Serotype-independent pneumococcal vaccines

Streptococcus pneumoniae remains an important cause of disease with high mortality and morbidity, especially in children and in the elderly. The widespread use of the polysaccharide conjugate vaccines in some countries has led to a significant decrease in invasive disease caused by vaccine serotypes, but an increase in disease caused by non-vaccine serotypes has impacted on the overall efficacy of these vaccines on pneumococcal disease. The obvious solution to overcome such shortcomings would be the development of new formulations that provide serotype-independent immunity. This review focuses on the most promising approaches, including protein antigens, whole cell pneumococcal vaccines, and recombinant bacteria expressing pneumococcal antigens. The protective capacity of these vaccine candidates against the different stages of pneumococcal infection, including colonization, mucosal disease, and invasive disease in animal models is reviewed. Some of the human trials that have already been performed or that are currently ongoing are presented. Finally, the feasibility and the possible shortcomings of these candidates in relation to an ideal vaccine against pneumococcal infections are discussed.     

Inventing paradigms,monopoly, methodology,and mythology at ‘Chicago’: Nutter,Stigler, and Milton Friedman

This paper aims to contribute to a better understanding of the formation of the so-called Chicago-school of economics; it does so by focusing on (i) previously unpublished correspondence between George Stigler and Thomas Kuhn as well as (ii) Warren Nutter’s The Extent of Enterprise Monopoly in the United States, 1899–1939. Nutter’s book started out as a (1949) doctoral dissertation at The University of Chicago, part of Aaron Director’s Free Market Study. Besides Director, O.H. Brownlee and Milton Friedman were closely involved with supervising it. It was published by The University of Chicago Press in 1951. The book was explicitly understood as belonging to the “Chicago School” (Dow & Abernathy, 1963). But by the time of Reder’s well known (1982) review paper Nutter does not figure at all. I argue that the Stigler-Kuhn correspondence helps us better understand why Nutter disappeared from sight. More important, by contrasting the work of Nutter with that of Harberger, the episode reveals how Milton Friedman’s methodological statements became the rhetoric for a paradigm that was committed to a very different approach than the one advocated by Nutter or Friedman.     

How to make a university history of science museum: Lessons from Leeds

The historic scientific collections of well-established University Museums—the Whipple at Cambridge and the Museum of the History of Science at Oxford, for example—have long served in university teaching and as objects of research for historians. But what is involved in starting such a museum from scratch? This paper offers some reflections based on recent experiences at the University of Leeds. In a relatively short period, the Leeds project has grown from a small volunteer initiative, aimed at salvaging disparate scientific collections from all over the campus, to a centrally supported and long-term scheme to provide collections care, exhibitions, and public events, as well as material for teaching and research within history and philosophy of science. Recent work undertaken on a range of Leeds objects and collections, including a camera reportedly used to take the first X-ray diffraction photographs of DNA in the 1930s and the Mark 1 prototype of the MONIAC (Monetary National Income Automatic Computer), built and designed at Leeds in 1949 to model the flow of money through the economy, highlights the national and international significance of the University’s scientific heritage as well as the project’s ambition of providing students with on-going collections care responsibilities and object-research experience. Sketching possible futures for the Leeds project, the paper considers challenges confronting the heritage sector more broadly, and how those involved with historic scientific collections can make use of new opportunities for teaching, research, and public engagement.     

Amino acid and allozyme frequency changes in overwinteringChymomyza amoena (Diptera: Drosophilidae) larvae

Summary Proline is accumulated by overwinteringC. amonea larvae. Mortality averages over 50% by spring. PGM^F in the population shifts from 70% in summer to less than 50% during winter, increasing again in summer. Product synthesis from stored glycogen may be mandated in dipteran larvae also using larval proteins for cold hardiness when completion of development is delayed until spring.Thanks are gratefully extended to Derek Lamport and Patrick Muldoon of the MSU/DOE Plant Biology Laboratory for the amino acid analyses. Thanks are also extended to Jerry Wolfe, Director of Mt. Lake Biological Station in summer, 1985 and Blaine Cole, Director beginning summer, 1986 for research space, to the University of Virginia, Charlottesville for a fellowship for the work at MLBS in summer, 1986 and to all the property owners in Michigan and Virginia who allowed collection at their orchards, farms, gardens or residences. Apples in January and March, 1986 were from a university research orchard. — This paper is dedicated to Hampton L. Carson on his retirement.     

