Doctor of Philosophy

dissertationHeart disease is the leading cause of death in the United States. Mechanical circulatory support by ventricular assist devices (VADs) is a means by which deteriorating heart function can be supplemented, and is a leading therapy for latestage heart failure patients. The devices are commonly connected to the apex of the left ventricle (LV) to move oxygenated blood to the body via the aorta. Recent developments have made continuous-flow pumps commonplace in the clinical environment when compared to their pulsatile-flow predecessors. Typically, continuous-flow VADs are designed with axial- or centrifugal- (radial) configurations. The pressures and flow rates vary dramatically in the native heart as blood is moved from the LV to the aorta. This dissertation presents pressure-flow characteristics for both axial- and centrifugal-flow VADs within a wide range of pressure differential values under uniform conditions, by means of a novel, open-loop flow system. Current techniques employ a closed-loop system to determine pump performance. A closed-loop system does not allow pressure differentials less than or equal to zero to be achieved. The native heart experiences pressure gradients near zero across the aortic valve during systole, which is essentially where the VAD is placed. Thus, an open-loop flow system with independently adjustable preload and afterload pressures is required to reach physiologically-relevant pressure differential regions that approximate the pressure gradient across the aortic valve during systole. Additional modifications made to the open-loop flow system generate pulsatile flow type conditions, which mimic those of the native LV. With this type of in vitro test system, not only can general hydrodynamic performance and hydraulic efficiency of VADs be measured, but also off-design operational performance under dynamic flow conditions can be characterized. This research explores hydrodynamic performance characteristics of axial- and centrifugal-flow VADs to determine design advantages that each have. Device characteristics include pressure-flow performance curves, pressure sensitivity, pulsatility index, and pulsatility ratio. Performance curves and other relevant attributes are investigated at previously unreported pressure-flow regions. Performance is evaluated theoretically, computationally, and experimentally under both steady-state, continuous-flow and pulsatile-flow circumstances

Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120

A substantial fraction of broadly neutralizing antibodies (bnAbs) in certain HIV-infected donors recognizes glycan-dependent epitopes on HIV-1 gp120. Here, we elucidate how bnAb PGT 135 recognizes its Asn332 glycan-dependent epitope from its crystal structure with gp120, CD4 and Fab 17b at 3.1 Å resolution. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield to access the gp120 protein surface. Electron microscopy reveals PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. The combined structural studies of PGT 135, PGT 128 and 2G12 show this Asn332-dependent epitope is highly accessible and much more extensive than initially appreciated, allowing for multiple binding modes and varied angles of approach, thereby representing a supersite of vulnerability for antibody neutralization

Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses

Der seltene Nierentumor

Renewable energy is one of the most important and widely researched topics today. It is classically defined as any form of energy coming from any naturally replenish-able source. This may include everything from solar to wind power, as well as biomass or biofuels. When considering biomass, or any (living or recently-dead) biological material, the chemical energy of the molecules is generally collected through combustion. The area of liquid fuels from biomass has especially gained much notoriety and support in recent years. This is due to the lower emissions and clean-burning nature of these fuels when compared to more traditional approaches, as well as the obvious renewable nature of the starting material. While vegetable oils or animal fats can be used as a replacement for diesel fuels, corn, switchgrass, or other grains are more widely used to produce ethanol for use in common combustion engines. Today’s E85 fuel is sold to customers with a chemical makeup of 85% ethanol and 15% gasoline. The use of solid biomass as a direct supplier of energy, however, is an area still left relatively unexplored in this growing field. In theory, and as preliminary research suggests, harvesting energy directly from solid biomass may be considerably more efficient than gathering it from its processed liquid counterpart. In fact, some studies suggest that the energy acquired from burning ethanol is up to 67% lower than is contained in the plant cellulose from which it is derived.[1] There are, however, several other factors besides energy projections to consider when looking at the economic and market viability of such an approach. For example, one of the main advantages of liquid fuels over solid is the ease of transportation and storage. Additionally, the feasibility of developing a whole new process of biomass collection and processing must be balanced with economic and logistical constraints. This includes not only careful analysis of energy and cost balances, but also in-depth examination of all equipment, manpower and environmental limitations. IPRO 349 was established to examine these (and many more) considerations in the viability of sold fuel from biomass. Specifically, we have narrowed the scope of our research to biomass derived from corn stover (leaves and stalk left in the ground after harvesting) within the state of Illinois. Illinois was chosen because it is currently the largest producer of corn in the nation.[2] Corn stover has been shown to have an energy content of 5,290 Btu/lb. wet, and 7,560 Btu/lb. dry.[2]With such an approach, it may be possible to utilize what would otherwise be considered “waste” to produce useable, renewable energy. For the purposes of this project, cogeneration, or the simultaneous generation of both electricity and useful heat will be examined.Deliverable

