On the structure of Carnot's theory of heat

A simple connection is pointed out between the theory of heat formulated in Sadi Carnot's: Réflexions sur la puissance motrice du feu (1824) and the later Kelvin-Clausius thermodynamics. In both theories two well-defined quantities, a heat function and a work function, exist and can be calculated by integrating along a reversible path. In thermodynamics the work function (energy) is conserved, whereas the heat function (entropy) increases by irreversible processes. In Carnot's theory the heat function is conserved, whereas the work function decreases, so that in this theory the irreversible process is characterized by a loss of work.     

The use of the information-theoretic entropy in thermodynamics

When considering controversial thermodynamic scenarios such as Maxwell's demon, it is often necessary to consider probabilistic mixtures of macrostates. This raises the question of how, if at all, to assign entropy to them. The information-theoretic entropy is often used in such cases; however, no general proof of the soundness of doing so has been given, and indeed some arguments against doing so have been presented. We offer a general proof of the applicability of the information-theoretic entropy to probabilistic mixtures of macrostates that is based upon a probabilistic generalisation of the Kelvin statement of the second law. We defend the latter and make clear the other assumptions on which our main result depends. We also briefly discuss the interpretation of our result.     

The discovery of nature's biosynthetic pathways

Uro'gen-III is a key intermediate on the biosynthetic pathways to the vitally important natural pigments haem, chlorophyll and the cytochromes. How the unexpected structure of uro'gen-III is synthesized by living things has long been a major puzzle. Studies based on 13C-labelling are described which show a) that a single intramolecular rearrangement occurs and b) that this step occurs after the open-chain linear tetrapyrrole system has been built. A second study involves stereospecific labelling with deuterium and tritium to elucidate the absolute stereochemistry of the enzymic reaction sequence which produces the vinyl groups of haem. The third and last section of the lecture is focussed on the biosynthetic intermediates lying between uro'gen-III and cobyrinic acid on the pathway to vitamin B12. An octacarboxylic isobacteriochlorin is isolated from a vitamin B12-producing organism and this is shown to be identical with sirohydrochlorin, previously obtained by Kamin and Siegel as the metal-free prosthetic group of certain sulphite-reducing bacteria. The structure and absolute stereochemistry of sirohydrochlorin are studied and comment is made on the evolutionary interest of these findings.     

The discovery of nature's biosynthetic pathways

Summary Uro'gen-III is a key intermediate on the biosynthetic pathways to the vitally important natural pigments haem, chlorophyll and the cytochromes. How the unexpected structure of uro'gen-III is synthesized by living things has long been a major puzzle. Studies based on¹³C-labelling are described which show a) that a single intramolecular rearrangement occurs and b) that this step occurs after the open-chain linear tetrapyrrole system has been built.A second study involves stereospecific labelling with deuterium and tritium to elucidate the absolute stereochemistry of the enzymic reaction sequence which produces the vinyl groups of haem. The third and last section of the lecture is focussed on the biosynthetic intermediates lying between uro'gen-III and cobyrinic acid on the pathway to vitamin B₁₂. An octacarboxylic isobacteriochlorin is isolated from a vitamin B₁₂-producing organism and this is shown to be identical with sirohydrochlorin, previously obtained by Kamin and Siegel as the metal-free prosthetic group of certain sulphite-reducing bacteria. The structure and absolute stereochemistry of sirohydrochlorin are studied and comment is made on the evolutionary interest of these findings.This account is a slightly extended version of the Paul Karrer Lecture given on July 5th, 1977 at the University of Zürich.     

