Inhibiting protein-protein interactions to achieve a therapeutically desired effect has been a goal in the field of drug discovery for decades. Recently, advances in peptidomimetics have led researches to the use of cyclized peptides to achieve this goal. Cyclization of linear peptides restricts the number of conformations of the peptide, increasing the peptide's affinity to binding to the desired target. Cyclization also stabilizes the peptide, allowing the peptide to be resistant to proteases. This study explores the optimization of solution phase synthesis of an important integrin-mediated cell adhesion cyclic peptide for the therapeutic inhibition of multiple myeloma, cHYD1. cHYD1 was originally synthesized via solid phase peptide synthesis, and the need for a scaled up synthesis version was needed after positive bioactivity results were obtained. Chapter 3 includes the molecular modeling exploration of a possible new mechanism to which cyclized peptides could work, in which, rather than a recognition and non-recognition strand being implemented, a specific directional face is used for protein-protein interaction. This was done with the implementation of an antagonistic cyclic peptide to replace human growth hormone in its interaction with the human growth hormone receptor, and the subsequent di-cyclic peptide agonist.

In the search for alternative energy technologies, low temperature fuel cells continue to feature as technologies with the most promise for mass commercialization. Among the low temperature fuel cells, alkaline and proton exchange membrane fuel cells are the most popular. Alkaline fuel cells have typically been used for water generation as well as auxiliary power for space shuttles. Their bulkiness however makes them undesirable for other applications, especially in automobiles, where there is a great demand for alternative technologies to internal combustion engines. Proton exchange membrane fuel cells on the other hand possess numerous qualities including their compact size, high efficiency and versatility. Their mass implementation has however been delayed, because of cost among other reasons. Most of this cost is owed to the Pt/C catalyst that accounts for about half of the price of the PEM Fuel Cell. This catalyst is used to drive the sluggish oxygen reduction reaction that occurs at the cathode of the PEM Fuel Cell. To overcome this obstacle, which is to make PEM Fuel Cell technology more affordable, reducing the amount Pt has traditionally been the approach. Another approach has been to find new ideal catalyst-support combinations that increase the intrinsic activity of the supported material. One more strategy has been to find lower cost alternative materials to Pt through synthetic and kinetic manipulations to rival or exceed the current oxygen reduction reaction activity benchmark. To this end, Palladium has garnered significant interest as a monometallic entity. Its manipulation through synthetic chemistry to achieve different morphologies - which favor select lattice planes - in turn promotes the oxygen reduction reaction to different degrees. In bimetallic or, in more recent times multimetallic frameworks, geometric and ligand effects can be used to form ideal compositions and morphologies that are synergistic for improved oxygen reduction reaction kinetics. In this dissertation, we have explored three different approaches to make contributions to the catalysis and electrocatalysis body of literature. In the first instance, we look at the influence of ligand effects through the active incorporation of a PVP capping agent on the stability of ~3nm Pt NPs. Washed (no capping agent) and unwashed (with capping agent) batches of NPs were evaluated via cyclic voltammogram analyses to evaluate differences there might be between them. It was found that the current density measurements for unwashed particle batches were higher. This increase in current density was attributed to the monodentate and bidentate ligand bonding from the PVP, which increased as a function of cycle number and plateaued when the PVP was completely decomposed. The complete decomposition of PVP during the CV experiment was estimated to occur around 200 cycles. The remaining portion of the dissertation explores the electrocatalytic properties of Palladium based NPs. The first instance, a monometallic study of Palladium cubes and dendrites was aimed at building on a recent publication on the enhanced ORR activity that was achieved with a PdPt bimetallic dendrite morphology. In our work, we sought to isolate the dendritic morphology properties of the monometallic Pd composition in order to understand what advantages could be achieved via this morphology. Pd cubes were used as a comparison, since they could be generated through the combination of a similar set of reagents simply by switching the order of addition. It was found that while there was no significant variation in the ORR activity as a function of morphology / shape, there was an interesting interaction between hydrogen and the palladium NPs in the hydrogen oxidation region that varied as a function of shape. This led to further sorption and ethylene hydrogenation studies, which suggested that, the interaction between hydrogen and Pd depended on the environment. Within the electrochemical environment, the ECSA measured, suggested that hydrogen was being reversibly absorbed into the sub-surface octahedral sites of Pd. The higher ECSA for Pd cubes corroborated with higher sorption for Pd cubes as well. However ethylene hydrogenation showed that the fringes of the Pd dendrites provided additional sites for reaction, which in turn translated to higher conversion. Furthermore, through a Koutecky-Levich analysis, it was found out that the Pd dendrites while exhibiting slightly lower activity, favored the 4-electron oxygen reduction process more than the Pd cubes. In the last part of this dissertation we explored the electrocatalytic properties of Pd-based bimetallic NPs under different morphologies including nanocages and sub-10nm alloys. With the inclusion of Ag, it was found out, through Koutecky-Levich analysis that the 4-electron process was better observed under alkaline conditions using a 0.1M NaOH(aq) electrolyte solution instead of a 0.1M HClO4 (aq) for acidic media testing. It was found that, for PdAg nanocage morphologies, where the Pd galvanically replaced the Ag to form cages, the four-electron process was suited to thinner Pd shells. Indeed the average electron numbers measured for Ag nanocubes coated with a 6nm shell was in agreement, within reason of literature values for bulk Ag. However, since the binding energy that both metals have for OH is so close, the potential for contributions to the ORR kinetics in alkaline media by Pd is a potential consideration.