Solid Fuel from Biomass for Cogeneration (Semester Unknown) IPRO 349

Renewable energy is one of the most important and widely researched topics today. It is classically defined as any form of energy coming from any naturally replenish-able source. This may include everything from solar to wind power, as well as biomass or biofuels. When considering biomass, or any (living or recently-dead) biological material, the chemical energy of the molecules is generally collected through combustion. The area of liquid fuels from biomass has especially gained much notoriety and support in recent years. This is due to the lower emissions and clean-burning nature of these fuels when compared to more traditional approaches, as well as the obvious renewable nature of the starting material. While vegetable oils or animal fats can be used as a replacement for diesel fuels, corn, switchgrass, or other grains are more widely used to produce ethanol for use in common combustion engines. Today’s E85 fuel is sold to customers with a chemical makeup of 85% ethanol and 15% gasoline. The use of solid biomass as a direct supplier of energy, however, is an area still left relatively unexplored in this growing field. In theory, and as preliminary research suggests, harvesting energy directly from solid biomass may be considerably more efficient than gathering it from its processed liquid counterpart. In fact, some studies suggest that the energy acquired from burning ethanol is up to 67% lower than is contained in the plant cellulose from which it is derived.[1] There are, however, several other factors besides energy projections to consider when looking at the economic and market viability of such an approach. For example, one of the main advantages of liquid fuels over solid is the ease of transportation and storage. Additionally, the feasibility of developing a whole new process of biomass collection and processing must be balanced with economic and logistical constraints. This includes not only careful analysis of energy and cost balances, but also in-depth examination of all equipment, manpower and environmental limitations. IPRO 349 was established to examine these (and many more) considerations in the viability of sold fuel from biomass. Specifically, we have narrowed the scope of our research to biomass derived from corn stover (leaves and stalk left in the ground after harvesting) within the state of Illinois. Illinois was chosen because it is currently the largest producer of corn in the nation.[2] Corn stover has been shown to have an energy content of 5,290 Btu/lb. wet, and 7,560 Btu/lb. dry.[2]With such an approach, it may be possible to utilize what would otherwise be considered “waste” to produce useable, renewable energy. For the purposes of this project, cogeneration, or the simultaneous generation of both electricity and useful heat will be examined.Deliverable

Solid Fuel from Biomass for Cogeneration (Semester Unknown) IPRO 349: Solid Fuel from Biomass for Cogeneration IPRO 349 Ethics Sp08

