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Design, Synthesis, And Evaluation Of Molecular Inhibitors For Biologically Relevant Enzymes, Sarah Emma St. John

Open Access Dissertations

The work in this thesis details the design, synthesis, and biological evaluation of molecular inhibitors for the inhibition of biologically relevant enzymes. The first three chapters of this thesis concern the polyphenol resveratrol and its inhibition of the quinone reductase 2 (QR2) enzyme. The work on this subject resulted in the complete design, synthesis, biological and structural evaluation of a second generation library of resveratrol analogues. From this work we identified a novel resveratrol analogue that inhibits QR2 in a previously unknown binding orientation. The fourth chapter of this thesis details the de novo design of molecules for the inhibition …

The Chemistry Of Flavonoids In Model Beverages And Human Milk, Brian Jay Song

Open Access Dissertations

Interest in the chemistry and stability of flavonoids in foods has been generated by countless epidemiological, in vitro, and in vivo studies that suggest a variety of potential health promoting effects of diets rich in flavonoids. Flavonoids have been shown to interact with multiple components in beverages including macromolecules, minerals, certain vitamins, and other flavonoids. Furthermore, environmental conditions including light exposure, elevated temperatures, and relative humidity have been shown to modify flavonoid stability. However, specific mechanisms, relative kinetics of degradation reactions and the impact of macromolecules in model beverages and biological fluids on flavonoid stability remain largely unknown.

Recently, interest …

Natural Genetic Variation Affecting Calcium Homeostasis, Rebecca Anna Replogle

Open Access Dissertations

Calcium (Ca) is essential for multiple functions within the body including skeletal health. The level of Ca in the serum is tightly regulated. During periods of habitual low Ca intake, the body senses a decrease in serum Ca and increases renal conversion of 25 hydroxyvitamin D (25(OH)D) to 1,25 dihydroxyvitamin D (1,25(OH)2D). 1,25(OH)2D acts through the vitamin D receptor (VDR) to increase intestinal Ca absorption, renal Ca reabsorption and skeletal Ca resorption. Efficient intestinal Ca absorption, especially during periods of low Ca intake, is critical for protecting bone mass. Ca absorption and its primary regulator, 1,25(OH)2D, are affected by both …

Synthesis Of Novel Isoprenoid Diphosphate Analogs As Chemical Tools To Investigate Protein Geranylgeranylation, Kayla Jo Temple

Open Access Dissertations

Many proteins require prenylation in order to be biologically functional. Some such proteins include the small Ras and Rho GTPase superfamilies, nuclear lamins A and B, and the kinesin motor proteins CENP-E and F. Prenyltransferase (PTase) inhibition is currently being explored as a possible treatment not only for cancer but for a wide variety of other diseases.

Clinical studies revealed that the effectiveness of farnesyltransferase inhibitors (FTIs) to treat Ras-dependent tumors is determined by which isoform of Ras is overactive. Unfortunately the majority of Ras-dependent tumors have a mutation in either the N- or K-Ras isoforms; both of these isoforms …

Management Of Potato Leafhopper And Maple Spider Mite On Nursery Grown Maples, Julia Prado Beltran

Open Access Dissertations

Potato leafhopper Empoasca fabae (Harris) (Homoptera: Cicadellidae) and maple spider mite Oligonychus aceris (Shimer) (Acarina: Tetranychidae) are important pests of maple trees. Investigations determined how insecticide use and fertilization impacted the abundance of E. fabae and O. aceris on `Red Sunset' red maple and `Autumn Blaze' Freeman maples. Bifenthrin applications directed against leafhoppers reduced damage to both cultivars, but increased O. aceris on Autumn Blaze. Using a threshold of one leafhopper per branch to trigger pesticide applications protected Red Sunset maples from leafhopper injury. It also prevented outbreaks of O. aceris on Autumn Blaze because few trees reached this density. …

Characterization Of Caxck31, A Bacterial Calcium/Proton Antiporter, Marc Robert Ridilla

