Intraclonal heterogeneity and distinct molecular mechanisms characterize the development of t(4;14) and t(11;14) myeloma.

We have used whole exome sequencing to compare a group of presentation t(4;14) with t(11;14) cases of myeloma to define the mutational landscape. Each case was characterized by a median of 24.5 exonic nonsynonymous single-nucleotide variations, and there was a consistently higher number of mutations in the t(4;14) group, but this number did not reach statistical significance. We show that the transition and transversion rates in the 2 subgroups are similar, suggesting that there was no specific mechanism leading to mutation differentiating the 2 groups. Only 3% of mutations were seen in both groups, and recurrently mutated genes include NRAS, KRAS, BRAF, and DIS3 as well as DNAH5, a member of the axonemal dynein family. The pattern of mutation in each group was distinct, with the t(4;14) group being characterized by deregulation of chromatin organization, actin filament, and microfilament movement. Recurrent RAS pathway mutations identified subclonal heterogeneity at a mutational level in both groups, with mutations being present as either dominant or minor subclones. The presence of subclonal diversity was confirmed at a single-cell level using other tumor-acquired mutations. These results are consistent with a distinct molecular pathogenesis underlying each subgroup and have important impacts on targeted treatment strategies. The Medical Research Council Myeloma IX trial is registered under ISRCTN68454111.

Advertising Colonial Romance and Imperial Masculinity: The Promotion of Philip Meadows Taylor's Novels in Britain

The comments of Charles Kegan Paul, the Victorian publisher who was involved in publishing the novels of the nineteenth-century British-Indian author Philip Meadows Taylor as single volume reprints in the 1880s, are illuminating. They are indicative of the publisher's position with regard to publishing - that there was often no correlation between commercial success and the artistic merit of a work. According to Kegan Paul, a substandard or mediocre text would be commercially successful as long it met a perceived want on the part of the public. In effect, the ruminations of the publisher suggests that a firm desirous of acquiring commercial success for a work should be an astute judge of the pre-existing wants of consumers within the market. Yet Theodor Adorno, writing in the mid-twentieth century, offers an entirely distinctive perspective to Kegan Paul's observations, arguing that there is nothing foreordained about consumer demand for certain cultural tropes or productions. They in fact are driven by an industry that preempts and conditions the possible reactions of the consumer. Both Kegan Paul's and Adorno's insights are illuminating when it comes to addressing the key issues explored in this essay. Kegan Paul's comments allude to the ways in which the publisher's promotion of Philip Meadows Taylor's fictional depictions of India and its peoples were to a large extent driven in the mid- to late-nineteenth century by their expectations of what metropolitan readers desired at any given time, whereas Adorno's insights reveal the ways in which British-Indian narratives and the public identity of their authors were not assured in advance, but were, to a large extent, engineered by the publishing industry and the literary marketplace.

Session organiser/chair: The architecture of coal and other energies

Coal ignited the industrial revolution. An organic sedimentary rock that energized the globe, transforming cities, landscapes and societies for generations, the importance of ‘King Coal’ to the development and consolidation of modernity has been well-recognised. And yet, as a critical factor in the production of modern architecture, coal—as well as other forms of energy—has been mostly overlooked.

From Appalachia to Lanarkshire, from the pits of northern France, Belgium and the Ruhr valley, to the monumental opencast excavations of Russia, China, Africa and Australia, mining operations have altered the immediate social and physical landscapes of coal-rich areas. But in contrast to its own underground conditions of production, the winning of coal, especially in the twentieth-century, has produced conspicuously enlightened and humane approaches to architecture and urbanism. In the twentieth century, educational buildings, holiday camps, hospitals, swimming pools, convalescent homes and housing prevailed alongside model collieries in mining settlements and areas connected to them. In 1930s Britain, pit head baths—funded by a levy on each ton produced—were often built in the International Style. Many won praise for architectural merit, appearing in Nicholas Pevsner’s guides to the buildings of England alongside cathedrals, village manors and Masonic halls as testimonies to the public good.

The deep relationships between coal and modernity, and the expressions of architecture it has articulated, in the collieries from which it was hewn, the landscape and towns it shaped, and the power stations and other infrastructure where it was used, offer innumerable opportunities to explore how coal produced architectures which embodied and expressed both social and technological conditions. While proposals on coal are preferred, we also welcome papers that interrogate the complexity, heterogeneity and hybridity of other forms of energy production and how these have also interceded into architectural form at a range of scales.