We analyze a self-assembly model of flexible DNA tiles and develop a theoretical description of possible assembly products. The model is based on flexible branched DNA junction molecules, which are designed in laboratories and could serve for performing computation. They are also building blocks for make of even more complex molecules or structures. The branched junction molecules are flexible with sticky ends on their arms. They are modeled with "tiles", which are star like graphs, and "tile types", which are functions that give information about the number of sticky ends. A complex is a structure that is obtained by gluing several tiles via their sticky ends. A complex without free sticky ends is called "complete complex". Complete complexes are our main interest. In most experiments, besides the desired end product, a lot of unwanted material also appears in the test tube (or pot). The idea is to use the proper proportions of tiles of different types. The set of vectors that represent these proper proportions is called the "spectrum" of the pot. We classify the types of pots according to the complexes they acan admit, and we can identify the class of each pot from the spectrum and affine spaces. We show that the spectrum is a convex polytope and give an algorithm (and a MAPLE code), which calculates it, and classify the pots in PTIME. In the second part of the dissertation, we approach molecular self-assembly from a graph theoretical point of view. We assign a star-like graph to each tile in a pot, which induces a "pot-graph". A pot-graph is a labeled multigraph corresponding to a given pot type, whose vertices represent tile types. The complexes can be represented by "complex-graphs", and each such graph is mapped homomorphically into a pot-graph. Therefore, the pot-graph can be used to distinguish between pot types according to the structure of the complexes that can be assembled. We begin the third part of the dissertation with a pot containing uniformly distributed DNA junction molecules capable of forming a cyclic graph structure, in which all possible Watson-Crick connections have already been established, and compute the expectation and the variance of the number of self-assembled cycles of any size. We also tested our theoretical results in wet lab experiments performed at Prof. Nadrian C. Seeman's laboratory at New York University. Our main concern was the probability of obtaining cyclic structures. We present the obtained results, which also helped in defining an important parameter for the theoretical model.

