bluuebunny/crossref_metadata_2025 huggingface dataset:
Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer
Authors: Seaman Matthew N.J.
Published: April 2004

fEndosome-to-Golgi retrieval of the mannose 6-phosphate receptor (MPR) is required for lysosome biogenesis. Currently, this pathway is poorly understood. Analyses in yeast identified a complex of proteins called “retromer” that is essential for endosome-to-Golgi retrieval of the carboxypeptidase Y receptor Vps10p. Retromer comprises five distinct proteins: Vps35p, 29p, 26p, 17p, and 5p, which are conserved in mammals. Here, we show that retromer is required for the efficient retrieval of the cation-independent MPR (CI-MPR). Cells lacking mammalian VPS26 fail to retrieve the CI-MPR, resulting in either rapid degradation of or mislocalization to the plasma membrane. We have localized mVPS26 to multivesicular body endosomes by electron microscopy, and through the use of CD8 reporter protein constructs have examined the effect of loss of mVPS26 upon the trafficking of membrane proteins that cycle between the endosome and the Golgi. The data presented here support the hypothesis that retromer performs a selective function in endosome-to-Golgi transport, mediating retrieval of the CI-MPR, but not furin.
Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor
Authors: Arighi Cecilia N. , Hartnell Lisa M. , Aguilar Ruben C. , Haft Carol R. , Bonifacino Juan S.
Published: April 2004

The cation-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precursors from the TGN to endosomes. After releasing the hydrolase precursors into the endosomal lumen, the unoccupied receptor returns to the TGN for further rounds of sorting. Here, we show that the mammalian retromer complex participates in this retrieval pathway. The hVps35 subunit of retromer interacts with the cytosolic domain of the CI-MPR. This interaction probably occurs in an endosomal compartment, where most of the retromer is localized. In particular, retromer is associated with tubular–vesicular profiles that emanate from early endosomes or from intermediates in the maturation from early to late endosomes. Depletion of retromer by RNA interference increases the lysosomal turnover of the CI-MPR, decreases cellular levels of lysosomal hydrolases, and causes swelling of lysosomes. These observations indicate that retromer prevents the delivery of the CI-MPR to lysosomes, probably by sequestration into endosome-derived tubules from where the receptor returns to the TGN.
John Swinton, F.R.S., identified as the author of a 1734 travel journal
Authors: Shaw T.
Published: April 2004

‘The Travels of three English Gentlemen, from Venice to Hamburgh … in 1734’ was printed in
The Harleian Miscellany
from a now lost manuscript. The anonymous author, FRS and an Oxford man, is here identified for the first time as John Swinton (1703–1777), keeper of the University archives from 1767. A portrait and his signature are reproduced. Attention is drawn to his other travels not hitherto recorded, and the significance of this 1734 journal is assessed. Its special value is in the practical aspects of travel—languages used (including Latin), roads, horses, inns, costs and even carriage maintenance.
Nathaniel and Edward Pigott, itinerant astronomers
Authors: McConnell A. , Brech A.
Published: April 2004

Accounts of Nathaniel Pigott and his son Edward were written by Agnes Clerke in 1895 for the
Dictionary of national biography
, and by Zdenek Kopal for the
Dictionary of scientific biography
. Both are incomplete and have errors of fact concerning the lives and scientific works of these men, these authors having relied largely on the published astronomical papers. When one of the present authors (A.M.) came to revise the accounts for the
New dictionary of national biography
, a wealth of biographical material was discovered in sources for Catholic history, and in those relating to Yorkshire and the City of York. The investigation has been shared with the other author (A.B.), who lives in Yorkshire. The personal lives of the Pigotts, and their continual movements between France, the Austrian Netherlands, Yorkshire and indeed several other regions of England, explain why their astronomical interests were so diverse, although several questions remain answered.
John Tyndall, the rhetorician of molecularity. Part two. Questions put to nature
Authors: Yamalidou M.
Published: April 2004

Following the discussion in Part One of this paper, an attempt is made here to understand the way in which Tyndall justified his bold claim that the introduction of molecular explanans in science necessitated an act of the imagination. Being conscious of the prospective emergence of a new scientific field out of the extensive dialogue of scientists over the conditions of material molecularity, and having the ambition to place his own research on absorption and radiation at the centre of the relevant developments, Tyndall was prepared to couple his imaginative suggestions with meticulous experimentation. With his unparalleled ability to master all the minute details of the experimental procedures he was following, Tyndall not only realized the significance of what he thought to be a basic constituent of scientific ethics, but could also design and perform the crucial experiments that enabled him to take a closer look at the submicroscopic level of physical reality. In so doing, he attempted to go far beyond the minimal expectations of 19th-century molecular discourse, insofar as he claimed to have given not only a proof of the molecular underpinnings of physical phenomena but also a definite picture of the individual molecule itself.
A century of physics in Oxford
Authors: Bleaney B.
Published: April 2004