Open Access Dissertations

To better understand a class of transporters known as Calcium/Cation Antiporters (CaCAs), the bacterial calcium/proton antiporter CAXCK31 was purified and characterized. New methods were developed for its heterologous overexpression and purification. These methods help to define stress responses to toxic membrane overproduction in E. coli and may be broadly applicable to studies of membrane proteins. The results from a variety of biochemical and biophysical experiments demonstrated that CAXCK31 exists as a dimer in the membrane and can be purified in the dimeric state. The methods used include chemical cross-linking, FRET, and SEC-MALS. In addition, various transport properties of CAXCK31, including …

Degree Program Changes And Curricular Flexibility: Addressing Long Held Beliefs About Student Progression, George Dante Ricco

Open Access Dissertations

In higher education and in engineering education in particular, changing majors is generally considered a negative event - or at least an event with negative consequences. An emergent field of study within engineering education revolves around understanding the factors and processes driving student changes of major. Of key importance to further the field of change of major research is a grasp of large scale phenomena occurring throughout multiple systems, knowledge of previous attempts at describing such issues, and the adoption of metrics to probe them effectively. The problem posed is exacerbated by the drive in higher education institutions and among …

Quantifying Crop Yield, Bioenergy Production And Greenhouse Gas Emissions From Cropland And Marginal Land Using A Model-Data Fusion Approach, Zhangcai Qin

Open Access Dissertations

Bioenergy is becoming increasingly attractive to many countries, but has sparked an intensive debate regarding energy, economy, society and environment. Biofuels provide alternative energy to conventional fossil fuels. However, the environmental impact of producing and using biofuel is a major concern to our society. This study is dedicated to quantifying and evaluating biofuel production and potential climate change mitigation due to potential large-scale bioenergy expansion in the conterminous United States, using model-data fusion approaches.

Biofuel made from conventional (e.g., maize (Zea mays L.)) and cellulosic crops (e.g., switchgrass (Panicum virgatum L.) and Miscanthus (Miscanthus × giganteus)) …

Welfare Impacts Of False Codling Moth Threatening California Oranges, Azza Mohamed Kamal Ahmed Mohamed

Open Access Dissertations

Welfare impacts of alternative pest management strategies of False Codling Moth (FCM) threatening California's oranges are examined. Different economic agents along the supply chain of fresh oranges and orange products in the United States are considered, including consumers, retailers, wholesalers, and growers. A partial equilibrium dynamic framework that accounts for supply response from the other US orange producing states is developed. Data for supply shocks (orange yield losses and control costs) are obtained from the Animal and Plant Health Inspection Service of the United States Department of Agriculture (APHIS).

FCM is not presently in the United States. If introduced to …

Silica Colloidal Crystals As Emerging Materials For The High-Throughput Sizing Of Proteins By Packed Capillary Electrophoresis, Nadine K. Njoya

Open Access Dissertations

Protein heterogeneity is currently one of the leading problems in formulation of therapeutic proteins. The effectiveness of therapeutic proteins is diminished when they exhibit heterogeneity due to aggregates and degradation by-products. Furthermore, guidelines set forth by the FDA require therapeutic proteins to have high stability as well as high purity. With development time on the order of years and costs incurred in the millions, pharmaceutical companies are investing more time in finding fast and efficient ways to screen for protein heterogeneity. Current methods such as native polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC) and capillary electrophoresis (CE) are time consuming, …

Invasive Silver Carp (Hypophthalmichthys Molitrix) Protein Hydrolysates- A Potential Source Of Natural Antioxidant, Sravanthi Priya Malaypally

Open Access Dissertations

Invasive silver carp (Hypophthalmichthys molitrix), continue to spread over the Mississippi River causing a great concern for the river ecosystem due to their impact on native fish species. To minimize the negative effects of silver carp, many strategies were implemented including using it for animal feed, as fertilizers or simply discarding them into waste. However, these fish are high in protein content, making them excellent starting material for protein-derived by-products. One alternative is to recover and modify the protein in the fish into bioactive food ingredient. In the functional/ nutraceutical food industry, there is high demand for antioxidant agents. In …

Store-Operated Calcium Entry And Its Function During Fertilization In Porcine Eggs, Chunmin Wang

