Theoretical analysis of the onset of liquid entrainment for slots of finite width

The onset of liquid entrainment during discharge from large reservoirs containing a stratified mixture of two immiscible fluids through a side slot of a finite width is considered theoretically. A previously reported analysis in which the slot was approximated as a two-dimensional line sink has been extended to account for the finite width of the slot. The model resulting from the present analysis is expressed in terms of two simple algebraic equations suitable for hand calculations. According to the present results, the ratio of the critical height to the slot width is dependent only on the Froude number. Numerical results show that the present model approaches the correct physical limits at low Froude numbers and it converges to the predictions of the previously reported simple model at high Froude numbers.     

Pyrimethamine analogs as strong inhibitors of double and quadruple mutants of dihydrofolate reductase in human malaria parasites

Pyrimethamine acts against malarial parasites by selectively inhibiting their dihydrofolate reductase-thymidylate synthase. Resistance to pyrimethamine in Plasmodium falciparum is due to point mutations in the DHFR domain, initially at residue 108 (S108N), with additional mutations imparting much greater resistance. Our previous work, the development of a simple rational drug design strategy to overcome such resistance, used suitable meta-substituents in the pyrimethamine framework to avoid the unfavorable steric clash with mutant side chains at position 108. Interestingly, the meta-chloro analog of pyrimethamine not only overcame the resistance due to S108N, but also that contributed by the more remote mutation, C59R. The present work improves on this by means of other meta-substituents. Against wild type DHFR, double mutant types A16V + S108T and C59R + S108T, and the highly pyrimethamine/cycloguanil-resistant quadruple-mutant form N51I + C59R + S108N + I164L, pyrimethamine itself gave Ki values of 1.5, 2.4, 72.3 and 859 nM, respectively. The meta-substituted analogs, especially the meta-bromo analog, were much more powerful inhibitors of these DHFRs, including the quadruple-mutant form (meta-bromo analog, Ki 5.1 nM). For comparison, the dihydropyrazine antifolate, WR99210, gave Ki values of 0.9, 3.2, 0.8 and 0.9 nM, respectively. Ki values were also measured against recombinant human DHFR, as were their activities against the growth of Plasmodium falciparum cultures bearing the double mutations (FCB and K1 strains) and quadruple mutation (V1/S) and the wild type (3D7). The meta-analogs were highly active against all of these, with the meta-bromo again being the strongest, having an IC50 of 37 nM against V1/S, compared to > 5000 nM for pyrimethamine itself and 1.1 nM for WR99210.     

Synthesis of 3-oxo-δ-lactones via hetero-Diels-Alder reactions

The hetero-Diels-Alder reaction between aldehydes, 2, and bis-1,1-dimethoxy-3-trimethyl-1-siloxy-1,3-butadiene, 1, produces 2-methoxy-5,6-dihydro-γ-pyrones, 4, which are subsequently hydrolyzed to afford substituted 3-oxo-δ-lactones, 5, in high yields, providing a new and efficient approach to these synthetically useful intermediates.     

Calibration of quartz load cells; An in-situ procedure for instrumented falling weight impact machines

Quartz load cells have particular problems concerning signal drift and time of load application during calibration. There is currently no available standard method for dealing with these problems. A procedure is suggested that may be used as a routine check in situ on the complete system of quartz cell, amplifier, recording device and data processing unit. It involves loading and unloading a quartz cell with a known mass, recording the output on a suitable storage device and manipulating the data with a computer program to provide a permanent record. The accuracy of the method is considered and the results of a comprehensive series of calibrations in tension and compression are reported.

It was found that, providing good axiality was obtained, then either tensile or compressive loading gave the same calibration. The preferred method was to apply a tensile load, via a hanger system on the end of the striker, which obviates any necessity to remove the load cell from the impact mass and avoids possible errors associated with non-axial loading. Using the procedure, the quartz load cell was calibrated to an accuracy of better than 0·1%.     

UCT-Kirchberg algebras have nuclear dimension one

We prove that every Kirchberg algebra in the UCT class has nuclear dimension 1. We first show that Kirchberg 2-graph algebras with trivial _K0$K_0$ and finite _K1$K_1$ have nuclear dimension 1 by adapting a technique developed by Winter and Zacharias for Cuntz algebras. We then prove that every Kirchberg algebra in the UCT class is a direct limit of 2-graph algebras to obtain our main theorem.     

Fermi surface of CeIn3 above the Néel critical field

We report measurements of the de Haas-van Alphen effect in CeIn(3) in magnetic fields extending to approximately 90 T, well above the Néel critical field of mu(0)H(c) approximately 61 T. The unreconstructed Fermi surface a sheet is observed in the high magnetic field polarized paramagnetic limit, but with its effective mass and Fermi surface volume strongly reduced in size compared to that observed in the low magnetic field paramagnetic regime under pressure. The spheroidal topology of this sheet provides an ideal realization of the transformation from a "large Fermi surface" accommodating f electrons to a "small Fermi surface" when the f-electron moments become polarized.     

Ubi Caritas? — Modelling beliefs about charities

In this paper we report on a project in which we explored with a number of officers from different charities their beliefs about charitable giving, and built explicit models of these beliefs so that they might be examined in a more systematic way than they can be when just talking about them. We discuss some of the issues and problems around creating and using explicit models of individuals' beliefs to share wisdom, and report some of the things that happened when we sought to do this. We suggest that our approach provides practical help with the problems of sharing views.OR has traditionally been geared to those organizations who are able and willing to pay for it; in this paper we report on an OR project in organizations to whom it has not usually been available.