A beautiful sea: P. A. M. Dirac's epistemology and ontology of the vacuum

This paper charts P.A.M. Dirac's development of his theory of the electron, and its radical picture of empty space as an almost-full plenum. Dirac's Quantum Electrodynamics famously accomplished more than the unification of special relativity and quantum mechanics. It also accounted for the ‘duplexity phenomena’ of spectral line splitting that we now attribute to electron spin. But the extra mathematical terms that allowed for spin were not alone, and this paper charts Dirac's struggle to ignore or account for them as a sea of strange, negative-energy, particles with positive ‘holes’. This work was not done in solitude, but rather in exchanges with Dirac's correspondence network. This social context for Dirac’s work contests his image as a lone genius, and documents a community wrestling with the ontological consequences of their work. Unification, consistency, causality, and community are common factors in explanations in the history of physics. This paper argues on the basis of materials in Dirac's archive that --- in addition --- mathematical beauty was an epistemological factor in the development of the electron and hole theory. In fact, if we believe that Dirac's beautiful mathematics captures something of the world, then there is both an epistemology and an ontology of mathematical beauty.     

Theoretical construction in physics – The role of Leibniz for Weyl's ‘Philosophie der Mathematik und Naturwissenschaft’

This paper aims at closing a gap in recent Weyl research by investigating the role played by Leibniz for the development and consolidation of Weyl's notion of theoretical (symbolic) construction. For Weyl, just as for Leibniz, mathematics was not simply an accompanying tool when doing physics—for him it meant the ability to engage in well-guided speculations about a general framework of reality and experience. The paper first introduces some of the background of Weyl's notion of theoretical construction and then discusses particular Leibnizian inheritances in Weyl's ‘Philosophie der Mathematik und Naturwissenschaft’, such as the general appreciation of the principles of sufficient reason and of continuity. Afterwards the paper focuses on three themes: first, Leibniz's primary quality phenomenalism, which according to Weyl marked the decisive step in realizing that physical qualities are never apprehended directly; second, the conceptual relation between continuity and freedom; and third, Leibniz's notion of ‘expression’, which allows for a certain type of (surrogative) reasoning by structural analogy and which gave rise to Weyl's optimism regarding the scope of theoretical construction.     

Laminin: loss-of-function studies

Laminin, one of the most widely expressed extracellular matrix proteins, exerts many important functions in multiple organs/systems and at various developmental stages. Although its critical roles in embryonic development have been demonstrated, laminin’s functions at later stages remain largely unknown, mainly due to its intrinsic complexity and lack of research tools (most laminin mutants are embryonic lethal). With the advance of genetic and molecular techniques, many new laminin mutants have been generated recently. These new mutants usually have a longer lifespan and show previously unidentified phenotypes. Not only do these studies suggest novel functions of laminin, but also they provide invaluable animal models that allow investigation of laminin’s functions at late stages. Here, I first briefly introduce the nomenclature, structure, and biochemistry of laminin in general. Next, all the loss-of-function mutants/models for each laminin chain are discussed and their phenotypes compared. I hope to provide a comprehensive review on laminin functions and its loss-of-function models, which could serve as a reference for future research in this understudied field.     

The origins and early years of the Magnetic and Meteorological department at Greenwich Observatory, 1834-1848*

As one of his first acts upon becoming Astronomer Royal in 1835, George Airy made moves to set up a new observatory at Greenwich to study the Earth’s magnetic field. This paper uses Airy’s correspondence to argue that, while members of the reform movement in British science were putting pressure on the Royal Observatory to branch out into geomagnetism and meteorology, Airy established the magnetic observatory on his own initiative, ahead of Alexander von Humboldt’s request for British participation in the worldwide magnetic charting project that later became known as the ‘Magnetic Crusade’. That the Greenwich magnetic observatory did not become operational until 1839 was due to a series of incidental factors that provide a case study in the technical and political obstacles to be overcome in building a new government observatory. Airy attached less importance to meteorology than he did to geomagnetism. In 1840, he set up a full programme of meteorological observations at Greenwich – and thus turned his magnetic observatory into the ‘Magnetic and Meteorological department’ – only as the price of foiling an attempt by Edward Sabine and others in the London scientific elite to found a rival magnetic and meteorological observatory. Studying the origins of Airy’s Magnetic and Meteorological department highlights how important the context of other institutions and trends in science is to understanding the development of Britain’s national observatory.     

