Structural features of prions explored by sequence analysis. II. A PrP<Superscript>Sc</Superscript> model

Prion diseases are neurodegenerative disorders associated with a conformational conversion of the prion PrP protein, in which the β-strand content increases and that of the α helix decreases. However, the structure of the pathogenous form PrP^Sc, occurring after conformational conversion of the normal cellular form PrP^C, is not yet known. From sequence analysis, we have previously proposed that helix H2 of the prion PrP^C structure might be a key region for this structural conversion. More recently, we identified the TATA box-binding protein fold as a putative scaffold that may locally satisfy the predicted secondary-structure organisation of PrP^Sc. In the present analysis, we detail the schematic construction of PrP^Sc monomeric and dimeric models, based on this hypothesis. These models are globally compatible with available data and therefore may provide further insights into the structurally and functionally elusive PrP protein. Some comments are also devoted to a comparison of the yeast Ure2p prion and animal prions. Received 29 July 2002; received after revision 24 October 2002; accepted 24 October 2002 RID="*" ID="*"Corresponding author.     

Synthesis of ovulation-inhibiting compounds; structure-activity relationship.

We describe the synthesis of some new derivatives of benzo(4, 5)cyclohepta(1, 2-b)thiophene which inhibit ovulation and the secretion of luteinizing hormone (LH) in the rat. We also describe the relationship between the structure and activity of these compounds.     

Leibniz and the post-Copernican universe. Koyré revisited

This paper employs the revised conception of Leibniz emerging from recent research to reassess critically the ‘radical spiritual revolution’ which, according to Alexandre Koyré’s landmark book, From the closed world to the infinite universe (1957) was precipitated in the seventeenth century by the revolutions in physics, astronomy, and cosmology. While conceding that the cosmological revolution necessitated a reassessment of the place of value-concepts within cosmology, it argues that this reassessment did not entail a spiritual revolution of the kind assumed by Koyré, in which ‘value-concepts, such as perfection, harmony, meaning and aim’ were shed from the conception of the structure of the universe altogether. On the contrary, thanks to his pioneering intuition of the distinction between physical and metaphysical levels of explanation, Leibniz saw with great clarity that a scientific explanation of the universe which rejected the ‘closed world’ typical of Aristotelian cosmology did not necessarily require the abandonment of key metaphysical doctrines underlying the Aristotelian conception of the universe. Indeed the canon of value-concepts mentioned by Koyré—meaning, aim, perfection and harmony—reads like a list of the most important concepts underlying the Leibnizian conception of the metaphysical structure of the universe. Moreover, Leibniz’s universe, far from being a universe without God—because, as Clarke insinuated, it does not need intervention from God—is a universe which in its deepest ontological fabric is interwoven with the presence of God.     

Why was M. S. Tswett’s chromatographic adsorption analysis rejected?

The present paper claims that M. S. Tswett’s chromatographic adsorption analysis, which today is a ubiquitous and instrumentally sophisticated chemical technique, was either ignored or outright rejected by chemists and botanists in the first three decades of the twentieth century because it did not make sense in terms of accepted chemical theory or practice. Evidence for this claim is culled from consideration of the botanical and chemical context of Tswett’s technique as well as an analysis of the protracted debate over Tswett’s chromatographic analysis of chlorophyll between him and Leon Marchlewski, a noted chlorophyll chemist of the period. In this way, the paper expands and amends what it calls the ‘textbook story’ of the early history of chromatography, examples of which may be found in historical notes in many textbooks of chemical instrumental analysis and numerous short articles in chemistry journals. The paper also provides an accessible introduction to the early history of chromatography for historians of science likely to know little or nothing about it.     

On the verge of <Emphasis Type="Italic">Umdeutung</Emphasis> in Minnesota: Van Vleck and the correspondence principle. Part one

In October 1924, The Physical Review, a relatively minor journal at the time, published a remarkable two-part paper by John H. Van Vleck, working in virtual isolation at the University of Minnesota. Using Bohr’s correspondence principle and Einstein’s quantum theory of radiation along with advanced techniques from classical mechanics, Van Vleck showed that quantum formulae for emission, absorption, and dispersion of radiation merge with their classical counterparts in the limit of high quantum numbers. For modern readers Van Vleck’s paper is much easier to follow than the famous paper by Kramers and Heisenberg on dispersion theory, which covers similar terrain and is widely credited to have led directly to Heisenberg’s Umdeutung paper. This makes Van Vleck’s paper extremely valuable for the reconstruction of the genesis of matrix mechanics. It also makes it tempting to ask why Van Vleck did not take the next step and develop matrix mechanics himself. This paper was written as part of a joint project in the history of quantum physics of the Max Planck Institut für Wissenschaftsgeschichte and the Fritz-Haber-Institut in Berlin.     