Open Access Dissertations

In a variety of mammalian cells, the depletion of intracellular Ca^{2+ stores leads to Ca2+ influx across the plasma membrane though a process known as store-operated Ca2+ entry. It not only plays a critical role in the replenishment of the Ca2+ stores but it is also responsible for the maintenance of long-lasting high intracellular Ca2+ levels and sustaining repetitive Ca2+ oscillations. During fertilization a Ca2+ signal, which can take the form of a single or multiple Ca2+ elevations (depending on the species) is the universal trigger for the egg-to-embryo transition. For sustaining …}

Long-Term Disturbance Histories Of Managed And Natural Mixed-Hardwood Forests Of Central Indiana, Robert Charles Morrissey

Open Access Dissertations

Over the course of the last century, we have observed changes in forest composition and structure related to changes in disturbance regimes. Reduced frequency and severity of disturbance events has allowed for the ingrowth of shade-tolerant, mesophytic species into forest understories; the result is shifting species compositions and changes in forest structure. In some cases, the loss of masting species, such as oak (Quercus spp.) and hickory (Carya spp.), may also accompany a shift in forest function and further accommodate other species shifts among mammal, insect, and bird populations. Management efforts have been suggested as a possible means …

Structural Studies On The Rubella Virus Capsid Protein And Its Organization In The Virion, Vidya Mangala Prasad

Open Access Dissertations

Rubella virus is a leading cause of birth defects due to infectious agents. When contracted during pregnancy, rubella infection leads to severe damage in fetuses. Despite its medical importance, very little is known about the structure of the pleomorphic rubella virus as compared to its alphavirus relatives. The rubella capsid protein is a critical structural component of virions as well as a key factor in virus-host interactions. Three crystal structures of the structural domain of the rubella capsid protein have been described here. The polypeptide fold of the capsid protomer has not been observed previously. The capsid protein structure, along …

Utilizing Electron Microscopy And Spectroscopy Methods To Understand Water Structure And Water Doping, Lior Miller

Open Access Dissertations

Water is the second most common element in the universe and the most studied material on earth. Most of the studies concerning water are from the fields of chemistry and biology. Hence, the structure of water molecules and short range order and interactions are well characterized and understood. However, the collective arrangement of water molecules and the long range order are still missing. Understanding of this long range order in water is needed, as it is the key to many water activities.

To fill this gap, this study utilizes a new direct method for characterization of water in the vapor …

Control-Theoretic Decision Support For Mitigation Of Modeled Software Project Cost Overruns, Scott David Miller

Open Access Dissertations

Despite sixty years of practice, the production of software remains an endeavor that is difficult to manage according to a schedule. Control theory studies the ability to influence the dynamical behavior of systems to achieve desired behaviors or eliminate undesired behaviors. In this work, the management problem of software project schedule adherence is re-cast as a problem in control theory.

Below, a modeling framework is proposed for capturing the constraints and dependencies found in the arbitrary organization specific work-flows underlying software production. Combined with proposed models for productivity, defect introduction, and defect detection, the framework completes a method for producing …

Mispronunciation Detection For Language Learning And Speech Recognition Adaptation, Zhenhao Ge

Open Access Dissertations

The areas of "mispronunciation detection" (or "accent detection" more specifically) within the speech recognition community are receiving increased attention now. Two application areas, namely language learning and speech recognition adaptation, are largely driving this research interest and are the focal points of this work.

There are a number of Computer Aided Language Learning (CALL) systems with Computer Aided Pronunciation Training (CAPT) techniques that have been developed. In this thesis, a new HMM-based text-dependent mispronunciation system is introduced using text Adaptive Frequency Cepstral Coefficients (AFCCs). It is shown that this system outperforms the conventional HMM method based on Mel Frequency Cepstral …

Top-Down Interrogation And Characterization Of Biological Macromolecules, Yang Gao

Open Access Dissertations

Analytical mass spectrometry has been widely applied in the field of biomolecule identification and characterization. It provides fast, accurate and robust information relevant to the molecular mass, composition and structure of the target analytes.