Artful Physics

This paper gives an account of the establishment and expansion of a Faculty of Science at the Calvinist ‘Free University’ in the Netherlands in the 1930s. It describes the efforts of a group of orthodox Christians to come to terms with the natural sciences in the early twentieth century. The statutes of the university, which had been founded in 1880, prescribed that all research and teaching should be based on Calvinist, biblical principles. This ideal was formulated in opposition to the claim of nineteenth-century scientific naturalists that there was an inherent conflict between science and religion. However, despite their selection on the basis of their strict Calvinist beliefs, the first science professors attributed a certain independence to the domain of science. They agreed with the criticism of the conflict thesis, and tried to defuse the tensions between science and religion, although mainly at the level of philosophy and history, looking for example for harmony between science and religion in the past. Ironically, as a result of this approach, the Calvinist scientists mainly contributed to the acceptance of mainstream science in Dutch Calvinist circles, contrary to developments in other countries (notably the USA) where the conflict between science and orthodox Christianity has reasserted itself.     

The American Philosophical Society and the rise of astronomy in the United States in the middle of the nineteenth century

Early geological investigations in the St David's area (Pembrokeshire) are described, particularly the work of Murchison. In a reconnaissance survey in 1835, he regarded a ridge of rocks at St David's as intrusive in unfossiliferous Cambrian; and the early Survey mapping (chiefly the work of Aveline and Ramsay) was conducted on that assumption, leading to the publication of maps in 1845 and 1857. The latter represented the margins of the St David's ridge as ‘Altered Cambrian’. So the supposedly intrusive ‘syenite’ was regarded as younger, and there was no Precambrian. These views were challenged by a local doctor, Henry Hicks, who developed an idea of the ex-Survey palaeontologist John Salter that the rocks of the ridge were stratified and had formed a Precambrian island, round which Cambrian sediments (now confirmed by fossil discoveries) had been deposited. Hicks subsequently proposed subdivision of his Precambrian into ‘Dimetian’, ‘Pebidian’, and (later) ‘Arvonian’, and he attempted correlations with rocks in Shropshire, North Wales, and even North America, seeking to develop the neo-Neptunist ideas of Sterry Hunt. The challenge to the Survey's work was countered in the 1880s by the Director General, Geikie, who showed that Hicks's idea of stratification in the Dimetian was mistaken. A heated controversy developed, several amateur geologists, supported by a group of Cambridge Sedgwickians, forming a coalition of ‘Archaeans’ against the Survey. Geikie was supported by Lloyd Morgan. Attention focused particularly on Ogof Lle-sugn Cave and St Non's Arch, with theory/controversy-ladenness of observations evident on both sides. Evidence from an eyewitness student record of a Geological Society meeting reveals the ‘sanit`ized’ nature of the official summary of the debate in QJGS. Field mapping early in the twentieth century by J. F. N. Green allowed a compromise consensus to be achieved, but Green's evidence for unconformity between the Cambrian and the Dimetian, obtained by excavation, can no longer be verified, and his consensual history of the area may need revision. Unconformity between the Cambrian and the Pebidian tuffs is not in doubt, however, and Precambrian at St David's is accepted. The study exhibits features of geological controversy and the British geological community in the nineteenth century. It also furnishes a further instance of the great influence of Murchison in nineteenth-century British geology and the side-effects of his controversy with Sedgwick.     

Correspondence principle versus Planck-type theory of the atom

This article examines the problem of the origins of the correspondence principle formulated by Bohr in 1920 and intends to test the correctness of the argument that the essential elements of that principle were already present in the 1913 “trilogy”. In contrast to this point of view, moreover widely shared in the literature, this article argues that it is possible to find a connection between the formulation of the correspondence principle and the assessment that led Bohr to abandon the search for a Planck-type theory. In fact, a thorough examination of Bohr’s works shows that the birth of this principle coincided with the depletion of a research program whose origins may date back to Bohr’s stay at the Rutherford’s laboratory (summer 1912). Finally, this article argues that original program of research was abandoned when it became clear that Planck’s quantum hypothesis for the harmonic oscillator was not an adequate support for the theoretical architecture of atomic physics; namely, there was evidence enough to justify a most drastic conclusion, according to Bohr: “I do not think that a theory of the Planck type can be made logical consistent”.     

