Cytochrome c oxidase (COX) is a multimeric protein complex whose enzymatic activity contributes to the generation of an electrochemical potential required to synthesize adenosine triphosphate (ATP). Synthesis of Cytochrome c Oxidase 1 (SCO1) and SCO2 are two of the many accessory factors that are required to assemble individual structural subunits of COX into a functional holoenzyme complex. Mutations in either SCO gene cause severe, early onset forms of human disease. SCO1 and SCO2 are closely related paralogues localized to the inner mitochondrial membrane. Both proteins bind copper and exhibit a thiol disulphide oxidoreductase activity. Copper is bound by a highly conserved Cysteine x x x Cysteine motif and a histidine found within a thioredoxin fold, which is contained in the C-terminal half of the protein and projects into the mitochondrial intermembrane space. Mutations in either SCO1 or SCO2 affect their ability to deliver copper to COX II and metallate its CuA site, and also result in an increased rate of copper efflux from the cell. However, the relative importance of the ability to bind and transfer copper to SCO protein function remains poorly understood. Therefore, to investigate the significance of several cysteine residues and the conserved histidine to the copper-binding properties of SCO1, I functionally characterized a series of N- and C-terminal SCO1 mutant proteins by transducing them into control and patient fibroblasts, and quantifying their phenotypic effect on COX activity. I found that the two cysteines within the soluble, N-terminal matrix domain of SCO1 are not required for protein function. Overexpression of C-terminal SCO1 mutants only affected COX activity in SCO1-2 patient fibroblasts. To further characterize the copper-binding properties of these C-terminal mutants, soluble forms of each SCO1 variant were expressed and purified from bacteria, and the amount of total bound copper and the relative abundance of Cu(I) and Cu(II) were quantified. Although these analyses suggested that one mutant, SCO1 C169H, binds significantly more Cu(I) than the wild-type protein, none of the SCO1 variants exhibited properties that furthered our understanding of the precise role of SCO1 in the biogenesis of the CuA site of COX II.

Potato chips are very popular in the United States. Recently, an enormous interest in developing snacks from fruits and vegetables with high quality has been assessed. Mango, due to its characteristic flavor and nutritional value, is excellent for snack production. Osmotic dehydration (OD) as a pre-treatment and vacuum frying (1.33 kPa) processes were proposed to obtain high quality mango chips. Mango ?Tommy Atkins? slices were pre-treated with different OD concentrations (40, 50, and 65w/v), times (45, 60, and 70 min), and temperatures (22, 40, and 57oC). Physical and chemical properties (aw, pH, oBrix, sugar gain, water loss, and shrinkage) after OD were studied. The pre-treated slices were vacuum fried (1.33 kPa) at 120, 130, and 138oC and product quality attributes (PQA) (oil content, texture, porosity, color, microstructure, and carotenoid content) were determined. Microstructure of the chips was analyzed using an environmental scanning electron microscope. Effect of frying temperatures at optimum OD (65 w/v at 40oC) times was tested. The consumer tests showed that samples were all acceptable. The best mango chips process was the one with 65 w/v concentration for 60 min (pre-treatment) and vacuum frying at 120oC. Kinetic studies on oil content, texture, porosity, color, and carotenoid retention were performed. Oil absorption was modeled by a fractional conversion kinetic model. Absorption rate constant increased with frying temperature. Diameter changes in the chips, although not significant (P>0.05), followed an initial expansion to later decrease. Thickness of the slices increased (puffed) (around 60%) with time for all frying temperatures. Texture changes were for two frying periods: (1) water removal and crust formation and (2) slices became tougher and crispier and the end of frying. Porosity in the samples increased with frying, and a fractional conversion best described this phenomenon. Color *a (redness) increased with frying time and temperature and was modeled using a logistic model. Color *b (yellowness) increased up to 30 s of frying and then decreased. Carotenoids degradation followed a first order model, with a significant (P<0.05) decrease with frying temperature. Mango chips fried under atmospheric fryer had less carotenoid retention (25%) than with a vacuum fryer.