The discovery of antidepressants: A winding path

Summary Modern treatment of mental depression started with the availability of monoamine oxidase (MAO) inhibitors and tricyclic antidepressants. These drugs also contributed to the early development of psychopharmacology. Attempts to improve the anti-tuberculous action of the hydrazine derivative isoniazid by developing derivatives thereof led to the synthesis of iproniazid. Its introduction as the first modern antidepressant was based on three unexpected actions of the drug: MAO-inhibition, reversal of reserpine-induced sedation, and the presence of psychostimulation as a clinical side effect in man. However, the initial success of iproniazid and other MAO inhibitors, hydrazides and non-hydrazides, was curtailed by the occurrence of undesirable side effects such as potentiation of the blood-pressure elevating action of food amines. The tricyclic antidepressants were a development of the class of antihistamines, one of which, chlorpromazine, showed neuroleptic activity. A congener of this compound, imipramine, was discovered by clinical observation to have unexpected antidepressant effects. The clinical success of this drug (which is still in use) led to the development of a successful series of other tricyclic and non-tricyclic antidepressants. Progress in the elucidation of possible mechanisms of the action of the tricyclic compounds has helped this development. Recent advances in basic research have also induced a revival of MAO-inhibitors since, due to the discovery of MAO-subtypes, inhibitors with higher specificity and fewer undesirable side effects are now available.     

The discovery of antidepressants: a winding path

Modern treatment of mental depression started with the availability of monoamine oxidase (MAO) inhibitors and tricyclic antidepressants. These drugs also contributed to the early development of psychopharmacology. Attempts to improve the anti-tuberculous action of the hydrazine derivative isoniazid by developing derivatives thereof led to the synthesis of iproniazid. Its introduction as the first modern antidepressant was based on three unexpected actions of the drug: MAO-inhibition, 'reversal' of reserpine-induced sedation, and the presence of psychostimulation as a clinical side effect in man. However, the initial success of iproniazid and other MAO inhibitors, hydrazides and non-hydrazides, was curtailed by the occurrence of undesirable side effects such as potentiation of the blood-pressure elevating action of food amines. The tricyclic antidepressants were a development of the class of antihistamines, one of which, chlorpromazine, showed neuroleptic activity. A congener of this compound, imipramine, was discovered by clinical observation to have unexpected antidepressant effects. The clinical success of this drug (which is still in use) led to the development of a successful series of other tricyclic and non-tricyclic antidepressants. Progress in the elucidation of possible mechanisms of the action of the tricyclic compounds has helped this development. Recent advances in basic research have also induced a revival of MAO-inhibitors since, due to the discovery of MAO-subtypes, inhibitors with higher specificity and fewer undesirable side effects are now available.     

The pre-history of hemocyanin. The discovery of copper in the blood of molluscs

The presence of copper in molluscs was discovered in 1833 by Bartolomeo Bizio, a Venetian chemist, who found copper in marine gastropods of the family Muricidae during his studies on the purple dye he had isolated from these animals. Bizio was so surprised by this finding that he extended his analysis to several other invertebrate species in which he identified the metal.     

Weinberg's proof of the spin-statistics theorem

The aim of this paper is to offer a conceptual analysis of Weinberg's proof of the spin-statistics theorem by comparing it with Pauli's original proof and with the subsequent textbook tradition, which typically resorts to the dichotomy positive energy for half-integral spin particles/microcausality for integral-spin particles. In contrast to this tradition, Weinberg's proof does not directly invoke the positivity of the energy, but derives the theorem from the single relativistic requirement of microcausality. This seemingly innocuous difference marks an important change in the conceptual basis of quantum physics. Its historical, theoretical, and conceptual roots are here reconstructed. The link between Weinberg's proof and Pauli's original is highlighted: Weinberg's proof turns out to do justice to Pauli's anti-Dirac lines of thought. The work of Furry and Oppenheimer is also surveyed as a “third way” between the textbook tradition established by Pauli and Weinberg's approach.     

Biogenesis of mitochondrial porin: the import pathway.

We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavable 'signal' sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein which is characterized by its extreme protease resistance.     

The preprotein translocase of the outer mitochondrial membrane: receptors and a general import pore

Cytosol-synthesized preproteins destined for the mitochondria are transported across the outer membrane by the translocase of the mitochondrial outer membrane (TOM complex). This dynamic transport machinery can be divided into receptors that recognize preprotein targeting signals and components of the general import pore complex that mediate preprotein transport across the outer membrane. This review focuses on recent studies dealing with the central questions regarding the pore-forming subunits, and architecture and gating of the translocation channel of the outer membrane.     

Historical development of the Chinese remainder theorem

Communicated by C. Truesdell