WNT signaling,the development of the sympathoadrenal–paraganglionic system and neuroblastoma

Neuroblastoma (NB) is a tumor of the sympathoadrenal system arising in children under 15 years of age. In Germany, NB accounts for 7% of childhood cancer cases, but 11% of cancer deaths. It originates from highly migratory progenitor cells that leave the dorsal neural tube and contribute neurons and glial cells to sympathetic ganglia, and chromaffin and supportive cells to the adrenal medulla and paraganglia. Clinically, histologically and molecularly, NBs present as extremely heterogeneous, ranging from very good to very poor prognosis. The etiology of NB still remains unclear and needs to be elucidated, however, aberrant auto- and paracrine embryonic cell communications seem to be likely candidates to initiate or facilitate the emergence, progression and regression of NB. The wingless-type MMTV integration site (WNT) family of proteins represents an evolutionary highly conserved signaling system that orchestrates embryogenesis. At least 19 ligands in the human, numerous receptors and co-receptors are known, which control not only proliferation, but also cell polarity, migration and differentiation. Here we seek to interconnect aspects of WNT signaling with sympathoadrenal and paraganglionic development to define new WNT signaling cues in the etiology and progression of NB.     

The platinum pyrometers of Louis Bernard Guyton de Morveau,F.R.S. (1737–1816)

As we have seen, it was clearly Guyton's intention, in 1808, to supply details of his improved platinum pyrometer, and he did submit a drawing of the instrument at the meeting of the Class in December 1810. It would seem that on that occasion he did not supply those details which are to be found in the fourth, unpublished, part of the ‘Essay’. The existence of a text fit to be sent to the printer, and the execution of a drawing relating to the improved version of his platinum pyrometer, might be taken as evidence that Guyton intended to publish. His paper of 1810 did not appear until 1814, however, so that publication of the fourth part of the ‘Essay’ could scarcely have occurred until 1815 or later. Guyton probably hoped to be able to read it to the Class of Physical and Mathematical Sciences before publishing it in the Annales de Chimie, but his death on 2 January 1816 robbed him of the opportunity.     

Crossing the Olentangy River: The Figure of the Earth and the Military-Industrial-Academic-Complex, 1947–1972

This paper explores the history of a unique assemblage of researchers in the geodetic and allied sciences organised at Ohio State University (OSU) in 1947 at the beginning of the Cold War. From about 1950 to 1970, the OSU geodetic sciences group was the most significant group of geodetic researchers in the world. Funded almost entirely by military and intelligence agencies, they pioneered the technologies, organised the research initiatives, ordered the data sets, and trained the generation of geodesists who eventually created the Cold War Figure of the Earth to both prosecute and prevent global nuclear war. They devised elaborate mechanisms to pursue in secrecy and isolation research that had hitherto been performed collaboratively and globally. They invented methods to maintain professional associations and protocols, both to distribute—and disguise—the fruits of their geodetic research. In accomplishing this, their work also undermined the basic hypothesis of isostasy that had been foundational to geodesy for the previous century.Fundamental progress in the geosciences and military and intelligence directives were inextricably linked during the Cold War, although the extent of their convergence has been masked by the security protocols organised to disguise it. With the declassification of key programmes underway, it is now both possible and necessary to substantially revise the history of Cold War-era geosciences and their associated technologies.     

Science and the Mechanics' Institutes, 1820–1850: The case of Sheffield

This paper points out that the provincial mechanics' institutes of England in their early years were as much the product of a general and pervasive scientific culture as they were of a particular educational movement. To this extent the institutes can be interpreted within the context of wider social and economic changes. The bulk of the paper relates to the Mechanics' Institute at Sheffield in the period 1832–50, but through this and other material it is argued that this case study deserves general consideration.     

