Calving of tabular icebergs from ice shelves accounts for around half of all the ice lost from Antarctica each year. The icebergs form when full-thickness fractures (known as rifts) propagate horizontally through the ice shelf. The resulting icebergs can be thousands of square kilometres in size, can impact wildlife, shipping and ocean circulation and can modify the shape and stability of the ice shelves which remain, with a subsequent impact on ice discharge and sea level rise. The timing of calving is currently unpredictable and is only included superficially in some ice sheet models, for example by removing ice once a certain thickness is reached. Rifts have been observed to propagate very rapidly, at up to several kilometres per day, or very slowly, stagnating for years or even decades. Whilst it is well established that ice shelf collapse can lead to glacier acceleration, recent observations also show moderate calving events directly and immediately impacting ice flow and basal melt rate, indicating an urgent need to constrain the timing of this process and whether it will accelerate in the future. Simultaneously, developments in fracture approximation methods driven by engineering applications have made it possible to represent discrete fractures numerically, provided the behaviour at the small-scale and large-scale is calibrated with observations. Lack of observations currently limits the value of this type of modelling in glaciology. Our research combines direct observations of rift growth on the Brunt Ice Shelf in Antarctica with laboratory experiments on samples of the same ice, which when linked together produce unprecedented detail on the fracture process across multiple scales. This level of detail will be applied to the fracture problem using a new scalable phase-field model that allows microscale processes to be mapped onto a low-resolution ice-sheet-scale grid using diffuse interfaces at crack boundaries. We will conduct laboratory observations of how cracks interact with ice at the crystal level, and in situ observations of how rifts interact with the ice shelf at the kilometre level to validate and test this model. This will illuminate the three-dimensional mechanism behind rift growth and the physical ice properties that control its rate. A step-change improvement in how the calving process is represented in ice sheet models has benefits across the geoscience community, from ice sheet modellers who need to estimate ice shelf buttressing stress and the impact of calving on grounding line dynamics, to large scale earth-system modellers which rely on accurate ice shelf geometry to constrain freshwater fluxes and rates of sea ice formation.

Tuberculosis is one of the top 10 causes of death worldwide. In 2017, 10 million people developed the disease; it caused 1.6 million deaths (World Health Organisation). The disease is caused by the infectious mycobacterium Mycobacterium tuberculosis and current treatment strategies rely on taking a combination of drugs over an extended period with unpleasant and damaging side-effects; in addition, growing antibiotic-resistance threatens to compromise even these treatments. A new strategy uses drugs which target energy metabolism, an approach which has not previously been used to target bacteria. However, the new clinical candidates were discovered without an understanding of the target or mechanism of action, as the details of mycobacterial energy metabolism remain to be elucidated. We need this fundamental knowledge to design more effective antibacterial drugs, and understand the synergy arising from using antibacterials together. Energy metabolism comprises the reactions that generate ATP, the energy currency of the cell. Most of this energy comes from passing electrons from food molecules, such as sugars, to oxygen. As the electrons are passed down an electron transport chain, the released energy is used to synthesise ATP. The large enzyme complexes that catalyse these reactions in mycobacteria are little understood, as is their organisation within the cell. This work will combine cell-level biophysical techniques on living bacteria with molecular-level structural and functional investigations of individual components to answer critical questions on how mycobacterial energy metabolism works and how it can be exploited. Our overarching questions are: -How do some of the unusual enzymes found in mycobacteria convert energy and allow the organism to respond to lethal stresses? -How are energy-converting systems organised in mycobacteria? -What are the mechanisms that allow mycobacteria to survive in different oxygen concentrations in the body? -What happens when these essential processes are attacked by antibiotics? A number of non-invasive biophysical techniques will be brought together in a single device to create a 'bioenergetic chamber'; these techniques have not been previously used together. This device will allow us to measure key cellular molecules without needing to break open or disrupt the bacteria, providing a unique window into the workings of the cell. It is important to measure these parameters noninvasively as even very mild perturbations to the cell, with an antibiotic for example, lead to rapid changes so that 'quench-and-measure' techniques are often compromised. These noninvasive measurements will be complemented by studies on the in vivo organisation of the electron transport chain. Once we have an understanding of how the systems work in untreated bacteria, we will add clinical antibiotics, such as bedaquiline and isoniazid, to observe how these drugs work to disrupt the cell. By clarifying their mechanism of action, we should be able to offer insights into how to make more effective antibiotics. These measurements made on the cellular level will be expanded with molecular-level biophysical investigations of how key enzymes function using electron cryomicroscopy (cryoEM) and specialised functional assays. CryoEM has recently undergone a revolution and now allows us to image enzymes and computationally reconstruct their structure at near atomic resolution. We will focus on the 'bd oxidase', which has an important role in allowing tuberculosis to survive in the low oxygen conditions found deep inside the tubercles that grow in patients' lungs; the enzyme also breaks down hydrogen peroxide, a molecule often made by the body to kill invading bacteria. We will complement these studies by examining the three related enzymes at the 'succinate:quinone' junction, which are also critical in allowing tuberculosis to adapt to different oxygen conditions.

