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.     

Carbon-carbon bond forming reactions with substrates absorbed non-covalently on a cellulose chromatography paper support

Reactions and purifications, including carbon-carbon bond forming reactions, can be carried out on a cellulose support on which the substrates are non-covalently absorbed.     

Critical Reynolds number and galloping instabilities: experiments on circular cylinders

The current paper considers large galloping-like vibrations of circular cylinders, generically inclined and yawed to the flow. The case of a round section prone to galloping is seemingly a paradox since rotational symmetry (or close to it) and classical galloping are apparently contradictory. Still there seems to be a range of wind speeds far from those for typical Kármán vortex shedding resonance where such a phenomenon does occur. Experimental results from both static and dynamic large-scale rigid cable models, presented here, show that this range coincides with the critical Reynolds number regime, where notable symmetry-breaking characteristics such as nonzero mean lift emerge. It is shown that a fundamental difference between the inclined and non-inclined cylinder aerodynamics may exist accommodating different pressure distributions and different resulting dynamic behaviours. Unsteady pressure measurements showing avalanche-like “jumps” and vortex dislocations building between cell structures in the cylinder spanwise direction are conjectured to be a key element in the unstable behaviour experienced.     

TITAN: an ion trap for accurate mass measurements of ms-half-life nuclides

The introduction of Paul traps, in particular linear radio-frequency quadrupoles in the early 2000s, has revolutionized the use of ion traps for probing the properties of radioactive nuclides. It opened the path to trapping all available nuclides, independent of their chemical properties. We present an overview of direct mass measurements of short-lived nuclides using TITAN, a Penning trap mass spectrometer facility particularly suitable for precision measurements of ms-half-life nuclides.     

Biomechanically inspired modelling of pedestrian-induced forces on laterally oscillating structures

Despite considerable interest among engineers and scientists, bi-directional interaction between walking pedestrians and lively bridges has still not been well understood. In an attempt to bridge this gap a biomechanically inspired model of the human response to lateral bridge motion is presented and explored. The simple inverted pendulum model captures the key features of pedestrian lateral balance and the resulting forces on the structure. The forces include self-excited components that can be effectively modelled as frequency-dependent added damping and mass to the structure. The results of numerical simulations are in reasonable agreement with recent experimental measurements of humans walking on a laterally oscillating treadmill, and in very good agreement with measurements on full-scale bridges. In contrast to many other models of lateral pedestrian loading, synchronisation with the bridge motion is not involved. A parametric study of the model is conducted, revealing that as pedestrians slow down as a crowd becomes more dense, their resulting lower pacing rates generate larger self-excited forces. For typical pedestrian parameters, the potential to generate negative damping arises for any lateral bridge vibration frequency above 0.43 Hz, depending on the walking frequency. Stability boundaries of the combined pedestrian–structure system are presented in terms of the structural damping ratio and pedestrian-to-bridge mass ratio, revealing complex relations between damping demand and bridge and pedestrian frequencies, due to the added mass effect. Finally it is demonstrated that the model can produce simultaneous self-excited forces on multiple structural modes, and a realistic full simulation of a large number of pedestrians, walking randomly and interacting with a bridge, produces structural behaviour in very good agreement with site observations.     

Universal One-Way Light Speed from a Universal Light Speed Over Closed Paths

This paper gives two complete and elementary proofs that if the speed of light over closed paths has a universal value c, then it is possible to synchronize clocks in such a way that the one-way speed of light is c. The first proof is an elementary version of a recent proof. The second provides high precision experimental evidence that it is possible to synchronize clocks in such a way that the one-way speed of light has a universal value. We also discuss an old incomplete proof by Weyl which is important from an historical perspective.     

Entanglement, Joint Measurement, and State Reduction

Entanglement is perhaps the most important new feature of the quantum world. It is expressed in quantum theory by the joint measurement formula. We prove the formula for projection valued observables from a plausible assumption, which for spacelike separated measurements is a consequence of causality. State reduction is simply a way to express the joint measurement formula after one measurement has been made, and its result known.