With increasing computational power, simulations of regional climate are now becoming possible on convective-resolving grids, thus eliminating the need for a convective parameterization. In the present study, a series of seasonal calculations using the Weather Research and Forecasting (WRF) model are computed at 4-km grid spacing, which reasonably resolves most convective systems. Simulations are computed for both the DJF and MAM seasons as averaged over 2005-2008, with a model domain covering the majority of the Amazon Basin and the adjacent South American coastline. Precipitation statistics are computed and compared to satellite rainfall retrieval data from the 13-year Tropical Rainfall Measuring Mission (TRMM) record. For comparison, a set of companion simulations with 12-km grid spacing are also computed, using the Kain-Fritsch convective parameterization. As compared to the 12-km runs, the 4-km simulations show significant improvement in the overall mean rain rate, the rain rate probability distributions, and the diurnal evolution and timing of precipitation. Both the 4-km and 12-km cases capture the coastal propagating signal and the interior basin-wide diurnal oscillation; however, the 4-km case shows better timing and evolution statistics. Compared to TRMM, the 4-km case rains too infrequently, but is more likely to produce rain events at high rain rates, thus resulting in a similar overall average rain rate. Overall, the present calculations show significant promise for computing regional rainfall patterns on convective-resolving grids.

Potato chips are very popular in the United States. Recently, an enormous interest in developing snacks from fruits and vegetables with high quality has been assessed. Mango, due to its characteristic flavor and nutritional value, is excellent for snack production. Osmotic dehydration (OD) as a pre-treatment and vacuum frying (1.33 kPa) processes were proposed to obtain high quality mango chips. Mango ?Tommy Atkins? slices were pre-treated with different OD concentrations (40, 50, and 65w/v), times (45, 60, and 70 min), and temperatures (22, 40, and 57oC). Physical and chemical properties (aw, pH, oBrix, sugar gain, water loss, and shrinkage) after OD were studied. The pre-treated slices were vacuum fried (1.33 kPa) at 120, 130, and 138oC and product quality attributes (PQA) (oil content, texture, porosity, color, microstructure, and carotenoid content) were determined. Microstructure of the chips was analyzed using an environmental scanning electron microscope. Effect of frying temperatures at optimum OD (65 w/v at 40oC) times was tested. The consumer tests showed that samples were all acceptable. The best mango chips process was the one with 65 w/v concentration for 60 min (pre-treatment) and vacuum frying at 120oC. Kinetic studies on oil content, texture, porosity, color, and carotenoid retention were performed. Oil absorption was modeled by a fractional conversion kinetic model. Absorption rate constant increased with frying temperature. Diameter changes in the chips, although not significant (P>0.05), followed an initial expansion to later decrease. Thickness of the slices increased (puffed) (around 60%) with time for all frying temperatures. Texture changes were for two frying periods: (1) water removal and crust formation and (2) slices became tougher and crispier and the end of frying. Porosity in the samples increased with frying, and a fractional conversion best described this phenomenon. Color *a (redness) increased with frying time and temperature and was modeled using a logistic model. Color *b (yellowness) increased up to 30 s of frying and then decreased. Carotenoids degradation followed a first order model, with a significant (P<0.05) decrease with frying temperature. Mango chips fried under atmospheric fryer had less carotenoid retention (25%) than with a vacuum fryer.

