The epistemological virtues of assumptions: towards a coming of age of Boltzmann and Meinong’s objections to ‘the prejudice in favour of the actual’?

Two complementary debates of the turn of the nineteenth and twentieth century are examined here: the debate on the legitimacy of hypotheses in the natural sciences and the debate on intentionality and ‘representations without object’ in philosophy. Both are shown to rest on two core issues: the attitude of the subject and the mode of presentation chosen to display a domain of phenomena. An orientation other than the one which contributed to shape twentieth-century philosophy of science is explored through the analysis of the role given to assumptions in Boltzmann’s research strategy, where assumptions are contrasted to hypotheses, axioms, and principles, and in Meinong’s criticism of the privileged status attributed to representations in mental activities. Boltzmann’s computational style in mathematics and Meinong’s criticism of the confusion between representation and judgment give prominence to an indirect mode of presentation, adopted in a state of suspended belief which is characteristic of assumptions and which enables one to grasp objects that cannot be reached through direct representation or even analogies. The discussion shows how assumptions and the movement to fiction can be essential steps in the quest for objectivity. The conclusion restates the issues of the two debates in a contemporary perspective and shows how recent developments in philosophy of science and philosophy of language and mind can be brought together by arguing for a twofold conception of reference.     

Nicotianamine,the ‘normalizing factor’ for the auxotroph tomato mutantChloronerva; a representative of a new class of plant effectors

Summary The article surveys our knowledge of the normalizing factor, gained from its discovery a quarter of a century ago up to the present time, under the following headings: Discovery; Physiological properties; Isolation and characterization; Structure determination (Identity of the normalizing factor with nicotianamine); Chemical properties; Analysis; Synthesis; Occurrence and physiological role; Related compounds; Prospects.     

BlaB,a protein involved in the regulation of <Emphasis Type="Italic">Streptomyces cacaoi</Emphasis> β-lactamases,is a penicillin-binding protein

Streptomyces cacaoi -lactamase genes are controlled by two regulators named blaA and blaB. Whereas BlaA has been identified as a LysR-type activator, the function of BlaB is still unknown. Its primary structure is similar to that of the serine penicillin-recognizing enzymes (PREs). Indeed, the SXXK and KTG motifs are perfectly conserved in BlaB, whereas the common SXN element found in PREs is replaced by a SDG motif. Site-directed mutations were introduced in these motifs and they all disturb -lactamase regulation. A water-soluble form of BlaB was also overexpressed in the Streptomyces lividans TK24 cytoplasm and purified. To elucidate the activity of BlaB, several compounds recognized by PREs were tested. BlaB could be acylated by some of them, and it can therefore be considered as a penicillin-binding protein. BlaB is devoid of -lactamase, D-aminopeptidase, DD-carboxypeptidase or thiolesterase activity.Received 13 January 2003; received after revision 9 April 2003; accepted 11 April 2003     

Is Newton a ‘radical empiricist’ about method?

Recently, some Newton scholars have argued that Newton is an empiricist about metaphysics—that ideally, he wants to let advances in physical theory resolve either some or all metaphysical issues. But while proponents of this interpretation are using ‘metaphysics’ in a very broad sense, to include the ‘principles that enable our knowledge of natural phenomena’, attention has thus far been focused on Newton’s approach to ontological, not epistemological or methodological, issues. In this essay, I therefore consider whether Newton wants to let physical theory bear on the very ‘principles that enable our knowledge’. By examining two kinds of argument in the Principia, I contend that Newton can be considered a methodological empiricist in a substantial respect. I also argue, however, that he cannot be a ‘radical empiricist’—that he does not and cannot convert all methodological issues into empirical issues.     

‘The happy thought of a single man’: On the legendary beginnings of a style of reasoning

In this paper I direct attention to one feature of Hacking’s recent work on styles of reasoning and argue that this feature is of far greater philosophical significance than Hacking’s limited discussion of this suggests. The feature in question is his use of ‘legendary beginnings’ in setting out a given style, viz. the method of introducing a style of reasoning by recounting a popular and quasi-mythical narrative that ties the crystallisation of that style to a particular person in a particular place and at a particular time. Whilst Hacking both deploys and discusses this method, his comments suggest that this is primarily a stylistic device employed for reasons of expedience. In contrast, it is argued here that recounting the legendary origins of a style of reasoning affords a distinctive way of vindicating that style, a vindication from within the style itself.     