This paper gives a concise history of the development of physics in Oxford, mainly from the middle of the 19th century to 1945. The first part covers the origins of the old Clarendon Laboratory and the Electrical Laboratory. The second part is devoted to the new Clarendon Laboratory, constructed in 1938–39, and the work there during the Second World War, together with a brief summary of important changes in 1945–46.
Patrick Blackett in India: Military Consultant and Scientific Intervenor, 1947–72. Part Two
Authors: Anderson R. S.
Published: April 2004

Patrick Blackett's role as a military consultant to India was described in Part One of this article. But Blackett was and is best known in India as an intervenor in scientific affairs and as an adviser to the research system. Here, Part Two shows how he came to understand the political economy of science, specifically the political limits of the influence of the scientific community and the way that very scarce economic resources were (or were not) mobilized within it.
Essay review. Lancelot Hogben, F.R.S. (1895–1975): A review of his autobiography
Authors: Keynes M.
Published: April 2004

Adrian and Anne Hogben,
Lancelot Hogben–scientific humanist
. Merlin Press, Woodbridge, Suffolk, 1998. Pp. 254, £14.95 (hardback). ISBN 0 85036 470 1.
Book reviews
Authors: Russell C. A.
Published: April 2004

Four book reviews in the September 1999 issue of
Notes and Records
L.M. Principe,
The aspiring adept: Robert Boyle and his alchemical quest
. John Gascoigne,
Science in the service of Empire: Joseph Banks, the British State and the uses of science in the Age of Revolution
. Carlo Cercignani,
Ludwig Boltzmann: the man who trusted atoms
. E.A. Davis and I.J. Falconer,
J.J. Thomson and the discovery of the electron
.
In this issue
Authors: Cook A.
Published: April 2004

We hope our readers appreciate our new pictorial cover, which will, from year to year, display different aspects of the history of the Society. With whom else could we start but Newton? Yet he is not the only Fellow of his day who set natural philosophy on the course we still follow. In this issue, we recall the influence of John Ray on the classification of plants, insects, birds and fishes.
Shining through the centuries: John Ray's life and legacy
Authors: Ford B. J.
Published: April 2004

A major conference on John Ray and other clerical naturalists, entitled ‘John Ray and his successors; the clergyman as biologist’, was held at Braintree, Essex, from 18 to 21 March 1999. Speakers considered Ray's work and beliefs in the context of the theology of his day, and the interplay between religion and biology up to the present time. Some of the outstanding protagonists were, like Ray, ordained Fellows of the Royal Society.
Christopher Merret's use of experiment
Authors: Koinm A. J.
Published: April 2004

Christopher Merret's
Pinax Rerum Naturalium Britannicarum
has been criticized because he only collected material rather than doing research himself. However, Merret, first Harveian Librarian of the Royal College of Physicians and charter member of the Royal Society of London, used his talents as curator to ensure as accurate a description of plants and animals as was possible in 1666, to make the most complete compilation of his day. His steps to collect new plants, his translation of and interpolations to Neri's
The Art of Glass
, his garden of herbs, and his reports to the Royal Society on his experiments show his recognition of the importance of experiment.
By ‘the light of his own mind’: The story of James Ferguson, astronomer
Authors: Rothman P.
Published: April 2004

James Ferguson, the self-taught astronomer, scientific instrument maker, author and lecturer was a remarkable 18th century figure. This paper traces his life from humble origins as a shepherd boy in Banffshire, Scotland. There he observed the stars and planets by night and conjectured on the mechanics of the heavens. He taught himself to make and repair clocks and his outstanding talent as a portraitist enabled him to earn a living while he invented scientific instruments. He eventually came to London where he continued to design instruments and globes and commenced his career as lecturer and author. His later years as an esteemed recipient of a royal pension from King George III brought him Fellowship of the Royal Society with extraordinary provisions, and contact with Benjamin Franklin, Samuel Johnson and many other leading figures of his day.
Foster and Sharpey's tour of Europe
Authors: Sykes A. H.
Published: April 2004

An account by Michael Foster of a tour of European physiological laboratories he made with William Sharpey in 1870.
The Reverend Dr William Henry Dallinger, F.R.S. (1839-1909)
Authors: Hass J. W.
Published: April 2004

The parson-naturalist long played a respected role in English scientific culture. By the close of the 19th century this tradition had almost disappeared due, in part, to increasing educational standards and professional responsibilities. William Dallinger illustrates these challenges to the earlier tradition. Dallinger, a Wesleyan minister, came from nowhere to enter the portals of the scientific elite, yet found himself on the fringes of the scientific research community during the later part of his life. Dallinger followed the pattern of the older ideal typified by the wealthy Charles Darwin, who paid for his research out of his own pocket and used his home as his laboratory, while their scientific friends T. H. Huxley and John Tyndall were paid for their labours in the new scientific institutions of London. This paper follows Dallinger's dual career as cleric and scientist and seeks to identify the ‘invisible resources’ and ’motivations‘ that propelled an obscure Methodist cleric to be a pioneer in the emerging field of ‘protozoology’ and play a leading role in the spontaneous generation controversy.
The Raman effect and Krishnan's diary
Authors: Mallik D. C. V.
Published: April 2004

