PROTEIN-TRIGGERED SUSTAINED DRUG RELEASE CONTROLLED BY APTAMERS BOUND TO OLIGOMER-CROSSLINKED ALGINATE

Sustained drug release systems provide many advantages over traditional delivery methods such as extending the time in which the drug is found to be within an effective concentration within the therapeutic window, which decreases the frequency of administration of the drug, and increases patient compliance. Research using polyacrylamide crosslinked by oligomers containing an aptamer sequence, has demonstrated a pulsatile release over 50 minutes triggered by a 2 mM target adenosine concentration. This thesis aims to build off this concept by designing a system that delivers in a sustained manner when triggered by micromolar target concentrations reflective of disease in vivo, using macromolecular targets. For example, the disease wet age related macular degeneration (wet AMD) is associated with increased concentrations of the protein vascular endothelial growth factor (VEGF-A) – a macromolecule. Patients with wet AMD would benefit from the implantation of devices or microspheres that release drugs in a sustained manner in response to local VEGF concentrations. In this thesis, we hypothesize that the protein lysozyme, used to demonstrate proof-of-concept, could trigger the increased release of drugs from oligomer-crosslinked alginate. The objectives are to (i) demonstrate sustained release from alginate, (ii) design oligomer crosslinked alginate that degrades in response to lysozyme, and then (iii) use these systems to control the release of FITC-dextran with and without lysozyme. A series of control experiments and analyses were used to optimize the crosslinking of alginate by annealed oligomers. The cumulative release of FITC-dextran (MW 20,000) from oligomer crosslinked alginate increased by 3.4 μg when lysozyme (3 μM) was introduced at 48 hours, as opposed to controls which released only 0.2 μg. FITC-loaded alginate microspheres coated by oligomer-crosslinked alginate released 15% more FITC-dextran over 120 hours when placed into 3 μM of lysozyme than without lysozyme. Controls of alginate crosslinked with PEG or control oligomers (without a lysozyme aptamer sequence) had no changes in release with lysozyme. The incorporation of a lysozyme aptamer onto oligomers used to crosslink alginate disks or alginate coatings on microspheres resulted in different diffusion and release of FITC-dextran into PBS with or without lysozyme. This approach could be adapted for the delivery of drugs to diseases with specific protein profiles such as wet AMD.

A NEW DC UPS FOR DC POWER DISTRIBUTION SYSTEM IN DATA CENTER

In recent years, the 380V DC and 48V DC distribution systems have been extensively studied for the latest data centers. It is widely believed that the 380V DC system is a very promising candidate because of its lower cable cost compared to the 48V DC system. However, previous studies have not adequately addressed the low reliability issue with the 380V DC systems due to large amount of series connected batteries. In this thesis, a quantitative comparison for the two systems has been presented in terms of efficiency, reliability and cost. A new multi-port DC UPS with both high voltage output and low voltage output is proposed. When utility ac is available, it delivers power to the load through its high voltage output and charges the battery through its low voltage output. When utility ac is off, it boosts the low battery voltage and delivers power to the load form the battery. Thus, the advantages of both systems are combined and the disadvantages of them are avoided. High efficiency is also achieved as only one converter is working in either situation. Details about the design and analysis of the new UPS are presented. For the main AC-DC part of the new UPS, a novel bridgeless three-level single-stage AC-DC converter is proposed. It eliminates the auxiliary circuit for balancing the capacitor voltages and the two bridge rectifier diodes in previous topology. Zero voltage switching, high power factor, and low component stresses are achieved with this topology. Compared to previous topologies, the proposed converter has a lower cost, higher reliability, and higher efficiency. The steady state operation of the converter is analyzed and a decoupled model is proposed for the converter. For the battery side converter as a part of the new UPS, a ZVS bidirectional DC-DC converter based on self-sustained oscillation control is proposed. Frequency control is used to ensure the ZVS operation of all four switches and phase shift control is employed to regulate the converter output power. Detailed analysis of the steady state operation and design of the converter are presented. Theoretical, simulation, and experimental results are presented to verify the effectiveness of the proposed concepts.

Examination of the Effect of Time Delay on Fragmentation

The main objective of blasting is to produce optimum fragmentation for downstream processing. Fragmentation is usually considered optimum when the average fragment size is minimum and the fragmentation distribution as uniform as possible. One of the parameters affecting blasting fragmentation is believed to be time delay between holes of the same row. Although one can find a significant number of studies in the literature, which examine the relationship between time delay and fragmentation, their results have been often controversial. The purpose of this work is to increase the level of understanding of how time delay between holes of the same row affects fragmentation. Two series of experiments were conducted for this purpose. The first series involved tests on small scale grout and granite blocks to determine the moment of burden detachment. The instrumentation used for these experiments consisted mainly of strain gauges and piezoelectric sensors. Some experiments were also recorded with a high speed camera. It was concluded that the time of detachment for this specific setup is between 300 and 600 μs. The second series of experiments involved blasting of a 2 meter high granite bench and its purpose was the determination of the hole-to-hole delay that provides optimum fragmentation. The fragmentation results were assessed with image analysis software. Moreover, vibration was measured close to the blast and the experiments were recorded with high speed cameras. The results suggest that fragmentation was optimum when delays between 4 and 6 ms were used for this specific setup. Also, it was found that the moment at which gases first appear to be venting from the face was consistently around 6 ms after detonation.