Renewable energy is one of the most important and widely researched topics today. It is classically defined as any form of energy coming from any naturally replenish-able source. This may include everything from solar to wind power, as well as biomass or biofuels. When considering biomass, or any (living or recently-dead) biological material, the chemical energy of the molecules is generally collected through combustion. The area of liquid fuels from biomass has especially gained much notoriety and support in recent years. This is due to the lower emissions and clean-burning nature of these fuels when compared to more traditional approaches, as well as the obvious renewable nature of the starting material. While vegetable oils or animal fats can be used as a replacement for diesel fuels, corn, switchgrass, or other grains are more widely used to produce ethanol for use in common combustion engines. Today’s E85 fuel is sold to customers with a chemical makeup of 85% ethanol and 15% gasoline. The use of solid biomass as a direct supplier of energy, however, is an area still left relatively unexplored in this growing field. In theory, and as preliminary research suggests, harvesting energy directly from solid biomass may be considerably more efficient than gathering it from its processed liquid counterpart. In fact, some studies suggest that the energy acquired from burning ethanol is up to 67% lower than is contained in the plant cellulose from which it is derived.[1] There are, however, several other factors besides energy projections to consider when looking at the economic and market viability of such an approach. For example, one of the main advantages of liquid fuels over solid is the ease of transportation and storage. Additionally, the feasibility of developing a whole new process of biomass collection and processing must be balanced with economic and logistical constraints. This includes not only careful analysis of energy and cost balances, but also in-depth examination of all equipment, manpower and environmental limitations. IPRO 349 was established to examine these (and many more) considerations in the viability of sold fuel from biomass. Specifically, we have narrowed the scope of our research to biomass derived from corn stover (leaves and stalk left in the ground after harvesting) within the state of Illinois. Illinois was chosen because it is currently the largest producer of corn in the nation.[2] Corn stover has been shown to have an energy content of 5,290 Btu/lb. wet, and 7,560 Btu/lb. dry.[2]With such an approach, it may be possible to utilize what would otherwise be considered “waste” to produce useable, renewable energy. For the purposes of this project, cogeneration, or the simultaneous generation of both electricity and useful heat will be examined.Deliverable

Solid Fuel from Biomass for Cogeneration (Semester Unknown) IPRO 349: Solid Fuel from Biomass for Cogeneration IPRO 349 Project Plan Sp08

Renewable energy is one of the most important and widely researched topics today. It is classically defined as any form of energy coming from any naturally replenish-able source. This may include everything from solar to wind power, as well as biomass or biofuels. When considering biomass, or any (living or recently-dead) biological material, the chemical energy of the molecules is generally collected through combustion. The area of liquid fuels from biomass has especially gained much notoriety and support in recent years. This is due to the lower emissions and clean-burning nature of these fuels when compared to more traditional approaches, as well as the obvious renewable nature of the starting material. While vegetable oils or animal fats can be used as a replacement for diesel fuels, corn, switchgrass, or other grains are more widely used to produce ethanol for use in common combustion engines. Today’s E85 fuel is sold to customers with a chemical makeup of 85% ethanol and 15% gasoline. The use of solid biomass as a direct supplier of energy, however, is an area still left relatively unexplored in this growing field. In theory, and as preliminary research suggests, harvesting energy directly from solid biomass may be considerably more efficient than gathering it from its processed liquid counterpart. In fact, some studies suggest that the energy acquired from burning ethanol is up to 67% lower than is contained in the plant cellulose from which it is derived.[1] There are, however, several other factors besides energy projections to consider when looking at the economic and market viability of such an approach. For example, one of the main advantages of liquid fuels over solid is the ease of transportation and storage. Additionally, the feasibility of developing a whole new process of biomass collection and processing must be balanced with economic and logistical constraints. This includes not only careful analysis of energy and cost balances, but also in-depth examination of all equipment, manpower and environmental limitations. IPRO 349 was established to examine these (and many more) considerations in the viability of sold fuel from biomass. Specifically, we have narrowed the scope of our research to biomass derived from corn stover (leaves and stalk left in the ground after harvesting) within the state of Illinois. Illinois was chosen because it is currently the largest producer of corn in the nation.[2] Corn stover has been shown to have an energy content of 5,290 Btu/lb. wet, and 7,560 Btu/lb. dry.[2]With such an approach, it may be possible to utilize what would otherwise be considered “waste” to produce useable, renewable energy. For the purposes of this project, cogeneration, or the simultaneous generation of both electricity and useful heat will be examined.Deliverable

Solid Fuel from Biomass for Cogeneration (Semester Unknown) IPRO 349: Solid Fuel from Biomass for Cogeneration IPRO 349 Poster2 Sp08