The 800-page folio Reliquiae Baxterianae: or, Mr. Richard Baxter's narrative of the Most Memorable Passages of his Life and Times (1696) consists of autobiographical papers, with supporting documents, written in the main in 1664, 1665 and 1670-85, covering the seventy-year period from Baxter's birth in 1615, most expansively the years following the restoration of monarchy and Charles II's return in 1660. Its editor was the nonconformist minister Matthew Sylvester (1636?-1708). \n\nThe significance of Reliquiae Baxterianae is three-fold. First, it is an unrivalled primary historical source for seventeenth-century English political, religious, social, cultural and literary history. Baxter offers a first-hand account of events at the highest level (he met, and comments on, Cromwell, Charles II, Clarendon, Sheldon) but he is also (particularly through his ministry) a witness to the experiences of a great range of provincial members of the mercantile, clerical, artisan and agricultural classes. \n\nSecondly, the Reliquiae is a foundation text for eighteenth-century ecclesiastical and historiographical traditions. Its vindication of moderate Puritanism and its accounts of the early nonconformists passed Baxterianism on to eighteenth-century dissent. In this respect, the Reliquiae was an early contributor to the literary civil war prompted by the 'Glorious Revolution' of 1688/89 to determine the master narrative of seventeenth-century English history. \n\nThirdly, Baxter's was one of the most acute intelligences and complex personalities of the period. He was fascinated by individuality, by temperament and by psychology, his own as much as others'. The Reliquiae is rich in sharply realised and acute characterisations and in passages of remarkably perceptive self-scrutiny and reflection, leading to its being hailed as one of the masterpieces of early autobiographical writing in the English tradition and as a key text in the development of both historiography and autobiography as distinct literary genres.\n\nSylvester, however, was an unskilful editor, confessing himself 'deeply sensible of my inability for such Work' as editing Baxter's 'great quantity of loose Papers'. His edition is disfigured by an inconsistent formal arrangement, confused in its narrative shape and chronology, interrupted by blocks of documentation, textually inaccurate and incomplete. Scholars have repeatedly lamented that the range and richness of the primary evidence in this densely referential work of great length (c. 1,000,000 words) is consequently largely inaccessible. 'No book of its importance was ever worse edited' observed the Unitarian historian Alexander Gordon. The Reliquiae is the most significant and substantial seventeenth-century work of personal record never to have received scholarly editorial attention (compare Bunyan, Burnet, Clarendon, Evelyn, Morrice, Pepys). \n\nTo address this need N. H. Keeble is leading an editorial team that has been commissioned by OUP to prepare a fully annotated five-volume scholarly edition. The edition will establish an accurate and reliable text, working from the manuscript where this is extant; it will identify, gloss and index every person, incident and topic mentioned; it will give a full bibliographical account of the text, set out the history of its composition and publication, and discuss its reception; and a full introduction will explore the nature and significance of the text.\n\nThis project is strongly supported by the Trustees of Dr. Williams's Library, which holds much of the extant manuscript, and by the Dr. Williams's Centre for Dissenting Studies, of which Dr. David Wykes and Professor Isabel Rivers are co-directors. (An account of the project is available at http://www.english.qmul.ac.uk/drwilliams/research/baxter.html.) There is one coinvestigator, Professor John Coffey of Leicester University, and one academic partner, Dr Tim Cooper of Otago University.

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