HIV-1 protease binds to its peptide/protein substrates in extended conformations. Therefore protease inhibitors that are constrained to form extended conformations are likely to produce very active protease inhibitors. This is because they are pre-organized to form favorable interactions with the enzyme environment immediately surrounding the active site. With this hypothesis in mind, we designed a family of structurally related molecules, which contain dipeptide analogs constrained to adopt the extended conformation. Core structural intermediates that are required for the total synthesis of the novel class of HIV-1 protease inhibitors are outlined in Chapter One. Chapter Two discusses the enantioselective synthesis of 2-alkyl-3-nitropropionates (NPA's) that is the part A of the cyclic urea molecule 8, and can also be used as the building block for the synthesis of unnatural beta-amino acids. In conclusion on this project, we were able to successfully achieve the novel enantioselective route for the synthesis of NPA's and also obtain the absolute stereochemistry of one of the NPA's by solving the crystal structure. Various routes were explored for the synthesis of the substituted orthogonally protected geminal diamino acids (OPGDA's) and these were discussed in Chapter Three. Chapter Three also discusses the synthesis of a versatile N-Boc transfer reagent and the applications of it in the synthesis of alpha-helix mimics. The outcomes of this project were the efficient synthesis of oxaziridine (104) and the methods that show how we cannot make the "substituted OPGDA's" which can serve as the guidance for future research on them. The proteasome is cellular machinery that is responsible for the breakdown of the complex proteins that are not required by a living cell. The inhibition of its activity in cancerous cells can promote apoptosis. Chapter Four discusses the synthesis of a new class of 20S proteasome inhibitors, their biological testing and lead optimization by molecular modeling, library synthesis and biological evaluation. In short this project achieves our goal for the synthesis of a novel class of 20S proteasome inhibitors that have a potential to act as drug molecules in the future.

When choosing k random elements from a group the kth expectation number is the expected size of the subgroup generated by those specific elements. The main purpose of this thesis is to study the asymptotic properties for the first and second expectation numbers of large cyclic groups. The first chapter introduces the kth expectation number. This formula allows us to determine the expected size of any group. Explicit examples and computations of the first and second expectation number are given in the second chapter. Here we show example of both cyclic and dihedral groups. In chapter three we discuss arithmetic functions which are crucial to computing the first and second expectation numbers. The fourth chapter is where we introduce and prove asymptotic results for the first expectation number of large cyclic groups. The asymptotic results for the second expectation number of cyclic groups is given in the fifth chapter. Finally, the results are summarized and future work for expectation numbers is discussed.

In gas-condensate reservoirs, gas productivity declines due to the increasing accumulation of liquids in the near wellbore region as the bottom-hole pressure declines below the dew point pressure. This phenomenon occurs even in reservoirs containing lean gas-condensate fluid. Various methods were addressed to remediate the productivity decline, for example, fracturing, gas injection, solvent injection and chemical treatment. Among them, gas injection techniques have been used as options to prevent retrograde condensation by vaporizing condensate and/or by enhancing condensate recovery in gas-condensate reservoirs. It is of utmost importance that the behavior of liquid accumulation near the wellbore should be described properly as that provides a better understanding of the productivity decline due to the originated from impaired relative mobility of gas. In this research, several gas injection techniques were assessed by using compositional simulators. The feasibility of different methods such as periodic hot gas injection and gas reinjection using horizontal wells were assessed using different reservoir fluid and injection conditions. It is shown that both the temperature and composition of the injection fluids play a key role in the remediation of productivity and condensate recovery. The combined effect of these parameters were investigated and the resulting impact on gas and condensate production was calculated by numerical simulations in this study. Design parameters pertaining to field development and operations including well configuration and injection/production scheme were also investigated in this study along with the above parameters. Based on the results, guidelines on design issues relating gas injection parameters were suggested. The various simulation cases with different parameters helped with gaining insight into the strategy of gas injection techniques to remediate the gas productivity and condensate recovery. / text

