LoCuSS:the connection between brightest cluster galaxy activity, gas cooling and dynamical disturbance of X-ray cluster cores

We study the distribution of projected offsets between the cluster X-ray centroid and the brightest cluster galaxy (BCG) for 65 X-ray-selected clusters from the Local Cluster Substructure Survey, with a median redshift of z= 0.23. We find a clear correlation between X-ray/BCG projected offset and the logarithmic slope of the cluster gas density profile at 0.04r500(α), implying that more dynamically disturbed clusters have weaker cool cores. Furthermore, there is a close correspondence between the activity of the BCG, in terms of detected Hα and radio emission, and the X-ray/BCG offset, with the line-emitting galaxies all residing in clusters with X-ray/BCG offsets of ≤15 kpc. Of the BCGs with α < −0.85 and an offset <0.02r500, 96 per cent (23/24) have optical emission and 88 per cent (21/24) are radio active, while none has optical emission outside these criteria. We also study the cluster gas fraction (fgas) within r500 and find a significant correlation with X-ray/BCG projected offset. The mean fgas of the ‘small offset’ clusters (<0.02r500) is 0.106 ± 0.005 (σ= 0.03) compared to 0.145 ± 0.009 (σ= 0.04) for those with an offset >0.02r500, indicating that the total mass may be systematically underestimated in clusters with larger X-ray/BCG offsets. Our results imply a link between cool core strength and cluster dynamical state consistent with the view that cluster mergers can significantly perturb cool cores, and set new constraints on models of the evolution of the intracluster medium

Assigning function to genome wide association study variants associated with complex gastrointestinal disease

PhDThe genome‐wide association study era has identified numerous loci associated with many common polygenic diseases. The next challenge is to identify the functional consequences of these variants and elicit how they impact on disease risk. Using a combination of protein based assays, large scale microarrays and high‐throughput generation sequencing platforms this thesis aims to identify the functional effects of disease loci, with particular focus on Crohn’s disease and coeliac disease, two common complex gastrointestinal diseases. Variants located within the Interleukin 23 receptor are associated with both susceptibility and protection from Crohn’s disease, a debilitating chronic inflammatory disease of the bowel. A study was undertaken to investigate the effect of these variants, at the mRNA as well as the protein level, on both cytokine and receptor levels. Coeliac disease is a dietary intolerance to the gluten component of wheat, barley and rye and has an estimated prevalence of approximately 1%. Genome‐wide association studies have identified eight genomic different loci as associated with coeliac disease but none have been functionally characterised. To investigate the effect that genotype has on gene transcript levels, a genetical genomics study was undertaken in patients with coeliac disease generating results with relevance to a range of autoimmune disorders. Before disease based effects can be identified, it is first important to fully characterise the normal human transcriptome and methylome. To this end CD4 + T cells were studied using novel high‐throughput sequencing techniques, with the aim of providing some insight into novel genomic properties that may illuminate current and future disease associated loci. Given the base pair resolution approach of high‐throughput sequencing, a novel method of assaying for SNP effects on gene expression was developed. This allele specific method, using whole transcriptome sequencing, is capable of identifying alterations in transcript expression on a genome‐wide scale

Methods for nanoparticle labeling of ricin and effect on toxicity

The unique optical properties associated with nanostructured materials that support the excitation of surface plasmons offer many new opportunities for the enhanced optical investigation of biological materials that pose a security threat. In particular, ricin is considered a significant bioterrorism risk due to its high toxicity combined with its ready availability as a byproduct in castor oil production. Therefore, the development of optical techniques capable of rapid on-site toxin detection with high molecular specificity and sensitivity continues to be of significant importance. Furthermore, understanding of the ricin cell entry and intracellular pathways remains poor due to a lack of suitable bioanalytical techniques. Initial work aimed at simultaneously tackling both these issues is described where different approaches for the nanoparticle labeling of ricin are investigated along with changes in ricin toxicity associated with the labeling process

Reviews

Web‐Teaching ‐ A Guide to Interactive Teaching for the World‐Wide Web by David W. Brooks, New York: Plenum, 1997. ISBN: 0–306–45552–8. Paperback, 214 pages. $30

The German Melibeus and other vernacular versions of the works of Albertano da Brescia