The urokinase receptor: a ligand or a receptor? Story of a sociable molecule

In this last decade, the structure and functions of the receptor for the urokinase-type plasminogen activator have been extensively studied and characterized. This interesting receptor plays a key role in cell adhesion, migration and proliferation. It was identified 20 years ago as the specific cell-surface molecule that could bind and concentrate urokinase on the cell membrane, thus initiating the proteolytic cascade promoted by the activation of plasminogen. The identification of new extracellular ligands, such as vitronectin, and of cell-surface interactors, such as integrins and fMet-Leu-Phe receptors, shed new light on its possible roles, totally independent of the enzymatic properties of its ligand. uPAR ligands and interactors and the functional consequences of the multiple binding capability of this intriguing receptor are reviewed here. Received 19 September 2005; received after revision 4 December 2005; accepted 6 December 2005     

<Emphasis Type="Italic">Trichomonas vaginalis</Emphasis> degrades nitric oxide and expresses a flavorubredoxin-like protein: a new pathogenic mechanism?

Besides possessing many physiological roles, nitric oxide (NO) produced by the immune system in infectious diseases has antimicrobial effects. Trichomoniasis, the most widespread non-viral sexually transmitted disease caused by the microaerophilic protist Trichomonas vaginalis, often evolves into a chronic infection, with the parasite able to survive in the microaerobic, NO-enriched vaginal environment. We relate this property to the finding that T. vaginalis degrades NO under anaerobic conditions, as assessed amperometrically. This activity, which is maximal (133 ± 41 nmol NO/10⁸ cells per minute at 20°C) at low NO concentrations ( 1.2 M), was found to be: (i) NADH dependent, (ii) cyanide insensitive and (iii) inhibited by O₂. These features are consistent with those of the Escherichia coli A-type flavoprotein (ATF), recently discovered to be endowed with NO reductase activity. Using antibodies against the ATF from E. coli, a protein band was immunodetected in the parasite grown in a standard medium. If confirmed, the expression of an ATF in eukaryotes suggests that the genes coding for ATFs were transferred during evolution from anaerobic Prokarya to pathogenic protists, to increase their fitness for the microaerobic, parasitic life style. Thus the demonstration of an ATF in T. vaginalis would appear relevant to both pathology and evolutionary biology. Interestingly, genomic analysis has recently demonstrated that Giardia intestinalis and other pathogenic protists have genes coding for ATFs.Received 1 November 2003; received after revision 5 January 2004; accepted 13 January 2004     

The Predictive Power of Survey‐Based Exchange Rate Forecasts: Is there a Role for Dispersion?

Previous research has shown that the consensus of individual exchange rate forecasts performs no better than many commonly used forecasting models in predicting future exchange rates. Studies on equity and bond markets have explored the effects of dispersion in forecasts on the predictive power of forecasts; however, no earlier paper has investigated such effects in the context of the foreign exchange market. This study explores the role of consensus forecast dispersion as a factor leading to bias and anchoring in exchange rate forecasts. Our analysis of five currency pairs reveals that consensus forecasts mostly appear to be unbiased predictors of exchange rates in the long run, but most are unable to pass tests for short‐run unbiasedness. In three of the five currencies examined it appears that forecasters should take greater account of reported forecast dispersion. Copyright © 2015 John Wiley & Sons, Ltd.     

Crystal structure of <Emphasis Type="Italic">Enterobacter cloacae</Emphasis> 908R class C β-lactamase bound to iodo-acetamido-phenyl boronic acid,a transition-state analogue

The structures of the class C -lactamase from Enterobacter cloacae 908R alone and in complex with a boronic acid transition-state analogue were determined by X-ray crystallography at 2.1 and 2.3 Å, respectively. The structure of the enzyme resembles those of other class C -lactamases. The structure of the complex with the transition-state analogue, iodo-acetamido-phenyl boronic acid, shows that the inhibitor is covalently bound to the active-site serine (Ser64). Binding of the inhibitor within the active site is compared with previously determined structures of complexes with other class C enzymes. The structure of the boronic acid adduct indicates ways to improve the affinity of this class of inhibitors. This structure of 908R class C -lactamase in complex with a transition-state analogue provides further insights into the mechanism of action of these hydrolases.Received 16 May 2003; accepted 4 June 2003     

Does a lot help a lot? Forecasting stock returns with pooling strategies in a data‐rich environment