K.S. Krishnan, F.R.S. (1898–1961) is one of the most distinguished Indian scientists of this century. His collaboration with Sir C.V. Raman on the scattering of light by liquids--a collaboration which Raman described as ‘a partnership in scientific research of the Bowen-Millikan type’—led to the discovery of the effect that bears Raman's name. Krishnan recorded the events leading to this discovery in the form of a diary, extracts from which have often appeared in the past, although the diary itself has never been published before. Later, as a Reader in Physics at the University of Dacca and then as the first Mahendra Lal Sircar Professor of Physics at the Indian Association for the Cultivation of Science in Calcutta, Krishnan made seminal studies on crystal magnetism. These studies established him as one of the leading physicists working in this area and brought him international recognition, eventually winning him, in 1940, the Fellowship of the Royal Society. Krishnan was born a little over a hundred years ago; in a centenary tribute to him, I recall here his early work and the nature of his collaboration with Sir C.V. Raman, which produced the most spectacular scientific discovery in India to date. With the consent of the members of his family, I also transcribe in full the Krishnan Diary.
The Royal Society and the Antarctic
Authors: Fogg G. E.
Published: April 2004

Beginning with its dispatch of Halley on his geomagnetic cruise of 1699 to 1700, the Royal Society has played a sporadic, ad hoc, but nevertheless considerable role in the scientific investigation of the South Polar regions. In three ventures—Ross's geomagnetic survey of 1839 to 1843, the first Scott expedition of 1901 to 1904 and the British contribution to the International Geophysical Year of 1957 to 1958—it made major contributions to the planning and support of Antarctic scientific programmes. Throughout, it has given backing to polar expeditions but has been consistent in putting science before geographical discovery. It has numbered some 20 Antarctic scientists among its Fellows.
Address of the President, Sir Aaron Klug, O.M., P.R.S., given at the anniversary meeting on 30 November 1999
Authors: Klug A.
Published: April 2004

The Royal Society combines three different functions.

First, we are a learned society, established in 1660 to promote the—then radical—values of modern science and, particularly, the notion that knowledge about the natural world is best obtained by careful observations and controlled experiment. We do this by identifying and honouring high achievement, disseminating new science through meetings and publications, and, over time, acquiring and maintaining a pre–eminent library and archive in the history of science. Our function as a learned society is the foundation of everything else we do, since it is the standing of the Fellows, and their expertise, which gives the Society its authority.

Second, we are a funding body, using public and private monies to support the best individuals to undertake the most imaginative and far-reaching research, in Britain and internationally. We do this through Research Professorships and Fellowships, conference and research grants.

Third, we are, in effect, the Academy of Science for the UK, leading the UK scientific community in its relations with UK society, government and the scientific communities of other countries. As part of this role we have a long history of relations with other academies and of international scientific exchanges.

In each of these roles, the Society occupies a special niche. By combining the three roles within one organization, the Society is in a particularly strong, I would say unique, position to provide innovative and practical leadership to the scientific community.
ESSAY REVIEW: The gatekeeper of the modern world
Authors: Cook A.
Published: April 2004

Niccolo Guicciardini,
Reading the
Principia;
The debate on Newton's mathematical methods for natural philosophy from 1687 to 1736
. Cambridge University Press, 1999. Pp. 285, £50.00. ISBN 0–521–64066–0
Book reviews
Authors: Russell Colin A.
Published: April 2004

Six book reviews in the January 2000 issue of
Notes and Records
. R. Ian McCallum,
Antimony in medical history: an account of the medical uses of antimony and its compounds since early times to the present
. David E. Cartwright,
Tides: A scientific history
. Lydia M. Soo,
Wren's ‘Tracts’on architecture and other writings
.
‘Did the Royal Society matter in the eighteenth century?’
Edited by R. Sorrenson. D.K. Barkan,
Walther Nernst and the transition to modern physical science
. Veniamin Tsukerman and Zinaida Azarkh,
Arzamas–16. Soviet scientists in the Nuclear Age: a memoir
.
Recent publications concerning the Royal Society
Authors: Baker R.
Published: April 2004

The citations listed below include journal articles and books about the Society that have been published since 1996 and are in the Society's library. The citations are arranged alphabetically.
In this issue
Authors: Cook A.
Published: April 2004

There was in the January issue a report of a meeting held last year to celebrate the life and achievements of John Ray, F.R.S., together with an article on one of his successors as a clerical naturalist. Three further papers from the meeting appear in this number, two on Ray's religious and philosophical positions, and one on the famous
Historia Piscium
(
History of fishes
).
At the source of Western science: The organization of experimentalism at the Accademia del Cimento (1657–1667)
Authors: Beretta M.
Published: April 2004

The Accademia del Cimento, founded by the Medici princes, Ferdinando II, Grand Duke of Tuscany, and his brother, Leopoldo, later Cardinal, had members and programmes of research very different from earlier academies in Italy. The Cimento foreshadowed later European academies and institutions specifically devoted to research and improvement of natural knowledge. It issued only one publication, the
Saggi di naturali esperienze
, and most of the observations and experimental results from its brief life remain unpublished. The Roman Accademia fisica-matematica, associated with Queen Christina of Sweden, continued to some extent its emphasis on experiment, while The Royal Society, with which it maintained links, placed even greater reliance on experiment and its validation through unvarnished publication. Comparisons between the Cimento and its contemporaries, The Royal Society and the Frenchacademy, illuminate the origin of scientific institutions in the early modern period.
John Ray (1627-1705) and the Act of Uniformity 1662
Authors: McMahon S.
Published: April 2004

