Crystal structure of a complex between β-glucopyranose and a macrocyclic receptor with dendritic multicharged water solubilizing chains

International audienceUsing commercial screens for crystallization of biomolecules and taking advantage of the use of racemic crystallography allowed the production of x-ray quality single crystals and the elucidation at 1.08 Å resolution of the solid state structure of a difficult target: the complex between glucopyranose and a water soluble macrocyclic receptor equipped with dendritic multianionic solubilizing chains

The Nature and Necessity of Operational Flexibility in the Emergency Department

Hospital-based emergency departments (EDs), given their high cost and major role in allocating care resources, are at the center of the debate about how to maximize value in delivering health care in the United States. To operate effectively and create value, EDs must be flexible, having the ability to rapidly adapt to the highly variable needs of patients. The concept of flexibility has not been well described in the ED literature. We introduce the concept, outline its potential benefits, and provide some illustrative examples to facilitate incorporating flexibility into ED management. We draw on operations research and organizational theory to identify and describe 5 forms of flexibility: physical, human resource, volume, behavioral, and conceptual. Each form of flexibility may be useful individually or in combination with other forms in improving ED performance and enhancing value. We also offer suggestions for measuring operational flexibility in the ED. A better understanding of operational flexibility and its application to the ED may help us move away from reactive approaches of managing variable demand to a more systematic approach. We also address the tension between cost and flexibility and outline how "partial flexibility" may help resolve some challenges. Applying concepts of flexibility from other disciplines may help clinicians and administrators think differently about their workflow and provide new insights into managing issues of cost, flow, and quality in the ED

Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose

The ab initio design of synthetic molecular receptors for a specific biomolecular guest remains an elusive objective, particularly for targets such as monosaccharides, which have very close structural analogues. Here we report a powerful approach to produce receptors with very high selectivity for specific monosaccharides and, as a demonstration, we develop a foldamer that selectively encapsulates fructose. The approach uses an iterative design process that exploits the modular structure of folded synthetic oligomer sequences in conjunction with molecular modelling and structural characterization to inform subsequent refinements. Starting from a first-principles design taking size, shape and hydrogen-bonding ability into account and using the high predictability of aromatic oligoamide foldamer conformations and their propensity to crystallize, a sequence that binds to beta-D-fructopyranose in organic solvents with atomic-scale complementarity was obtained in just a few iterative modifications. This scheme, which mimics the adaptable construction of biopolymers from a limited number of monomer units, provides a general protocol for the development of selective receptors