Albertano da Brescia's three treatises are compilations, and therefore form a part of an enormous mass of mediaeval literature. This thesis performs two principal tasks as a step towards an assessment of the importance of Albertano as a compilist, and of his works as repositories of classical knowledge and therefore as source-material for the writings of many mediaeval and Renaissance authors. First, text-critical editions of two different translations into fifteenth-century German of Albertano's Liber consolationis et consilii (Melibeus) are given. An examination of the interrelationship and transmission of manuscripts and early prints reveals the great popularity of just one of these translations on the eve of the Renaissance. Second, a further indication of the popularity of Albertano's works throughout mediaeval Western Europe is given by the provision of details of all hitherto known manuscripts and early prints containing translations or workings of the treatises in the vernacular. Many of these are recent discoveries. In order to provide the reader with a wherever possible. Finally, an overview of works known to contain specific borrowings from Albertano is given, together with further literature, where this exists. The extent of the influence that Albertano's compilations exerted is indicated by the familiarity of the names of authors borrowing from him: Geoffrey Chaucer, Dante Alighieri, Christine de Pisan and Erhart Gross, to name just four

Spectroscopic monitoring of long-term AGN transients: threading the micro-needle

All active galactic nuclei (AGN) are known to vary in the rest-frame UV/optical. Typical variations are on the order of 30% or so and are stochastic in nature. Therefore, the discovery of a number of extreme AGN transients, which are smoothly evolving on year-long timescales and by a factor of four or more, is surprising and necessitates further analysis. Are these objects simply at the extreme end of the variability distribution seen in normal quasars or is there another mechanism which can explain their atypical behaviour? The primary focus for this work is on the possibility that a number of these extreme AGN transients are actually rare, high-amplitude microlensing events, caused by intervening stellar mass object(s). Not only do the microlensing models provide an explanation for the observed variability but they also allow constraints to be placed on the morphology of the emitting regions of the AGN, namely the accretion disc and broad line region (BLR). These transients have been monitored both photometrically and spectroscopically, since their discovery. The majority of spectroscopic observations have been conducted using the William Herschel Telescope. At time of writing (Sept. 2017), there are now 64 confirmed AGN and 235 individual spectra. The spectral reduction pipeline, calibration and initial measurements are described in Chapter 2. This chapter also details the microlensing models and procedures used in interpreting both the light curve information and spectral measurements. This includes: a comprehensive treatment of the simple point-source/point-lens model; quantitative point-lens models which allow for the use of extended sources; and also an initial exploration into more complex lensing morphologies involving multiple lensing objects and/or an external shear. Chapter 3 details the results of the spectroscopic monitoring campaign for the entire transient sample. A general classification scheme is developed which allows for a comparison of the evolutionary trends seen in objects exhibiting similar behaviour. A subset of transient AGN, the most extreme objects in the sample, is also discussed in detail, with a particular focus on the evolution of the continuum, line fluxes and equivalent widths. Chapter 4 details the results of the analysis of four key targets, selected for their suitability in addressing the microlensing hypothesis. For two targets the point-source point-lens model performs very well. Lens parameters for these objects are presented and in one particular case, the data is sufficient to allow constraints to be placed on the size of various components comprising the broad line region. Chapter 5 expands the microlensing analysis to include the entire AGN transient sample. Approximately 10% of objects are well matched by a simple point-source, point-lens microlensing model. In other objects, evidence is seen which requires a more complex lensing scenario to adequately explain. In one class of objects there is also evidence that the accretion disc is being resolved by the lens. Chapter 6 revisits a notable are seen in an AGN which lies behind M31. The analysis reaffirms that this event is well described by a simple microlensing model and provides an independent estimate that the most probable location for the lens is within M31 itself