John Ray was one of the most influential British natural philosophers of the 17th century. His model of natural history served as an organizing principle for the philosophic understanding of living nature and his works on natural theology were seminal. Many modern historians have placed Ray within the Puritan tradition, primarily based on Ray's choice, as an ordained Anglican priest, to leave his fellowship at Cambridge rather than subscribe to the Act of Uniformity in 1662. However, Ray left no explicit evidence of either his religious or political views during this period and his reasons for refusing to subscribe to the Act are not transparent. My analysis of his early Essex environment, his friends and associates at Cambridge University, his correspondence during the crucial years of 1660–62 and the strategies he pursued in his only contemporary published work, the
Catalogus Plantarum circa Cantabrigiam
(1660) provide no evidence to situate Ray within a Puritan framework and much evidence to suggest that Ray remained committed to Anglican and loyalist principles throughout his career.
The
Historia Piscium
(1686)
Authors: Kusukawa S.
Published: April 2004

In 1686, just as Newton was preparing for the publication of the
Principia
, the
Historia Piscium
was being printed under the auspices of The Royal Society. The
Historia Piscium
was a work begun by Francis Willughby (1635–1672, F.R.S. 1663), completed by John Ray (1627–1705, F.R.S. 1667) and brought into print with the financial support of The Royal Society. The text and illustrations of the
Historia Piscium
reflect the 17th-century origins of the enterprise: Ray's quest to recover the knowledge and language lost in the Fall, and The Royal Society's support for establishing a reformed natural history of fish through publication. Ray's biblical belief in the corruption of human language and knowledge led him to reform natural history through ‘characteristic marks’. He sought to define, classify and depict fishes through their external features, which when matched up, would yield the same nature, and thus allow humans to identify and give a name to a fish. The Royal Society helped Ray's task by confirming the validity or uselessness of a given author on the subject, suggesting other authorities and sources for illustrations, organizing the printing, checking the corrections and paying for the cost of the printing. Subscriptions were sought for the illustrations and the inscriptions of subscribers reflect the Society's concern to promote its institutional identity and its supporters. Some Fellows of the Society also helped Ray with identities and classification of fishes, and changes were made in response to suggestions and objections of other Fellows. Without the intellectual and financial support of the Society, especially Pepys, Lister and Robinson, the
Historia Piscium
would not have been published in the way that it was. Despite the subscription, however, the
Historia Piscium
was a costly venture, largely due to its lavish illustrations, and the subsequent flop of sales of the book meant that The Royal Society faced serious financial problems. This is perhaps the main reason why it could not meet the cost of publishing Newton's
Principia
.
‘Wise men nowadays think otherwise’: John Ray, natural theology and the meanings of anthropocentrism
Authors: Brooke J. H.
Published: April 2004

The object of this paper is to re–examine the extent to which anthropocentric readings of nature were dislodged as a consequence of developments in 17th–century natural philosophy. The natural theology in Ray's
Wisdom of God
(1691) provides access to the issues because Ray was explicitly critical of those who imagined that everything had been made for man alone. The paper begins by identifying familiar features of the ‘scientific revolution’ that contributed most to a decentring of the human self: the Copernican innovation, telescopic discoveries, speculations concerning a plurality of worlds, the Cartesian ban on the investigation of final causes and the collapse of microcosm/macrocosm analogies. There were, however, counter currents to these centrifugal tendencies, notably in Robert Boyle's response to Descartes's strictures. In the main section of the paper, I therefore identify the various ways in which an anthropocentricity was not only preserved but re–emphasized in the post–Copernican Universe. A reconfiguration of human centrality was achieved through cosmology, epistemology and anthropomorphic conceptions of divine activity. As Ray's writing indicates, there were also common qualifications to the mechanization of nature. An elevation rather than relegation of the human spirit was also evident in claims to imitate the creative activities of the deity and in the aesthetic appreciation of the Creator's works. The presence in the world of so many resources for human use also fed anthropocentric sentiments. Boyle restored anthropocentric perspectives through an appeal to scripture and Ray through the suggestion that objects which might appear to have no human use now would have their uses revealed in the future. While Ray did indeed repudiate the proposition that everything was made for man alone, he remained convinced that everything had some human use. The paper concludes with a Darwinian perspective from which Ray's natural theology was incurably anthropocentric, even if it was not in every respect as arrogant as Darwin deemed natural theology to be.
Bryan Edwards, F.R.S., 1743-1800
Authors: Blouet Olwyn M.
Published: April 2004