Lymphatic metastasis of tumour; persistent transport of cells.

A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumour cells was continuous over periods up to 90 min and ranged from 10(2)-10(5) cells/min.     

On the verge of <Emphasis Type="Italic">Umdeutung</Emphasis> in Minnesota: Van Vleck and the correspondence principle. Part two

This is the second installment of a two-part paper on developments in quantum dispersion theory leading up to Heisenberg’s Umdeutung paper. In telling this story, we have taken a 1924 paper by John H. Van Vleck in The Physical Review as our main guide. In this second part we present the detailed derivations on which our narrative in the first part rests. The central result that we derive is the Kramers dispersion formula, which played a key role in the thinking that led to Heisenberg’s Umdeutung paper. We derive classical formulae for the dispersion, emission, and absorption of radiation and use Bohr’s correspondence principle to construct their quantum counterparts both for the special case of a charged harmonic oscillator (Sect. 5) and for arbitrary non-degenerate multiply-periodic systems (Sect. 6). We then rederive these results in modern quantum mechanics (Sect. 7). This paper was written as part of a joint project in the history of quantum physics of the Max Planck Institut für Wissenschaftsgeschichte and the Fritz-Haber-Institut in Berlin. The authors gratefully acknowledge support from the Max Planck Institute for History of Science. The research of Anthony Duncan is supported in part by the National Science Foundation under grant PHY-0554660.     

The electrons of the dinosaurs and the center of the Earth: comments on D.D. Turner’s ‘The past vs. the tiny: historical science and the abductive arguments for realism’

Turner [The past vs. the tiny: Historical science and the abductive arguments for realism. Studies in History and Philosophy of Science 35A (2004) 1] claims that the arguments in favor of realism do not support with the same force both classes of realism, since they supply stronger reasons for experimental realism than for historical realism. I would like to make two comments, which should be seen as amplifications inspired by his proposal, rather than as a criticism. First, it is important to highlight that Turner’s distinction between ‘tiny’ and ‘past unobservables’ is neither excluding nor exhaustive. Second, even if we agreed with everything that Turner says regarding the arguments for realism and their relative weight in order to justify the experimental or historical version, there is an aspect that Turner does not consider and that renders historical realism less problematic than experimental realism.     

Newton’s substance monism, distant action, and the nature of Newton’s empiricism: discussion of H. Kochiras “Gravity and Newton’s substance counting problem”

This paper is a critical response to Hylarie Kochiras’ “Gravity and Newton’s substance counting problem,” Studies in History and Philosophy of Science 40 (2009) 267-280. First, the paper argues that Kochiras conflates substances and beings; it proceeds to show that Newton is a substance monist. The paper argues that on methodological grounds Newton has adequate resources to respond to the metaphysical problems diagnosed by Kochiras. Second, the paper argues against the claim that Newton is committed to two speculative doctrines attributed to him by Kochiras and earlier Andrew Janiak: i) the passivity of matter and ii) the principle of local causation. Third, the paper argues that while Kochiras’ (and Janiak’s) arguments about Newton’s metaphysical commitments are mistaken, it qualifies the characterization of Newton as an extreme empiricist as defended by Howard Stein and Rob DiSalle. In particular, the paper shows that Newton’s empiricism was an intellectual and developmental achievement that built on non trivial speculative commitments about the nature of matter and space.     

Epifluorescence microscopy of<Emphasis Type="Italic">Anabaena</Emphasis> sp.: Nucleoid configurations and evidence for inclusion-associated DNA

Vital staining of the nucleoid inAnabaena sp. PCC7118 was performed using the double stranded DNA-specific fluorochrome DAPI. In the unicellular mutant, the central epifluorescent zone had a dense skein configuration, while in the filamentous parent strain protrusions, lobes, and distinct isolated elements of the nucleoid were visible. Both variants contrasted with the mainly peripheral, partitioned structure typical of plastids and prochlorophytes. Blue-white emittance from the DNA-DAPI complex was maximum in dividing cells, suggesting that DNA configuration is linked to the cell cycle events. In stationary cultures, epifluorescent cell inclusions were conspicuous: based on this observation, we argue that DNA is associated with carboxysomes in situ.