Heart failure, predominately caused by myocardial infarction (MI), is the leading cause of death in the United States. Currently the only treatment for heart failure is cardiac transplantation, but studies show that progenitor cell, biomaterial, or combined therapies have improved cardiac function post-MI. The endogenous environment of CPCs is drastically different from commonly used culture conditions. Further the endogenous environment changes with age and disease state. We evaluated the behavior of CPCs cultured on a naturally-derived, cardiac extracellular matrix (cECM) as compared to the standard culture coating collagen I, that also mimics fibrotic tissue. In this study, CPCs cultured on cECM had improved cell numbers and cardiomyogenic maturation. However, the microenvironmental cues responsible for stimulating CPC activation are largely unknown. During development, aging and disease the myocardium changes in matrix composition and stiffness exposing endogenous cells to a wide variety of stimuli. In a combinatorial study, we evaluated the effect of cyclic strain and extracellular matrix composition on CPC behavior. The response of CPCs to signals from the microenvironment is complex, with more matrix-dependency observed at lower strains. Alignment, cell division and paracrine signaling are extracellular matrix and strain dependent. Extracellular matrix conditions affect CPC maturation and calcium signaling. Mechanotransduction pathways, including focal adhesion kinase and extracellular signal-regulated kinase, are activated through adhesion and maintained under cyclic strain. Insights from this work will advance pragmatic cell therapy attempts to regenerate healthy myocardium post-MI.

Trends show that the fraction of the world's population with electronic devices using modern integrated circuits is increasing at a rapid rate. To meet consumer demands: less expensive, faster, and smaller electronics; while still making a profit, manufacturers must shrink transistor dimensions while increasing the number of transistors per integrated circuit; a trend predicted by Gorden E. Moore more than 44 years prior. As CMOS transistors scale down in size, new techniques such as atomic-layer deposition (ALD) are used to grow features one atomic layer at a time. ALD and other manufacturing processes are requiring increasingly stringent purities of process gases and liquids in order to minimize circuit killing defects which reduces yield and drives up manufacturing cost. Circuit killing defects caused by impurity incursions into UHP gas distribution system can come from a variety of sources and one of the impurity transport mechanisms investigated was back diffusion; the transport of impurities against convective flow. Once impurity incursions transpire, entire production lines are shut down and purging with UHP gas is initiated; a process that can take months thus resulting in tens of millions of dollars in lost revenue and substantial environment, safety, and health (ESH) impacts associated with high purge gas consumption. A combination of experimental investigation and process simulation was used to analyze the effect of various operational parameters on impurity back diffusion into UHP gas distribution systems. Advanced and highly sensitive analytical equipment, such as the Tiger Optics MTO 1000 H2O cavity ring-down spectrometer (CRDS), was used in experiments to measure real time back diffusing moisture concentrations exiting an electro-polished stainless-steel (EPSS) UHP distribution pipe. Design and operating parameters; main and lateral flow rates, system pressure, restrictive flow orifice (RFO) aperture size, and lateral length were changed to impact the extent of back diffusing impurities from a venting lateral. The process model developed in this work was validated by comparing its predictions with data from the experiment test bed. The process model includes convection, molecular diffusion in the bulk, surface diffusion, boundary layer transport, and all modes of dispersion; applicable in both laminar and turbulent flow regimes. Fluid dynamic properties were directly measured or were obtained by solving Navier-Stokes and continuity equations. Surface diffusion as well as convection and dispersion in the bulk fluid played a strong role in the transport of moisture from vents and lateral branches into the main line. In this analysis, a dimensionless number (Peclet Number) was derived and applied as the key indicator of the relative significance of various transport mechanisms in moisture back-diffusion. Guidelines and critical values of Peclet number were identified for assuring the operating conditions meet the purity requirements at the point of use while minimizing UHP gas usage. These guidelines allowed the determination of lateral lengths, lateral diameters, flow rates, and restrictive flow device configurations to minimize contamination and UHP gas consumption. Once a distribution system is contaminated, a significant amount of purge time is required to recover the system background due to the strong interactions between moisture molecules and the inner surfaces of the components in a gas distribution system. Because of the very high cost of UHP gases and factory downtime, it is critical for high-volume semiconductor manufacturers to reduce purge gas usage as well as purge time during the dry-down process. The removal of moisture contamination in UHP gas distribution systems was approached by using a novel technique dubbed pressure cyclic purge (PCP). EPSS piping was contaminated with moisture, from a controlled source, and then purged using a conventional purge technique or a PCP technique. Moisture removal rates and overall moisture removal was determined by measuring gas phase moisture concentration in real time via a CRDS moisture analyzer. When compared to conventional purge, PCP reduced the time required and purge gas needed to clean the UHP gas distribution systems. However, results indicate that indiscriminately initiating PCP can have less than ideal or even detrimental results. An investigation of purge techniques on the removal of gas phase, chemisorbed, and physisorbed moisture, coupled with the model predictions, led to the testing of hybrid PCP. The hybrid PCP approach proved to be the most adaptable purge technique and was used in next phase of testing and modeling. Experiments and modeling progressed to include testing the effectiveness of hybrid PCP in systems with laterals; more specifically, laterals that are "dead volumes" and results show that hybrid PCP becomes more purge time and purge gas efficient in systems with increasing number and size of dead volumes. The process model was used as a dry-down optimization tool requiring inputs of; geometry and size, temperature, starting contamination level, pressure swing limits of inline equipment, target cleanliness, and optimization goals; such as, minimizing pure time, minimizing purge gas usage, or minimizing total dry-down cost.