This thesis is focused on the top-down analysis of various macrobiomolecules, nucleic acids and proteins, in the context of ion/ion reaction and gas-phase unimolecular dissociation. The first part of the thesis deals with gas phase fragmentation behavior of chemically modified oligonucleotides. Factors, such as the observation time-scale, the ion type and the energy deposition method, are explored using a quadrupole/time-of-flight mass spectrometer. Novel fragmentation pathway associated …

Wireless Sensors For Condition Monitoring Applications Operating In Complete Metallic Environment, Lokesh Anilkumar Gupta

Open Access Dissertations

Condition monitoring of machines is advantageous in predicting failure and estimating machine component lifetime. Continuous monitoring of parameters such as temperature, vibration, and strain using sensors and consequent data analysis can help in reducing machine downtime by taking corrective actions before failure. Various wireless and wired sensors may be attached to critical components such as bearings, gears, mechanical seals, shafts etc. for measurements. These sensors however are often inadequate solutions as wired sensors are dicult to mount on rotating components, especially in millimeter-size spaces that may exist in some of these components. Wireless sensors provide a viable solution for measurements …

The Genetic Architecture Of Juvenile Migration In Rainbow Trout (Oncorhynchus Mykiss), Benjamin Charles Hecht

Open Access Dissertations

Animal migrations play a critical role in the health and balance of ecological systems and in the evolution and diversification of species, and this is perhaps best displayed amongst salmonid fishes (salmon, trout, and char) who exhibit variation in the propensity to migrate both within and among species. Rainbow and steelhead trout (Oncorhynchus mykiss), members of the salmonid family of fishes, capture this variation throughout their native range. Some populations and ecotypes will remain resident in freshwater habitats throughout their life history; while others have the ability to embark on tremendous marine migrations. Those that migrate undergo a suite of …

Student Success: Approaches To Modeling Student Matriculation And Retention, Jien-Jou Lin

Open Access Dissertations

Every year a group of graduates from high schools enter the engineering programs across this country with remarkable academic record. However, as reported in numerous studies, the number of students switching out of engineering majors continues to be an important issue. Previous studies have suggested various factors as predictors for student retention in engineering. To assist the engineering students with timely advising early in their program, an effective prediction model of matriculation and retention in engineering that use available student data are highly desirable.

In the first part of this work, the author developed new prediction models of student retention …

Effects Of Dna Methylation Pattern On The Chromatin Structure, Isabel Cristina Jimenez Useche

Open Access Dissertations

DNA methylation plays an essential role in various biological processes such as stem cell differentiation, imprinting, X-chromosome inactivation, etc. Increased DNA methylation levels have been associated with chromatin compaction leading to gene silencing. For example, abnormal DNA methylation is associated with silencing of tumor suppressor genes and is observed in the onset of tumorigenesis. There is evidence suggesting that not all methylation events are relevant in chromatin compaction and the initiation of cancer. It seems that methylation at certain locations of the DNA might be key to start chromatin compaction and gene silencing, but the location of this methylation sites …

The Termite Digestome: Understanding The Digestive Physiology Involved In Lignocellulosic Biomass Degradation, Zachary John Karl

Open Access Dissertations

The purpose of this research was to advance the understanding of lower termite digestive physiology and discover potential biocatalysts that can aid in the degradation of lignocellulosic biomass. Various protein characterization and gene expression methods were used throughout this research in order to accomplish these objectives. The results of this dissertation indicate that: 1) termites and their symbionts act in a synergistic manner to degrade biomass in vitro, 2) the host fraction of the gut (i.e., foregut and midgut) is the likely site of glucose absorption, 3) the termite and its symbionts contribute specific enzymes to the digestive process, 4) …

Development Of Tyrosine Kinase Peptide Biosensors And Methods For Detection, Andrew Michael Lipchik

Open Access Dissertations

New methods to monitor tyrosine kinase activity are critical for studying kinases in cell biology, drug discovery and the clinic. Peptide-based biosensors for detection of kinase activity utilitize a kinase specific artificial peptide substrate, which can report intercellular kinase activity through the incorporation of phosphate.

