Lord Justice of Appeal John Fletcher Moulton and explosives production in World War I: 'the mathematical mind triumphant'.

At the end of November 1914 Lord Moulton (1844-1921) became the director of explosives production in the War Office. A 70-year-old jurist may seem an extraordinary choice, but he was an extraordinary man. He was Senior Wrangler at Cambridge, was elected to the Royal Society for research on electricity, and learned about chemistry as a barrister for dye and explosives manufacturers. He assembled an able team of administrators and chemists who designed and managed mammoth new national explosives factories. They could not make enough TNT and picric acid from obtainable precursors, so Moulton persuaded the reluctant armed services to adopt mixtures of TNT and ammonium nitrate, which enabled them to make even more than was needed. In mid-1915 they moved to the new Ministry of Munitions, where they also became responsible for fertilizers and poison gases. In 1917 they produced explosives at a higher rate than was attained in World War II.

Mirrors and smoke: A. V. Hill, his Brigands, and the science of anti-aircraft gunnery in World War I.

In 1916 Captain A. V. Hill was transferred from the infantry to the Ministry of Munitions to work on anti-aircraft gunnery. He determined the three-dimensional coordinates of flying objects by placing two mirrors far apart. The mirrors were viewed from a fixed distance above them and observers simultaneously marked the position of the object. He gathered brilliant men, most too old or too young for conscription, who became known as Hill's Brigands. They determined the coordinates of the explosions of shots fired with different fuse settings and fitted them with the ballistic equations to construct accurate gunnery tables. They solved the puzzle of erratic fuse timing at high altitudes. They developed apparatus to locate aircraft by sound. Travelling groups of Brigands worked with anti-aircraft gunners, which Hill regarded as the dawn of operations research. Hill was as adept at leading scientists as he was at doing science.

Loading and recycling of synaptic vesicles in the Torpedo electric organ and the vertebrate neuromuscular junction.

In vertebrate motor nerve terminals and in the electromotor nerve terminals of Torpedo there are two major pools of synaptic vesicles: readily releasable and reserve. The electromotor terminals differ in that the reserve vesicles are twice the diameter of the readily releasable vesicles. The vesicles contain high concentrations of ACh and ATP. Part of the ACh is brought into the vesicle by the vesicular ACh transporter, VAChT, which exchanges two protons for each ACh, but a fraction of the ACh seems to be accumulated by different, unexplored mechanisms. Most of the vesicles in the terminals do not exchange ACh or ATP with the axoplasm, although ACh and ATP are free in the vesicle interior. The VAChT is controlled by a multifaceted regulatory complex, which includes the proteoglycans that characterize the cholinergic vesicles. The drug (-)-vesamicol binds to a site on the complex and blocks ACh exchange. Only 10-20% of the vesicles are in the readily releasable pool, which therefore is turned over fairly rapidly by spontaneous quantal release. The turnover can be followed by the incorporation of false transmitters into the recycling vesicles, and by the rate of uptake of FM dyes, which have some selectivity for the two recycling pathways. The amount of ACh loaded into recycling vesicles in the readily releasable pool decreases during stimulation. The ACh content of the vesicles can be varied over eight-fold range without changing vesicle size.

Ernest Starling's analysis of the energy balance of the German people during the blockade, 1914-19.

Ernest H. Starling FRS (1866-1927) is remembered as a great physiologist; nevertheless a paper of his that is of substantial historical interest has dropped out of sight. It is a quantitative analysis of the effects of the Allied food blockade during World War I on the energy available to the German population and of the failure by the German government to distribute the available energy fairly. He shows that by 1919 a substantial proportion of the urban Germans were starving. His data are summarized in this article. Starling concluded that empty stomachs were a major reason for the German capitulation. His analysis grew out of his work as the second chairman of the Food [War] Committee of The Royal Society and as one of the two British members of the International Scientific Food Commission, pioneering bodies in using science to help to set public policy.

A chloride channel blocker reduces acetylcholine uptake into synaptic vesicles at the frog neuromuscular junction.

A key mechanism for loading acetylcholine (ACh(+)) into synaptic vesicles uses energy to transport H(+) into the vesicle interior and then exchanges H(+) for ACh(+). This mechanism requires anions to follow the H(+) into the vesicles to prevent the building up of an overwhelming electrical gradient across the vesicle membrane. Frog nerve-muscle preparations were treated with hypertonic solution in which sodium gluconate was the major constituent, which substantially increases the sizes of the quanta by increasing their ACh(+) content. The Cl(-) channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) antagonized the increases in quantal size, so it seems likely that Cl(-) follows H(+) to prevent the buildup of a potential gradient across the vesicular membrane.

Vesicle size and transmitter release at the frog neuromuscular junction when quantal acetylcholine content is increased or decreased.

We investigated whether the synaptic vesicles at the neuromuscular junction change size when their acetylcholine (ACh) content is altered. The size of the miniature endplate potential (MEPP) increased 3- or 4-fold in preparations pre-treated in a hypertonic solution in which the anion was gluconate. We measured the dimensions of synaptic vesicles in such preparations and in controls. The size of the vesicles and size distribution were indistinguishable. Quanta contained about half of the usual amount of ACh in preparations stimulated in the presence of hemicholinium-3, an inhibitor of choline uptake, or in NH(4)(+), which diminishes the proton gradient for ACh uptake into the vesicles. Neither treatment changed the size of the synaptic vesicles. ACh content and vesicle size were both decreased in preparations stimulated in (-)-vesamicol, an inhibitor of ACh uptake in vesicles. Since the other inhibitors decreased ACh content by a similar amount without altering vesicle size, (-)-vesamicol may decrease vesicle size by acting on another target. We also found that a hypertonic solution in which the anion was aspartate increased quantal size similar to gluconate. Both anions have high hydration energy and a large volume. When these treatments increased quantal size the mean 20-80 % rise time of MEPPs recorded with an extracellular electrode was 170 micros. In the controls it was 97 micros. Perhaps some of the added ACh is bound within the vesicles, which slows the rise. Our major conclusion is that ACh content can change notably without any change in the size of the synaptic vesicles.