization of the instantaneous velocity field over the entire crossflow plane at a desired angle of attack.Contours of constant streamwise vorticity are calculated from the crossflow velocity field at various pitching rates. The vorticity distribution occurring during the pitch-up motion differs substantially from that on the stationary wing at the same angle of attack. During the pitch-up motion, the leading-edge vortex is remarkably coherent, in contrast to the disordered structure on the stationary wing. During the corresponding pitch-down motion, the vorticity distribution is quite similar to that on the stationary wing at the same angle of attack. This behavior is evident for a range of pitching rates.