Income variability explains a significant fraction of the increase in annual income inequality. Chapter 1 considers the impact of variability on tax unit inequality. Using income tax return panel data, I estimate that between a tenth and a quarter of the increase in top one percent income shares between the early 1980s and 2000s was caused by variability. Increased income variability over this period resulted from mean-reverting fluctuations in the bottom quintile and top one percent. Variability in the top of the distribution seems partly driven by permanent income shifting in response to the Tax Reform Act of 1986. Chapter 2 examines the individual earnings distribution. Using Social Security Administration earnings panel data, I estimate that variability explains half of the increase in annual inequality in the bottom half of the distribution between 1973 and 1985. When workers with years of zero earnings are included, increasing earnings variability explains almost all of this group's increase in inequality. The increase in earnings variability appears to be explained by an increased fraction of working age men with years of zero earnings. Annual individual earnings inequality in the bottom half of the distribution not only increased with variability in the 1970s and 1980s, but also fell with variability in the 1950s and early 1960s. This suggests that the U-shaped trend in income inequality observed over these four decades was partly caused by first a fall and then a rise in earnings variability. Between 1985 and 2000, falling variability caused most of the decline in annual earnings inequality within the bottom half of the distribution. Within the top of the distribution, earnings inequality increased over this period because of changes in permanent earnings and not increasing variability. Income variability means that in a progressive tax system annual and lifetime federal tax rates can diverge. Chapter 3 shows that on an annual basis, those at the bottom of the distribution pay little or no federal income taxes, while on a lifetime basis they pay average tax rates about five percentage points higher. Income variability also means there is a trade-off between vertical and horizontal equity.

This thesis takes the typical one-to-one relationship between a tower and a lobby and asks what if a three-layer base that produces a higher density and a scale exceeding the physical boundary of a single office tower replaces the lobby. Combing retail, conference facilities and recreation the base at once consolidates the programmatic needs of office workers and thickens the singular exchange of lobby-office-lobby to one of recreation-lobby-retail-office-lobby. Spanning the length of a ten-acre site in London, the base establishes a large horizontal floor plate and introduces big-box retail and an economy privileging lower prices onto a site surrounded by boutiques and mom-and-pop stores. Instead of planar adjacencies, retail and towers overlay in section. Vertical, horizontal and transverse circulations intersect, turn and unite, forming new programmatic possibilities and proliferating the cultural, economic and social life of a tower onto the city.

QA bearing technologies Ltd. (hereafter QA) is a custom manufacturer of bearings in a variety of types and sizes. This research concerns one of the processes in QA’s bearing manufacturing in which the individual bearings, once assembled, are packaged to prevent corrosion and attack from any environmental influence. QA currently employs a manual process, which is time-consuming and significantly limits QA’s productivity. This greatly raises a need to improve this process through the design of an automated process for bearing packaging. Various kinds of packaging machine are available in the market for this application. However, most of them are designed for general packaging purpose and simply combining them may result in the functional overlap as applied to the packaging process. This research aims to design an automatic bearing packaging system (ABPS) based on an advanced design theory, i.e., Axiomatic Design Theory (ADT). In the first part of this research, a set of general functional requirements (FRs) and constraints (CONs) were defined specifically based on the needs from the customers. All FRs were maintained independent to each other such that the following design wouldn’t result in functional overlap. Then, design parameters (DPs) in general level were created to satisfy the defined FRs, each being a functionally independent subsystem consists of both custom-design components and products existing in the market. The second part of the research was to decompose the FRs and DPs based on independent axiom of ADT into further levels until the conceptual design was accomplished. In this process, acceptable alternatives in different hierarchies were proposed for comparison in the decision making process. Also, the relationship between FRs and DPs in the same level was always maintained one-to-one, which allows readily for modification in future, if needed. In the third part of this research, the information axiom of ADT was utilized to find the best solution from alternatives. For this, each alternative was evaluated in terms of the information content that reflects the possibility of satisfying the objective FR. The one with least information content was determined as the best alternative. As a result of this research, two solutions with different degree of automation were recommended for the bearing packaging system. The first solution is featured with higher degree of automation and capable of packaging bearings with limited human interface and as result, the total cost for its implementation is relatively high. The second solution integrates semi-automated machines and simplified sealing strategy and as such, the cost for its implementation is significantly reduced. After the conceptual design is complete, ADT is further applied in the detailed design level for oiling system with custom-designed components and mechanism. For the design of certain DPs, the design process applying ADT is used to compare with conventional methods, proved to be more efficient and simplified. Eventually, the final solution proposed for the detailed design of oiling system is consistent with independent axiom of ADT.

