Learning a Functional Grammar of Protein Domains using Natural Language Word Embedding Techniques

In this paper, using word2vec, a widely-used natural language processing method, we demonstrate that proteins domains may have a learnable implicit semantic "meaning" in the context of their functional contributions to multi-domain proteins in which they are found. Word2vec is a group of models which can be used to produce semantically meaningful embeddings of words or tokens in a fixed-dimension vector space. In this work, we treat multi-domain proteins as "sentences" where domain identifiers are tokens which may be considered as "words". Using all InterPro [1] pfam domain assignments we observe that the embedding could be used to suggest putative GO assignments for Pfam [2] Domains of Unknown Function. This article is protected by copyright. All rights reserved

A physically based parameterization of gravity drainage for sea-ice modeling

We incorporate a physically derived parameterization of gravity drainage, in terms of a convective upwelling velocity, into a one-dimensional, thermodynamic sea- ice model of the kind currently used in coupled climate models. Our parameterization uses a local Rayleigh number to represent the important feedback between ice salinity, porosity, permeability and desalination rate. It allows us to determine salt fluxes from sea ice and the corresponding evolution of the bulk salinity of the ice, in contrast to older, established models that prescribe the ice salinity. This improves the predictive power of climate models in terms of buoyancy fluxes to the polar oceans, and also the thermal properties of sea ice, which depend on its salinity. We analyze the behaviour of exist- ing fixed-salinity models, elucidate the physics by which changing salinity affects ice growth and compare against our dynamic-salinity model, both in terms of laboratory experiments and also deep-ocean calculations. These comparisons explain why the direct effect of ice salinity on growth is relatively small (though not always negligible, and sometimes dif- ferent from previous studies), and also highlight substantial differences in the qualita- tive pattern and quantitative magnitude of salt fluxes into the polar oceans. Our study is particularly relevant to growing first-year ice, when gravity drainage is the dominant mechanism by which ice desalinates. We expect that our dynamic model, which respects the underlying physics of brine drainage, should be more robust to changes in polar cli- mate and more responsive to rapid changes in oceanic and atmospheric forcing.This is the accepted manuscript. The final version is available from Wiley/American Geophysical Union at http://onlinelibrary.wiley.com/doi/10.1002/2013JC009296/abstract

Fast magma ascent, revised estimates from the deglaciation of Iceland

Partial melting of asthenospheric mantle generates magma that supplies volcanic systems. The timescale of melt extraction from the mantle has been hotly debated. Microstructural measurements of permeability typically suggest relatively slow melt extraction (1 m/yr) whereas geochemical (Uranium-decay series) and geophysical observations suggest much faster melt extraction (100 m/yr). The deglaciation of Iceland triggered additional mantle melting and magma flux at the surface. The rapid response has been used to argue for relatively rapid melt extraction. However, this episode must, at least to some extent, be unrepresentative, because the rates of magma eruption at the surface increased about thirty-fold relative to the steady state. Our goal is to quantify this unrepresentativeness. We develop a one-dimensional, time-dependent and nonlinear (far from steady-state), model forced by the most recent, and best mapped, Icelandic deglaciation. We find that 30 m/yr is the best estimate of the steady-state maximum melt velocity. This is a factor of about 3 smaller than previously claimed, but still relatively fast. We translate these estimates to other mid-ocean ridges accounting for differences in passive and active upwelling and degree of melting. We find that fast melt extraction greater than about 10 m/yr prevails globally.Leverhulme Trus

Evaluating Bayesian spatial methods for modelling species distributions with clumped and restricted occurrence data

