Order and disorder in Europe: Parliamentary agents and Royalist thugs 1649-1650

After the execution of Charles I in 1649 a series of daring and desperate attempts were made on the lives of agents and ambassadors dispatched to continental Europe by the fledgling republic. This essay explores the evidence relating to these plots, and to the murders of Isaac Dorislaus and Anthony Ascham, in an attempt to show that the royalists responsible were not merely desperadoes seeking revenge for the murder of their king, but the employees and emissaries of prominent exiled courtiers. The complicity of Montrose, Cottington and Hyde in such conspiracy can be both documented and explained, in the context of the struggle for diplomatic recognition and financial assistance in the months of shock, outrage and uncertainty after the regicide. The concerns of diplomacy and high politics which lay behind these plots also helped to determine the reaction of European leaders, as it gradually became clear on whose side fortune smiled in Britain

John Lilburne and the Long Parliament

This piece reinterprets the career of the Leveller, John Lilburne, during the English Civil War, by re-examining the official sources pertaining to him, and the multitude of pamphlets written by himself and his enemies. The article recovers the chronology of Lilburne's story, by stripping away the layers of propaganda with which he later surrounded himself. It shows that he had powerful friends at Westminster, and that his tribulations were caused by political rivalries within Westminster rather than his development of a radical political theory. He is shown to have formed part of the Independent alliance during the mid-1640s, although his protected position was eventually imperilled by the fracturing of this group after the end of the first Civil War. The aim is to improve not just our understanding of Lilburne, but the complexity of parliamentarian politics during the 1640s

Synthetic chemical inducers and genetic decoupling enable orthogonal control of the rhaBAD promoter

External control of gene expression is crucial in synthetic biology and biotechnology research and applications, and is commonly achieved using inducible promoter systems. The E. coli rhamnose-inducible rhaBAD promoter has properties superior to more commonly-used inducible expression systems, but is marred by transient expression caused by degradation of the native inducer, L-rhamnose. To address this problem, 35 analogs of L-rhamnose were screened for induction of the rhaBAD promoter, but no strong inducers were identified. In the native configuration, an inducer must bind and activate two transcriptional activators, RhaR and RhaS. Therefore, the expression system was reconfigured to decouple the rhaBAD promoter from the native rhaSR regulatory cascade so that candidate inducers need only activate the terminal transcription factor RhaS. Re-screening the 35 compounds using the modified rhaBAD expression system revealed several promising inducers. These were characterised further to determine the strength, kinetics and concentration-dependence of induction; whether the inducer was used as a carbon source by E. coli; and the modality (distribution) of induction among populations of cells. L-Mannose was found to be the most useful orthogonal inducer, providing an even greater range of induction than the native inducer Lrhamnose, and crucially, allowing sustained induction instead of transient induction. These findings address the key limitation of the rhaBAD expression system, and suggest it may now be the most suitable system for many applications

In praise of tedious anatomy

Functional neuroimaging is fundamentally a tool for mapping function to structure, and its success consequently requires neuroanatomical precision and accuracy. Here we review the various means by which functional activation can be localized to neuroanatomy and suggest that the gold standard should be localization to the individual’s or group’s own anatomy through the use of neuroanatomical knowledge and atlases of neuroanatomy. While automated means of localization may be useful, they cannot provide the necessary accuracy, given variability between individuals. We also suggest that the field of functional neuroimaging needs to converge on a common set of methods for reporting functional localization including a common “standard” space and criteria for what constitutes sufficient evidence to report activation in terms of Brodmann’s areas

Growth factors in idiopathic pulmonary fibrosis: relative roles

Treatment of idiopathic pulmonary fibrosis patients has evolved very slowly; the fundamental approach of corticosteroids alone or in combination with other immunosuppressive agents has had little impact on long-term survival. The continued use of corticosteroids is justified because of the lack of a more effective alternative. Current research indicates that the mechanisms driving idiopathic pulmonary fibrosis reflect abnormal, dysregulated wound healing within the lung, involving increased activity and possibly exaggerated responses by a spectrum of profibrogenic growth factors. An understanding of the roles of these growth factors, and the way in which they modulate events at cellular level, could lead to more targeted therapeutic strategies, improving patients' quality of life and survival

Effects of changing mosquito host searching behaviour on the cost effectiveness of a mass distribution of long-lasting, insecticidal nets : a modelling study

The effectiveness of long-lasting, insecticidal nets (LLINs) in preventing malaria is threatened by the changing biting behaviour of mosquitoes, from nocturnal and endophagic to crepuscular and exophagic, and by their increasing resistance to insecticides.; Using epidemiological stochastic simulation models, we studied the impact of a mass LLIN distribution on Plasmodium falciparum malaria. Specifically, we looked at impact in terms of episodes prevented during the effective life of the batch and in terms of net health benefits (NHB) expressed in disability adjusted life years (DALYs) averted, depending on biting behaviour, resistance (as measured in experimental hut studies), and on pre-intervention transmission levels.; Results were very sensitive to assumptions about the probabilistic nature of host searching behaviour. With a shift towards crepuscular biting, under the assumption that individual mosquitoes repeat their behaviour each gonotrophic cycle, LLIN effectiveness was far less than when individual mosquitoes were assumed to vary their behaviour between gonotrophic cycles. LLIN effectiveness was equally sensitive to variations in host-searching behaviour (if repeated) and to variations in resistance. LLIN effectiveness was most sensitive to pre-intervention transmission level, with LLINs being least effective at both very low and very high transmission levels, and most effective at around four infectious bites per adult per year. A single LLIN distribution round remained cost effective, except in transmission settings with a pre-intervention inoculation rate of over 128 bites per year and with resistant mosquitoes that displayed a high proportion (over 40%) of determined crepuscular host searching, where some model variants showed negative NHB. Shifts towards crepuscular host searching behaviour can be as important in reducing LLIN effectiveness and cost effectiveness as resistance to pyrethroids. As resistance to insecticides is likely to slow dow the development of behavioural resistance and vice versa, the two types of resistance are unlikely to occur within the same mosquito population. LLINs are likely cost effective interventions against malaria, even in areas with strong resistance to pyrethroids or where a large proportion of host-mosquito contact occurs during times when LLIN users are not under their nets

Convergence towards an asymptotic shape in first-passage percolation on cone-like subgraphs of the integer lattice

In first-passage percolation on the integer lattice, the Shape Theorem provides precise conditions for convergence of the set of sites reachable within a given time from the origin, once rescaled, to a compact and convex limiting shape. Here, we address convergence towards an asymptotic shape for cone-like subgraphs of the $\Z^d$ lattice, where $d\ge2$. In particular, we identify the asymptotic shapes associated to these graphs as restrictions of the asymptotic shape of the lattice. Apart from providing necessary and sufficient conditions for $L^p$- and almost sure convergence towards this shape, we investigate also stronger notions such as complete convergence and stability with respect to a dynamically evolving environment.Comment: 23 pages. Together with arXiv:1305.6260, this version replaces the old. The main results have been strengthened and an earlier error in the statement corrected. To appear in J. Theoret. Proba

Steps in immunosuppression for renal transplantation

The authors provide a historical survey of the immunosuppressive agents that have been used to prevent allograft rejection. Attention is given to the expected effect of cyclosporin in kidney translations