In order and out of time : compositions exploring processes, polymeters and balance

These compositions explore concepts based on processes and polymeter. Drawing on influences ranging from Steve Reich to Conlon Nancarrow and Nik Bärtsch they use and develop an approach to rhythmic thinking based on ostinati constructed of layers of different speeds. Through the use of click tracks, they look at how an ensemble can be enabled to perform rhythms that, without the electronic support, would be unplayable – crossing a line between the possible and the impossible. By means of processes built on a number of different ideas, the pieces explore how these can be used to affect both the behaviour and evolution of musical material, as well as using them to create fixed structures within which I then move subjectively and more intuitively. The question of balance, of moving between two points or approaches that are seemingly opposites, has also been examined: looking at how the journey affects the destination, where the simple becomes complex, and where personal meets impersonal.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence

Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19

Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death

End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n=256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. 203 proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3) and epithelial injury (e.g. KRT19). Machine learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets

Low Cost Tuberculosis Vaccine Antigens in Capsules: Expression in Chloroplasts, Bio-Encapsulation, Stability and Functional Evaluation In Vitro

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading fatal infectious diseases. The development of TB vaccines has been recognized as a major public health priority by the World Health Organization. In this study, three candidate antigens, ESAT-6 (6kDa early secretory antigenic target) and Mtb72F (a fusion polyprotein from two TB antigens, Mtb32 and Mtb39) fused with cholera toxin B-subunit (CTB) and LipY (a cell wall protein) were expressed in tobacco and/or lettuce chloroplasts to facilitate bioencapsulation/oral delivery. Site-specific transgene integration into the chloroplast genome was confirmed by Southern blot analysis. In transplastomic leaves, CTB fusion proteins existed in soluble monomeric or multimeric forms of expected sizes and their expression levels varied depending upon the developmental stage and time of leaf harvest, with the highest-level of accumulation in mature leaves harvested at 6PM. The CTB-ESAT6 and CTB-Mtb72F expression levels reached up to 7.5% and 1.2% of total soluble protein respectively in mature tobacco leaves. Transplastomic CTB-ESAT6 lettuce plants accumulated up to 0.75% of total leaf protein. Western blot analysis of lyophilized lettuce leaves stored at room temperature for up to six months showed that the CTB-ESAT6 fusion protein was stable and preserved proper folding, disulfide bonds and assembly into pentamers for prolonged periods. Also, antigen concentration per gram of leaf tissue was increased 22 fold after lyophilization. Hemolysis assay with purified CTB-ESAT6 protein showed partial hemolysis of red blood cells and confirmed functionality of the ESAT-6 antigen. GM1-binding assay demonstrated that the CTB-ESAT6 fusion protein formed pentamers to bind with the GM1-ganglioside receptor. The expression of functional Mycobacterium tuberculosis antigens in transplastomic plants should facilitate development of a cost-effective and orally deliverable TB booster vaccine with potential for long-term storage at room temperature. To our knowledge, this is the first report of expression of TB vaccine antigens in chloroplasts

A thermodynamic model for C-(N-)A-S-H gel: CNASH_ss. Derivation and validation

The main reaction product in Ca-rich alkali-activated cements and hybrid Portland cement (PC)-based materials is a calcium (alkali) aluminosilicate hydrate (C-(N-)A-S-H) gel. Thermodynamic models without explicit definitions of structurally-incorporated Al species have been used in numerous past studies to describe this gel, but offer limited ability to simulate the chemistry of blended PC materials and alkali-activated cements. Here, a thermodynamic model for C-(N-)A-S-H gel is derived and parameterised to describe solubility data for the CaO–(Na2O,Al2O3)–SiO2–H2O systems and alkali-activated slag (AAS) cements, and chemical composition data for C-A-S-H gels. Simulated C-(N-)A-S-H gel densities and molar volumes are consistent with the corresponding values reported for AAS cements, meaning that the model can be used to describe chemical shrinkage in these materials. Therefore, this model can provide insight into the chemistry of AAS cements at advanced ages, which is important for understanding the long-term durability of these materials

Risk Prediction for Acute Kidney Injury in Acute Medical Admissions in the UK

Background Acute Kidney Injury (AKI) is associated with adverse outcomes; identifying patients who are at risk of developing AKI in hospital may lead to targeted prevention. This approach is advocated in national guidelines but is not well studied in acutely unwell medical patients. We therefore aimed to undertake a UK-wide study in acute medical units (AMUs) with the following aims: to define the proportion of acutely unwell medical patients who develop hospital-acquired AKI (hAKI); to determine risk factors associated with the development of hAKI; and to assess the feasibility of using these risk factors to develop an AKI risk prediction score. Methods In September 2016, a prospective multicentre cohort study across 72 UK AMUs was undertaken. Data were collected from all patients who presented over a 24-hour period. Chronic dialysis, community-acquired AKI (cAKI) and those with fewer than two creatinine measurements were subsequently excluded. The primary outcome was the development of h-AKI. Results 2,446 individuals were admitted to the AMUs of the 72 participating centres. 384 patients (16%) sustained AKI of whom 287 (75%) were cAKI and 97 (25%) were hAKI. After exclusions, 1,235 participants remained in whom chronic kidney disease (OR 3.08, 95% CI 1.96-4.83), diuretic prescription (OR 2.33, 95% CI 1.5-3.65), a lower haemoglobin concentration and an elevated serum bilirubin were independently associated with development of hAKI. Multivariable model discrimination was moderate (c-statistic 0.75), and this did not support the development of a robust clinical risk prediction score. Mortality was higher in those with hAKI (adjusted OR 5.22; 95% CI 2.23-12.20). Conclusion AKI in AMUs is common and associated with worse outcomes, with the majority of cases community acquired. The smaller proportion of hAKI cases, only moderate discrimination of prognostic risk factor modelling and the resource implications of widespread application of an AKI clinical risk score across all AMU admissions suggests that this approach is not currently justified. More targeted risk assessment or automated methods of calculating individual risk may be more appropriate alternatives

ACBD3, Its Cellular Interactors, and Its Role in Breast Cancer

ACBD3 breast cancer research to date reveals that overexpression at mRNA and protein level is near universal in breast tumour tissue and that high ACBD3 expression is associated with worse patient prognosis. ACBD3 has been shown to have an important role in specifying cell fate and maintaining stem cell pools in neurological development and deletion of ACBD3 in human cell lines prevents cell division. Combined with observations that β-catenin expression and activity is increased when ACBD3 is overexpressed it has been hypothesised that ACBD3 promotes breast cancer by increasing Wnt signalling. This may only be one aspect of ACBD3’s effects as its expression and localisation regulates steroidogenesis, calcium mediated redox stress and inflammation, glucose import and PI(4)P production which are all intrinsically linked to breast cancer dynamics. Given the wide scope for a role of ACBD3 in breast cancer, we explore its interactors and the implications of preventing these interactions