Statistical approaches for inferring the spatial distribution of taxa (Species Distribution Models, SDMs) commonly rely on available occurrence data, which is often clumped and geographically restricted. Although available SDM methods address some of these factors, they could be more directly and accurately modelled using a spatially-explicit approach. Software to fit models with spatial autocorrelation parameters in SDMs are now widely available, but whether such approaches for inferring SDMs aid predictions compared to other methodologies is unknown. Here, within a simulated environment using 1000 generated species’ ranges, we compared the performance of two commonly used non-spatial SDM methods (Maximum Entropy Modelling, MAXENT and boosted regression trees, BRT), to a spatial Bayesian SDM method (fitted using R-INLA), when the underlying data exhibit varying combinations of clumping and geographic restriction. Finally, we tested how any recommended methodological settings designed to account for spatially non-random patterns in the data impact inference. Spatial Bayesian SDM method was the most consistently accurate method, being in the top 2 most accurate methods in 7 out of 8 data sampling scenarios. Within high-coverage sample datasets, all methods performed fairly similarly. When sampling points were randomly spread, BRT had a 1–3% greater accuracy over the other methods and when samples were clumped, the spatial Bayesian SDM method had a 4%-8% better AUC score. Alternatively, when sampling points were restricted to a small section of the true range all methods were on average 10–12% less accurate, with greater variation among the methods. Model inference under the recommended settings to account for autocorrelation was not impacted by clumping or restriction of data, except for the complexity of the spatial regression term in the spatial Bayesian model. Methods, such as those made available by R-INLA, can be successfully used to account for spatial autocorrelation in an SDM context and, by taking account of random effects, produce outputs that can better elucidate the role of covariates in predicting species occurrence. Given that it is often unclear what the drivers are behind data clumping in an empirical occurrence dataset, or indeed how geographically restricted these data are, spatially-explicit Bayesian SDMs may be the better choice when modelling the spatial distribution of target species

Colonel Elisha Jones of Weston and the crisis of colonial government in Massachusetts, 1773-1776

This paper contends that without the Tory dimension no factual account of the Civil War in 1774 and the beginning of the Revolution in the Colony of Massachusetts Bay is possible, and that there is no better way of demonstrating actuality in this, as in other historic problems, than by direct examination of events through the lives of those who shaped them. This paper is the first historic study of the last and most crucial crisis of Colonial Government in Massachusetts - that is, from the setting up of the Committees of Correspondence in 1772-3 (the Whig extension from Boston of single-party rule by caucus to supplant the Constitution-Charter of 1691 and political pluralism in Town Meetings) to the strategic and military victory in the Siege of Boston of rebellion, created and manipulated by a dedicated Radical minority, and the enforced withdrawal of the Loyalists, the Loyal Militia(including Brig. Timothy Ruggles' corps of Loyal Associators) with the Regular forcer, to Halifax, I. arch 17,1776-as it happened, and from the experience of one of the most active and prominent of the largely Tory soldier-Representative-magistrates that since the Mayflower Compact served as the leaders of Massachusetts: Col. Elisha Jones (1710-1776), the "famous" Tory squire of Weston, on Charles River in Middlesex County and less than a day's walk from Boston. None more than Col. Jones stood for one of the two main Tory political groups in Massachusetts in the 1770's, the "Reformers, " so often at cross-purposes with the Hutchinson- Sewall-0liver faction that supported the status quo and the undivided sovereignty of Parliament, and who when the Civil War began at the time of the Powder Alarm,Sept.1,1774, left their homes for Boston, and the fighting of the Whig political mobs with their weapons of assault and violence to property to men like Col. Jones, Brig. Ruggles, and Col. Thomas Gilbert and the Regulars, and who became the early "refugees"in England. Col. Jones was a leader of the "Reformist" Tories that supported the Constitution-Charter of 1691, and government by law and precedent in the manner of Blackstone(a best-seller in the Colonies) and who worked for the greatest measure of "home rule" and needed reforms(such as adequate pay for judges)initiated whenever possible by the General Court. Their "Charter" was the Middlesex Magistrates' Address to Gov. Hutchinson of May, 1774(signed by Col. Jones and possibly drafted by him) which looked toward an association with Britain based upon mutual economic and political interest: concepts so forward-looking as not to he fully accepted until the 20th century, and so dangerous in their own time as to merit oblivion by the Whigs and vetoes for such measures as the "Prevention of Bribery and Corruption" bill by Hutchinson. It was the "Reformers"that carried the burden of resisting the Whig assault upon the rule of law and maintenance of public order. One of fewer than a dozen Tories elected to the House in 1773 and 1774, Col. Jones opposed all the unconstitutional Whig measures, including Committees of Correspondence, impeachment of Chief Justice Oliver and the Continental Congress. One of the last magistrates to hold court he raised (Nov 1774) one of the first military Tory Corps of the War. Driven to Boston (Dec 1774) by the mobs, he served under Gage and Howe as Forage Commissioner, and three of his sons with Ruggles' Associators. Col. Jones died in Boston just before the Evacuation, but the ideas he fought for were taken to Nova Scotia and Upper Canada by five of his Tory sons, who with their descendants took a distinguished part of the foundation of a new Empire and independent nation of Canada

