A Human-Machine Framework for the Classification of Phonocardiograms

In this thesis, we present and evaluate a framework for combining machine learning algo- rithms, crowd workers, and experts in the classification of heart sound recordings. The development of a hybrid human-machine framework for heart sound recordings is moti- vated by the past success in utilizing human computation to solve problems in medicine as well as the use of human-machine frameworks in other domains. We describe the methods that decide when and how to escalate the analysis of heart sound recordings to different resources and incorporate their decision into a final classification. We present and discuss the results of the framework which was tested with a number of different machine classi- fiers and a group of crowd workers from Amazon’s Mechanical Turk. We also provide an evaluation of how crowd workers perform in various different heart sound analysis tasks, and how they compare with machine classifiers. In addition, we investigate how machine and human analysis are effected by different types of heart sounds and provide a strategy for involving experts when these methods are uncertain. We conclude that the use of a hybrid framework is a viable method for heart sound classification

Novel development tools for processing of recombinant virus-like particles

The focus of this thesis is laid on the implementation of integrated bioprocesses and the development of novel methods for recombinant protein-based virus-like particles (VLPs). Due to their pathogen-associated molecular patterns and the lack of viral nucleic acids, VLPs represent promising bionanoparticles for vaccine applications. This thesis aims to generate straightforward production, purification and analytical procedures for VLPs by advancing rational design tools for large biomolecules

High-Throughput Process Development in the Field of Protein Purification - Method Development, Application, and Characterization

High-throughput methods were developed for the quantification of mAb aggregate/monomer ratios, and the analysis of content, purity, and activity of the egg white protein avidin. Furthermore, by using high-throughput screenings, a new avidin purification process was developed using precipitation, aqueous two-phase extraction and mixed-mode chromatography. Finally, method-specific effects present in high-throughput column chromatography were evaluated using both experimental and simulation data

Design a CPW antenna on rubber substrate for multiband applications

This paper presents a compact CPW monopole antenna on rubber substrate for multiband applications. The multi band applications (2.45 and 3.65 GHz) is achieved on this antenna design with better antenna performances. Specially this antenna focused on ISM band application meanwhile some of slots (S1, S2, S3) have been used and attained another frequency band at 3.65 GHz for WiMAX application. The achievement of the antenna outcomes from this design that the bandwidth of 520 MHz for first band, the second band was 76 MHz for WiMAX application and the radiation efficiency attained around 90%. Moreover, the realized gain was at 4.27 dBi which overcome the most of existing design on that field. CST microwave studio has been used for antenna simulation

Particle-based immobilized enzymatic reactors in microfluidic chips

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Development of Diverse Size and Shape RNA Nanoparticles and Investigation of their Physicochemical Properties for Optimized Drug Delivery

RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo. In vivo biodistribution and pharmacokinetics are affected by the physicochemical properties, such as size, shape, stability, and surface chemistry/properties, of the nanoparticles being delivered. RNA has an inherent advantage for nanoparticle construction as each of these properties can be finely tuned. The focus of this study is as follows: (1) Construction of diverse size and shape RNA nanoparticles with tunable physicochemical properties; (2) Investigation of the effect that size, shape, and nanoparticle properties have on in vivo biodistribution; (3) Development of drug encapsulation and release mechanism utilizing RNA nanotechnology; and (4) Establishment of large-scale synthesis and purification methods of RNA nanoparticles. In (1), RNA triangle, square, and pentagon shaped nanoparticles were constructed using the phi29 pRNA-3WJ as a core motif. Square nanoparticles were constructed with sizes of 5, 10, and 20 nanometers. The RNA polygons were characterized by AFM to demonstrate formation of their predicted geometry per molecular models. Furthermore, the properties of RNA polygons were tuned both thermodynamically and chemically by substitution of nucleic acid type used during nanoparticle assembly. In (2), the biodistribution of RNA nanosquares of diverse sizes and RNA polygons of diverse shapes were investigated using tumor models in nude mice. It was found that increasing the size of the nanosquares led to prolonged circulation time in vivo and higher apparent accumulation in the tumor. However, it was observed that changing of shape had little effect on biodistribution. Furthermore, the effect of the hydrophobicity on RNA nanoparticles biodistribution was examined in mouse models. It was found that incorporation of hydrophobic ligands into RNA nanoparticles causes non-specific accumulation in healthy organs, while incorporation of hydrophilic ligands does not. Lower accumulation in vital organs of hydrophobic chemicals was observed after conjugation to RNA nanoparticles, suggesting RNA has the property to solubilize hydrophobic chemicals and reduce accumulation and toxicity in vital organs. In (3), a 3D RNA nanoprism was constructed to encapsulate a small molecule fluorophore acting as a model drug. The fluorophore was held inside the nanoprism by binding to an RNA aptamer. The ability of the stable frame of the nanoprism to protect the fragile aptamer inside was evidenced by a doubling of the fluorescent half-life in a degrading environment. In (4), a method for large-scale in vitro synthesis and purification of RNA nanoparticles was devised using rolling circle transcription (RCT). A novel method for preparing circular double stranded DNA was developed, overcoming current challenges in the RCT procedure. RCT produced more than 5 times more RNA nanoparticles than traditional run-off transcription, as monitored by gel electrophoresis and fluorescence monitoring. Finally, large-scale purification methods using rate-zonal and equilibrium density gradient ultracentrifugation, as well as gel electrophoresis column, were developed