The Quantification and Differentiation of the Drug Receptor Theory,c. 1910–1960

While historians have dealt with the origins of the concept of drug receptors in the work of Paul Ehrlich (1854–1915) and John N. Langley (1852–1925) as well as with some of its applications in modern pharmaceutical research, the history of the receptor theory as such has been neglected. Discussing major developments and conceptual changes in receptor theory between about 1910 and 1960 (including relevant contributions by A. V. Hill, A. J. Clark, J. H. Gaddum, E. J. Ariëns and others), this paper attempts to fill this gap in historiography. It provides a case study of the unfolding of research under a new paradigm, but it considers also contemporary criticism and scepticism. By the early 1960s, quantitative investigations of drug action and interpretations of the experimental findings in terms of the receptor concept had become constitutive of the emerging field of ‘molecular pharmacology’. Even then, however, receptors were still hypothetical entities.     

The adoption of self-induction by telephony, 1886–1889

Through 1886 to 1889 understanding of the mechanism of telephone transmission was transformed from an electrostatic and traditional view to an electrodynamic one conforming with Maxwell's scheme. Observed at the level of commercial application this painful adjustment occurred via a sequence of controversies connected with self-induction—on techniques of telephony, on electrical measurement, on lightning conductors and on matters of professional ethics—in which the parts played by evidence, by theory, and by authority were strangely mixed. The well-known confrontation of O. Heaviside and W. H. Preece was at the centre of the debate. An open division between traditionalists and progressives amongst electrical engineers was provoked, and the effectiveness of mathematical theory as against pure pragmatism at the practical level had in the end to be conceded.     

The effect of cyclic cytidine 3′,5′-monophosphate (cCMP) on the in vitro development,hatching and attachment of the mouse blastocyst

Summary The in vitro development and attachment of hatched mouse blastocysts on the untreated substratum was enhanced by 10 M dibutyryl cCMP (dbcCMP). The result suggests that cCMP has an effect on embryonic development and on the blastocyst attachment process.25 November1986     

The chemists go to war: The mobilization of civilian chemists and the british war effort, 1914–1918

The outbreak of war in 1914 found Britain unprepared for a lengthy conflict. British science and industry were particularly ill-prepared to meet the demands of static warfare. Within two years, however, mobilization had made appreciable strides, and, as Britain's munitions industries moved from crisis to confidence, Britain's chemical industry was transformed by an arsenal of ‘garrison chemists’, with skills either born of necessity or borrowed from overseas. At the same time, Britain's chemical leadership traced a path that led them from voluntarist to corporate methods, from private to public initiatives, and from individual to collective behaviours. This paper suggests four key stages in this mobilization, and hints at the significance of the war for the emergence of new sub-disciplines, for the careers of chemists, for academic-government relations in research, and for the image, status, and international position of British chemistry on the threshold of the postwar world.     

The platypus in Edinburgh: Robert Jameson,Robert Knox and the place of the Ornithorhynchus in nature, 1821–24

The duck-billed platypus, or Ornithorhynchus, was the subject of an intense debate among natural historians in the late eighteenth and early nineteenth centuries. Its paradoxical mixture of mammalian, avian and reptilian characteristics made it something of a taxonomic conundrum. In the early 1820s Robert Jameson (1774–1854), the professor of natural history at the University of Edinburgh and the curator of the University's natural history museum, was able to acquire three valuable specimens of this species. He passed one of these on to the anatomist Robert Knox (1791–1862), who dissected the animal and presented his results in a series of papers to the Wernerian Natural History Society, which later published them in its Memoirs. This paper takes Jameson's platypus as a case study on how natural history specimens were used to create and contest knowledge of the natural world in the early nineteenth century, at a time when interpretations of the relationships between animal taxa were in a state of flux. It shows how Jameson used his possession of this interesting specimen to provide a valuable opportunity for his protégé Knox while also helping to consolidate his own position as a key figure in early nineteenth-century natural history.     

