Epistasis among Drosophila persimilis factors conferring hybrid male sterility with D. pseudoobscura bogotana.

The Bateson-Dobzhansky-Muller model posits that hybrid incompatibilities result from genetic changes that accumulate during population divergence. Indeed, much effort in recent years has been devoted to identifying genes associated with hybrid incompatibilities, often with limited success, suggesting that hybrid sterility and inviability are frequently caused by complex interactions between multiple loci and not by single or a small number of gene pairs. Our previous study showed that the nature of epistasis between sterility-conferring QTL in the Drosophila persimilis-D. pseudoobscura bogotana species pair is highly specific. Here, we further dissect one of the three QTL underlying hybrid male sterility between these species and provide evidence for multiple factors within this QTL. This result indicates that the number of loci thought to contribute to hybrid dysfunction may have been underestimated, and we discuss how linkage and complex epistasis may be characteristic of the genetics of hybrid incompatibilities. We further pinpoint the location of one locus that confers hybrid male sterility when homozygous, dubbed "mule-like", to roughly 250 kilobases.

Coal-fired Power Plants with Flexible Amine-based CCS and Co-located Wind Power: Environmental, Economic and Reliability Outcomes

Carbon Capture and Storage (CCS) technologies provide a means to significantly reduce carbon emissions from the existing fleet of fossil-fired plants, and hence can facilitate a gradual transition from conventional to more sustainable sources of electric power. This is especially relevant for coal plants that have a CO2 emission rate that is roughly two times higher than that of natural gas plants. Of the different kinds of CCS technology available, post-combustion amine based CCS is the best developed and hence more suitable for retrofitting an existing coal plant. The high costs from operating CCS could be reduced by enabling flexible operation through amine storage or allowing partial capture of CO2 during high electricity prices. This flexibility is also found to improve the power plant’s ramp capability, enabling it to offset the intermittency of renewable power sources. This thesis proposes a solution to problems associated with two promising technologies for decarbonizing the electric power system: the high costs of the energy penalty of CCS, and the intermittency and non-dispatchability of wind power. It explores the economic and technical feasibility of a hybrid system consisting of a coal plant retrofitted with a post-combustion-amine based CCS system equipped with the option to perform partial capture or amine storage, and a co-located wind farm. A techno-economic assessment of the performance of the hybrid system is carried out both from the perspective of the stakeholders (utility owners, investors, etc.) as well as that of the power system operator.

In order to perform the assessment from the perspective of the facility owners (e.g., electric power utilities, independent power producers), an optimal design and operating strategy of the hybrid system is determined for both the amine storage and partial capture configurations. A linear optimization model is developed to determine the optimal component sizes for the hybrid system and capture rates while meeting constraints on annual average emission targets of CO2, and variability of the combined power output. Results indicate that there are economic benefits of flexible operation relative to conventional CCS, and demonstrate that the hybrid system could operate as an energy storage system: providing an effective pathway for wind power integration as well as a mechanism to mute the variability of intermittent wind power.

In order to assess the performance of the hybrid system from the perspective of the system operator, a modified Unit Commitment/ Economic Dispatch model is built to consider and represent the techno-economic aspects of operation of the hybrid system within a power grid. The hybrid system is found to be effective in helping the power system meet an average CO2 emissions limit equivalent to the CO2 emission rate of a state-of-the-art natural gas plant, and to reduce power system operation costs and number of instances and magnitude of energy and reserve scarcity.

The evolution of airplanes

The prevailing view is that we cannot witness biological evolution because it occurred on a time scale immensely greater than our lifetime. Here, we show that we can witness evolution in our lifetime by watching the evolution of the flying human-and-machine species: the airplane. We document this evolution, and we also predict it based on a physics principle: the constructal law. We show that the airplanes must obey theoretical allometric rules that unite them with the birds and other animals. For example, the larger airplanes are faster, more efficient as vehicles, and have greater range. The engine mass is proportional to the body size: this scaling is analogous to animal design, where the mass of the motive organs (muscle, heart, lung) is proportional to the body size. Large or small, airplanes exhibit a proportionality between wing span and fuselage length, and between fuel load and body size. The animal-design counterparts of these features are evident. The view that emerges is that the evolution phenomenon is broader than biological evolution. The evolution of technology, river basins, and animal design is one phenomenon, and it belongs in physics. © 2014 AIP Publishing LLC.

Stochastic switching in infinite dimensions with applications to random parabolic PDE

© 2015 Society for Industrial and Applied Mathematics.We consider parabolic PDEs with randomly switching boundary conditions. In order to analyze these random PDEs, we consider more general stochastic hybrid systems and prove convergence to, and properties of, a stationary distribution. Applying these general results to the heat equation with randomly switching boundary conditions, we find explicit formulae for various statistics of the solution and obtain almost sure results about its regularity and structure. These results are of particular interest for biological applications as well as for their significant departure from behavior seen in PDEs forced by disparate Gaussian noise. Our general results also have applications to other types of stochastic hybrid systems, such as ODEs with randomly switching right-hand sides.

