Portfolio of compositions

As we begin a new century we find ourselves at a crossroads. It is a time to reappraise earlier achievements whilst continuing the quest for new forms of expression. In an analysis of seven of my own compositions it can be seen that it is possible to venture down more than one path and to explore a range of methods whilst still working within the same aesthetic boundaries. In emphasising the overriding significance of the vertical plane I propose a system of broadly non-functional harmony which provides a framework for developing musical ideas. To create a sense of harmonic progression the composer must find new ways of enabling the listener and performer to understand the time dimension. Using techniques of transformation both within ordered systems of note cells and within a freer approach to harmonic structure it is possible to organise the overall structure of a work and to establish a consistent and personal harmonic idiom. The portfolio of compositions includes scores of the following works together with recordings: 1. A STREET UNDER SIEGE, for symphony orchestra 17' 2. MAGNIFICAT AND NUNC DIMITTIS, for a capella eight part choir 14' 3. STRING QUARTET NO 6 9' 4. CLOSED CIRCUIT, for clarinet, piano and live electronics 9' 5. TURNING TABLES, for viola and harp 9' 6. ARIA - COMMEMORATION, for bassoon and piano 8'

Quantitative microscopy workflows for the study of cellular receptor trafficking

The trafficking and signalling of cellular receptors are complex, intertwined processes with many feedback mechanisms. Confocal microscopy is a powerful tool to study the trafficking of receptors. The aim of this thesis was to report and develop workflows to quantify the spatio-temporal dynamics of receptor trafficking and colocalization using confocal microscopy. Importantly, the workflows should be reproducible and unbiased, as well as automated and accurate. A 4D level set approach is developed to enable accurate cellular segmentation. Temporal constraints are introduced to further improve segmentation accuracy. This novel approach is thoroughly validated, and statistically significant performance increase over equivalent 2D and 3D approaches is demonstrated. We present a confocal microscopy based RNAi depletion screen. Specifically, quantitative workflows to identify genes which perturb the trafficking of receptor are described. Finally, a critical review of current approaches to the quantification of colocalization between receptors and endosomes is presented. Improvements to existing techniques and complete workflows are provided for 4D data (3D time-lapse). Together the described protocols provide a complete microscopy based platform to identify and investigate regulators of receptor signalling and trafficking

Relationships Between Land Uses and Indicator Bacteria in a Riverine Environment

2008 S.C. Water Resources Conference - Addressing Water Challenges Facing the State and Regio

Warfare, Demography & Anthropogenic Transformation at Angel Mounds State Historic Site

poster abstractRecent investigations by the Department of Anthropology (IU School of Liberal Arts) and the Glenn A. Black Laboratory of Archaeology (IU-Bloomington) at Angel Mounds have greatly enhanced our understanding of this Mississippian period (AD 1050-1450) village located on the Ohio River in southwestern Indiana. During this timeframe, the Ohio Valley and adjoining regions witnessed an evolution in social complexity with the emergence of small-scale polities, population aggregation in fortified towns, and associated earthwork construction. Angel Mounds was established, grew in prominence, and was eventually abandoned. However, until recently, absolute ages from the site were sparse and the chronology of the town’s settlement, growth and abandonment was poorly understood. Similarly, chronological models for earthwork and fortification construction were non-existent. Our research has revealed that Angel Mounds began as a ceremonial center between AD 1100 and 1300 with few occupants. The residential population at Angel Mounds grew precipitously after AD 1300. By AD 1400, we estimate that as many as 1,000 people lived at Angel Mounds. Concurrently, a series of fortifications were erected at the site to protect the inhabitants from neighboring polities. Meanwhile, earthworks on site were “capped” and abandoned soon thereafter, which may reflect the sociopolitical disintegration of Angel Mounds. Depending on the type of agricultural production and environmental change with the onset of the Little Ice Age, these patterns have important implications for settlement longevities, the historical ecology of land-use, and population estimates in the Eastern Woodlands of North America by AD 1500. With support from the Nation Science Foundation, the next three years of investigations at Angel Mounds will continue to focus on population dynamics, earthwork construction and use, anthropogenic transformation of the landscape, and environmental change during the Medieval Warm and Little Ice Age

Chronology of a Fortified Mississippian Village in the Central Illinois River Valley