Spatial, seasonal and climatic predicitve models of Rift Valley Fever disease across Africa

Understanding the emergence and subsequent spread of human infectious diseases is a critical global challenge, especially for high-impact zoonotic and vector-borne diseases. Global climate and land-use change are likely to alter host and vector distributions, but understanding the impact of these changes on the burden of infectious diseases is difficult. Here, we use a Bayesian spatial model to investigate environmental drivers of one of the most important diseases in Africa, Rift Valley fever (RVF). The model uses a hierarchical approach to determine how environmental drivers vary both spatially and seasonally, and incorporates the effects of key climatic oscillations, to produce a continental risk map of RVF in livestock (as a proxy for human RVF risk). We find RVF risk has a distinct seasonal spatial pattern influenced by climatic variation, with the majority of cases occurring in South Africa and Kenya in the first half of an El Niño year. Irrigation, rainfall and human population density were the main drivers of RVF cases, independent of seasonal, climatic or spatial variation. By accounting more subtly for the patterns in RVF data, we better determine the importance of underlying environmental drivers, and also make space- and time-sensitive predictions to better direct future surveillance resources. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’

Evidence that cytokine-mediated immune interactions induced by Schistosoma mansoni alter disease outcome in mice concurrently infected with Trichuris muris.

In murine models of Schistosoma mansoni infection, egg production is associated with a switch from T helper cell (Th)1- to Th2-type responses to both schistosome-specific and unrelated antigens. Polyparasitism is common in human populations within S. mansoni endemic areas. We have, therefore, examined whether coinfection with S. mansoni could affect the outcome of a second parasitic infection, through Th2 cytokine-dependent modifications to the host immune response. We find that when mice susceptible to infection with the gut nematode Trichuris muris are coinfected with S. mansoni, they acquire the capacity to resolve T. muris infection, thus demonstrating a resistant phenotype. This ability to expel T. muris is associated with the production of Th2-associated cytokines, and corresponding antibody isotypes, in response to S. mansoni egg antigens. The Th2 response shows that there is no compartmentalization between spleen and mesenteric lymph nodes, and that the expulsion of T. muris is not caused by any changes in the host intestine associated with excretion of schistosome eggs. This influence of schistosome infections may be important, not only for the outcome of infections with unrelated pathogens in endemic areas, but also for the efficacy of vaccines in such areas

Sea-ice thermodynamics and brine drainage

Significant changes in the state of the Arctic ice cover are occurring. As the summertime extent of sea ice diminishes, the Arctic is increasingly characterized by first-year rather than multi-year ice. It is during the early stages of ice growth that most brine is injected into the oceans, contributing to the buoyancy flux that mediates the thermo-haline circulation. Current operational sea-ice components of climate models often treat brine rejection between sea ice and the ocean similarly to a thermodynamic segregation process, assigning a fixed salinity to the sea ice, typical of multi-year ice. However, brine rejection is a dynamical, buoyancy-driven process and the salinity of sea ice varies significantly during the first growth season. As a result, current operational models may over predict the early brine fluxes from newly formed sea ice, which may have consequences for coupled simulations of the polar oceans. Improvements both in computational power and our understanding of the processes involved have led to the emergence of a new class of sea-ice models that treat brine rejection dynamically and should enhance predictions of the buoyancy forcing of the oceans