Biomedical Sciences and Technology: Book Chapters
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12521/718
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Item Metadata only Temporal and Spatial Analyses of TB Granulomas to Predict Long-term Outcomes(Springer, 2021) Butler, J. RussellMycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), kills more individuals worldwide per year than any other infectious agent. As the hallmark of TB, lung granulomas are complex structures composed of immune cells that interact with and surround bacteria, infected cells, and a necrotic core. This interaction leads to diverse granuloma outcomes across time, ranging from bacterial sterilization to uncontrolled bacterial growth, as well as diverse spatial structures. At this time, there are no systematic quantitative methods to classify the formation, function, and spatial characteristics of granulomas. This type of analysis would enable better understanding and prediction of granuloma behaviors that have known associations with poor clinical outcomes for TB patients. Herein, we develop a temporal and spatial analysis framework for TB granulomas using a systems biology approach combining in silico granuloma modeling, geographic information systems, topological data analysis, and machine learning. We apply this framework to simulated granulomas to understand temporal granuloma dynamics, quantify granuloma spatial structure, and predict the relationship between granuloma structure and bacterial growth. As a proof-of-concept, we apply our in silico predictions to in vivo derived data to test our framework for future applications and as a personalized medicine intervention.Item Metadata only Role of Platelets in Immunomodulation in Pancreatic and Colorectal Cancers(Elsevier Academic Press, 2024) Amirkhosravi, AliItem Metadata only Fluorescence Photobleaching Recovery: A Primer(Springer, 2008) Edwin, Nadia J.Item Metadata only β-amyloid Protein Aggregation(Humana Press, 2007) Edwin, Nadia J.The β-amyloid peptide aggregates via a nucleation pathway where micellar aggregates propagate to form oligomers (protofibrils), which then polymerize into insoluble fibrils. This fibrillogenic process has been linked to the pathogenesis associated with Alzheimer’s disease. One purpose of this chapter is to provide a protocol for reliably producing monomeric Aβas a starting point for physical and biological studies. Many research groups have used organic solvents to disaggregate pre-seeded Aβ in an attempt to acquire monomeric starting materials. Others have used instrumental techniques such as size exclusion chromatography to isolate monomer, structural intermediates, and fibrils and study their affects on A β nucleation. This chapter discusses a modified method of A βpreparation using organic solvents followed by dissolution into aqueous phosphate buffer systems that renders monomeric A β starting solutions for kinetic experiments. Additionally, this chapter details a number of physical techniques such as scanning force microscopy, circular dichroism spectroscopy, transmission electron microscopy, fluorescence spectroscopy, fluorescence photobleaching recovery, and dynamic light scattering, together with physiological techniques such as cell viability assays to characterize Aβ nucleation, aggregation, and fibrillization and the potential biological activity of the various A βparticles.Item Metadata only Elucidating the Kinetics of β-amyloid Fibril Formation(American Chemical Society, 2005) Edwin, Nadia J.The formation of β-Amyloid peptide (Aβ1-40) aggregates was monitored by dynamic light scattering. Various sizes of materials may be present throughout the aggregation process, but small scatterers are difficult to detect in the presence of large ones. Fluorescence photobleaching recovery studies on 5-carboxyfluorescein-labeled Aβ1-40 peptide solutions readily confirmed the presence of large and small species simultaneously. The effects of dye substitution on the aggregation behavior of Aβ1-40 peptide are subtle, but should not prevent further investigations by fluorescence photobleaching recovery or other fluorescence methods.