Physical Sciences and Mathematics Commons^™

Engineering Surface Functionality Of Nanoparticles For Biological Applications, Yi-Cheun Yeh

Doctoral Dissertations

Engineering the surface functionality of nanomaterials is the key to investigate the interactions between nanomaterials and biomolecules for potent biological applications such as therapy, imaging and diagnostics. My research has been orientted to engineer both of the surface monolayers and core materials to fabricate surface-functionalized nanomaterials through the synergistic multidisciplinary approach that combine organic chemistry, materials science and biology. This thesis illustrates the design and synthesis of the surface-funcitonalized quantum dots (QDs) and gold nanoparticles (AuNPs) for the fundamental studies and practical applications. For QDs, A new class of cationic QDs with quaternary ammonium derivatives was synthesized to provide permanent …

Guanidinium-Rich Romp Polymers Drive Phase, Charge, And Curvature-Specific Interactions With Phospholipid Membranes, Michael T W Lis

Doctoral Dissertations

Protein transduction domains (PTDs) and their and their synthetic mimics are short sequences capable of unusually high uptake in cells. Several varieties of these molecules, including the arginine-rich Tat peptide from HIV, have been extensively used as vectors for protein, DNA, and siRNA delivery into cells. Despite the wide-ranging utility of PTDs and their mimics, their uptake mechanism is still under considerable debate. How the molecules are able to cross phospholipid membranes, and what structural components are necessary for optimal activity are poorly understood. This thesis explores how PTDMs interact with phospholipid membrane phase, anionic lipid content and negative Gaussian …

Nanoparticle Building Blocks For Functional Structures, Youngdo Jeong

Doctoral Dissertations

A major goal in material science is achieving a desired function using structures fabricated with designed building blocks. Advanced synthetic and self-assembly techniques allow various nanomaterials to become promising building blocks, providing the control of the interaction between building blocks. The unique properties of nanomaterials can be transferred to structured systems. Among nanomaterials, inorganic nanoparticles such as gold nanoparticles (AuNPs), magnetic particles, and quantum dots (QDs) provide useful physical properties stemming from their inorganic core, large surface areas, and oriented surface functionalities. My research has focused on fabricating functional systems using gold nanoparticles (AuNPs), manipulating the interaction between AuNPs, bio-entities, …

Factor Inhibiting Hif's (Fih) Structure Controls O2 Activation And Reactivity, John A. Hangasky Iii

Doctoral Dissertations

Factor Inhibiting HIF (FIH) is a Fe(II)-αKG dependent oxygenase that acts as a cellular oxygen sensor in humans. FIH regulates the transcriptional activity of the hypoxia-inducible factor-1 (HIF-1a or HIF), a transcription factor responsible cellular O₂ homeostasis. Hydroxylation of the target residue HIF-Asn⁸⁰³, found in the C-terminal transactivation domain (CTAD), inactivates HIF-dependent gene expression. Central to FIH’s function is the activation of O₂ after CTAD binding. The mechanistic and structural features of FIH leading to tight coupling between CTAD binding and subsequent O₂-activation and reactivity are key for efficient O₂ sensing. Our mechanistic …

Evaluating Predictors Of An Individual’S Dietary Intake Latent Value Under Different Mixed Models, Shuli Yu

Doctoral Dissertations

The accurate estimation of an individual’s usual dietary intake is important since the estimates are essential to uncover the diet-disease relationships. This study explores a more accurate method to estimate an individual’s latent value of usual dietary intake when it is repeatedly measured using a 24-hour dietary recall (24HR) and seven day dietary recall (7DDR), accounting for random measurement error and bias. The performance of the (empirical) predictor of subject’s latent value obtained under the finite population mixed model (FPMM) framework is compared with those obtained under the usual mixed model and the measurement error model through a simulation study. …

Protein Behavior Directed By Heparin Charge And Chain Length, Burcu Baykal Minsky

Doctoral Dissertations

Glycosaminoglycans (GAGs), highly charged biological polyelectrolytes, are of growing importance as biomaterials and pharmaceutical drugs due to their immense range of physiological functions. They bind to many proteins; however, the degree of structural selectivity in GAG-protein interactions is largely unknown .Our studies have focused on the importance of heparin (a model GAG) charge and chain length in protein binding in order to explore its potential applications in biofunctional tissue scaffold materials, as polysaccharide drugs in anticoagulation, and as inhibitory agents in protein aggregation. We used electrospray ionization mass spectrometry, capillary electrophoresis, size exclusion chromatography, dynamic/static light scattering and electrostatic protein …

Microbe-Mineral Relationships And Biogenic Mineral Transformations In Actively Venting Deep-Sea Hydrothermal Sulfide Chimneys, Tzihsuan J. Lin

