Metabolomics and biosensor approaches to the detection of fever associated diseases

Febrile illnesses are still a major cause of mortality and morbidity globally and the failure to detect and correctly diagnose a specific disease associated with fever is partly responsible for this. This thesis aimed to investigate a biosensor-based method for the detection of fever associated diseases and to further explore the molecular mechanisms and possible biomarkers of febrile illnesses by employing a metabolomics-based approach. The biosensor platform is based on a complementary metal oxide semiconductor technology, which has both technological and economic advantages. Due to the small size of the microchip, accurate signal processing becomes challenging and, thus, computational methods were developed and tested for the quantitative detection of antibodies in a solution tested on the biosensor platform. Three methods, one based on a deterministic approach and two others based on machine learning (ML) algorithms, were tested and compared for the detection of a reaction spot intensity using synthetically generated images. Next, in order to develop an immunoassay protocol for the detection of one specific fever associated infectious disease, human African trypanosomiasis (HAT), several steps were taken. First of all, a suitable and sensitive method of detection was selected, i.e. enzyme linked immunosorbent assay (ELISA). Next, four recombinant antigens currently used for the detection of HAT were selected based on previous evidence and developed using molecular cloning techniques in E.coli. These were tested on infected and control humans serum samples obtained from endemic regions of the Democratic Republic of Congo (DRC). Disposable poly-methyl methacrylate (PMMA) slides which were chemically functionalised were used on top of the chip as the immunoassay surface. Titrations for the selected antigens/antibody were tested using an indirect ELISA-like protocol and the best results after fitting a calibration curve were obtained for an antigen concentration of 2.5 µg/ml. The detection of the antibody to the trypanosome antigen invariant surface glycoprotein 65 (ISG65) proved to be successful and the protocol could be replicated for all the other antigens. However, technical challenges and the closure of the laboratory during the Covid-19 pandemic precluded my taking this part of the project to its conclusion. Following this, metabolomics datasets studying disparate febrile infectious illnesses obtained using liquid chromatography coupled to mass spectrometry (LC-MS) were used in order to investigate and detect possible metabolite-based biomarkers common to fever-associated diseases. A warping based method was developed in order to enable integration by alignment of disparate LC-MS metabolomics datasets. Integration was performed by correcting the RT drift between the datasets using fitted Gaussian Process regression models, a supervised ML method, which was followed by direct matching alignment using MZmine2. The correction was performed by using the standard reference mixture (SRM) information. Statistical analysis on the meta-dataset was performed using linear modelling implemented in the limma R-package. Comparison was made between infected and control samples and commonality was established using the fold change values obtained for the individual datasets. Annotation was carried out by matching the compounds against metabomlomics datasets and through mummichog software, which was also used for pathway analysis. The features obtained from this analysis which were putatively annotated were classified into categories (amino acids, sugars, lipids, nucleotides, etc.). Features in common to all datasets were used to make a connection to the previously established molecular basis of fever. Significant changes were identified to several metabolic pathways, with the most notable perturbations being within the kynurenine pathway, a branch of tryptophan metabolism. Also, features specific to each dataset were used to evaluate the accuracy of the fever biomarkers and investigate possible biomarkers for each different fever-associated disease

Aerial Vehicles

This book contains 35 chapters written by experts in developing techniques for making aerial vehicles more intelligent, more reliable, more flexible in use, and safer in operation.It will also serve as an inspiration for further improvement of the design and application of aeral vehicles. The advanced techniques and research described here may also be applicable to other high-tech areas such as robotics, avionics, vetronics, and space

Proceedings of the European Conference on Agricultural Engineering AgEng2021

This proceedings book results from the AgEng2021 Agricultural Engineering Conference under auspices of the European Society of Agricultural Engineers, held in an online format based on the University of Évora, Portugal, from 4 to 8 July 2021. This book contains the full papers of a selection of abstracts that were the base for the oral presentations and posters presented at the conference. Presentations were distributed in eleven thematic areas: Artificial Intelligence, data processing and management; Automation, robotics and sensor technology; Circular Economy; Education and Rural development; Energy and bioenergy; Integrated and sustainable Farming systems; New application technologies and mechanisation; Post-harvest technologies; Smart farming / Precision agriculture; Soil, land and water engineering; Sustainable production in Farm buildings

Measuring Behavior 2018 Conference Proceedings

These proceedings contain the papers presented at Measuring Behavior 2018, the 11th International Conference on Methods and Techniques in Behavioral Research. The conference was organised by Manchester Metropolitan University, in collaboration with Noldus Information Technology. The conference was held during June 5th – 8th, 2018 in Manchester, UK. Building on the format that has emerged from previous meetings, we hosted a fascinating program about a wide variety of methodological aspects of the behavioral sciences. We had scientific presentations scheduled into seven general oral sessions and fifteen symposia, which covered a topical spread from rodent to human behavior. We had fourteen demonstrations, in which academics and companies demonstrated their latest prototypes. The scientific program also contained three workshops, one tutorial and a number of scientific discussion sessions. We also had scientific tours of our facilities at Manchester Metropolitan Univeristy, and the nearby British Cycling Velodrome. We hope this proceedings caters for many of your interests and we look forward to seeing and hearing more of your contributions