An artificial Syk substrate peptide was developed and incorporated with other functional modules to produce a Syk biosensor. These modules included a biotin-tag for affinity capture, a photo-cleavable amino acid to allow release of the substrate from the delivery module and the cell penetrating peptides TAT. A live cell kinase assay utilizing this biosensor was …

Establishing The Role Of The Pancreatic Transcription Factor Mist1 In Xbp1-Mediated Maintenance Of Pancreatic Acinar Cell Homeostasis, David Alan Hess

Open Access Dissertations

Pancreatic acinar cells (PACs) continuously produce more protein than any other cell type in the human body. As a result, PACs and other specialized secretory cells have a constant demand placed on their protein synthetic and packaging machinery. When demand for secreted products exceeds the capacity of the cell's basal protein production facilities, dangerous accumulations of misfolded proteins can build up, resulting in a condition known as ER stress. To ameliorate this stress, secretory cells activate a coordinated, three-part compensatory network collectively known as the unfolded protein response (UPR) to both expand the capacity of the ER and directly assist …

Structural Analysis Of Carbohydrates By Mass Spectrometry, Chiharu Konda

Open Access Dissertations

Protein glycosylation is a highly frequent post-translational modification. Glycosylation is actively involved in intermolecular and intercellular binding events that are important to a wide range of biological functions such as immunity and fertility. The unique functions of glycans are directly related to their structures. In order to fully characterize the structure of an unknown glycan, 5 levels of structural information is needed: sugar unit identity, anomeric configuration, linkage types, sequence, and branching location. One of the grand challenges limiting the advance of glycosciences is the lack of sensitive tools for detailed glycan structural analysis. Tandem mass spectrometry (MS/MS) is a …

Generation And Statistical Modeling Of Active Protein Chimeras: A Sequence Based Approach, Nicholas Fico

Open Access Dissertations

Generation of active protein chimeras is a valuable tool to probe the functional space of proteins. Statistical modeling is the next logical step, allowing us to build a model of gene fragment replaceability between species. In this thesis I begin to develop the statistical tools that are needed to systematically describe combinatorial protein libraries. I present three sets of diverse chimeric protein libraries developed using sequence information. The statistical model of the human N-Ras and human K-Ras-4B genes reveal a set previously unidetifed surface residues on the N-Ras G-Domain that may be involved in cellular localization. Statistical modeling of a …

Hybrid And Smart Topologically Interlocking Materials, Somesh Khandelwal

Open Access Dissertations

This thesis explores the mechanical properties of a new class of multifunctional architectured materials, Topologically Interlocking Materials (TIMs). These materials are created as an assembly of unit elements arranged in an interlocking pattern such that the load transfer between unit elements occurs by contact only. In the absence of adhesive interaction, the tensile component of the load is carried by complementary tensile elements in the form of external constraints or integrated filaments. By virtue of the bottom up design used in creating these materials, their mechanical properties are influenced by a number of controllable parameters including shape, confinement force, scale, …

The Application And Analysis Of Automated Triangulation Of Video Imagery By Successive Relative Orientation, Jae Sung Kim

Open Access Dissertations

The purpose of this thesis is the analysis and evaluation of methods to orient a strip of images using an automated approach. Automatic orientation of strips of video frame imagery would facilitate the construction of three dimensional models with less demand on a human operator for tedious measurement. Often one has no control points, so only relative orientation is possible. The relative orientation process gives camera parameters such as attitudes and selected baseline components and it can be implemented by using either collinearity or coplanarity equations. To automate the point selection, the pass and/or tie points were detected by the …

Using X-Ray Imaging Techniques To Determine Density Of Foods, Shivangi Mohan Kelkar

Open Access Dissertations

Density depends on the experimental technique and structural properties of food. True, apparent and bulk are different types of densities. For porous foods such as baked food products and complex food systems, accurate measurement of density is challenging. Empirical correlations dependent on composition and temperature exist to calculate true density. Thus if composition and apparent density are known, porosity can be calculated, porosity = [1 - (apparent density/ true density)]. Various non-destructive diagnostic tools have been employed to study food microstructure. Among these, computed tomography (CT) and digital radiography (DR) utilizing x-ray imaging showed greater capability for evaluation of food …