In vivo, biomechanical stress plays an important role in tissue physiology and pathology, affecting cell and tissue behavior. Even though conventional outflow tissues in the eye are constantly exposed to dynamic changes in intraocular pressure (IOP), the effects of such biomechanical stressors on outflow tissue function have not been analyzed. In particular, changes in IOP with each heartbeat have been measured in human eyes approximating 2.7 mmHg/sec. The purpose of this dissertation is to determine the effect(s) of ocular pulse on conventional outflow tissue regulation and the effect that contractility plays in this mechanical stress-mediated response. The central hypothesis directing this research is that cyclic intraocular pulsations (i.e. ocular pulse) play a significant role in conventional outflow facility.In order to address our hypothesis we studied the effect of biomechanical stressors on conventional outflow physiology using three different strategies: (1) by comparing conventional outflow endothelial cells to blood and lymphatic capillary endothelia, we gained a better understanding of the effects of biomechanical stress on conventional outflow tissue physiology, (2) by modifying the anterior segment perfusion model, we were able to measure the effect of ocular pulse on conventional outflow facility, and (3) by exposing trabecular meshwork cell monolayers to cyclic biomechanical pressure oscillations in the presence of compounds known to affect trabecular meshwork contractility, we were able to analyze the effect of rho-kinase-mediated contractility on the ocular pulse-associated response.Perfused human and porcine anterior segments showed a significant ocular pulse-mediated decrease in outflow facility; in addition, perfused trabecular meshwork monolayers showed an increase in intra-chamber pressure when exposed to cyclic pressure oscillations. This effect was blocked by Y27632 inhibition of rho-kinase-mediated contraction.In conclusion, the work shown in this dissertation demonstrates for the first time that trabecular outflow tissues are capable of responding to a physiologically-relevant cyclic biomechanical stress. This response can be observed as an increase in outflow resistance that translates to lower baselines in outflow facility of anterior segments and lower hydraulic conductivity of trabecular meshwork monolayers. In addition, we concluded that the observed ocular pulse-mediated response of trabecular meshwork cells is regulated by rho-kinase-induced contractility.

Corrosion of steel reinforcement in concrete structures results in significant repair and rehabilitation costs. In the past several years, new fiber reinforced polymer (FRP) reinforcing bars have been introduced as an alternative to steel reinforcing bars. Several national and international organizations have recently developed standards based on preliminary test results. However, limited validation testing has been performed on the recommendations of these standards. High variability of the tensile properties, degradation of tensile strength, direct shear capacity, predicted deflections due to creep, cracking behavior of FRP-reinforced concrete flexural members, bond behavior and development length, and effects of thermal expansion on cracking of FRP reinforced concrete have all been reported, but are areas that need further investigation and validation. The objective of this study is to evaluate the characteristics of glass FRP reinforcing bars and provide recommendations on the design and construction of concrete structures containing these bar types with regard to the areas described. The recently developed ACI 440 design guidelines were analyzed and modifications proposed.