Doctoral Dissertations

This dissertation uses a combination of microbiology, mineralogy, and geochemistry to understand dissimilatory iron reduction in hyperthermophilic archaea and the role and potential impact of these and other vent microorganisms within active deep-sea hydrothermal vent chimneys. The central objective of the dissertation is to determine if mineral composition and chimney type are among the primary determinants of microbial community composition and hyperthermophilic, dissimilatory iron reducer growth, in addition to other environmental factors such as nutrient availability, temperature, pH, and chlorinity. This is done using samples and organisms collected from the Endeavour Segment of the Juan de Fuca Ridge in the …

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

New Remote Sensing Methods For Detecting And Quantifying Forest Disturbance And Regeneration In The Eastern United States, Michael Joseph Hughes

Doctoral Dissertations

Forest disturbances, such as wildfires, the southern pine beetle, and the hemlock woolly adelgid, affect millions of hectares of forest in North America with significant implications for forest health and management. This dissertation presents new methods to quantify and monitor disturbance through time in the forests of the eastern United States using remotely sensed imagery from the Landsat family of satellites, detect clouds and cloud-shadow in imagery, generate composite images from the clear-sky regions of multiple images acquired at different times, delineate the extents of disturbance events, identify the years in which they occur, and label those events with an …

Improvements On Segment Based Contours Method For Dna Microarray Image Segmentation, Yang Li

Doctoral Dissertations

DNA microarray is an efficient biotechnology tool for scientists to measure the expression levels of large numbers of genes, simultaneously. To obtain the gene expression, microarray image analysis needs to be conducted. Microarray image segmentation is a fundamental step in the microarray analysis process. Segmentation gives the intensities of each probe spot in the array image, and those intensities are used to calculate the gene expression in subsequent analysis procedures. Therefore, more accurate and efficient microarray image segmentation methods are being pursued all the time.

In this dissertation, we are making efforts to obtain more accurate image segmentation results. We …

Associations Of Total Activity Counts And Physical Activity Intensity Levels With The Metabolic Syndrome: A Structural Equation Modeling Approach, Dana Lizbeth Wolff

Doctoral Dissertations

To clarify the protective benefits of physical activity (PA), epidemiologists and public health researchers continue to seek improved methods of assessing PA. In particular, accelerometers have gained acceptance with researchers as they provide reliable estimates of PA and can record both the amount and intensity of ambulatory movement. However, there is concern that accelerometer data reduction techniques may not provide quantitatively accurate measurements of time spent in various PA intensity categories. One way to circumvent these inaccuracies is to use the accelerometer-derived total activity counts (TAC), which is a more direct expression of what the monitor records.

In order to …

Biophysical Studies Of Axonal Transport, Leslie Cyle Conway

Doctoral Dissertations

Intracellular transport provides a mechanism by which cellular material, such as organelles, vesicles, and protein, can be actively transported throughout the cell. This process relies on the activity of the cytoskeletal filament, microtubules, and their associated motor proteins. These motors are able to walk along microtubule tracks while carrying cellular cargos to enable the fast, regulated transport of these cargos. In cells, these microtubule filaments act as a binding platform for numerous different motor species as well as microtubule-associated proteins (MAPs). In addition, these filaments often form higher order structures, such as microtubule bundles. How motors navigate such complex, crowded …

Reactive Probes For Manipulating Polyketide Synthases, And Photoreactive Probes For Strained Alkyne Click Chemistry, Jon William Amoroso

Doctoral Dissertations

Polyketides are a broad class of natural products that have received attention from the scientific community because they are a rich mine of bioactive structures. The common thread that binds the class together is the method by which they are synthesized, by large enzymatic complexes called polyketide synthases (PKSs) which display assembly line like organization. A great deal of effort has been put into studying PKSs, but their mechanistic steps are still not perfectly understood. In order to further the study of PKSs and their components, we have developed a series of reactive small molecules that covalently modify specific sites …

Roosting, Site Fidelity, And Food Sources Of Urban Gulls In Massachusetts: Implications For Protecting Public Water Supplies, Daniel E. Clark

Doctoral Dissertations

Anyone who has spent time in coastal New England has seen gulls flying overhead and heard their familiar sound; gulls may be one of the most recognizable birds in the world. There are over 50 species of gulls worldwide, and many of them are closely associated with human development or activities. In Massachusetts, there are several common gull species including herring (Larus argentatus), great black-back (Larus marinus), laughing (Leucophaeus atricilla), and ring-billed (Larus delawarensis). While coastal encounters with gulls are ubiquitous, gulls can also be found inland, and ring-billed and herring gulls …