Geophysical survey and excavations from 2010–2016 at Lawrenz Gun Club (11CS4), a late pre-Columbian village located in the central Illinois River valley in Illinois, identified 10 mounds, a central plaza, and dozens of structures enclosed within a stout 10 hectare bastioned palisade. Nineteen radiocarbon (14C) measurements were taken from single entities of wood charcoal, short-lived plants, and animal bones. A site chronology has been constructed using a Bayesian approach that considers the stratigraphic contexts and feature formation processes. The village was host to hundreds of years of continuous human activity during the Mississippi Period. Mississippian activity at the site is estimated to have begun in cal AD 990–1165 (95% probability), ended in cal AD 1295–1450 (95% probability), and lasted 150–420 yr (95% probability) in the primary Bayesian model with similar results obtained in two alternative models. The palisade is estimated to have been constructed in cal AD 1150–1230 (95% probability) and was continuously repaired and rebuilt for 15–125 yr (95% probability), probably for 40–85 yr (68% probability). Comparison to other studies demonstrates that the bastioned palisade at Lawrenz was one of the earliest constructed in the midcontinental United States

An adaptable analysis workflow for characterization of platelet spreading and morphology

The assessment of platelet spreading through light microscopy, and the subsequent quantification of parameters such as surface area and circularity, is a key assay for many platelet biologists. Here we present an analysis workflow which robustly segments individual platelets to facilitate the analysis of large numbers of cells while minimizing user bias. Image segmentation is performed by interactive learning and touching platelets are separated with an efficient semi-automated protocol. We also use machine learning methods to robustly automate the classification of platelets into different subtypes. These adaptable and reproducible workflows are made freely available and are implemented using the open-source software KNIME and ilastik

msbB deletion confers acute sensitivity to CO2 in Salmonella enterica serovar Typhimurium that can be suppressed by a loss-of-function mutation in zwf

<p>Abstract</p> <p>Background</p> <p>Pathogens tolerate stress conditions that include low pH, oxidative stress, high salt and high temperature in order to survive inside and outside their hosts. Lipopolysaccharide (LPS), which forms the outer-leaflet of the outer membrane in Gram-negative bacteria, acts as a permeability barrier. The lipid A moiety of LPS anchors it to the outer membrane bilayer. The MsbB enzyme myristoylates the lipid A precursor and loss of this enzyme, in <it>Salmonella</it>, is correlated with reduced virulence and severe growth defects that can both be compensated with extragenic suppressor mutations.</p> <p>Results</p> <p>We report here that <it>msbB </it>(or <it>msbB somA</it>) <it>Salmonella </it>are highly sensitive to physiological CO₂(5%), resulting in a 3-log reduction in plating efficiency. Under these conditions, <it>msbB Salmonella </it>form long filaments, bulge and lyse. These bacteria are also sensitive to acidic pH and high osmolarity. Although CO₂acidifies LB broth media, buffering LB to pH 7.5 did not restore growth of <it>msbB </it>mutants in CO₂, indicating that the CO₂-induced growth defects are not due to the effect of CO₂on the pH of the media. A transposon insertion in the glucose metabolism gene <it>zwf </it>compensates for the CO₂sensitivity of <it>msbB Salmonella</it>. The <it>msbB zwf </it>mutants grow on agar, or in broth, in the presence of 5% CO₂. In addition, <it>msbB zwf </it>strains show improved growth in low pH or high osmolarity media compared to the single <it>msbB </it>mutant.</p> <p>Conclusion</p> <p>These results demonstrate that <it>msbB </it>confers acute sensitivity to CO₂, acidic pH, and high osmolarity. Disruption of <it>zwf </it>in <it>msbB </it>mutants restores growth in 5% CO₂and results in improved growth in acidic media or in media with high osmolarity. These results add to a growing list of phenotypes caused by <it>msbB </it>and mutations that suppress specific growth defects.</p

CRISPR-Cas9 mediated labelling allows for single molecule imaging and resolution

AbstractSingle molecule imaging approaches like dSTORM and PALM resolve structures at 10–20 nm, and allow for unique insights into protein stoichiometry and spatial relationships. However, key obstacles remain in developing highly accurate quantitative single molecule approaches. The genomic tagging of PALM fluorophores through CRISPR-Cas9 offers an excellent opportunity for generating stable cell lines expressing a defined single molecule probe at endogenous levels, without the biological disruption and variability inherent to transfection. A fundamental question is whether these comparatively low levels of expression can successfully satisfy the stringent labelling demands of super-resolution SMLM. Here we apply CRISPR-Cas9 gene editing to tag a cytoskeletal protein (α-tubulin) and demonstrate a relationship between expression level and the subsequent quality of PALM imaging, and that spatial resolutions comparable to dSTORM can be achieved with CRISPR-PALM. Our approach shows a relationship between choice of tag and the total expression of labelled protein, which has important implications for the development of future PALM tags. CRISPR-PALM allows for nanoscopic spatial resolution and the unique quantitative benefits of single molecule localization microscopy through endogenous expression, as well as the capacity for super-resolved live cell imaging.</jats:p