Renewable energy is one of the most important and widely researched topics today. It is classically defined as any form of energy coming from any naturally replenish-able source. This may include everything from solar to wind power, as well as biomass or biofuels. When considering biomass, or any (living or recently-dead) biological material, the chemical energy of the molecules is generally collected through combustion. The area of liquid fuels from biomass has especially gained much notoriety and support in recent years. This is due to the lower emissions and clean-burning nature of these fuels when compared to more traditional approaches, as well as the obvious renewable nature of the starting material. While vegetable oils or animal fats can be used as a replacement for diesel fuels, corn, switchgrass, or other grains are more widely used to produce ethanol for use in common combustion engines. Today’s E85 fuel is sold to customers with a chemical makeup of 85% ethanol and 15% gasoline. The use of solid biomass as a direct supplier of energy, however, is an area still left relatively unexplored in this growing field. In theory, and as preliminary research suggests, harvesting energy directly from solid biomass may be considerably more efficient than gathering it from its processed liquid counterpart. In fact, some studies suggest that the energy acquired from burning ethanol is up to 67% lower than is contained in the plant cellulose from which it is derived.[1] There are, however, several other factors besides energy projections to consider when looking at the economic and market viability of such an approach. For example, one of the main advantages of liquid fuels over solid is the ease of transportation and storage. Additionally, the feasibility of developing a whole new process of biomass collection and processing must be balanced with economic and logistical constraints. This includes not only careful analysis of energy and cost balances, but also in-depth examination of all equipment, manpower and environmental limitations. IPRO 349 was established to examine these (and many more) considerations in the viability of sold fuel from biomass. Specifically, we have narrowed the scope of our research to biomass derived from corn stover (leaves and stalk left in the ground after harvesting) within the state of Illinois. Illinois was chosen because it is currently the largest producer of corn in the nation.[2] Corn stover has been shown to have an energy content of 5,290 Btu/lb. wet, and 7,560 Btu/lb. dry.[2]With such an approach, it may be possible to utilize what would otherwise be considered “waste” to produce useable, renewable energy. For the purposes of this project, cogeneration, or the simultaneous generation of both electricity and useful heat will be examined.Deliverable

Solid Fuel from Biomass for Cogeneration (Semester Unknown) IPRO 349: Solid Fuel from Biomass for Cogeneration IPRO 349 Brochure Sp08

Renewable energy is one of the most important and widely researched topics today. It is classically defined as any form of energy coming from any naturally replenish-able source. This may include everything from solar to wind power, as well as biomass or biofuels. When considering biomass, or any (living or recently-dead) biological material, the chemical energy of the molecules is generally collected through combustion. The area of liquid fuels from biomass has especially gained much notoriety and support in recent years. This is due to the lower emissions and clean-burning nature of these fuels when compared to more traditional approaches, as well as the obvious renewable nature of the starting material. While vegetable oils or animal fats can be used as a replacement for diesel fuels, corn, switchgrass, or other grains are more widely used to produce ethanol for use in common combustion engines. Today’s E85 fuel is sold to customers with a chemical makeup of 85% ethanol and 15% gasoline. The use of solid biomass as a direct supplier of energy, however, is an area still left relatively unexplored in this growing field. In theory, and as preliminary research suggests, harvesting energy directly from solid biomass may be considerably more efficient than gathering it from its processed liquid counterpart. In fact, some studies suggest that the energy acquired from burning ethanol is up to 67% lower than is contained in the plant cellulose from which it is derived.[1] There are, however, several other factors besides energy projections to consider when looking at the economic and market viability of such an approach. For example, one of the main advantages of liquid fuels over solid is the ease of transportation and storage. Additionally, the feasibility of developing a whole new process of biomass collection and processing must be balanced with economic and logistical constraints. This includes not only careful analysis of energy and cost balances, but also in-depth examination of all equipment, manpower and environmental limitations. IPRO 349 was established to examine these (and many more) considerations in the viability of sold fuel from biomass. Specifically, we have narrowed the scope of our research to biomass derived from corn stover (leaves and stalk left in the ground after harvesting) within the state of Illinois. Illinois was chosen because it is currently the largest producer of corn in the nation.[2] Corn stover has been shown to have an energy content of 5,290 Btu/lb. wet, and 7,560 Btu/lb. dry.[2]With such an approach, it may be possible to utilize what would otherwise be considered “waste” to produce useable, renewable energy. For the purposes of this project, cogeneration, or the simultaneous generation of both electricity and useful heat will be examined.Deliverable