A variety of recent studies provide a skeptical view on the predictability of stock returns. Empirical evidence shows that most prediction models suffer from a loss of information, model uncertainty, and structural instability by relying on low‐dimensional information sets. In this study, we evaluate the predictive ability of various lately refined forecasting strategies, which handle these issues by incorporating information from many potential predictor variables simultaneously. We investigate whether forecasting strategies that (i) combine information and (ii) combine individual forecasts are useful to predict US stock returns, that is, the market excess return, size, value, and the momentum premium. Our results show that methods combining information have remarkable in‐sample predictive ability. However, the out‐of‐sample performance suffers from highly volatile forecast errors. Forecast combinations face a better bias–efficiency trade‐off, yielding a consistently superior forecast performance for the market excess return and the size premium even after the 1970s.     

The story of ‘Scientist: The Story of a Word’

This examination of an important paper by Sydney Ross is the first in a projected series of occasional reflections on ‘Annals of Science Classic Papers’ that have had enduring utility within the field of history of science and beyond. First the messages of the paper are examined, some well known but others, particularly Ross's own contemporary concerns about the use of the word ‘scientist’, less so. The varied uses made of the paper by scholars are then traced before Ross's biography is examined in order to try to understand how a figure professionally marginal to the field of history of science came to write such a significant piece. Ross’s interest in the topic appears to have been informed by a romantically tinged scientific progressivism and a deep concern with the importance of linguistic precision in science and in public affairs. The inspirations of the author and the interests of his audience have been only partially aligned, but the paper's insights remain of broad historical interest and have wider ramifications since the denotation ‘scientist’ and its proper application are much debated today in contests over the authority of science.     

Goitrin — a nitrosatable constituent of plant foodstuffs

Summary N-nitrosamides are known as direct-acting carcinogens at the site of their formation; they do not need any metabolic activation in vivo. The conditions leading to their formation in the stomach, and also their genotoxicity, have been thoroughly studied with some model compounds^{1, 2}. Several reports link this type of compound to the induction of gastric cancer in human^{3, 4}. However, only limited data are presently available about possible precursors of N-nitrosamides in foods. In the present study we found that goitrin — a naturally occurring compound in cruciferous vegetables and rape—could be easily nitrosated by treatment with nitrite under stomach conditions, yielding with loss of sulfur the N-nitroso-oxazolidone4 (fig.). This product has a mutagenicity pattern and potency similar to that of N-nitroso-N-methyl-N-nitroguanidine (MNNG) in the Ames Salmonella/mammalian microsome test.     

Occurrence of β-chitin in the cuticle of a Pentastomid Raillietiella gowrii

Summary The purified chitin from the cuticle of a pentastomid was examined by X-ray method. The X-ray photograph discloses that the chitin in question is of -type. Since the arthropod cuticle contains -chitin, it is suggested that Pentastomida may be considered an independent phylum.Thanks are due to Prof. Dr. G. Sundara Rajulu for guidance and encouragement.     

Sirenids: a family of polyploid urodeles?

Riassunto I tre Sirenidi viventi hanno 46, 52 e 64 cromosomi; il corredo diS. lacertina sembra tetraploide (4n=52). Viene fatta l'ipotesi che anche i corredi delle altre due specie derivino per (allo-)poliploidia da corredi a minor numero cromosomico, come si ritrovano nelle famiglie superiori dell'Ordine.

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Research carried out through a contribution from the C.N.R.     

Sterols of the pine processionary caterpillar; effects of diflubenzuron (Dimilin®)

Summary Cholesterol in pine processionary caterpillars (Thaumetopoea pityocampa Schiff.; Lepidoptera is produced mainly from -sitosterol present in their food (pine needles); it can also be synthesized from acetic acid. This synthesis is stimulated by the insecticide Dimilin but inhibited by the antibiotic tetracycline.This work has been partly realized at the Institut de Chimie des Substances naturelles of CNRS. Thanks to the amiability of Mr Michel Barbier.     

Biosynthesis of a monoene and a conjugated diene sex pheromone component of the lightbrown apple moth by Δ11 desaturation

Summary Fatty acyl moieties present in the female sex pheromone gland of the lightbrown apple moth,Epiphyas postvittana, include the analogues of the two sex pheromone components, (E)-11-tetradecenyl acetate and (E,E)-9,11-tetradecadienyl acetate. Application of deuterium-labelled fatty acids followed by analysis by gas chromatographymass spectrometry showed that biosynthesis of the two pheromone components involved initial 11-desaturation of myristic and palmitic acids respectively.     

