Evaluation Of An Extended Duct Air Delivery System For Spaces Conditioned By Rooftop Units

Traditional air delivery to high-bay buildings involves ceiling level supply and return ducts that create an almost-uniform temperature in the space. Problems with this system include potential recirculation of supply air and higher-than-necessary return air temperatures. A new air delivery strategy was investigated that involves changing the height of conventional supply and return ducts to have control over thermal stratification in the space. A full-scale experiment using ten vertical temperature profiles was conducted in a manufacturing facility over one year. The experimental data was utilized to validated CFD and EnergyPlus models. CFD simulation results show that supplying air directly to the occupied zone increases stratification while holding thermal comfort constant during the cooling operation. The building energy simulation identified how return air temperature offset, set point offset, and stratification influence the building’s energy consumption. A utility bill analysis for cooling shows 28.8% HVAC energy savings while the building energy simulation shows 19.3 – 37.4% HVAC energy savings.

Drug Delivery through the Blood-Brain Barrier through Use of Vascular Cell Adhesion Molecule 1- Targeted Nanoparticles

The blood brain barrier (BBB) is a semi-permeable membrane separating the brain from the bloodstream, preventing many drugs that treat neurological diseases, such as Alzheimer’s and Parkinson’s, from reaching the brain. Our project aimed to create a novel drug delivery system targeting the brain during neural inflammation. We developed a cationic solid lipid nanoparticle (CSLN) complex composed of cationic nanoparticles, biotin, streptavidin, and anti-vascular cell adhesion molecule-1 (anti- VCAM-1) antibodies. The anti-VCAM-1 antibody is used to target VCAM-1, a cell adhesion protein found on the BBB endothelium. VCAM-1 expression is elevated in the presence of inflammatory molecules, such as tumor necrosis factor-alpha (TNF- α). Through the use of a simple BBB model, results showed that our novel drug delivery system experienced some level of success in targeting the brain inflammation due to increasing TNF-α concentrations. This is promising for drug delivery research and provides support for VCAM-1 targeting using more robust and complex BBB models.

Therapeutic Potential of RNAi Through Endocytotic Methods

The ability to manipulate gene expression promises to be an important tool for the management of infectious diseases and genetic disorders. However, a major limitation to effective delivery of therapeutic RNA to living cells is the cellular toxicity of conventional techniques. Team PANACEA’s research objective was to create new reagents based on a novel small-molecule delivery system that uses a modular recombinant protein vehicle consisting of a specific ligand coupled to a Hepatitis B Virus-derived RNA binding domain (HBV-RBD). Two such recombinant delivery proteins were developed: one composed of Interleukin-8, the other consisting of the Machupo Virus GP1 protein. The ability of these proteins to deliver RNA to cells were then tested. The non-toxic nature of this technology has the potential to overcome limitations of current methods and could provide a platform for the expansion of personalized medicine.

Joint Optimization for Social Content Delivery in Wireless Networks

Over the last decade, success of social networks has significantly reshaped how people consume information. Recommendation of contents based on user profiles is well-received. However, as users become dominantly mobile, little is done to consider the impacts of the wireless environment, especially the capacity constraints and changing channel. In this dissertation, we investigate a centralized wireless content delivery system, aiming to optimize overall user experience given the capacity constraints of the wireless networks, by deciding what contents to deliver, when and how. We propose a scheduling framework that incorporates content-based reward and deliverability. Our approach utilizes the broadcast nature of wireless communication and social nature of content, by multicasting and precaching. Results indicate this novel joint optimization approach outperforms existing layered systems that separate recommendation and delivery, especially when the wireless network is operating at maximum capacity. Utilizing limited number of transmission modes, we significantly reduce the complexity of the optimization. We also introduce the design of a hybrid system to handle transmissions for both system recommended contents ('push') and active user requests ('pull'). Further, we extend the joint optimization framework to the wireless infrastructure with multiple base stations. The problem becomes much harder in that there are many more system configurations, including but not limited to power allocation and how resources are shared among the base stations ('out-of-band' in which base stations transmit with dedicated spectrum resources, thus no interference; and 'in-band' in which they share the spectrum and need to mitigate interference). We propose a scalable two-phase scheduling framework: 1) each base station obtains delivery decisions and resource allocation individually; 2) the system consolidates the decisions and allocations, reducing redundant transmissions. Additionally, if the social network applications could provide the predictions of how the social contents disseminate, the wireless networks could schedule the transmissions accordingly and significantly improve the dissemination performance by reducing the delivery delay. We propose a novel method utilizing: 1) hybrid systems to handle active disseminating requests; and 2) predictions of dissemination dynamics from the social network applications. This method could mitigate the performance degradation for content dissemination due to wireless delivery delay. Results indicate that our proposed system design is both efficient and easy to implement.