Mechanistic Models of Anti-HIV Microbicide Drug Delivery

A new modality for preventing HIV transmission is emerging in the form of topical microbicides. Some clinical trials have shown some promising results of these methods of protection while other trials have failed to show efficacy. Due to the relatively novel nature of microbicide drug transport, a rigorous, deterministic analysis of that transport can help improve the design of microbicide vehicles and understand results from clinical trials. This type of analysis can aid microbicide product design by helping understand and organize the determinants of drug transport and the potential efficacies of candidate microbicide products.

Microbicide drug transport is modeled as a diffusion process with convection and reaction effects in appropriate compartments. This is applied here to vaginal gels and rings and a rectal enema, all delivering the microbicide drug Tenofovir. Although the focus here is on Tenofovir, the methods established in this dissertation can readily be adapted to other drugs, given knowledge of their physical and chemical properties, such as the diffusion coefficient, partition coefficient, and reaction kinetics. Other dosage forms such as tablets and fiber meshes can also be modeled using the perspective and methods developed here.

The analyses here include convective details of intravaginal flows by both ambient fluid and spreading gels with different rheological properties and applied volumes. These are input to the overall conservation equations for drug mass transport in different compartments. The results are Tenofovir concentration distributions in time and space for a variety of microbicide products and conditions. The Tenofovir concentrations in the vaginal and rectal mucosal stroma are converted, via a coupled reaction equation, to concentrations of Tenofovir diphosphate, which is the active form of the drug that functions as a reverse transcriptase inhibitor against HIV. Key model outputs are related to concentrations measured in experimental pharmacokinetic (PK) studies, e.g. concentrations in biopsies and blood. A new measure of microbicide prophylactic functionality, the Percent Protected, is calculated. This is the time dependent volume of the entire stroma (and thus fraction of host cells therein) in which Tenofovir diphosphate concentrations equal or exceed a target prophylactic value, e.g. an EC50.

Results show the prophylactic potentials of the studied microbicide vehicles against HIV infections. Key design parameters for each are addressed in application of the models. For a vaginal gel, fast spreading at small volume is more effective than slower spreading at high volume. Vaginal rings are shown to be most effective if inserted and retained as close to the fornix as possible. Because of the long half-life of Tenofovir diphosphate, temporary removal of the vaginal ring (after achieving steady state) for up to 24h does not appreciably diminish Percent Protected. However, full steady state (for the entire stromal volume) is not achieved until several days after ring insertion. Delivery of Tenofovir to the rectal mucosa by an enema is dominated by surface area of coated mucosa and whether the interiors of rectal crypts are filled with the enema fluid. For the enema 100% Percent Protected is achieved much more rapidly than for vaginal products, primarily because of the much thinner epithelial layer of the mucosa. For example, 100% Percent Protected can be achieved with a one minute enema application, and 15 minute wait time.

Results of these models have good agreement with experimental pharmacokinetic data, in animals and clinical trials. They also improve upon traditional, empirical PK modeling, and this is illustrated here. Our deterministic approach can inform design of sampling in clinical trials by indicating time periods during which significant changes in drug concentrations occur in different compartments. More fundamentally, the work here helps delineate the determinants of microbicide drug delivery. This information can be the key to improved, rational design of microbicide products and their dosage regimens.

Ultra High Pressure Hydrogen Studies

Hydrogen has been called the fuel of the future, and as it’s non- renewable counterparts become scarce the economic viability of hydrogen gains traction. The potential of hydrogen is marked by its high mass specific energy density and wide applicability as a fuel in fuel cell vehicles and homes. However hydrogen’s volume must be reduced via pressurization or liquefaction in order to make it more transportable and volume efficient. Currently the vast majority of industrially produced hydrogen comes from steam reforming of natural gas. This practice yields low-pressure gas which must then be compressed at considerable cost and uses fossil fuels as a feedstock leaving behind harmful CO and CO2 gases as a by-product. The second method used by industry to produce hydrogen gas is low pressure electrolysis. In comparison the electrolysis of water at low pressure can produce pure hydrogen and oxygen gas with no harmful by-products using only water as a feedstock, but it will still need to be compressed before use. Multiple theoretical works agree that high pressure electrolysis could reduce the energy losses due to product gas compression. However these works openly admit that their projected gains are purely theoretical and ignore the practical limitations and resistances of a real life high pressure system. The goal of this work is to experimentally confirm the proposed thermodynamic gains of ultra-high pressure electrolysis in alkaline solution and characterize the behavior of a real life high pressure system.