Direct thrombin inhibitors – a survey of recent developments

Thrombin is a plasma serine protease that plays a key role in coagulation and hemostasis but also in thromboembolic diseases. Direct thrombin inhibitors could, therefore, be beneficial for future anticoagulant therapy in the prophylaxis of venous and arterial thrombosis as well as myocardial infarction. However, development of direct thrombin inhibitors has brought researchers more heartache than success. The most recent setback came this year when AstraZeneca withdrew Ximelagatran, the first orally bioavailable direct thrombin inhibitor that had received regulatory approval (France, 2003), after reports of serious hepatoxicity in a fraction of patients. This review describes the status of direct thrombin inhibitors, focusing on drug candidates that are at present in clinical trials. In addition, some more recent research strategies in the design of novel direct thrombin inhibitors are discussed, which may very well contribute to future developments of potent anticoagulants. Received 9 May 2006; received after revision 15 June 2006; accepted 23 August 2006     

Hoplonemertine worms—a new source of pyridine neurotoxins

Summary Two pyridine bases were isolated from the marine hoplonemertineAmphiporus angulatus (Fabricius) and identified by mass and PMR-spectroscopy as 2,3-bipyridyl and 3,2; 3,2; 4,3'-tetrapyridyl (Nemertelline). Nemertelline, the first tetrapyridyl natural product to be reported, shows a structural resemblance to the tobacco constituent nicotelline. The crustacean toxicity of 2,3-bipyridyl is very similar to that of nicotine, but its mammalian toxicity is negligible.We thank DoctorsN. Meinkoth andN. Riser for collecting specimens, Dr.F. Kuffner for providing the nicotelline sample, Dr.C. Westerman for recording initial PMR-spectra, and Dr.R. King for furnishing the computer simulation program and recording the high resolution mass spectra, and Mr.J. Babashak for use of the Kontes densitometer. This research was supported by an NIH-GRS grant and by the Veterans Administration (No. MRIS-9416).     

Synthesis of a pregnancy-associatedα-macroglobulin by human leucocytes

Résumé Le sang des femmes enceintes peut contenir plusierus protéines sériques uniques en leur genre. Celle qui se présente le plus souvent est une -globuline de grand poids moléculaire. Un test in vitro utilisant l'incorporation de¹⁴C-glutamine ou³H-leucine dans la glycoprotéine a montré que celle-ci peut être synthétisée par des leucocytes.

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We thank Dr.J. E. O'Grady and Dr.A. Shephard for obtaining the blood samples. This work was supported by a grant from the Scottish Home and Health Department.     

The “Unknown Heritage”: trace of a forgotten locus of mathematical sophistication

The “unknown heritage” is the name usually given to a problem type in whose archetype a father leaves to his first son 1 monetary unit and \({\frac{1}{n}}\) (n usually being 7 or 10) of what remains, to the second 2 units and \({\frac{1}{n}}\) of what remains, and so on. In the end, all sons get the same, and nothing remains. The earliest known occurrence is in Fibonacci’s Liber abbaci, which also contains a number of much more sophisticated versions, together with a partial algebraic solution for one of these and rules for all which do not follow from his algebraic calculation. The next time the problem turns up is in Planudes’s late thirteenth century Calculus according to the Indians, Called the Great. After that the simple problem type turns up regularly in Provençal, Italian and Byzantine sources. It seems never to appear in Arabic or Indian writings, although two Arabic texts (one from c. 1190) contain more regular problems where the number of shares is given; they are clearly derived from the type known from European and Byzantine works, not its source. The sophisticated versions turn up again in Barthélemy de Romans’ Compendy de la praticque des nombres (c. 1467) and, apparently inspired from there, in the appendix to Nicolas Chuquet’s Triparty (1484). Apart from a single trace in Cardano’s Practica arithmetice et mensurandi singularis, the sophisticated versions never surface again, but the simple version spreads for a while to German practical arithmetic and, more persistently, to French polite recreational mathematics. Close examination of the texts shows that Barthélemy cannot have drawn his familiarity with the sophisticated rules from Fibonacci. It also suggests that the simple version is originally either a classical, strictly Greek or Hellenistic, or a medieval Byzantine invention; and that the sophisticated versions must have been developed before Fibonacci within an environment (located in Byzantium, Provence, or possibly in Sicily?) of which all direct traces has been lost, but whose mathematical level must have been quite advanced.