Establishment of left–right asymmetry in vertebrate development: the node in mouse embryos

Establishment of vertebrate left–right asymmetry is a critical process for normal embryonic development. After the discovery of genes expressed asymmetrically along the left–right axis in chick embryos in the mid 1990s, the molecular mechanisms responsible for left–right patterning in vertebrate embryos have been studied extensively. In this review article, we discuss the mechanisms by which the initial symmetry along the left–right axis is broken in the mouse embryo. We focus on the role of primary cilia and molecular mechanisms of ciliogenesis at the node when symmetry is broken and left–right asymmetry is established. The node is considered a signaling center for early mouse embryonic development, and the results we review here have led to a better understanding of how the node functions and establishes left–right asymmetry.     

The role of mammalian target of rapamycin (mTOR) in the regulation of pancreatic β-cell mass: implications in the development of type-2 diabetes

Type-2 diabetes mellitus (T2DM) is a disorder that is characterized by high blood glucose concentration in the context of insulin resistance and/or relative insulin deficiency. It causes metabolic changes that lead to the damage and functional impairment of organs and tissues resulting in increased morbidity and mortality. It is this form of diabetes whose prevalence is increasing at an alarming rate due to the 'obesity epidemic', as obesity is a key risk factor in the development of insulin resistance. However, the majority of individuals who have insulin resistance do not develop diabetes due to a compensatory increase in insulin secretion in response to an increase in insulin demand. This adaptive response is sustained by an increase in both β-cell function and mass. Importantly, there is increasing evidence that the Serine/Threonine kinase mammalian target of rapamycin (mTOR) plays a key role in the regulation of β-cell mass and therefore likely plays a critical role in β-cell adaptation. Therefore, the primary focus of this review is to summarize our current understanding of the role of mTOR in stimulating pancreatic β-cell mass and thus, in the prevention of type-2 diabetes.     

The International Association of Refrigeration through the correspondence of Heike Kamerlingh Onnes and Charles-Édouard Guillaume, 1908–1914

Summary In 1908 the First International Congress of Refrigeration took place in Paris, organised by a score of French industrialists and supported by some of the major railway and shipping companies. A few months later, in January 1909, the International Association of Refrigeration was founded with the aim of encouraging the general progress of the science and industries of artificial cold. The aim of this paper consists in examining the early years of the Association with a particular focus on its scientific character. The research is based on the documents published by the Association from 1908 to 1914, and on private correspondence between two of the main scientists, both Nobel Prize recipients, who played an important role in its establishment: the Swiss physicist Édouard Guillaume (1861–1938) and the Dutch physicist Heike Kamerlingh Onnes (1853–1926). Both scientists had a specific vision for their own role in the Association and for the Association itself. Their correspondence reveals a great range of tensions between the various nation-state members of the Association, its various spheres of activity, but also tensions due to personal ambitions and conflicts of interest.     

The life and death of a scientific instrument: The marine chronometer, 1770–1920

Successful prototype marine chronometers, developed by Harrison and others in the eighteenth century, stimulated a sector of the British watchmaking industry to supply Admiralty and commercial demand for this instrument. Chronometers, like other British-made timepieces, were constructed by an elaborate pre-industrial method of production. The instrument's static technology and extreme durability meant replacement demand was minimal, and new demand was low relative to existing stock and the industry's capacity. The First World War created a final surge of demand that left supplies far in excess of peacetime needs; and a new technology—radio transmissions of time signals—offered an alternative method of determining Greenwich time, and thus longitude, at sea.     

The best of many worlds,or, is quantum decoherence the manifestation of a disposition?

In this paper I investigate whether the phenomenon of quantum decoherence, the vanishing of interference and detectable entanglement on quantum systems in virtue of interactions with the environment, can be understood as the manifestation of a disposition. I will highlight the advantages of this approach as a realist interpretation of the quantum formalism, and demonstrate how such an approach can benefit from advances in the metaphysics of dispositions. I will also confront some commonalities with and differences to the many worlds interpretation, and address the difficulties induced by quantum non-locality. I conclude that there are ways to deal with these issues and that the proposal hence is an avenue worth pursuing.