Bryan Edwards was a Jamaican planter and politician who published a well–respected
History of the West Indies
in 1793. He articulated the planter view concerning the value of the West Indian colonies to Great Britain, and opposed the abolition of the slave trade. Edwards disputed European scientific speculation that the ‘New World’ environment retarded nature, although his scientific interests have largely gone unnoticed. Elected a Fellow of The Royal Society in 1794, he became a Member of Parliament in 1796, and wrote a History of Haiti in the following year. As Secretary of the African Association, Edwards edited the African travel journals of Mungo Park.
James Ivory, F.R.S., mathematician: ‘The most unlucky person that ever existed’
Authors: Craik D. D.
Published: April 2004

James Ivory (1765–1842) has been described as the finest British mathematician of his time, and he received many honours. Yet his career was largely unsuccessful and unhappy, and from the age of 51 he lived reclusively in retirement in London. The explanation for this paradox is that he suffered repeatedly from mental illness, perhaps paranoid schizophrenia.
Johann Kiessling, the Krakatoa event and the development of atmosheric optics after 1883
Authors: Schröder W. , Wiederkehr K-. H.
Published: April 2004

Johann Kiessling studied the sensational twilights that followed the eruption of Krakatoa (1883) and looked for their physical explanation. He believed that the cause of the extraordinary optical appearances essentially lay in diffraction through particles in the condensation and dust clouds which, following the eruption of the volcano, reached high strata in the atmosphere and travelled around the globe. Research concerning the generation of fog in the atmosphere was greatly forwarded by Kiessling's ideas and experiments. The studies of C.T.R. Wilson, F.R.S., which led to the construction of his cloud chamber and its use in nuclear physics, were strongly influenced by Kiessling's work.
The end of the Millenium
Authors: Cook A.
Published: April 2004

Introduction to the September 2000 issue of Notes and Records.
The publications of John Pell FRS (1611-1685): some new light and some old confusions
Authors: Malcolm N.
Published: April 2004

The mathematician John Pell is a significant figure in the intellectual history of 17th century England—significant, however, more because of his activities, contacts and correspondence than because of his published work. His few publications are, nevertheless, valuable sources of information about his intellectual biography. Previous listings of them have been both incomplete and subject to error. This article gives a complete listing of the items published during the 17th century. It identifies a hitherto unknown work by Pell, a book published in 1635; it attempts to correct a common misunderstanding about the dating of his best–known work,
An Idea of Mathematics
; and it presents evidence confirming Pell's responsibility for the introduction of the division sign. In addition, it discusses nine non-existent publications by Pell—items whose titles derive from materials among Pell's manuscripts, but which have been mistakenly listed as publications in modern reference works.
Catching Proteus: the collaborations of Wallis and Brounker. II. Number problems
Authors: Stedall Jacqueline A.
Published: April 2004

Following the discussion of Brouncker's work on quadrature, rectification and continued fractions in Part I of this paper, Part II analyses the disputes between Brouncker and Wallis in England and Fermat in France over problems in what would now be called number theory. Contemporary and later observers regarded Brouncker and Wallis as equally responsible for the English contribution, but it was Brouncker who took the greater interest in Fermat's challenges and who produced the more sophisticated solutions. The paper ends with an assessment of Brouncker's contribution to mathematics and argues that his contemporary reputation was well deserved and his mathematics of lasting value.
A forgotten paper on the fundamental theorem of algebra
Authors: Smithies F.
Published: April 2004

In 1798, there appeared in the
Philosophical Transactions of the Royal Society
a paper by James Wood, purporting to prove the fundamental theorem of algebra, to the effect that every non-constant polynomial with real coefficients has at least one real or complex zero. Since the first generally accepted proof of this result was given by Gauss in 1799, Wood's paper deserves careful examination. After giving a brief outline of Wood's career, I describe the argument of his paper. His proof turns out to be incomplete as it stands, but it contains an original idea, which was to be used later, in the same context, by von Staudt, Gordan and others, without knowledge of Wood's work. After putting Wood's work in context, I conclude by showing how his idea can be used to prove the complex form of the fundamental theorem of algebra, stating that every non-constant polynomial with complex coefficients has at least one zero in the complex field.
Darwin in the Galápagos: his footsteps through the archipelago
Authors: Estes G. , Grant K. T. , Grant P. R.
Published: April 2004

Charles Darwin visited Galápagos for five weeks, from 15 September to 20 October, in 1835. This is a small fraction of the total of 248 weeks he spent on the voyage of the HMS
Beagle
(27 December 1831 to 2 October 1836), yet his experiences in Galápagos were of disproportionate importance in the development of his scientific thinking. As he wrote in his autobiography, he was deeply influenced by his discovery of the similarity of Galápagos plants and animals to those on mainland South America, and especially ‘by the manner in which they differ slightly on each island in the group’. But while in Galápagos, Darwin was primarily a geologist. He repeatedly attempted to explain the geomorphology he observed in terms of processes he could only infer: uplift, the direction of lava flows, their terrestrial or subaqueous origin and the eroding effects of seas. He also developed a theory of magmatic differentiation from looking at crystals embedded in the volcanic rock. Where was Darwin in Galápagos and what did he see? Much has been written about him on his visit to the islands, but there is still confusion about exactly where Darwin set foot upon the four islands he visited: Chatham (San Cristóbal), Charles (Floreana), Albemarle (Isabela) and James (Santiago). Only one study has attempted to elucidate his whereabouts, but it lacked information from the most revealing manuscripts and so was incomplete and incorrect on points of detail. We attempted to answer these questions by first conducting an extensive search in bibliographic material for relevant information, and then by retracing his steps as best as we could from 19 October to 14 December 1996, that is at approximately the same time of year and season (dry) as Darwin's visit. Here we describe the route he took, several of his key geological observations, and changes that have taken place to the fauna and flora since his visit 165 years ago. By visiting the places he visited we were able to appreciate what caught Darwin's attention, and why. The geological features seen and noted by Darwin are still extant today. The living world is in sad contrast, for it is no longer possible to see several components of the fauna and flora he observed. Thus the information presented here is of potential value to scholars wishing to revisit his sites for historical or for scientific purposes (figure 1; see table 1 for GPS readings).
Peterhouse, The Royal Society and molecular biology
Authors: Thomas J. M.
Published: April 2004