Structural studies of herbicide detoxifying enzymes

Glutathione S-transferases (GSTs) [EC 2.5.1.18] are a ubiquitous family of multifunctional enzymes that are widely distributed in nature. GSTs have been identified from bacteria, fungi, insects, cephalopods, fish, amphibians, reptiles, avians, mammals and plants. The major role of GSTs is the conjugation of the tripeptide glutathione (GSH; gamma-L-glutamyl-L-cysteinyl-glycine) to a range of electrophilic substances. Ten GSTs from rice, wheat, petunia and Arabidopsis thaliana were overexpressed in Escherichia coli and purified using an Orange A agarose column, S-hexyl glutathione sepharose column, or a nickel chelation column. Using a variety of crystallization screens, crystals were grown for six of the proteins. The X-ray diffraction data collected for two of these proteins enabled their structure to be solved. The first structure to be solved was that of OsGSTU1-1 in complex with GSH, which is a different subgroup of Tau class GSTs from that of the previously reported TaGSTU4-4. OsGSTUI is similar in sequence to the well characterized ZmGSTUI and ZmGSTU2, safener induced enzymes from maize highly active against the diphenyl ether herbicide fluorodifen. In order to determine the structural basis of OsGSTU1 substrate specificity a number of GSH conjugates were prepared. A conjugate of CDNB with GSH was prepared by enzymatic routes using the enzyme ZmGSTF1. The reaction product of the herbicide fluorodifen with GSH was prepared by a two-step synthetic route by preparing a sulfonamide of the phenyl ring and reacting this with GSH. The structure of OsGSTU1-1 was solved with both of these conjugates bound as well as with that of a conjugate of the chloracetanilide herbicide metolachlor with GSH. The structure with metolachlor-GSH bound was useful in structurally characterizing the mode of binding of chloracetanilide herbicides. The structures with the CDNB conjugate with GSH and the reaction product of fluorodifen with GSH were less useful in determining the mode of binding of diphenyl ether herbicides. Both ligands were similar to each other and were found to be sitting between the two lobes of the active site with the nitro group facing inwards. This suggests that the orientation of the molecule within the active site predicted by Dixon et al., 2003 may be incorrect. The structure of OsGSTU4-4 has also been solved in complex with GSH. This enzyme is similar to TaGSTU4-4 and is highly expressed in rice under a variety of stress conditions. A comparison of the three Tau class GST structures now available, along with enzyme assays against a range of xenobiotics substrates has helped to partially understand the activity of Tau class GSTs in herbicide detoxification. The H-site of Tau class GSTs has two lobes. The previously reported structure of TaGSTU4-4 in complex with S-hexylglutathione has the hexyl chain sitting in lobe 'A', but in the structure with metolachlor-GSH the ligand is sitting in lobe 'B' with the gatekeeper Tyr 116 swung away from the active site and disordered. Conformational changes in plant GSTs were also investigated. A comparison of the structures of apo-form ZmGSTF1-1 with the structures of the enzyme in complex with herbicides showed that a conformation change seemed to occur upon ligand binding. Using UV Difference spectroscopy and circular dichroism a change in the conformation of ZmGSTF1-l was seen upon binding of GSH. However, there were problems with the reproducibility of these results. In the case of AtGSTT1-1, which shows a large difference in conformations between molecules in the apo-form of the crystal structure, both UV difference spectroscopy and circular dichroism showed no spectroscopic changes upon GSH binding

Intraperitoneal Rupture of Ectopic Varices—a Rare Complication of Portal Hypertension

A 50 year old man presented with sudden abdominal pain, abdominal distension and shock. At emergency laparotomy a large amount of blood was found in the peritoneal cavity. There was micronodular cirrhosis of the liver and the spleen was enlarged. The bleeding was traced to distended veins in the right paracolic gutter which were oversewn and the abdomen closed. A coagulopathy was diagnosed and treatment including high dose aprotinin commenced. However, he continued to bleed and at a second laparotomy the area of previous haemorrhage was packed. Further deterioration continued until death 12 hours later. Intraperitoneal haemorrhage from ectopic varices is a rare occurrence. There is a high mortality rate usually due to an advanced coagulopathy. This is the first report of aprotinin being used in an attempt to treat this. On the basis of this report aprotinin would not seem to be of benefit for this condition

The diary of James Brownlee

James Brownlee was born in April 1824. He was the second of three sons (and five daughters) born to the missionary John Brownlee, and his colonial born wife Catharine. The importance of James as an historical character is obscured by that of his father and elder brother Charles. James had a varied career which was cut short by his untimely death in March 1851 at the youthful age of twenty-six years and eleven months. We are fortunate that he has left a vivid account of several aspects of the seventh Frontier War in a diary which he kept from April to September 1846. The diary also points to the significance of his family in the history of the Eastern Cape. Thesis, p. 1