Retention of<Emphasis Type="Italic">B. burgdorferi</Emphasis> pathogenicity and infectivity after multiple passages in a co-culture system

In vitro cultivation ofB. burgdorferi in BSK medium results in the loss of infectivity and pathogenicity after repeated passages. To prevent this loss, a feeder layer of tibio-tarsal joint tissue derived from newborn LEW/N rats was grown on Cytodex 3 microcarriers in ESG (formerly BSKE), a novel medium developed to support the growth of both the feeder layer andB. burgdorferi. A new pathogenic isolate (FNJ) and a high passage, non-pathogenic strain (TNJ) grew well in this co-culture system with high yields of viable organism. FNJ caused no growth inhibition or visible damage to the cells in the feeder layer. FNJ remained arthritogenic for newborn LEW/N rats after 22 passages in the co-culture system, but lost its arthritogenicity after 7 passages when cultured in BSK medium. This borrelia-mammalian tissue co-culture technique presents an experimental system to study the long term interactions ofB. burgdorferi with the infected host tissues in vitro, as well as facilitate diagnostic tests and vaccine development.     

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.     

Galileo as a ‘bad theologian’: a formative myth about Galileo’s trial

For 150 years after Galileo’s condemnation in 1633, there were many references to the trial, but no sustained, heated or polarized discussions. Then came the thesis that Galileo was condemned not for being a good astronomer but for being a bad theologian (using Scripture to support astronomical hypotheses); it began in 1784–1785 with an apology of the Inquisition by Mallet du Pan in the Mercure de France and the printing in Tiraboschi’s Storia della letteratura italiana of an apocryphal letter attributed to Galileo but forged by Onorato Gaetani. This thesis is not only untenable and false but inverts and subverts the truth; it proved to be long-lasting and widely accepted; so it may be labeled a myth. It was held by such writers as Bergier; Bergier; B; Feller; Cooper; Purcell; Marini; Reumont; Madden and Duhem. Afterwards, it was generally abandoned, its death knell being pope John Paul II’s speeches in 1979–1992. The myth seems to have acted as a catalyst insofar as its creation encouraged the proliferation of pro-clerical accounts and the articulation of pro-Galilean ones, thus making the discussion of Galileo’s trial the cause célèbre it is today.     

Thought styles and paradigms—a comparative study of Ludwik Fleck and Thomas S. Kuhn

At first glance there seem to be many similarities between Thomas S. Kuhn’s and Ludwik Fleck’s accounts of the development of scientific knowledge. Notably, both pay attention to the role played by the scientific community in the development of scientific knowledge. But putting first impressions aside, one can criticise some philosophers for being too hasty in their attempt to find supposed similarities in the works of the two men. Having acknowledged that Fleck anticipated some of Kuhn’s later theses, there seems to be a temptation in more recent research to equate both theories in important respects. Because of this approach, one has to deal with the problem of comparing the most notable technical terms of both philosophers, namely “thought style” and “paradigm”.This paper aims at a more thorough comparison between Ludwik Fleck’s concept of thought style and Thomas Kuhn’s concept of paradigm. Although some philosophers suggest that these two concepts are essentially equal in content, a closer examination reveals that this is not the case. This thesis of inequality will be defended in detail, also taking into account some of the alleged similarities which may be responsible for losing sight of the differences between these theories.     

Biochemical studies of pigments from a pathogenic fungus;Microsporum cookei VI. Formation of a xanthomegnin-bypass to the mitochondrial electron transport system

Summary Enzymatic redox response of xanthomegnin was studied by means of rat liver mitochondria and the possibility of a xanthomegnin-bypass to mitochondrial electron transport system is suggested.     

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.     

Decomposition; a strategy for judgemental forecasting

This paper reports the results of studies concerning the accuracy and efficiency of time-series extrapolation decisions made with the assistance of an interactive graphical tool called GRAFFECT. The tool facilitates the decomposition of the extrapolation task by permitting the serial decomposition of the cue data as the task proceeds. GRAFFECT uses an interactive graphical interface controlled substantially with the use of a mouse. The extrapolation task is divided into the following: (1) trend modelling and extrapolation, (2) seasonal pattern modelling, and (3) extrapolation from the noise residual series. As each component is modelled its effect is stored and the information is washed out of the cue series. The ultimate forecast is produced by automatic recomposition of the judgementally determined components. The results show a significant improvement in forecast accuracy over unaided judgment, resulting in a subjective extrapolation that betters deseasonalized single exponential smoothing.     

Hypoprolinemia in parkinsonism; a case report

Zusammenfassung Im Vergleich zu einer Kontrollgruppe zeigten Aminosäurenanalysen im Plasma eines Patienten mit Parkinsonismus eine starke und isolierte Reduktion vonl-Prolin.

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This study was supported by Deutsche Forschungsgemeinschaft.     

Direction‐of‐change forecasting using a volatility‐based recurrent neural network

This paper investigates the profitability of a trading strategy, based on recurrent neural networks, that attempts to predict the direction‐of‐change of the market in the case of the NASDAQ composite index. The sample extends over the period 8 February 1971 to 7 April 1998, while the sub‐period 8 April 1998 to 5 February 2002 has been reserved for out‐of‐sample testing purposes. We demonstrate that the incorporation in the trading rule of estimates of the conditional volatility changes strongly enhances its profitability, after the inclusion of transaction costs, during bear market periods. This improvement is being measured with respect to a nested model that does not include the volatility variable as well as to a buy‐and‐hold strategy. We suggest that our findings can be justified by invoking either the ‘volatility feedback’ theory or the existence of portfolio insurance schemes in the equity markets. Our results are also consistent with the view that volatility dependence produces sign dependence. Copyright © 2008 John Wiley & Sons, Ltd.     

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.