The term molecular biology was coined by Warren Weaver, a mathematician who was head of the natural sciences section of the Rockefeller Foundation, in his report to the president of the Foundation in 1938. The origins of the subject may be located in various places or periods, but Sir Peter Medawar used to argue that it was Sir William Bragg and W.T. Astbury at the Davy Faraday Laboratory in London who began it, when they investigated the structures of materials such as silk, wool and hair by X–ray diffraction. Others say that J.D. Bernal was the progenitor. Peterhouse, a Cambridge college, was a hothouse of the subject.
Book reviews
Authors: Perutz Max
Published: April 2004

Twelve book reviews in the September 2003 issue of
Notes and Records
: Georgina Ferry,
Dorothy Hodgkin: a life
.
J.D. Bernal: a life in science and politics
. Edited by Brenda Swann and Francis Aprahamian. Max Perutz,
I wish I'd made you angry earlier. Essays on science and scientists
. A. Rupert Hall,
Isaac Newton: eighteenth-century perspectives
. G.I. Brown,
Count Rumford. The extraordinary life of a scientific genius
.
The correspondence of Michael Faraday
, volume 4. Edited by Frank A.J.L. James.
The philosopher's tree: A selection of Michael Faraday's writings
. Compiled, with commentary, by Peter Day.
Science and exploration in the Pacific. European voyages to the Southern Oceans in the 18th century
. Edited by Margarette Lincoln. Gillian Beer,
Open fields: science in cultural encounter
. Rocky Kolb,
Blind watchers of the sky
. Jan Golinski,
Making natural knowledge. Constructivism and the history of science
. Simon Conway Morris,
The crucible of Creation: the Burgess Shale and the rise of animals
.
URFs become FRS
Authors: Cook A.
Published: April 2004

Three of the new Fellows elected to The Royal Society in 1999 had previously held Royal Society University Research Fellowships (RSURFs). They were not, in fact, the first Fellows of the Society to have held RSURFs, for Richard Borcherds was elected in 1994 and Jean Beggs in 1998, but the election of three in the same year is sufficiently notable to be recorded in
Notes and Records
as a journal of record for the Society. The RSURF scheme continues to achieve its aim of affording opportunities to outstanding young scientists to continue research careers in circumstances of everincreasing constriction in university departments. It would naturally be expected that some of the RSURFs would eventually be elected to the Society, and the election of three in one year, relatively soon after the inception of the scheme, demonstrates that the aims of the scheme are indeed being achieved, and that it, and the Fellows, are becoming mature and established. To mark such a milestone in the history of the scheme and the Society, we print below reflections on their experiences as RSURFs and subsequently, by the three Fellows elected in 1999.
Book reviews
Authors: Fara Patricia
Published: April 2004

Nine book reviews in the May 2000 issue of
Notes and Records
. Penelope Gouk,
Music, science and natural magic in seventeenth-century England
. J.M. Olson and J.M. Pasachoff,
Fire in the sky: comets and meteors, the decisive centuries, in British art and science
.
Nuncius, Annali di Storia della Scienza
. Anno XIV, fasc. 1. Olschki, Firenze, 1999. Pp. 417, Lit. 200 000 per year outside Italy. Desmond King-Hele,
Erasmus Darwin, a life of unequalled achievement
. John E. Thornes,
John Constable's skies: a fusion of art and science
. Colin A. Russell,
Edward Frankland: chemistry, controversy and conspiracy in Victorian England
. J. R. Smith,
Everest: the man and the mountain
. Barbara T. Gates,
Kindred nature: Victorian and Edwardian women embrace the living world
. Karl Sabbagh,
A rum affair
.
TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival
Authors: Liu Kang , Luo Yuhong , Lin Fang-Tsyr , Lin Weei-Chin
Published: April 2004