This inquiry explores the possibility of applying principles from Plato?s education system in the Republic to modern military leadership development programs. Both are concerned with producing a ?guard-dog? that will serve the interests of the state rather than exploit vulnerable civilians. Plato proposes educating guardians with a natural disposition to believe the ?noble lie,? that it is better to serve others than to pursue selfinterest for personal gain; but, would the proper tension in moral sensibilities prescribed by the Platonic Grid help or hinder a military leader to successfully act on the battlefield? First, I examine Plato?s theory to familiarize military leaders with the education system from the Republic; including his views on unity, reality, the theory of the forms, and recollection of knowledge that underlie Plato?s enquiry into the nature of justice, and lead to the need for inner harmony of the soul through the proper tension of wisdom, courage, and temperance to rule the three elements of the soul. Then I analyze the key leaders from the Battle of Balaclava, the Battle of Gettysburg, and the siege of the Alamo for possible correlations of the application of the Platonic Grid aligned with the ?noble lie? to success on the battlefield. This includes inquiry into the likelihood that belief in the ?noble lie? can motivate soldiers to make the ultimate sacrifice. I conclude by examining how Plato?s theories could be assimilated into a military pedagogy to produce modern day ?dogs of war? that leads to the startling conclusion that adherence to the ?noble lie? could also be in the self-interest of the guardian who seeks to serve the best interest of her nation.

Lipid bi-layers are ubiquitous components of biological cells and are found in a variety of cell components. In biological membranes, lipid bi-layer membranes carry membrane proteins, which control transport of material and communication of signals in and out the cell. There are several disadvantages involved with patch clamping method as a way of studying biological membranes and protein interactions. Hence, artificial synthesis of bi-layer has been of great interest in basic biophysical studies, drug discoveries in pharmaceutical studies and study of protein nanopores for precise engineering applications. However, conventional lipid bi-layer synthesis techniques require skilled operators, have low repeatability (reliability), have portability restrictions and result in unstable bi-layers having a short lifetime. In this investigation a novel microfluidic device and a method for artificial synthesis of lipid bi-layer in-situ are explored. In the proposed method, lipid trapped at an aperture on a Teflon sheet, is thinned to form a lipid bi-layer by a continuous flow of buffer solution on both sides of the aperture in the microfluidic device. The microfluidic device is expected to have advantages from its compact design. Further, the new approach is expected to be repetitive and good for automation removing the requirement of a skilled operator. The microfluidic device was fabricated using two glass substrates. Two channels of ? ? shape were etched and through holes were fabricated at all four terminal ends of the microchannels on each glass substrate. A thin Teflon sheet carrying a 100?m diameter hole was sandwiched between the two glass wafers forming two sets of microchannels on both sides of the aperture. An analytical microfluid model of the microchannels was developed to investigate the nature of the flow and to select microchannel parameters. Experiments using the proposed device were performed to verify the feasibility of the novel approach for lipid bi-layer synthesis. Experimental results suggest formation of a lipid bi-layer at an aperture on the Teflon sheet but further investigation might be necessary for verification. Life time of the bi-layer is short mainly due to low quality of the used aperture.

This study constructs a two-step model to test the most prominent market timing factors. We decompose equity issuances into 1) firm-specific components, which are predicted by firms’ characteristics, and 2) market-wide components, which are predicted by aggregate time series measures. Our evidence shows that, at the firm level, firms with higher market-to-book ratio, smaller size, more growth opportunities, and fewer tangible assets are more likely to issue equity. At the aggregate level, a greater proportion of firms issue equity in years with higher aggregate market-to-book ratio and lower asymmetric information. After controlling for the aggregate market-to-book ratio and information asymmetry, sentiment has no direct effect on equity issuance. This paper provides direct evidence that firms time their favorable market conditions to reduce adverse selection costs, and to exploit higher individual security valuations or capture growth opportunities.