Dynamic Coculture of a Prevascularized Engineered Bone Construct

The generation of functional, vascularized tissues is a key challenge for the field of tissue engineering. Before clinical implantations of tissue engineered bone constructs can succeed, in vitro fabrication needs to address limitations in large-scale tissue development, including controlled osteogenesis and an inadequate vasculature network to prevent necrosis of large constructs. The tubular perfusion system (TPS) bioreactor is an effective culturing method to augment osteogenic differentiation and maintain viability of human mesenchymal stem cell (hMSC)-seeded scaffolds while they are developed in vitro. To further enhance this process, we developed a novel osteogenic growth factors delivery system for dynamically cultured hMSCs using microparticles encapsulated in three-dimensional alginate scaffolds. In light of this increased differentiation, we characterized the endogenous cytokine distribution throughout the TPS bioreactor. An advantageous effect in the ‘outlet’ portion of the uniaxial growth chamber was discovered due to the system’s downstream circulation and the unique modular aspect of the scaffolds. This unique trait allowed us to carefully tune the differentiation behavior of specific cell populations. We applied the knowledge gained from the growth profile of the TPS bioreactor to culture a high-volume bone composite in a 3D-printed femur mold. This resulted in a tissue engineered bone construct with a volume of 200cm3, a 20-fold increase over previously reported sizes. We demonstrated high viability of the cultured cells throughout the culture period as well as early signs of osteogenic differentiation. Taking one step closer toward a viable implant and minimize tissue necrosis after implantation, we designed a composite construct by coculturing endothelial cells (ECs) and differentiating hMSCs, encouraging prevascularization and anastomosis of the graft with the host vasculature. We discovered the necessity of cell to cell proximity between the two cell types as well as preference for the natural cell binding capabilities of hydrogels like collagen. Notably, the results suggested increased osteogenic and angiogenic potential of the encapsulated cells when dynamically cultured in the TPS bioreactor, suggesting a synergistic effect between coculture and applied shear stress. This work highlights the feasibility of fabricating a high-volume, prevascularized tissue engineered bone construct for the regeneration of a critical size defect.

Recombinant Adeno-Associated Virus-Mediated Gene Therapy for Treatment of Familial Hypercholesterolemia in Rabbits

Familial hypercholesterolemia (FH) is a genetic disorder characterized by abnormally high concentrations of low-density lipoprotein-cholesterol (LDLcholesterol) in the blood that can contribute to heart disease. FH can result from a defect in the gene for the LDL receptor (LDL-R). FH patients lacking functional LDL-R may benefit from viral-mediated transfer of a functional copy of the open reading frame (ORF) of the LDL-R. Since a recombinant adeno-associated virus (rAAV) is not immunogenic and can be mass-produced, it shows promise for gene therapy applications. AAV6 and AAV8 have been shown to specifically transduce hepatocytes in several species, which normally remove the majority of LDL-cholesterol from the blood via LDL-R-mediated endocytosis. Because of the potential of rAAV to treat FH by delivery of a correct LDL-R ORF to hepatocytes, the liver specificity of these two AAV serotypes was evaluated. Additionally, rabbits were chosen as the animal model for this study because a specific strain of rabbits, Watanabe heritable hyperlipidemic (WHHL), adequately mimics the pathology of FH in humans. Exposure of rabbit liver to rAAV with the marker LacZ and subsequent inspection of liver tissue showed that AAV8 transduced rabbit liver more efficiently than AAV6. To assess the feasibility of producing a rAAV capable of transferring the LDL-R ORF to rabbit hepatocytes in vivo, rAAV8-LDL-R was mass-produced by a baculovirus system in suspension grown insect cells.