TopBP1 (DNA topoisomerase IIβ binding protein I) contains multiple BRCT domains and is involved in replication and the DNA damage checkpoint. Through its BRCT domain, TopBP1 interacts with and represses exclusively E2F1 but not other E2F factors. This regulation of E2F1 transcriptional activity is mediated by a pRb-independent, but Brg1/Brm-dependent mechanism. TopBP1 recruits Brg1/Brm, a central component of the SWI/SNF chromatin-remodeling complex, to E2F1-responsive promoters and represses the activities of E2F1, but not E2F2 or E2F3. This regulation is crucial in the control of E2F1-dependent apoptosis during normal cell growth and DNA damage. Interestingly, TopBP1 is induced by E2F and interacts with E2F1 during G1/S transition. Thus, TopBP1 functions as a critical modulator and serves as a negative feedback regulator of E2F1 by inhibiting E2F1-dependent apoptosis during G1/S transition as well as DNA damage to promote cell survival.
The Wealth and Information Effects of Insurers' Open Market Stock Repurchase Announcements
Authors: Born Patricia , Giaccotto Carmelo , Ritsatos Titos
Published: April 2004

Abstract

This article examines the use of an increasingly popular method of cash disbursement in the insurance industry: stock repurchase programs. Using a sample of stock repurchase announcements between 1981 and 1997, we examine the motivation for stock repurchase, estimate the market reaction to the repurchase announcement, and evaluate the magnitude of the reaction as it relates to particular insurance industry and firm characteristics. We examine the abnormal returns around the announcement day and find a significant positive wealth effect associated with repurchase announcements—a result that is consistent with that of other studies of both nonfinancial and financial firms. However, we suspect that the nature of the insurance product and the highly regulated status of the insurance industry might serve to mitigate the magnitude of an announcement effect. In fact, we find that the effect for all insurers is smaller than that obtained in samples of industrial firms. Finally, we examine the relationships between the magnitude of the announcement effect and various firm characteristics and test the significance of information signaling and Jensen's free cash flow theories in the insurance setting.
Exposure Triggers and Allocation Methods: Learning Lessons From Prior Court Rulings
Authors: McGuire Charles R. , McCullough Kathleen A. , Flanigan George B.
Published: April 2004

Abstract

This study provides a review of some of the major court rulings that have shaped and continue to shape the commercial general liability (CGL) market. The evolution of the concepts of “triggers” and allocations systems is examined to gain a perspective on the way in which courts reinterpret contract language to apply to new and emerging exposures. A review of the issues impacting the CGL provides valuable insights into the way court rulings can create a significant impact in the insurance market. A stream of court decisions provides the backdrop for today's challenges, including the reemergence of asbestos claims. The study also fills a gap in the literature related to the crisis in the CGL marketplace and changes in the pricing, regulation, and solvency of insurers operating in those lines. As old risks continue to evolve and new risks emerge, courts have begun to reinterpret liability contracts in much the same way as they reinterpreted contracts with regard to pollution and products in the 1970s and 1980s. Recent rulings related to asbestos and environmental liability underscore the importance of these issues in today's marketplace. By reviewing these events related to the CGL policy, insurers, insureds, and regulators may gain a new perspective on the importance of developing a clear standard wording that will be consistently interpreted in light of new exposures.
Immunotherapy safety: a prospective multi‐centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases
Authors: Moreno C. , Cuesta‐Herranz J. , Fernández‐Távora L. , Alvarez‐Cuesta E. ,   on behalf of the SEAIC
Published: April 2004

Background
The fear of side‐effects has led to strict regulations preventing a more widespread use of specific immunotherapy (SIT) in some countries, in spite of the low risk of systemic reactions (SRs) reported in well‐controlled studies. The goal of the study was to carry out a prospective and multi‐centric trial to evaluate the safety, risk factors and compliance degree of commercially available SIT.

Materials and methods
The study was carried out in 14 allergy departments from Spain. Four‐hundred and eighty‐eight patients with rhinitis and/or asthma were submitted to treatment with biologically standardized allergen extracts commercially available. They were administered following the European Academy of Allergy and Clinical Immunology guidelines.

Results
Four hundred and twenty‐three patients (86.7%) completed the treatment and remained under control at the end of the trial. Out of 17 526 administered doses, 17 368 doses (99.1%) were not associated with a reaction. Eighteen patients (3.7%) experienced 53 (0.3% of the doses) SRs. All immediate SRs were mild or moderate and responded well to ordinary treatment measures. There were no fatal reactions, anaphylactic shock or life‐threatening reactions. A higher ratio of SRs was found among asthmatic and dust mite allergic patients, although multi‐variable logistic analysis did not demonstrate any risk factor associated with SRs. There was also a subgroup of patients at risk for recurrent reactions, and therefore 40% of SRs had been avoided if the maximal number of SRs had been previously limited to only three SRs.

Conclusions
This multi‐centric study showed that SIT was a safe treatment with a very good compliance. Future guidelines of SIT should limit the maximal number of SRs.
Urinary leukotriene E4 and 9α, 11β‐prostaglandin F2 concentrations in mild, moderate and severe asthma, and in healthy subjects
Authors: Misso N. L. A. , Aggarwal S. , Phelps S. , Beard R. , Thompson P. J.
Published: April 2004

Background
Airway inflammation in asthma is associated with cysteinyl leukotriene and prostaglandin D2 production. Measurement of urinary metabolites of these eicosanoids may be useful for monitoring asthma patients. However, the influence of asthma phenotype and severity on basal urinary excretion of these metabolites is unknown.