The coming-to-be of Hansen’s method

This article by Curtis Wilson is an account of the origin of Hansen’s powerful systematic method for finding contributions of higher order perturbations in celestial mechanics. Hansen’s method was developed in the course of improving on Laplace’s treatment of the mutual perturbations of Jupiter and Saturn. This method, an entirely new way of doing celestial mechanics when it first appeared, later made possible the successful treatment of the complicated motions of our moon (see Wilson 2010). In this paper Wilson gives a brief historical introduction followed by an account of relevant technical details of the Laplacian background, an account illustrating technical details in Hansen’s initial development in his Disquisitions of 1829, and a treatment illustrating details contributing to the achievement of Hansen’s more refined development in his Untersuchung of 1831. These details include conditional equations Hansen provides for checking the accuracy of calculations. Wilson also includes a detailed assessment showing the extraordinary improvement in empirical accuracy of Hansen’s treatment over the best earlier treatment of the Jupiter-Saturn  interactions.     

Early research on the biological effects of microwave radiation: 1940–1960

Two overriding considerations shaped the development of early research on the biological effects of microwave radiation—possible medical application (diathermy) and uncertainty about the hazards of exposure to radar. Reports in the late 1940s and early 1950s of hazards resulting from microwave exposure led to the near abandonment of medical research related to microwave diathermy at the same time that military and industrial concern over hazards grew, culminating in the massive research effort known as ‘the Tri-Service program’ (1957–1960). Both the early focus on medical application and the later search for hazards played important roles in dictating how this field of research developed as a science.     

Model-as-replica,model-as-instrument: Representational power and contextual versatility in animal models

Existing scholarship on animal models tends to foreground either of the two major roles research organisms play in different epistemic contexts, treating their representational and instrumental roles separately. Based on an empirical case study, this article explores the changing relationship between the two epistemic roles of a research organism over the span of a decade, while the organism was used to achieve various knowledge ends. This rat model was originally intended as a replica of human susceptibility to cardiac arrest. In a fortunate stroke of serendipity, however, the experimenters detected the way mother-infant interactions regulated the pups’ resting cardiac rate. This intriguing outcome thus became the model’s new representational target and began driving the development of an experimental system. Henceforth, the model acquired an instrumental function, serving to detect and measure system-specific differences. Its subsequent development involved creating stimulus-response measures to explain and theorize those differences. It was this instrumental use of the model that pushed the experimenters into unchartered territory and conferred to the model an ability to adapt to varied epistemic contexts. Despite the prominence of this instrumental role, however, the model’s representational power continued to guide research. The model’s representational target was widened beyond heart rate to reflect other functional phenomena, such as behavioral activity and sleep/wake rhythm. The rat model was thus transformed from an experimental organism designed to instantiate cardiac regulation to a model organism taken to represent the development of a whole, intact animal under the regulatory influence of maternal care. This article examines this multifaceted transformation within the context of the salient shifts in modeling practice and variations in the model’s representational power. It thus explores how the relationship between the representational and instrumental uses of the model changed with respect to the varying exigencies of the investigative context, foregrounding its contextual versatility.     

From ultrasonic to frequency standards: Walter Cady’s discovery of the sharp resonance of crystals

