This paper describes the development of a simple empirical scoring function designed to estimate the free energy of binding for a protein-ligand complex when the 3D structure of the complex is known or can be approximated. The function uses simple contact terms to estimate lipophilic and metal-ligand binding contributions, a simple explicit form for hydrogen bonds and a term which penalises flexibility. The coefficients of each term are obtained using a regression based on 82 ligand-receptor complexes for which the binding affinity is known. The function reproduces the binding affinity of the complexes with a cross-validated error of 8.68 kJ/mol. Tests on internal consistency indicate that the coefficients obtained are stable to changes in the composition of the training set. The function is also tested on two test sets containing a further 20 and 10 complexes, respectively. The deficiencies of this type of function are discussed and it is compared to approaches by other workers.

A general expression is derived for the fluid force on a body of simple shape moving with a velocity v through inviscid fluid in which there is an unsteady non-uniform rotational velocity field u0(x,t) in two or three dimensions. It is assumed that the radius is small compared with the scale over which the strain rate changes, though for the sphere it is also assumed that the changes in the ambient velocity field over the scale of the sphere are small compared with the velocity of the body relative to the flow. Given these approximations it is shown that the effects of the rate of change of the vorticity of the ambient flow is of second order and can be neglected. However the rate of change of the irrotational straining motion is included in the analysis. It is shown that the inertial forces derived by many authors for irrotational flow can be simply added to a generalization of the lift force derived by Auton (1987) in a companion paper. It is shown how this lift force is made up of a rotational and an inertial or added-mass component. For three-dimensional bluff bodies the latter is generally larger (by a factor of three for a sphere), and can be simply calculated from the added-mass coefficient. For illustration, the general expression is used to derive formulae for (i) the motion of a spherical bubble in a steady non-uniform flow to contrast with the motion in an unsteady flow, and (ii) the motion of rigid volumes of neutral density across an inviscid shear flow. These results show how added-mass (and lift) forces lead to different motions for a sphere and a cylinder. The general expression is useful in two-phase flow calculations, and for indicating the forces and motions of ‘lumps of fluid’ in turbulent flows.

This paper concerns the flow about a sphere placed in a weak shear flow of an inviscid fluid. The secondary velocity resulting from advection of vorticity by the irrotational component of the flow is computed on the sphere surface, and on the upstream axis. The resulting lift force on the sphere is evaluated, and the result is confirmed by an analytical far-field calculation. The displacement of the stagnation streamline, far upstream of the sphere, is calculated more accurately than in previous papers.

After completing this course, the reader will be able to:1. Identify risk factors for kidney failure associated with high-dose MTX therapy.2. Discuss the therapeutic options in patients with delayed MTX elimination.3. Discuss the potential risks and benefits of glucarpidase intervention.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME Conclusions. Glucarpidase is well tolerated and produces a rapid inactivation of substantial amounts of MTX. However, overall results are still unsatisfactory in adult and elderly patients, suggesting that earlier recognition of delayed MTX elimination and more rapid intervention are needed. The Oncologist ABSTRACT

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