Objective
To compare urinary leukotriene (LT)E4 and 9α, 11β‐prostaglandin (PG)F2 concentrations in large groups of mild, moderate and severe asthmatic patients and healthy control subjects.

Methods
Asthma severity, treatment and aspirin sensitivity were assessed by questionnaire in 168 asthmatic patients. Basal LTE4 and 9α, 11β‐PGF2 concentrations were measured in urine samples from these patients and from 175 control subjects using enzyme immunoassays.

Results
Urinary LTE4 was correlated with 9α, 11β‐PGF2 in both control subjects and asthmatic patients (P<0.002). Median LTE4 and 9α, 11β‐PGF2 concentrations in patients with severe asthma were significantly reduced compared with mild asthmatic patients (P<0.05 and <0.001, respectively). Urinary 9α, 11β‐PGF2, but not LTE4 was lower in asthmatic patients using inhaled corticosteroids (P<0.02). Multiple regression analysis indicated that urinary 9α, 11β‐PGF2 concentration was negatively correlated with asthma severity (P=0.003) and also with % predicted FEV1 (forced expiratory volume in 1 s) (P=0.005).

Conclusions
Baseline urinary LTE4 and 9α, 11β‐PGF2 concentrations are of limited value in discriminating between patients with different severities of asthma. Reduced urinary LTE4 and 9α, 11β‐PGF2 in patients with severe asthma suggest that direct or indirect effects of high‐dose corticosteroid therapy combined with other factors associated with severe asthma may influence eicosanoid production. However, the negative association of urinary 9α, 11β‐PGF2 with lung function suggests an adverse effect of chronic PGD2 production on lung function in asthma, irrespective of severity.
Expression of growth factors by airway epithelial cells in a model of chronic asthma: regulation and relationship to subepithelial fibrosis
Authors: Kumar R. K. , Herbert C. , Foster P. S.
Published: April 2004

Background
Growth factors produced by airway epithelial cells may be important in the pathogenesis of subepithelial fibrosis, a distinctive lesion of chronic human asthma.

Objective
To examine the relationship between the development of subepithelial fibrosis and the expression of transforming growth factor‐β1 (TGF‐β1) and ligands for the epidermal growth factor receptor.

Methods
BALB/c mice sensitized to ovalbumin were chronically challenged by inhalation of low levels of antigen, leading to development of subepithelial fibrosis and other changes of airway wall remodelling. Growth factor expression was assessed by immunohistochemistry and enzyme immunoassay.

Results
Allergic sensitization directly correlated with airway epithelial expression of both the cleaved, potentially biologically active form of TGF‐β1 and of amphiregulin in response to allergen challenge. Accumulation of TGF‐β1 was related to remodelling of the airway wall in chronic asthma, whereas expression of amphiregulin did not exhibit a similar relationship. Production of epithelial cell‐derived TGF‐β1 appeared to be regulated by IL‐13, while both IL‐13 and CD4+ T cells regulated accumulation of TGF‐β1. In contrast to results reported in high‐level exposure models of airway fibrosis, eosinophils did not appear to be a significant source of TGF‐β1.

Conclusion
Airway epithelial cell‐derived TGF‐β1 has a potentially crucial role in the development of airway wall remodelling in asthma. Immunological mechanisms may regulate the release and accumulation of TGF‐β1.
Production of monoclonal antibodies for immunoaffinity purification and quantitation of Blo t 1 allergen in mite and dust extracts
Authors: Ramos J. D. A. , Cheong N. , Teo A. S. M. , Kuo I.‐C. , Lee B. W. , Chua K. Y.
Published: April 2004

Background
Blo t 1 is a cysteine protease‐like allergen from Blomia tropicalis. Recombinant Blo t 1 binds up to 90% of IgE from allergic patients and shows limited cross‐reactivity to Der p 1. The generation of monoclonal antibodies (mAbs) against Blo t 1 is important for the detection, isolation and characterization of the native form of the allergen.

Methods
Mice were immunized intramuscularly with naked plasmid DNA encoding Blo t 1 gene with in vivo electroporation and boosted intraperitoneally with recombinant Blo t 1. mAbs against Blo t 1 were generated using a methylcellulose‐based hybridoma cloning kit. The native Blo t 1 was isolated by mAb affinity purification and its allergenicity was determined by ELISA. A two‐site ELISA for Blo t 1 was developed using the mAbs generated.

Results
A DNA‐based immunization protocol induced high titre Blo t 1‐specific antibodies in mice. Six stable hybridoma clones secreting mAbs recognizing the native and recombinant Blo t 1 were generated. The native Blo t 1 was affinity‐purified from a B. tropicalis extract and its allergenicity was determined at 63% using a panel of Singaporean and Malaysian mite allergic patients' sera. A two‐site ELISA was developed, which showed a detection limit of 10 ng/mL of Blot t 1.

Conclusion
Six Blo t 1 mAbs were successfully generated by DNA immunization. These mAbs are useful for nBlo t 1 immunoaffinity isolation and quantitative immunoassays for Blo t 1 in mite and environmental dust extracts.