In 1918–1919 Walter G. Cady was the first to recognize the significant electrical consequences of the fact that piezoelectric crystals resonate at very sharp, precise and stable frequencies. Cady was also the first to suggest the employment of these properties, first as frequency standards and then to control frequencies of electric circuits—an essential component in electronic technology. Cady’s discovery originated in the course of research on piezoelectric ultrasonic devices for submarine detection (sonar) during World War I. However, for the discovery Cady had to change his research programme to crystal resonance. This change followed Cady’s experimental findings and the scientific curiosity that they raised, and was helped by the termination of the war. Cady’s transition was also a move from “applied” research, aimed at improving a specific technology, to “pure” research lacking a clear practical aim. This article examines how Cady reached the discovery and his early ideas for its use. It shows that the discovery was not an instantaneous but a gradual achievement. It further suggests that disinterested “scientific” research (rather than “engineering” research) was needed in this process, while research aimed at design was required for the subsequent development of technological devices. I am very grateful to Chris McGahey for providing me with his research notes taken from Walter Cady’s diaries kept by the Rhode Island Historical Society, henceforth Diaries. I would like to thank Aharon (Arkee) Eviatar for linguistic comments, Ido Yavetz for our helpful discussion and Jed Buchwald for his thoughtful comments and editorial work. I thank the Lemelson Center in the National Museum for American History for a grant that enabled me to study Walter Guyton Cady Papers, 1903–1974, Archives Center, National Museum of American History (henceforth, ACNMAH) and the staff of the center, especially Alison Oswald, for their help. The following abbreviations are used: NB—Cady’s research notebooks kept at ACNMAH, AIP - Niels Bohr Library, American Institute of Physics, Cady’s dossier.     

中小企业员工心理契约与离职倾向关系研究

以国内外现有心理契约测量量表为参考,开发出针对我国中小企业员工心理契约的测量量表。在此基础上,以辽宁省中小企业的员工为例,通过对问卷调查获得的有效数据进行分析,发现中小企业员工心理契约的具体结构分为交易维度、关系维度和发展维度,各个维度与离职倾向均存在不同程度的负相关关系。最后,从心理契约的视角对中小企业如何降低离职率提出了相应的对策和建议。     

From ‘Beastly Philosophy’ to Medical Genetics: Eugenics in Russia and the Soviet Union

This essay offers an overview of the three distinct periods in the development of Russian eugenics: Imperial (1900–1917), Bolshevik (1917–1929), and Stalinist (1930–1939). Began during the Imperial era as a particular discourse on the issues of human heredity, diversity, and evolution, in the early years of the Bolshevik rule eugenics was quickly institutionalized as a scientific discipline—complete with societies, research establishments, and periodicals—that aspired an extensive grassroots following, generated lively public debates, and exerted considerable influence on a range of medical, public health, and social policies. In the late 1920s, in the wake of Joseph Stalin's ‘Great Break’, eugenics came under intense critique as a ‘bourgeois’ science and its proponents quickly reconstituted their enterprise as ‘medical genetics’. Yet, after a brief period of rapid growth during the early 1930s, medical genetics was dismantled as a ‘fascist science’ towards the end of the decade. Based on published and original research, this essay examines the factors that account for such an unusual—as compared to the development of eugenics in other locales during the same period—historical trajectory of Russian eugenics.     

A periodization of research technologies and of the emergency of genericity

According to the historian and sociologist of science Terry Shinn, the creator of the concept of ‘research technologies’: “Research technologies may sometimes generate promising packets of instrumentation for yet undefined ends. They may offer technological answers to questions that have hardly been raised. Research technologists׳s instruments are then generic in the sense that they are base-line apparatus which can subsequently be transformed by experimenters into products tailored to specific economic ends or adapted by experimenters to further cognitive ends in academic research.”¹ Genericity thus manifests one of three fundamental characteristics of research technologies. At the same time, however, each research technology emerges out of the specific disciplinary context in which it is initially developed with entirely concrete aims. Consequently, genericity does not exist from the outset but first has to form, along a path that remains to be clarified. It is produced or constructed by the actors on two levels: as an instrument in the laboratory and as a way of speaking at the representational level. This issue yields the structure of this paper. Three options for the transition of a specific technique into a generic research technology are compared. One of them proves to be the most frequent pattern of this dynamic. This is explored further, taking as paradigmatic examples ‘computed tomography’ (CT), ‘nuclear magnetic resonance׳ (NMR) and its application known as ‘magnetic resonance imaging’ (MRI), together with several additional examples.     

Science policy and politics in post-war Japan: the establishment of the KEK high energy physics laboratory

This paper provides a detailed account of the prehistory of the KEK National Laboratory for High Energy Physics at Tsukuba in Japan. Attempts to establish Japan's first truly national laboratory marked the beginning of ‘big science’ in Japan. An examination of the debate and decision-making processes, which spanned over a decade, provide insight into the political aspects of policy making in the post-war period. History shows that even in Japan, self-interest has taken precedence over group interests in lobbying for research funds for science.